Top 50 cities: Quality of Living rankings 2010 – Mercer survey

* European cities continue to dominate the top of the ranking

* Vienna remains at the top, Baghdad at the bottom

* Calgary is first in the new Eco-city ranking



Regional focus

Americas
Europe
Middle East and Africa
Asia Pacific
City rankings

Vienna retains the top spot as the city with the world’s best quality of living, according to the Mercer 2010 Quality of Living Survey. Zurich and Geneva follow in second and third position, respectively, while Vancouver and Auckland remain joint fourth in the rankings.



Mercer conducts the ranking to help governments and multi-national companies compensate employees fairly when placing them on international assignments. The rankings are based on a point-scoring index, which sees Vienna score 108.6 and Baghdad 14.7. Cities are ranked against New York as the base city, with an index score of 100.



Mercer’s Quality of Living index list was revised and now covers 221 cities compared to 215 last year, which means direct trend comparison will not be possible until 2011. The new selection includes prominent capital and other major cities from across the world currently available in Mercer’s database and better reflects where companies are sending their expatriate employees in the current business environment.



Slagin Parakatil, Senior Researcher at Mercer, commented: “As the world economy becomes more globalised, cities beyond the traditional financial centres are emerging as attractive places in which to expand or establish a business. Cities in many emerging markets, such as in the Middle East or Asia, have seen a significant influx of foreign companies and their expatriate employees in recent years.”



“To ensure their expatriates are compensated appropriately and an adequate hardship allowance is included in their benefits package, companies seek a clear picture of the quality of living in these cities. We have reviewed our index to reflect these developments and it now better represents the cities that most interest our clients,” Mr Parakatil said.



European cities continue to dominate amongst the top 25 cities in the index. In the UK, London ranks at 39, while Birmingham is at 55 and Glasgow at 57. In the US, the highest ranking entry is Honolulu at position 31, followed by San Francisco at position 32. Singapore (28) is the top-scoring Asian city followed by Tokyo at 40. Baghdad, ranking 221, remains at the bottom of the list.



“Quality of living standards remained relatively stable on a global level throughout 2009 and the first half of 2010, but in certain regions and countries the economic recession had a noticeable impact on the business climate,” according to Mr Parakatil.



“Despite the economic downturn and companies’ efforts to contain costs, quality of living and hardship premiums remain important means of compensating expatriates for differences in living conditions. However, companies are more inclined to review the measurement of such allowances to ensure they are cost-effective."



This year’s ranking also identifies the cities with the best eco-ranking based on water availability and drinkability, waste removal, quality of sewage systems, air pollution and traffic congestion. Calgary is at the top of this index (score 145.7), followed by Honolulu in second place (score 145.1) and Ottawa and Helsinki in joint third (score 139.9). Wellington in New Zealand (5), Minneapolis (6), Adelaide (7) and Copenhagen fill the next four slots, while Kobe, Oslo and Stockholm share ninth place. Port-au-Prince in Haiti ranks at the bottom of this table with a score of only 27.8 (see attached table).



Mr Parakatil commented: “A high-ranking eco-city optimises its use of renewable energy sources and generates the lowest possible quantity of pollution (air, water, noise, etc). A city’s eco-status or attitude toward sustainability can have significant impact on the quality of living of its inhabitants. As a consequence these are also pertinent issues for companies that send employees and their families on long-term assignments abroad, especially considering the vast majority of expatriates are relocated to urban areas.”



“A certain standard of sustainability is essential for city living and forms a very important part of its inhabitants’ quality of living. Though a high standard of living may be taken for granted in certain cities, a lack thereof is much more noticeable and can even lead to severe hardship,” said Mr Parakatil.

Americas

Canadian cities still dominate the top of the index for this region with Vancouver (4) retaining the top spot, followed by Ottawa (14), Toronto (16) and Montreal (21). Calgary ranks 28 on the overall quality of living ranking.



Honolulu (31) is the city in the US with the highest quality of living, followed by San Francisco (32) and Boston (37). Chicago and Washington share position 45 and New York - the base city - is in position 49. Newly added cities Philadelphia and Dallas are ranked 55 and 61, respectively.



In Central and South America, Point-à-Pitre, the largest city and economic area of Guadeloupe and new to the index this year, ranks the highest for quality of living at 62. San Juan in Puerto Rico follows at 72 and Buenos Aires at 78. Havana (192) and Port-au-Prince (213) are the lowest-ranking cities in the region.



Mr Parakatil commented: “Quality of living remained stable in North American cities. However, in South and Central America a general decline is witnessed mostly due to political instability, economic woes and energy shortages in certain countries. High levels of crime also remain a major problem in many of the region’s cities.”



Canadian and US cities are strongly represented at the top of the eco-city ranking, both for this region and globally. Calgary grabs the top spot globally with a score of 145.7, closely followed by Honolulu (score 145.1) in second. Ottawa is in third position with a score of 139.9 and Minneapolis follows in sixth place (score 137.8). Mr Parakatil commented: “Calgary’s top ranking is down to its excellent level of service on waste removal, sewage systems, and water drinkability and availability, coupled with relatively low air pollution.”



The highest-ranking Central and South American city is again Pointe-à-Pitre (49), followed by San Juan (69) and Montevideo (70).


Europe

Europe has 16 cities amongst the world’s top 25 cities for quality of living. Vienna retains the highest ranking both for the region and globally and is again followed by Zurich (2), Geneva (3) and Düsseldorf (6). The lowest-ranking Western European cities are Leipzig (64) and Athens (75). In the UK, London is the highest-ranking city at 39, followed by newcomer to the list Aberdeen (53), Birmingham (55), Glasgow (57) and Belfast (63).



Levels of quality of living continue to improve in Eastern Europe, with most index scores increasing slightly. Prague is the highest-ranking city at 70 and its index score increased from 93.9 to 94.8 in 2010. Budapest follows in position 73 and Ljubljana in 77.



In the eco-city index, Nordic cities fare particularly well with Helsinki (3) the highest-ranked in the region, followed by Copenhagen (8) and Oslo in joint ninth place with Stockholm. “Nordic cities do particularly well because the modern parts of most of them have been designed with potential environmental impacts in mind,” said Mr Parakatil. Aberdeen (19) is the highest-ranking UK eco-city, followed by Belfast (30), Glasgow (47), London (63) and Birmingham (64).


Middle East and Africa

Dubai (75) in the United Arab Emirates and Port Louis in Mauritius (82) are the region’s cities with the best quality of living. Abu Dhabi (83), Cape Town (86) and Tunis (94) follow and are, along with Victoria in the Seychelles (95), Johannesburg (96) and Muscat in Oman (100), the region’s only other cities in the top 100. Following the revision of the index a selection of cities from this region has been added, including Doha in Qatar (110), Rabat in Morocco (112), Banjul in Gambia (164) and Abuja in Nigeria (205).



Baghdad (221) remains at the bottom of the table, though its index score has increased slightly (from 14.4 to 14.7 in 2010). A lack of security and stability continue to have a negative impact on Baghdad’s quality of living and its score remains far behind that of Bangui (27.4) in the Central African Republic which is second to last.



In the eco-city index, most of the region’s cities rank below 100. The highest-ranking cities are Cape Town (30), Victoria (38), Muscat (48), Johannesburg (54) and Abu Dhabi and Dubai (in joint 65). Antananarivo in Madagascar (217) is at the bottom of the list with an eco-city score of 39.7, while Baghdad is at 214, scoring 40.5.



Mr Parakatil commented: “The lack of adequate modern infrastructure in some of the African cities combined with relatively high air pollution explains why many of them are ranked below 100.”


Asia Pacific

Auckland (4) retains its position as the highest-ranking city for quality of living in the region. Sydney follows at 10, Wellington at 12, Melbourne at 18 and Perth at 21. At 26, Canberra is new to the index. Singapore remains the highest-ranking Asian city at 28, followed by Japanese cities Tokyo (40), Kobe and Yokohama (both at 41), Osaka (51) and Nagoya (57). The region’s lowest-ranking cities are Dhaka in Bangladesh (206) and two cities new to the list – Bishkek in Kyrgyzstan (209) and Dushanbe in Tajikistan (210).



Mr Parakatil commented: “Quality of living declined in a few countries in Asia between the start of 2009 and 2010. Increasing threats of violence and terrorism, coupled with natural disasters such as earthquakes, typhoons and cyclones have had a negative impact on the quality of living in Asian cities. This may result in higher hardship allowances for expatriates sent to these countries.”



With a score of 138.9, Wellington (5) is the highest-ranking eco-city in the region followed by Adelaide (7), Kobe (9), Perth (12) and Auckland (13). Dhaka in Bangladesh (220) ranks lowest with a score of 30.9.



--------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Expatriates in difficult locations: Determining appropriate allowances and incentives
Companies need to be able to determine their compensation packages rationally, consistently and systematically. Providing incentives to reward and recognise the efforts that employees and their families make when taking on international assignments remains a typical practice, particularly for difficult locations. Two common incentives include a quality of living allowance and a mobility premium.



* Quality of living or “hardship” allowances compensate expatriates for decreases in the quality of living between their home and host locations.

* By contrast, a mobility premium simply compensates for the inconvenience of being uprooted and having to work in another country.


A quality of living allowance is typically location-related whilst a mobility premium is usually independent of the host location. Some multi-national companies combine these premiums but the vast majority of international companies provide them separately. The latter approach is deemed to be clearer and more transparent.



Mercer hardship allowance recommendations
Mercer evaluates local living conditions in all the 420 cities it surveys worldwide. Living conditions are analysed according to 39 factors, grouped in 10 categories:



1. Political and social environment (political stability, crime, law enforcement, etc)

2. Economic environment (currency exchange regulations, banking services, etc)

3. Socio-cultural environment (censorship, limitations on personal freedom, etc)

4. Health and sanitation (medical supplies and services, infectious diseases, sewage, waste disposal, air pollution, etc)

5. Schools and education (standard and availability of international schools, etc)

6. Public services and transportation (electricity, water, public transport, traffic congestion, etc)

7. Recreation (restaurants, theatres, cinemas, sports and leisure, etc)

8. Consumer goods (availability of food/daily consumption items, cars, etc)

9. Housing (housing, household appliances, furniture, maintenance services, etc)

10. Natural environment (climate, record of natural disasters)





-------------------------------------------------------------------------------------------------------------------------------------------------
City rankings
Top 50 cities: Quality of living ranking

Base City: New York, US (=100)

Rank 2010

City Country QOL index 2010
1 VIENNA AUSTRIA 108.6
2 ZURICH SWITZERLAND 108
3 GENEVA SWITZERLAND 107.9
4 VANCOUVER CANADA 107.4
4 AUCKLAND NEW ZEALAND 107.4
6 DUSSELDORF GERMANY 107.2
7 FRANKFURT GERMANY 107
7 MUNICH GERMANY 107
9 BERN SWITZERLAND 106.5
10 SYDNEY AUSTRALIA 106.3
11 COPENHAGEN DENMARK 106.2
12 WELLINGTON NEW ZEALAND 105.9
13 AMSTERDAM NETHERLANDS 105.7
14 OTTAWA CANADA 105.5
15 BRUSSELS BELGIUM 105.4
16 TORONTO CANADA 105.3
17 BERLIN GERMANY 105
18 MELBOURNE AUSTRALIA 104.8
19 LUXEMBOURG LUXEMBOURG 104.6
20 STOCKHOLM SWEDEN 104.5
21 PERTH AUSTRALIA 104.2
21 MONTREAL CANADA 104.2
23 HAMBURG GERMANY 104.1
24 NURNBURG GERMANY 103.9
24 OSLO NORWAY 103.9
26 CANBERRA AUSTRALIA 103.6
26 DUBLIN IRELAND 103.6
28 CALGARY CANADA 103.5
28 SINGAPORE SINGAPORE 103.5
30 STUTTGART GERMANY 103.3
31 HONOLULU UNITED STATES 103.1
32 ADELAIDE AUSTRALIA 103
32 SAN FRANCISCO UNITED STATES 103
34 PARIS FRANCE 102.9
35 HELSINKI FINLAND 102.6
36 BRISBANE AUSTRALIA 102.4
37 BOSTON UNITED STATES 102.2
38 LYON FRANCE 101.9
39 LONDON UNITED KINGDOM 101.6
40 TOKYO JAPAN 101.4
41 MILAN ITALY 100.8
41 KOBE JAPAN 100.8
41 YOKOHAMA JAPAN 100.8
44 BARCELONA SPAIN 100.6
45 LISBON PORTUGAL 100.3
45 CHICAGO UNITED STATES 100.3
45 WASHINGTON UNITED STATES 100.3
48 MADRID SPAIN 100.2
49 NEW YORK CITY UNITED STATES 100
50 SEATTLE UNITED STATES 99.8

World's most livable cities

The world's most livable cities is an informal name given to any list of cities as they rank on a reputable annual survey of living conditions. Two examples are the Mercer Quality of Living Survey and The Economist's World's Most Livable Cities (using data from Mercer as well). The list does not necessarily include factors such as entertainment.


Mercer's Quality of Living Survey is released annually, comparing 221 cities based on 39 criteria. New York is given a baseline score of 100 and other cities are rated in comparison. Important criteria are safety, education, hygiene, health care, culture, environment, recreation, political-economic stability and public transportation.[1]

The importance of the list lies primarily in that internationally operating companies use it to determine where they will open offices or plants and how much they pay the employees.

In the 2010 list for city, the top is dominated by cities from Europe, with several entries from Canada, Scotland, Australia and New Zealand. Switzerland and Germany both have 3 cities in the top 10, which is especially striking for Switzerland, given the size of the country. The first entries from other countries are the USA at 31, Singapore at 22 and Japan at 37. Baghdad was at the bottom of the list. Of the 25 cities at the bottom, 15 are from Africa. Compared to lists from previous years, countries from South Asia (mainly India), East Asia (mainly China), the Middle East and Eastern Europe are clearly on the rise.

Mercer also has a 'Personal Safety' list, which is also dominated by EU and Swiss cities, with the top 5 being Luxembourg, Bern, Geneva, Helsinki and Zürich.

2010 year’s ranking also identifies the cities with the best eco-ranking based on water availability and drinkability, waste removal, quality of sewage systems, air pollution and traffic congestion. Calgary is at the top of this index (score 145.7), followed by Honolulu in second place (score 145.1) and Ottawa and Helsinki in joint third (score 139.9). Wellington in New Zealand (5), Minneapolis (6), Adelaide (7) and Copenhagen fill the next four slots, while Kobe, Oslo and Stockholm share ninth place. Port-au-Prince in Haiti ranks at the bottom of this table with a score of only 27.8.[2]

Global liveability report - January 2010 (EIU)

Vancouver (Canada) continues to top the Economist Intelligence Unit's global liveability survey. A score of 98% bodes well for visitors during the Winter Olympics this year. Conversely, as security concerns abound in Sub-Saharan Africa following the Africa Cup of Nations, Football World Cup host Johannesburg (South Africa) comes in joint 92nd place with a score of 69.1%. Nonetheless, this is still the highest score in Sub-Saharan Africa.

Jon Copestake, editor of the report, comments: "Vancouver scores well across all categories in the survey and the forthcoming Winter Games contribute to a strong score in the cultural and sporting events category. Johannesburg has had well-documented crime problems, but performs better in other categories, with the highest overall liveability rating in Sub-Saharan Africa."

Elsewhere, European and North American cities continue to dominate the top tier of the ranking, alongside cities in Australia and New Zealand. Other regions fair less well, especially Sub-Saharan Africa, with security concerns under renewed scrutiny following attacks on the Togo national football team in the 2010 Africa Cup of Nations in Angola. The ongoing social and economic crisis in Zimbabwe ensures that Harare is still the worst of the 140 cities surveyed.

The Economist Intelligence Unit's liveability survey assesses living conditions in 140 cities around the world. A rating of relative comfort for 30 indicators is assigned across five broad categories: stability; Healthcare; culture and environment; education; and infrastructure. The survey gives an overall rating of 0-100, where 1 is intolerable and 100 is ideal.

A tale of two cities

Vancouver (Canada) still sits atop the global ranking, with the city offering an excellent infrastructure and low crime levels ahead of playing host to the 2010 Winter Olympic Games. Despite controversy surrounding the growing number of homeless people in Vancouver, particularly proposals to force people into shelters during the Olympics, general liveability levels are high. Visitors will benefit from good transport links and broad cultural and recreational availability, notably the Olympics themselves although, as with any large event in any large city, there is still some prevalence of petty crime.

Johannesburg (South Africa), host to the world's other major sporting event this year, fares less well. Security concerns over the 2010 Football World Cup abound and this is reflected in the city's position of joint 92nd in the ranking with a score of 69.1%, almost 30 percentage points lower than that achieved by Vancouver. Security is the main concern in South Africa, owing to a well-documented struggle with violent crime rates. However, Johannesburg does enjoy strong availability of cultural and recreational activities, ensuring that visitors to this year's Football World Cup will have plenty to do in addition to watching the tournament. South African cities also achieve the highest liveability scores in a region plagued by instability and problems with health and infrastructure.

Looking ahead

Ironically, Johannesburg shares its joint 92nd position with two of the major cities of the next host of the Football World Cup, Brazil, which will stage the contest in 2014. Both Rio de Janeiro and São Paulo have the same overall liveability score as Johannesburg, although both benefit from slightly higher levels of stability, with lower scores in other categories resulting in parity (note that Rio de Janeiro will also host the 2016 Summer Olympic Games). Awarding high-level sporting events to developing cities provides an opportunity for investment in infrastructure needed to raise levels of liveability in these locations and also to prompt investment in countries more generally.

Turning to other upcoming sporting events, the Rugby World Cup in 2011 will be held in New Zealand, where liveability scores are at the top of the scale. Auckland, host to the Rugby World Cup final, is the tenth most liveable of the 140 locations surveyed and achieves a score of only 2.3 percentage points lower than top-rated Vancouver. Conversely, in the same year, the Cricket World Cup will take place in locations at the other end of the ranking amid security concerns following the 2009 attack on the Sri Lankan national cricket team in Pakistan. Although the 2009 attack led to Pakistan's exclusion as a host nation, other hosts such as Sri Lanka and Bangladesh are home to locations in the bottom ten of the league table, and worst category of liveability (Colombo is 132nd and Dhaka is 138th, with liveability scores of just 47.3% and 38.7% respectively). Locations in India, the third host nation, fare a little better, with Mumbai (117th) and New Delhi (113th) scoring 56.5% and 58.6% respectively.

In Western Europe, London, host to the 2012 Olympic Games, sits in 54th position with a liveability score of 88.4%. This is almost 10 percentage points below Vancouver's score, but London remains in the very top tier of the liveability ranking. Although concerns have been raised about the city's ability to meet the infrastructural demands of the Olympics, stability, particularly following terrorism attacks in July 2007, is the poorest-performing liveability category. Also in 2012, Warsaw and Ukraine are set to co-host the European Football Championship. Warsaw scores relatively well in areas important to visitors to the event, with stability, infrastructure, and culture and the environment all scoring 80% or more. Ukraine lies 91st in the ranking and only marginally outscores Johannesburg, Rio de Janeiro and São Paulo with a rating of 69.2%.

About the Liveability survey
The concept of liveability is simple: it assesses which locations around the world provide the best or the worst living conditions. Assessing liveability has a broad range of uses, from benchmarking perceptions of development levels to assigning a hardship allowance as part of expatriate relocation packages. The Economist Intelligence Unit's liveability rating, part of the Worldwide Cost of Living Survey, quantifies the challenges that might be presented to an individual's lifestyle in 140 cities worldwide. Each city is assigned a score for over 30 qualitative and quantitative factors across five broad categories:

* Stability
* Healthcare
* Culture and environment
* Education
* Infrastructure

Each factor in each city is rated as acceptable, tolerable, uncomfortable, undesirable or intolerable. For qualitative indicators, a rating is awarded based on the judgment of in–house analysts and in–city contributors. For quantitative indicators, a rating is calculated based on the relative performance of a number of external data points. The categories are compiled and weighted to provide an overall rating of 1–100, where 1 is considered intolerable and 100 is considered ideal. The report considers that any city with a rating of 80 or more will have few, if any, challenges to living standards. Liveability scores can be scaled as follows:

The suggested liveability scale
Rating Description
80–100 There are few, if any, challenges to living standards
70–80 Day–to–day living is fine, in general, but some aspects of life may entail problems
60–70 Negative factors have an impact on day-to-day living
50–60 Liveability is substantially constrained
50 or less Most aspects of living are severely restricted


Top 10 cities

Rank Country City Rating
1 Canada Vancouver 98.0
2 Austria Vienna 97.9
3 Australia Melbourne 97.5
4 Canada Toronto 97.2
5 Canada Calgary 96.6
6 Finland Helsinki 96.2
7 Australia Sydney 96.1
8= Australia Perth 95.9
8= Australia Adelaide 95.9
10 New Zealand Auckland 95.7


Bottom 10 cities

Rank Country City Rating
130= Senegal Dakar a 48.3
132 Sri Lanka Colombo 47.3
133 Nepal Kathmandu 47.1
134 Cameroon Douala 43.3
135 Pakistan Karachi 40.9
136 Nigeria Lagos 39.0
137 PNG Port Moresby 38.9
138= Algeria Algiers 38.7
138= Bangladesh Dhaka 38.7
140 Zimbabwe Harare 37.5

Top 50 cities: Eco-City ranking-Mercer

*Eco-City Ranking 2010 includes the following criteria: Water availability, water potability, waste removal, sewage, air pollution and traffic congestion.


Rank 2010 City Country Eco-city index* 2010
1 CALGARY CANADA 145.7
2 HONOLULU UNITED STATES 145.1
3 OTTAWA CANADA 139.9
3 HELSINKI FINLAND 139.9
5 WELLINGTON NEW ZEALAND 138.9
6 MINNEAPOLIS UNITED STATES 137.8
7 ADELAIDE AUSTRALIA 137.5
8 COPENHAGEN DENMARK 137.4
9 KOBE JAPAN 135.6
9 OSLO NORWAY 135.6
9 STOCKHOLM SWEDEN 135.6
12 PERTH AUSTRALIA 135.3
13 MONTREAL CANADA 133.6
13 VANCOUVER CANADA 133.6
13 NURNBERG GERMANY 133.6
13 AUCKLAND NEW ZEALAND 133.6
13 BERN SWITZERLAND 133.6
13 PITTSBURGH UNITED STATES 133.6
19 ZURICH SWITZERLAND 133.5
19 ABERDEEN UNITED KINGDOM 133.5
21 CANBERRA AUSTRALIA 133.3
22 SINGAPORE SINGAPORE 132.4
23 BRISBANE AUSTRALIA 131.6
23 WASHINGTON UNITED STATES 131.6
25 MELBOURNE AUSTRALIA 131.5
25 GENEVA SWITZERLAND 131.5
25 BOSTON UNITED STATES 131.5
28 DUSSELDORF GERMANY 130.7
28 MUNICH GERMANY 130.7
30 CAPE TOWN SOUTH AFRICA 129.4
30 BELFAST UNITED KINGDOM 129.4
32 LYON FRANCE 129.3
33 DUBLIN IRELAND 128.9
34 HAMBURG GERMANY 128.8
34 STUTTGART GERMANY 128.8
34 PHILADELPHIA UNITED STATES 128.8
37 YOKOHAMA JAPAN 128.7
38 VICTORIA SEYCHELLES 128.5
39 TORONTO CANADA 127.1
39 AMSTERDAM NETHERLANDS 127.1
41 BRUSSELS BELGIUM 126.8
41 LEIPZIG GERMANY 126.8
43 ST. LOUIS UNITED STATES 126.6
44 VIENNA AUSTRIA 126.2
44 LUXEMBOURG LUXEMBOURG 126.2
46 SYDNEY AUSTRALIA 125
47 GLASGOW UNITED KINGDOM 124.7
48 MUSCAT OMAN 124.2
49 POINT-A-PITRE GUADELOUPE 123.8
50 NAGOYA JAPAN 123.1
50 OSAKA JAPAN 123.1
50 FRANKFURT GERMANY 123.1


Mercer is a leading global provider of consulting, outsourcing and investment services. Mercer works with clients to solve their most complex benefit and human capital issues, designing and helping manage health, retirement and other benefits. It is a leader in benefit outsourcing. Mercer’s investment services include investment consulting and investment management. Mercer’s 18,000 employees are based in more than 40 countries. The company is a wholly owned subsidiary of Marsh & McLennan Companies, Inc., which lists its stock (ticker symbol: MMC) on the New York, Chicago and London stock exchanges. For more information, visit www.mercer.com

2007 List of cities by quality of living-Mercer

This is a list of the world's cities by quality of living, according to the "Mercer Human Resource Consulting Quality of Living Survey".

In 2008, Zurich retains its 2007 title as the highest ranked city, followed by Geneva (2), jointly Vienna (3) and Vancouver (3), finally Auckland (5). The quality of living survey covers 215 cities and is conducted to help governments and major companies place employees on international assignments. The survey also identifies those cities with the highest personal safety ranking based on internal stability, crime, effectiveness of law enforcement and relationships with other countries. In this case, Luxembourg is top, followed by Bern, Geneva, Helsinki and Zurich, all equally placed at number 2.

The 2007 survey identified Zurich, Geneva, Vancouver and Vienna as having the highest quality of living. The least desirable cities were found to be Brazzaville and Pointe Noire in the Republic of Congo which scored 23 and 30.5 respectively.

The cities — 218 in total — were evaluated on 39 factors including political, economic, environmental, personal safety, health, education, transportation and other public service factors. Cities were compared to New York City which was given a base score of 100.

2007 Rank↓ City↓ Country↓ Index 2007↓
1 Zürich Switzerland Switzerland 108.1
2 Geneva Switzerland Switzerland 108.0
3 Vancouver Canada Canada 107.7
3 Vienna Austria Austria 107.7
5 Auckland New Zealand New Zealand 107.3
5 Düsseldorf Germany Germany 107.3
7 Frankfurt Germany Germany 107.1
8 Munich Germany Germany 106.9
9 Bern Switzerland Switzerland 106.5
9 Sydney Australia Australia 106.5
11 Copenhagen Denmark Denmark 106.2
12 Wellington New Zealand New Zealand 105.8
13 Amsterdam Netherlands The Netherlands 105.7
14 Brussels Belgium Belgium 105.6
15 Toronto Canada Canada 105.4
16 Berlin Germany Germany 105.2
17 Melbourne Australia Australia 105.0
18 Luxembourg Luxembourg Luxembourg 104.8
18 Ottawa Canada Canada 104.8
20 Stockholm Sweden Sweden 104.7
21 Perth Australia Australia 104.5
22 Montreal Canada Canada 104.3
23 Nürnberg Germany Germany 104.2
24 Calgary Canada Canada 103.6
24 Hamburg Germany Germany 103.6
26 Oslo Norway Norway 103.5
27 Dublin Republic of Ireland Ireland 103.3
27 Honolulu United States United States 103.3
29 San Francisco United States United States 103.2
30 Helsinki Finland Finland 103.1
30 Adelaide Australia Australia 103.1
32 Brisbane Australia Australia 102.8
33 Paris France France 102.7
34 Singapore Singapore Singapore 102.5
35 Tokyo JapanJapan 102.3
36 Lyon France France 101.9
36 Boston United States United States 101.9
38 Yokohama Japan Japan 101.7
39 London United Kingdom United Kingdom 101.2
40 Kobe Japan Japan 101.0
41 Barcelona Spain Spain 100.6
42 Madrid Spain Spain 100.5
42 Osaka Japan Japan 100.5
44 Washington DC United States United States 100.4
44 Chicago United States United States 100.4
46 Portland, OR United States United States 100.3
47 Lisbon Portugal Portugal 100.1
48 New York City United States United States 100.0
49 Milan Italy Italy 99.9
49 Seattle United States United States 99.9
51 Lexington United States United States 99.8
52 Pittsburgh United States United States 99.7
52 Winston Salem United States United States 99.7
54 Nagoya Japan Japan 99.5
55 Riyadh Saudi Arabia Saudi Arabia 98.3
55 Jeddah Saudi Arabia Saudi Arabia 98.3
57 Glasgow United Kingdom United Kingdom 98.2
58 Los Angeles United States United States 98.1
58 Cleveland United States United States 98.1
60 Minneapolis United States United States 97.9
61 Rome Italy Italy 97.4
62 Miami United States United States 96.3
63 Yokkaichi Japan Japan 96.2
64 Detroit United States United States 96.1
65 San Pedro Garza García Mexico Mexico 96.1
66 St Louis United States United States 96.1
67 Atlanta United States United States 95.7
68 Leipzig Germany Germany 95.5
69 Houston United States United States 95.4
70 Omuta Japan Japan 94.9
71 Hong Kong Hong Kong Hong Kong 94.3
72 San Juan Puerto Rico Puerto Rico 92.9
73 Prague Czech Republic Czech Republic 92.3
74 Medinah Saudi Arabia Saudi Arabia 91.4
75 Budapest Hungary Hungary 90.2
76 Kuala Lumpur Malaysia Malaysia 88.9
77 Montevideo Uruguay Uruguay 88.2
78 Port Louis Mauritius Mauritius 87.7
79 Athens Greece Greece 87.6
80 Buenos Aires Argentina Argentina 87.4
81 Dubai United Arab Emirates United Arab Emirates 87.0
82 Ljubljana Slovenia Slovenia 87.0
83 Vilnius Lithuania Lithuania 86.6
84 Taipei Republic of China Taiwan 86.5
85 Santiago Chile Chile 86.5
86 Cape Town South Africa South Africa 85.7
87 Warsaw Poland Poland 85.7
88 Seoul South Korea South Korea 85.2
89 Abu Dhabi United Arab Emirates United Arab Emirates 84.1
90 Tallinn Estonia Estonia 83.7
91 Johannesburg South Africa South Africa 83.3
92 Limassol Cyprus Cyprus 83.2
93 Valletta Malta Malta 82.9
94 Panama City Panama Panama 82.9
95 Khobar Saudi Arabia Saudi Arabia 82.6
96 Tunis Tunisia Tunisia 82.4
97 Victoria Seychelles Seychelles 82.2
98 Papeete French Polynesia French Polynesia 82.0
99 Port Elizabeth South Africa South Africa 82.0
100 Bratislava Slovakia Slovakia 81.7
101 Shanghai People's Republic of China China 81.6

Global liveability report

Rank Country City Rating
1 Canada Vancouver 98.0
2 Austria Vienna 97.9
3 Australia Melbourne 97.5
4 Canada Toronto 97.2
5 Canada Calgary 96.6
6 Finland Helsinki 96.2
7 Australia Sydney 96.1
8= Australia Perth 95.9
8= Australia Adelaide 95.9
10 New Zealand Auckland 95.7

The Health Supplement Timeline

1970’s - Multivitamins

1980’s - Herbs

1990’s - Antioxidants

2000’s - Immune System Support

The 29 Healthiest Foods on the Planet

The following is a "healthy food hot list" consisting of the 29 food that will give you the biggest nutritional bang for you caloric buck, as well as decrease your risk for deadly illnesses like cancer, diabetes and heart disease. Along with each description is a suggestion as to how to incorporate these power-foods into your diet.

Fruits
01. ApricotsThe Power: Beta-carotene, which helps prevent free-radical damage and protect the eyes. The body also turns beta-carotene into vitamin A, which may help ward off some cancers, especially of the skin. One apricot has 17 calories, 0 fat, 1 gram of fiber. Snacks on them dried, or if you prefer fresh, buy when still firm; once they soften, they lose nutrients.

02. Avocados
The Power: Oleic acid, an unsaturated fat that helps lower overall cholesterol and raise levels of HDL, plus a good dose of fiber. One slice has 81 calories, 8 grams of fat and 3 grams of fiber. Try a few slices instead of mayonnaise to dress up your next burger.

03. RaspberriesThe Power: Ellagic acid, which helps stall cancer-cell growth. These berries are also packed with vitamin C and are high in fiber, which helps prevent high cholesterol and heart disease. A cup has only 60 calories, 1 gram of fat and 8 grams of fiber. Top plain low-fat yogurt or oatmeal (another high fiber food) with fresh berries.

05. CantaloupeThe Power: Vitamin C (117mg in half a melon, almost twice the recommended daily dose) and beta-carotene - both powerful antioxidants that help protect cells from free-radical damage. Plus, half a melon has 853mg of potassium - almost twice as much as a banana, which helps lower blood pressure. Half a melon has 97 calories, 1 gram of fat and 2 grams of fiber. Cut into cubes and freeze, then blend into an icy smoothie.

06. Cranberry Juice
The Power: Helps fight bladder infections by preventing harmful bacteria from growing. A cup has 144 calories, 0 grams of fat and 0 fiber. Buy 100 percent juice concentrate and use it to spice up your daily H20 without adding sugar.

07. TomatoThe Power: Lycopene, one of the strongest carotenoids, acts as an antioxidant. Research shows that tomatoes may cut the risk of bladder, stomach and colon cancers in half if eaten daily. A tomato has 26 calories, 0 fat and 1 gram of fiber. Drizzle fresh slices with olive oil, because lycopene is best absorbed when eaten with a little fat.

08. RaisinsThe Power: These little gems are a great source of iron, which helps the blood transport oxygen and which many women are short on. A half-cup has 218 calories, 0 fat and 3 grams of fiber. Sprinkle raisins on your morning oatmeal or bran cereal - women, consider this especially during your period.

09. Figs
The Power: A good source of potassium and fiber, figs also contain vitamin B6, which is responsible for producing mood-boosting serotonin, lowering cholesterol and preventing water retention. The Pill depletes B6, so if you use this method of birth control, make sure to get extra B6 in your diet. One fig has 37 to 48 calories, 0 fat and 2 grams of fiber. (Cookie lovers - fig bars have around 56 calories, 1 gram of fat and 1 gram of fiber per cookie). Fresh figs are delicious simmered alongside a pork tenderloin and the dried variety make a great portable gym snack.

10. Lemons/Limes
The Power: Limonene, furocoumarins and vitamin C, all of which help prevent cancer. A wedge has 2 calories, 0 fat and 0 fiber. Buy a few of each and squeeze over salads, fish, beans and vegetables for fat free flavor. See also: Beneficial Bytes: Lemons and Limes.

Vegetables
11. OnionsThe Power: Quercetin is one of the most powerful flavonoids (natural plant antioxidants). Studies show it helps protect against cancer. A cup (chopped) has 61 calories, 0 fat and 3 grams of fiber. Chop onions for the maximum phytonutrient boost, or if you hate to cry, roast them with a little olive oil and serve with rice or other vegetables.

12. ArtichokesThe Power: These odd-looking vegetables contain silymarin, an antioxidant that helps prevent skin cancer, plus fiber to help control cholesterol. One medium artichoke has 60 calories, 0 fat and 7 grams of fiber. Steam over boiling water for 30 to 40 minutes. Squeeze lemon juice on top, then pluck the leaves off with your fingers and use your teeth to scrape off the rich-tasting skin. When you get to the heart, you have found the best part!

13. GingerThe Power: Gingerols may help reduce queasiness; other compounds may help ward off migraines and arthritis pain by blocking inflammation-causing prostaglandins. A teaspoon of fresh gingerroot has only 1 calorie, 0 fat and 0 fiber. Peel the tough brown skin and slice or grate into a stir-fry.

14. BroccoliThe Power: Indole-3-carbinol and sulforaphane, which help protect against breast cancer. Broccoli also has lots of vitamin C and beta-carotene. One cup (chopped) has 25 calories, 0 fat and 3 grams of fiber. Don't overcook broccoli - instead, microwave or steam lightly to preserve phytonutrients. Squeeze fresh lemon on top for a zesty and taste, added nutrients and some vitamin C.

15. SpinachThe Power: Lutein and zeaxanthin, carotenoids that help fend off macular degeneration, a major cause of blindness in older people. Plus, studies show this green fountain of youth may help reverse some signs of aging. One cup has 7 calories, 0 fat and 1 gram of fiber. Add raw leaves to a salad or saut� with a little olive oil and garlic.

16. Bok Choy (Chinese cabbage) The Power: Brassinin, which some research suggests may help prevent breast tumors, plus indoles and isothiocyanates, which lower levels of estrogen, make this vegetable a double-barreled weapon against breast cancer. A cup will also give you 158mg of calcium (16 percent of your daily recommended requirement) to help beat osteoporosis. A cup (cooked) has 20 calories, 0 fat and 3 grams of fiber. Find it in your grocer's produce section or an Asian market. Slice the greens and juicy white stalks, then saute like spinach or toss into a stir-fry just before serving.

17. Squash (Butternut, Pumpkin, Acorn) The Power: Winter squash has huge amounts of vitamin C and beta-carotene, which may help protect against endometrial cancer. One cup (cooked) has 80 calories, 1 gram of fat and 6 grams of fiber. Cut on in half, scoop out the seeds and bake or microwave until soft, then dust with cinnamon.

18. Watercress and ArugulaThe Power: Phenethyl isothiocyanate, which, along with beta-carotene and vitamins C and E, may help keep cancer cells at bay. One cup has around 4 calories, 0 fat and 1 gram of fiber. Do not cook these leafy greens; instead, use them to garnish a sandwich or add a pungent, peppery taste to salad.

19. GarlicThe Power: The sulfur compounds that give garlic its pungent flavor can also lower LDL ("bad") cholesterol, lower blood pressure and even reduce your risk of stomach and colon cancer. A clove has 4 calories, 0 fat and 0 fiber. Bake a whole head for 15 to 20 minutes, until soft and sweet and spread on bread instead of butter.

Grains, Beans and Nuts
20. QuinoaThe Power: A half cup of cooked quinoa has 5 grams of protein, more than any other grain, plus iron, riboflavin and magnesium. A half-cup has 318 calories, 5 grams of fat and 5 grams of fiber. Add to soup for a protein boost. Rinse first, or it will taste bitter.

21. Wheat GermThe Power: A tablespoon gives you about 7 percent of your daily magnesium, which helps prevent muscle cramps; it is also a good source of vitamin E. One tablespoon has 27 calories, 1 gram of fat and 1 gram of fiber. Sprinkle some over yogurt, fruit or cereal.

22. LentilsThe Power: Isoflavones, which may inhibit estrogen-promoted breast cancers, plus fiber for heart health and an impressive 9 grams of protein per half cup. A half-cup (cooked) has 115 calories, 0 fat and 8 grams of fiber. Isoflavones hold up through processing, so buy lentils canned, dried or already in soup. Take them to work, and you will have a protein packed lunch.

23. PeanutsThe Power: Studies show that peanuts or other nuts (which contain mostly unsaturated "good" fat) can lower your heart-disease risk by over 20 percent. One ounce has 166 calories, 14 grams of fat and 2 grams of fiber. Keep a packet in your briefcase, gym bag or purse for a protein-packed post-workout nosh or an afternoon pick me up that will satisfy you until supper, or chop a few into a stir-fry for a Thai accent. See also: The Nut Case

24. Pinto BeansThe Power: A half cup has more than 25 percent of your daily requirement of folate, which helps protect against heart disease and reduces the risk of birth defects. A half-cup (canned) has 103 calories, 1 gram of fat and 6 grams of fiber. Drain a can, rinse and toss into a pot of vegetarian chili.

25. The Power: Bacteria in active-culture yogurt helps prevent yeast infections; calcium strengthens bones. A cup has 155 calories, 4 grams of fat, 0 grams of fiber. Get the plain kind and mix in your own fruit to keep calories and sugar down. If you are lactose intolerant, never fear -- yogurt should not bother your tummy.

26. Skim Milk
The Power: Riboflavin (a.k.a. vitamin B2) is important for good vision and along with vitamin A might help improve eczema and allergies. Plus, you get calcium and vitamin D, too. One cup has 86 calories, 0 fat and 0 fiber. If you are used to high fat milk, don't go cold turkey; instead, mix the two together at first. Trust this fact: In a week or two you won't miss it!

Seafood
27. Shellfish (Clams, Mussels) The Power: Vitamin B12 to support nerve and brain function, plus iron and hard-to-get minerals like magnesium and potassium. Three ounces has 126 to 146 calories, 2 to 4 grams of fat and 0 fiber. Try a bowl of tomato-based (and low fat) Manhattan clam chowder.

28. SalmonThe Power: Cold-water fish like salmon, mackerel and tuna are the best sources of omega-3 fatty acids, which help reduce the risk of cardiac disease. A 3-ounce portion (cooked) has 127 calories, 4 grams of fat, 0 fiber. Brush fillets with ginger-soy marinade and grill or broil until fish flakes easily with a fork.

29. CrabThe Power: A great source of vitamin B12 and immunity-boosting zinc. A 3-ounce portion has 84 calories, 1 gram of fat, 0 fiber. The "crab" in sushi is usually made from fish; buy it canned instead and make your own crab cakes.

The Top 10 Healthiest Foods

The top 10 healthiest foods below are all rich in vitamins, nutrients, and antioxidants and you should be incorporating these foods into your healthy eating plan on a daily basis.

Incorporate each of these foods into your diet and you will notice the difference. Each has its' own unique set of healthy benefits that are described below in more detail:

1. Olive Oil contains monounsaturated (good) fats, which have been shown to have some excellent health benefits, such as possibly lowering your risk of diseases such as heart disease and cancer. The popular Mediterranean Diet craze is well founded because people from these countries, who tend to get more of their fat from monounsaturated sources like olive oil and less from saturated and trans fat have lower incidences of heart disease, atherosclerosis, diabetes, colon cancer, and asthma. Be sure to buy Extra Virgin Olive Oil, which is the least processed and contains more polyphenols (antioxidants).


2. Blueberries are one of the 10 healthiest foods out there and contain powerful antioxidants that may help lower LDL cholesterol. In fact, these antioxidants were rated #1 in antioxidant activity in a recent Tufts University study that compared 40 fruit and vegetables. Blueberries have been linked to a multitude of health benefits, including lowering your risk of heart disease and cancer, promoting vision and urinary health, and anti-inflammatory properties.


3. Yogurt contains healthy bacteria that helps boost your immune system, fight infection and improve your gastrointestinal health. Yogurt may also help prevent osteoporosis, lower cholesterol and reduce your risk for high blood pressure. It is an excellent source of calcium and B vitamins. Be sure to choose low fat and low sugar yogurts – many flavored yogurts are loaded with sugar so make sure you understand how to read the nutrition label.






4. Broccoli makes the 10 healthiest foods list because it's high in antioxidants and loaded with vitamin C, calcium and folic acid. Broccoli is a proven cancer fighting food – eating broccoli stimulates the body to create natural cancer fighting substances and diets including broccoli have been shown to prevent a number of different types of cancers. Broccoli is also high in soluble fiber and low in calories. Among the other many healthy benefits of broccoli are its’ ability to help prevent osteoporosis and treat high blood pressure.


5. Spinach prevents muscle & bone loss and has been linked to decreased risk of cancer and heart diseases. It’s also very high in antioxidants and vitamins A, C, and K, as well as potassium and folate. Spinach is one the healthiest foods you can eat – calorie for calorie, not many foods can match the nutritional benefits and low calorie content of spinach and other green, leafy vegetables like kale and Swiss chard.





6. Tomatoes are high in lycopene, which is a powerful antioxidant that has a ton of health benefits, including helping prevent cancer. Tomatoes are packed with vitamins A and C, as well as potassium. Eating tomatoes also decreases the risk of developing heart disease, increases prostrate health and may lower cholesterol. When choosing ketchup, be sure to pick organic ketchup, which contains much higher amounts of lycopene. Also, tomato juice is a great option, but be sure to choose the low sodium varieties.

7. Apples aid in lowering cholesterol; prevent numerous types of cancer; and have health benefits related to many other conditions, including Alzheimer’s disease, asthma, and diabetes. Apples are extremely high in antioxidants and contain high amounts of vitamin C and fiber. However, apples tend to be one of the most contaminated fruits with pesticides, so choose organic varieties when possible.


8. Salmon is loaded with heart healthy omega-3 fatty acids, which have been linked to a decreased risk of sudden-death heart attacks, heart disease, memory loss, and Alzheimer's. Salmon has also been shown to help control symptoms of arthritis and depression as well. Be sure to choose wild salmon over farm raised (farm raised salmon contain lots of contaminants...check out this link to learn more about why wild salmon is always a better option.


9. Sweet potatoes are one the top 10 healthiest foods list for good reason: they're nutrient-rich foods that contain high amounts of fiber, potassium, and vitamins A and C. Sweet potatoes also have antioxidant and anti-inflammatory properties, and have been shown to stabilize blood sugar levels (making you feel fuller for longer periods of time) and have cancer and heart disease fighting properties.



10. Almonds round out the 10 healthiest food list. Almonds are loaded with healthy monounsaturated fats and also contain protein, fiber, potassium, and calcium. They are rich in vitamin E and potassium and have been shown to lower cholesterol levels, lower your risk of heart disease and diabetes, and they have cancer fighting properties as well.

Modern Day Life can be Hazardous to our Health

Toxins - Chemicals - Pollution -
Eating Disorders - Stress - New & Mutated microbes


FACT: There are more than 75,000 synthetic chemicals in our environment today
that were not present before 1940.
(U.S. Environment Protection Agency)

FACT: Food is often harvested while still green, leaving out precious nutrients
normally developed in the ripening process.
(Food Composition and Nutrition Tables Edition – CRC Press)

FACT: Vegetable contains herbicides and pesticide.
Our meat, poultry and dairy products are treated with antibiotics,
and growth hormone. Food is highly processed with artificial
colouring, flavouring and preservative. Our air and water are
polluted.

No one is immune to the health threats of 21st century life.

TODAY’S LEADING CAUSES OF DEATH

1. CARDIOVASCULAR DISEASES
Heart Disease – Number 1 killer in USA
Nearly 1 Million Deaths Annually (One death in every 33 seconds)
Affects 80 Million people in USA.
American Heart Association (Washington Post – 1st January 2002)

2. CANCER
About 1.3 Million NEW cases diagnosed each year
547,500 people die from cancer each year (1,500 a day)
Amercian Cancer Society

3. MEDICAL ERRORS
Third leading cause of death in USA with 250,000 deaths per year
Drug-prescription, diagnostic and surgical errors, drug reaction
and overdoses
Dr. Barbara Starfield (Journal of American Medical Journal Association)

4. PHARMACEUTICAL DRUGS
The known dangerous side-effects of pharmaceutical drugs have become
the fourth cause of death after heart-attack, cancer and strokes.
Journal of American Medical Association - 15 April, 1998

Immune System

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumour cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own healthy cells and tissues in order to function properly. Detection is complicated as pathogens can evolve rapidly, producing adaptations that avoid the immune system and allow the pathogens to successfully infect their hosts.

To survive this challenge, multiple mechanisms evolved that recognize and neutralize pathogens. Even simple unicellular organisms such as bacteria possess enzyme systems that protect against viral infections. Other basic immune mechanisms evolved in ancient eukaryotes and remain in their modern descendants, such as plants and insects. These mechanisms include antimicrobial peptides called defensins, phagocytosis, and the complement system. Jawed vertebrates, including humans, have even more sophisticated defense mechanisms. The typical vertebrate immune system consists of many types of proteins, cells, organs, and tissues, which interact in an elaborate and dynamic network. As part of this more complex immune response, the human immune system adapts over time to recognize specific pathogens more efficiently. This adaptation process is referred to as "adaptive immunity" or "acquired immunity" and creates immunological memory. Immunological memory created from a primary response to a specific pathogen, provides an enhanced response to secondary encounters with that same, specific pathogen. This process of acquired immunity is the basis of vaccination.

Disorders in the immune system can result in disease. Immunodeficiency occurs when the immune system is less active than normal, resulting in recurring and life-threatening infections. Immunodeficiency can either be the result of a genetic disease, such as severe combined immunodeficiency, or be produced by pharmaceuticals or an infection, such as the acquired immune deficiency syndrome (AIDS) that is caused by the retrovirus HIV. In contrast, autoimmune diseases result from a hyperactive immune system attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include Hashimoto's Thyroiditis, rheumatoid arthritis, diabetes mellitus type 1 and lupus erythematosus. Immunology covers the study of all aspects of the immune system which has significant relevance to human health and diseases. Further investigation in this field is expected to play a serious role in promotion of health and treatment of diseases.

Layered defense
The immune system protects organisms from infection with layered defenses of increasing specificity. Most simply, physical barriers prevent pathogens such as bacteria and viruses from entering the organism. If a pathogen breaches these barriers, the innate immune system provides an immediate, but non-specific response. Innate immune systems are found in all plants and animals. If pathogens successfully evade the innate response, vertebrates possess a third layer of protection, the adaptive immune system, which is activated by the innate response. Here the immune system adapts its response during an infection to improve its recognition of the pathogen. This improved response is then retained after the pathogen has been eliminated, in the form of an immunological memory, and allows the adaptive immune system to mount faster and stronger attacks each time this pathogen is encountered.


Both innate and adaptive immunity depend on the ability of the immune system to distinguish between self and non-self molecules. In immunology, self molecules are those components of an organism's body that can be distinguished from foreign substances by the immune system.Conversely, non-self molecules are those recognized as foreign molecules. One class of non-self molecules are called antigens (short for antibody generators) and are defined as substances that bind to specific immune receptors and elicit an immune response.


Surface barriers
Several barriers protect organisms from infection, including mechanical, chemical and biological barriers. The waxy cuticle of many leaves, the exoskeleton of insects, the shells and membranes of externally deposited eggs, and skin are examples of the mechanical barriers that are the first line of defense against infection.[5] However, as organisms cannot be completely sealed against their environments, other systems act to protect body openings such as the lungs, intestines, and the genitourinary tract. In the lungs, coughing and sneezing mechanically eject pathogens and other irritants from the respiratory tract. The flushing action of tears and urine also mechanically expels pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to trap and entangle microorganisms.


Chemical barriers also protect against infection. The skin and respiratory tract secrete antimicrobial peptides such as the β-defensins. Enzymes such as lysozyme and phospholipase A2 in saliva, tears, and breast milk are also antibacterials.
Vaginal secretions serve as a chemical barrier following menarche, when they become slightly acidic, while semen contains defensins and zinc to kill pathogens.
In the stomach, gastric acid and proteases serve as powerful chemical defenses against ingested pathogens.

Within the genitourinary and gastrointestinal tracts, commensal flora serve as biological barriers by competing with pathogenic bacteria for food and space and, in some cases, by changing the conditions in their environment, such as pH or available iron. This reduces the probability that pathogens will be able to reach sufficient numbers to cause illness. However, since most antibiotics non-specifically target bacteria and do not affect fungi, oral antibiotics can lead to an “overgrowth” of fungi and cause conditions such as a vaginal candidiasis (a yeast infection).
There is good evidence that re-introduction of probiotic flora, such as pure cultures of the lactobacilli normally found in unpasteurized yoghurt, helps restore a healthy balance of microbial populations in intestinal infections in children and encouraging preliminary data in studies on bacterial gastroenteritis, inflammatory bowel diseases, urinary tract infection and post-surgical infections.

Innate
Microorganisms or toxins that successfully enter an organism will encounter the cells and mechanisms of the innate immune system. The innate response is usually triggered when microbes are identified by pattern recognition receptors, which recognize components that are conserved among broad groups of microorganisms, or when damaged, injured or stressed cells send out alarm signals, many of which (but not all) are recognized by the same receptors as those that recognize pathogens. Innate immune defenses are non-specific, meaning these systems respond to pathogens in a generic way. This system does not confer long-lasting immunity against a pathogen. The innate immune system is the dominant system of host defense in most organisms.

Humoral and chemical barriers
Inflammation
For more details on this topic, see Inflammation.
Inflammation is one of the first responses of the immune system to infection.
The symptoms of inflammation are redness and swelling, which are caused by increased blood flow into a tissue. Inflammation is produced by eicosanoids and cytokines, which are released by injured or infected cells. Eicosanoids include prostaglandins that produce fever and the dilation of blood vessels associated with inflammation, and leukotrienes that attract certain white blood cells (leukocytes). Common cytokines include interleukins that are responsible for communication between white blood cells; chemokines that promote chemotaxis; and interferons that have anti-viral effects, such as shutting down protein synthesis in the host cell. Growth factors and cytotoxic factors may also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of any damaged tissue following the removal of pathogens.

Complement systemFor more details on this topic, see Complement system.
The complement system is a biochemical cascade that attacks the surfaces of foreign cells. It contains over 20 different proteins and is named for its ability to “complement” the killing of pathogens by antibodies. Complement is the major humoral component of the innate immune response. Many species have complement systems, including non-mammals like plants, fish, and some invertebrates.

In humans, this response is activated by complement binding to antibodies that have attached to these microbes or the binding of complement proteins to carbohydrates on the surfaces of microbes. This recognition signal triggers a rapid killing response. The speed of the response is a result of signal amplification that occurs following sequential proteolytic activation of complement molecules, which are also proteases. After complement proteins initially bind to the microbe, they activate their protease activity, which in turn activates other complement proteases, and so on. This produces a catalytic cascade that amplifies the initial signal by controlled positive feedback. The cascade results in the production of peptides that attract immune cells, increase vascular permeability, and opsonize (coat) the surface of a pathogen, marking it for destruction. This deposition of complement can also kill cells directly by disrupting their plasma membrane.

Cellular barriers
A scanning electron microscope image of normal circulating human blood. One can see red blood cells, several knobby white blood cells including lymphocytes, a monocyte, a neutrophil, and many small disc-shaped platelets.Leukocytes (white blood cells) act like independent, single-celled organisms and are the second arm of the innate immune system. The innate leukocytes include the phagocytes (macrophages, neutrophils, and dendritic cells), mast cells, eosinophils, basophils, and natural killer cells. These cells identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms. Innate cells are also important mediators in the activation of the adaptive immune system.

Phagocytosis is an important feature of cellular innate immunity performed by cells called 'phagocytes' that engulf, or eat, pathogens or particles. Phagocytes generally patrol the body searching for pathogens, but can be called to specific locations by cytokines. Once a pathogen has been engulfed by a phagocyte, it becomes trapped in an intracellular vesicle called a phagosome, which subsequently fuses with another vesicle called a lysosome to form a phagolysosome. The pathogen is killed by the activity of digestive enzymes or following a respiratory burst that releases free radicals into the phagolysosome. Phagocytosis evolved as a means of acquiring nutrients, but this role was extended in phagocytes to include engulfment of pathogens as a defense mechanism. Phagocytosis probably represents the oldest form of host defense, as phagocytes have been identified in both vertebrate and invertebrate animals.

Neutrophils and macrophages are phagocytes that travel throughout the body in pursuit of invading pathogens. Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, normally representing 50% to 60% of the total circulating leukocytes. During the acute phase of inflammation, particularly as a result of bacterial infection, neutrophils migrate toward the site of inflammation in a process called chemotaxis, and are usually the first cells to arrive at the scene of infection. Macrophages are versatile cells that reside within tissues and produce a wide array of chemicals including enzymes, complement proteins, and regulatory factors such as interleukin 1.[35] Macrophages also act as scavengers, ridding the body of worn-out cells and other debris, and as antigen-presenting cells that activate the adaptive immune system.

Dendritic cells (DC) are phagocytes in tissues that are in contact with the external environment; therefore, they are located mainly in the skin, nose, lungs, stomach, and intestines.[36] They are named for their resemblance to neuronal dendrites, as both have many spine-like projections, but dendritic cells are in no way connected to the nervous system. Dendritic cells serve as a link between the bodily tissues and the innate and adaptive immune systems, as they present antigen to T cells, one of the key cell types of the adaptive immune system.

Mast cells reside in connective tissues and mucous membranes, and regulate the inflammatory response. They are most often associated with allergy and anaphylaxis. Basophils and eosinophils are related to neutrophils. They secrete chemical mediators that are involved in defending against parasites and play a role in allergic reactions, such as asthma.Natural killer (NK cells) cells are leukocytes that attack and destroy tumor cells, or cells that have been infected by viruses.

AdaptiveFor more details on this topic, see Adaptive immune system.
The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as immunological memory, where each pathogen is "remembered" by a signature antigen. The adaptive immune response is antigen-specific and requires the recognition of specific “non-self” antigens during a process called antigen presentation. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it.

Lymphocytes
The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. B cells and T cells are the major types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow. B cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune response.


Association of a T cell with MHC class I or MHC class II, and antigen (in red)Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a “non-self” target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a “self” receptor called a major histocompatibility complex (MHC) molecule. There are two major subtypes of T cells: the killer T cell and the helper T cell. Killer T cells only recognize antigens coupled to Class I MHC molecules, while helper T cells only recognize antigens coupled to Class II MHC molecules. These two mechanisms of antigen presentation reflect the different roles of the two types of T cell. A third, minor subtype are the γδ T cells that recognize intact antigens that are not bound to MHC receptors.

In contrast, the B cell antigen-specific receptor is an antibody molecule on the B cell surface, and recognizes whole pathogens without any need for antigen processing. Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture.

Killer T cells

Killer T cells directly attack other cells carrying foreign or abnormal antigens on their surfaces.[42]Killer T cell are a sub-group of T cells that kill cells infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional.
As with B cells, each type of T cell recognises a different antigen. Killer T cells are activated when their T cell receptor (TCR) binds to this specific antigen in a complex with the MHC Class I receptor of another cell. Recognition of this MHC:antigen complex is aided by a co-receptor on the T cell, called CD8. The T cell then travels throughout the body in search of cells where the MHC I receptors bear this antigen. When an activated T cell contacts such cells, it releases cytotoxins, such as perforin, which form pores in the target cell's plasma membrane, allowing ions, water and toxins to enter. The entry of another toxin called granulysin (a protease) induces the target cell to undergo apoptosis.[44] T cell killing of host cells is particularly important in preventing the replication of viruses. T cell activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T cells (see below).

Helper T cells

Function of T helper cells: Antigen presenting cells (APCs) present antigen on their Class II MHC molecules (MHC2). Helper T cells recognize these, with the help of their expression of CD4 co-receptor (CD4+). The activation of a resting helper T cell causes it to release cytokines and other stimulatory signals (green arrows) that stimulate the activity of macrophages, killer T cells and B cells, the latter producing antibodies. The stimulation of B cells and macrophages succeeds a proliferation of T helper cells.Helper T cells regulate both the innate and adaptive immune responses and help determine which types of immune responses the body will make to a particular pathogen.[45][46] These cells have no cytotoxic activity and do not kill infected cells or clear pathogens directly. They instead control the immune response by directing other cells to perform these tasks.

Helper T cells express T cell receptors (TCR) that recognize antigen bound to Class II MHC molecules. The MHC:antigen complex is also recognized by the helper cell's CD4 co-receptor, which recruits molecules inside the T cell (e.g. Lck) that are responsible for the T cell's activation. Helper T cells have a weaker association with the MHC:antigen complex than observed for killer T cells, meaning many receptors (around 200–300) on the helper T cell must be bound by an MHC:antigen in order to activate the helper cell, while killer T cells can be activated by engagement of a single MHC:antigen molecule. Helper T cell activation also requires longer duration of engagement with an antigen-presenting cell. The activation of a resting helper T cell causes it to release cytokines that influence the activity of many cell types. Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells. In addition, helper T cell activation causes an upregulation of molecules expressed on the T cell's surface, such as CD40 ligand (also called CD154), which provide extra stimulatory signals typically required to activate antibody-producing B cells.[48]

γδ T cells
γδ T cells possess an alternative T cell receptor (TCR) as opposed to CD4+ and CD8+ (αβ) T cells and share the characteristics of helper T cells, cytotoxic T cells and NK cells. The conditions that produce responses from γδ T cells are not fully understood. Like other 'unconventional' T cell subsets bearing invariant TCRs, such as CD1d-restricted Natural Killer T cells, γδ T cells straddle the border between innate and adaptive immunity. On one hand, γδ T cells are a component of adaptive immunity as they rearrange TCR genes to produce receptor diversity and can also develop a memory phenotype. On the other hand, the various subsets are also part of the innate immune system, as restricted TCR or NK receptors may be used as pattern recognition receptors. For example, large numbers of human Vγ9/Vδ2 T cells respond within hours to common molecules produced by microbes, and highly restricted Vδ1+ T cells in epithelia will respond to stressed epithelial cells.


An antibody is made up of two heavy chains and two light chains. The unique variable region allows an antibody to recognize its matching antigen. B lymphocytes and antibodies
A B cell identifies pathogens when antibodies on its surface bind to a specific foreign antigen. This antigen/antibody complex is taken up by the B cell and processed by proteolysis into peptides. The B cell then displays these antigenic peptides on its surface MHC class II molecules. This combination of MHC and antigen attracts a matching helper T cell, which releases lymphokines and activates the B cell.[51] As the activated B cell then begins to divide, its offspring (plasma cells) secrete millions of copies of the antibody that recognizes this antigen. These antibodies circulate in blood plasma and lymph, bind to pathogens expressing the antigen and mark them for destruction by complement activation or for uptake and destruction by phagocytes. Antibodies can also neutralize challenges directly, by binding to bacterial toxins or by interfering with the receptors that viruses and bacteria use to infect cells.

Alternative adaptive immune system
Although the classical molecules of the adaptive immune system (e.g. antibodies and T cell receptors) exist only in jawed vertebrates, a distinct lymphocyte-derived molecule has been discovered in primitive jawless vertebrates, such as the lamprey and hagfish. These animals possess a large array of molecules called variable lymphocyte receptors (VLRs) that, like the antigen receptors of jawed vertebrates, are produced from only a small number (one or two) of genes. These molecules are believed to bind pathogenic antigens in a similar way to antibodies, and with the same degree of specificity.

Immunological memory
For more details on this topic, see Immunity (medical).
When B cells and T cells are activated and begin to replicate, some of their offspring will become long-lived memory cells. Throughout the lifetime of an animal, these memory cells will remember each specific pathogen encountered and can mount a strong response if the pathogen is detected again. This is "adaptive" because it occurs during the lifetime of an individual as an adaptation to infection with that pathogen and prepares the immune system for future challenges. Immunological memory can either be in the form of passive short-term memory or active long-term memory.

Passive memoryNewborn infants have no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother. During pregnancy, a particular type of antibody, called IgG, is transported from mother to baby directly across the placenta, so human babies have high levels of antibodies even at birth, with the same range of antigen specificities as their mother.[54] Breast milk or colostrum also contains antibodies that are transferred to the gut of the infant and protect against bacterial infections until the newborn can synthesize its own antibodies. This is passive immunity because the fetus does not actually make any memory cells or antibodies—it only borrows them. This passive immunity is usually short-term, lasting from a few days up to several months. In medicine, protective passive immunity can also be transferred artificially from one individual to another via antibody-rich serum.


The time-course of an immune response begins with the initial pathogen encounter, (or initial vaccination) and leads to the formation and maintenance of active immunological memory.

Active memory and immunizationLong-term active memory is acquired following infection by activation of B and T cells. Active immunity can also be generated artificially, through vaccination. The principle behind vaccination (also called immunization) is to introduce an antigen from a pathogen in order to stimulate the immune system and develop specific immunity against that particular pathogen without causing disease associated with that organism. This deliberate induction of an immune response is successful because it exploits the natural specificity of the immune system, as well as its inducibility. With infectious disease remaining one of the leading causes of death in the human population, vaccination represents the most effective manipulation of the immune system mankind has developed.

Most viral vaccines are based on live attenuated viruses, while many bacterial vaccines are based on acellular components of micro-organisms, including harmless toxin components. Since many antigens derived from acellular vaccines do not strongly induce the adaptive response, most bacterial vaccines are provided with additional adjuvants that activate the antigen-presenting cells of the innate immune system and maximize immunogenicity.

Disorders of human immunityThe immune system is a remarkably effective structure that incorporates specificity, inducibility and adaptation. Failures of host defense do occur, however, and fall into three broad categories: immunodeficiencies, autoimmunity, and hypersensitivities.

ImmunodeficienciesFor more details on this topic, see Immunodeficiency.
Immunodeficiencies occur when one or more of the components of the immune system are inactive. The ability of the immune system to respond to pathogens is diminished in both the young and the elderly, with immune responses beginning to decline at around 50 years of age due to immunosenescence. In developed countries, obesity, alcoholism, and drug use are common causes of poor immune function. However, malnutrition is the most common cause of immunodeficiency in developing countries. Diets lacking sufficient protein are associated with impaired cell-mediated immunity, complement activity, phagocyte function, IgA antibody concentrations, and cytokine production. Deficiency of single nutrients such as iron; copper; zinc; selenium; vitamins A, C, E, and B6; and folic acid (vitamin B9) also reduces immune responses.Additionally, the loss of the thymus at an early age through genetic mutation or surgical removal results in severe immunodeficiency and a high susceptibility to infection.

Immunodeficiencies can also be inherited or 'acquired'. Chronic granulomatous disease, where phagocytes have a reduced ability to destroy pathogens, is an example of an inherited, or congenital, immunodeficiency. AIDS and some types of cancer cause acquired immunodeficiency.

Autoimmunity
For more details on this topic, see Autoimmunity.
Overactive immune responses comprise the other end of immune dysfunction, particularly the autoimmune disorders. Here, the immune system fails to properly distinguish between self and non-self, and attacks part of the body. Under normal circumstances, many T cells and antibodies react with “self” peptides. One of the functions of specialized cells (located in the thymus and bone marrow) is to present young lymphocytes with self antigens produced throughout the body and to eliminate those cells that recognize self-antigens, preventing autoimmunity.

HypersensitivityFor more details on this topic, see Hypersensitivity.
Hypersensitivity is an immune response that damages the body's own tissues. They are divided into four classes (Type I – IV) based on the mechanisms involved and the time course of the hypersensitive reaction. Type I hypersensitivity is an immediate or anaphylactic reaction, often associated with allergy. Symptoms can range from mild discomfort to death. Type I hypersensitivity is mediated by IgE, which triggers degranulation of mast cells and basophils when cross-linked by antigen. Type II hypersensitivity occurs when antibodies bind to antigens on the patient's own cells, marking them for destruction. This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated by IgG and IgM antibodies. Immune complexes (aggregations of antigens, complement proteins, and IgG and IgM antibodies) deposited in various tissues trigger Type III hypersensitivity reactions. Type IV hypersensitivity (also known as cell-mediated or delayed type hypersensitivity) usually takes between two and three days to develop. Type IV reactions are involved in many autoimmune and infectious diseases, but may also involve contact dermatitis (poison ivy). These reactions are mediated by T cells, monocytes, and macrophages.

Other mechanismsFor more details on this topic, see Innate immune system#Other forms of innate immunity.
It is likely that a multicomponent, adaptive immune system arose with the first vertebrates, as invertebrates do not generate lymphocytes or an antibody-based humoral response. Many species, however, utilize mechanisms that appear to be precursors of these aspects of vertebrate immunity. Immune systems appear even in the structurally most simple forms of life, with bacteria using a unique defense mechanism, called the restriction modification system to protect themselves from viral pathogens, called bacteriophages. Prokaryotes also possess acquired immunity, through a system that uses CRISPR sequences to retain fragments of the genomes of phage that they have come into contact with in the past, which allows them to block virus replication through a form of RNA interference.

Pattern recognition receptors are proteins used by nearly all organisms to identify molecules associated with pathogens. Antimicrobial peptides called defensins are an evolutionarily conserved component of the innate immune response found in all animals and plants, and represent the main form of invertebrate systemic immunity. The complement system and phagocytic cells are also used by most forms of invertebrate life. Ribonucleases and the RNA interference pathway are conserved across all eukaryotes, and are thought to play a role in the immune response to viruses.

Unlike animals, plants lack phagocytic cells, but many plant immune responses involve systemic chemical signals that are sent through a plant. Individual plant cells respond to molecules associated with pathogens known as Pathogen-associated molecular patterns or PAMPs. When a part of a plant becomes infected, the plant produces a localized hypersensitive response, whereby cells at the site of infection undergo rapid apoptosis to prevent the spread of the disease to other parts of the plant. Systemic acquired resistance (SAR) is a type of defensive response used by plants that renders the entire plant resistant to a particular infectious agent.
RNA silencing mechanisms are particularly important in this systemic response as they can block virus replication.

Tumor immunology
Further information: Cancer immunology

Macrophages have identified a cancer cell (the large, spiky mass). Upon fusing with the cancer cell, the macrophages (smaller white cells) will inject toxins that kill the tumor cell. Immunotherapy for the treatment of cancer is an active area of medical research. Another important role of the immune system is to identify and eliminate tumors. The transformed cells of tumors express antigens that are not found on normal cells. To the immune system, these antigens appear foreign, and their presence causes immune cells to attack the transformed tumor cells. The antigens expressed by tumors have several sources; some are derived from oncogenic viruses like human papillomavirus, which causes cervical cancer, while others are the organism's own proteins that occur at low levels in normal cells but reach high levels in tumor cells. One example is an enzyme called tyrosinase that, when expressed at high levels, transforms certain skin cells (e.g. melanocytes) into tumors called melanomas. A third possible source of tumor antigens are proteins normally important for regulating cell growth and survival, that commonly mutate into cancer inducing molecules called oncogenes.

The main response of the immune system to tumors is to destroy the abnormal cells using killer T cells, sometimes with the assistance of helper T cells. Tumor antigens are presented on MHC class I molecules in a similar way to viral antigens. This allows killer T cells to recognize the tumor cell as abnormal. NK cells also kill tumorous cells in a similar way, especially if the tumor cells have fewer MHC class I molecules on their surface than normal; this is a common phenomenon with tumors. Sometimes antibodies are generated against tumor cells allowing for their destruction by the complement system.

Clearly, some tumors evade the immune system and go on to become cancers. Tumor cells often have a reduced number of MHC class I molecules on their surface, thus avoiding detection by killer T cells. Some tumor cells also release products that inhibit the immune response; for example by secreting the cytokine TGF-β, which suppresses the activity of macrophages and lymphocytes. In addition, immunological tolerance may develop against tumor antigens, so the immune system no longer attacks the tumor cells.

Paradoxically, macrophages can promote tumor growth when tumor cells send out cytokines that attract macrophages which then generate cytokines and growth factors that nurture tumor development. In addition, a combination of hypoxia in the tumor and a cytokine produced by macrophages induces tumor cells to decrease production of a protein that blocks metastasis and thereby assists spread of cancer cells.

Physiological regulation
Hormones can act as immunomodulators, altering the sensitivity of the immune system. For example, female sex hormones are known immunostimulators of both adaptive and innate immune responses. Some autoimmune diseases such as lupus erythematosus strike women preferentially, and their onset often coincides with puberty. By contrast, male sex hormones such as testosterone seem to be immunosuppressive. Other hormones appear to regulate the immune system as well, most notably prolactin, growth hormone and vitamin D. It is conjectured that a progressive decline in hormone levels with age is partially responsible for weakened immune responses in aging individuals. Conversely, some hormones are regulated by the immune system, notably thyroid hormone activity.

The immune system is affected by sleep and rest, and sleep deprivation is detrimental to immune function. Complex feedback loops involving cytokines, such as interleukin-1 and tumor necrosis factor-α produced in response to infection, appear to also play a role in the regulation of non-rapid eye movement (REM) sleep. Thus the immune response to infection may result in changes to the sleep cycle, including an increase in slow-wave sleep relative to REM sleep.
[edit] Nutrition and diet
The functioning of the immune system, like most systems in the body, is dependent on proper nutrition. It has been long known that severe malnutrition leads to immunodeficiency. Overnutrition is also associated with diseases such as diabetes and obesity which are known to affect immune function. More moderate malnutrition, as well as certain specific trace mineral and nutrient deficiencies, can also compromise the immune response.

Specific foods may also affect the immune system; for example, fresh fruits, vegetables, and foods rich in certain fatty acids may foster a healthy immune system.[98] Likewise, fetal undernourishment can cause a lifelong impairment of the immune system. In traditional medicine, some herbs are believed to stimulate the immune system, such as echinacea, licorice, ginseng, astragalus, sage, garlic, elderberry, and hyssop, as well as honey although further research is needed to understand their mode of action.

Medicinal mushrooms like Shiitake, Lingzhi mushrooms, the Turkey tail mushroom, Agaricus blazei, and Maitake have shown some evidence of immune system up-regulation in in vitro and in vivo studies, as well as in a limited number of clinical studies. Research suggests that the compounds in medicinal mushrooms most responsible for up-regulating the immune system are a diverse collection of polysaccharides, particularly beta-glucans, and to a lesser extent, alpha-glucans (such as Active Hexose Correlated Compound isolated from Shiitake). The mechanisms by which beta-glucans stimulate the immune system is only partially understood. One mechanism by which beta-glucans are thought affect immune function is through interaction with the complement receptor 3 (CD18), which is expressed on several types of immune cells. Other receptors–such as Toll-like receptor 2, Dectin-1, lactosylceramide, and scavenger receptors–have also been identified as being able to receive signals from beta-glucans.

Manipulation in medicine

The immunosuppressive drug dexamethasoneThe immune response can be manipulated to suppress unwanted responses resulting from autoimmunity, allergy, and transplant rejection, and to stimulate protective responses against pathogens that largely elude the immune system (see immunization). Immunosuppressive drugs are used to control autoimmune disorders or inflammation when excessive tissue damage occurs, and to prevent transplant rejection after an organ transplant.[26][113]

Anti-inflammatory drugs are often used to control the effects of inflammation. The glucocorticoids are the most powerful of these drugs; however, these drugs can have many undesirable side effects (e.g., central obesity, hyperglycemia, osteoporosis) and their use must be tightly controlled.[114] Therefore, lower doses of anti-inflammatory drugs are often used in conjunction with cytotoxic or immunosuppressive drugs such as methotrexate or azathioprine. Cytotoxic drugs inhibit the immune response by killing dividing cells such as activated T cells. However, the killing is indiscriminate and other constantly dividing cells and their organs are affected, which causes toxic side effects.[113] Immunosuppressive drugs such as ciclosporin prevent T cells from responding to signals correctly by inhibiting signal transduction pathways.

Larger drugs (>500 Da) can provoke a neutralizing immune response, particularly if the drugs are administered repeatedly, or in larger doses. This limits the effectiveness of drugs based on larger peptides and proteins (which are typically larger than 6000 Da). In some cases, the drug itself is not immunogenic, but may be co-administered with an immunogenic compound, as is sometimes the case for Taxol. Computational methods have been developed to predict the immunogenicity of peptides and proteins, which are particularly useful in designing therapeutic antibodies, assessing likely virulence of mutations in viral coat particles, and validation of proposed peptide-based drug treatments. Early techniques relied mainly on the observation that hydrophilic amino acids are overrepresented in epitope regions than hydrophobic amino acids;[116] however, more recent developments rely on machine learning techniques using databases of existing known epitopes, usually on well-studied virus proteins, as a training set. A publicly accessible database has been established for the cataloguing of epitopes from pathogens known to be recognizable by B cells. The emerging field of bioinformatics-based studies of immunogenicity is referred to as immunoinformatics.

Manipulation by pathogensThe success of any pathogen is dependent on its ability to elude host immune responses. Therefore, pathogens have developed several methods that allow them to successfully infect a host, while evading detection or destruction by the immune system. Bacteria often overcome physical barriers by secreting enzymes that digest the barrier — for example, by using a type II secretion system.[121] Alternatively, using a type III secretion system, they may insert a hollow tube into the host cell, providing a direct route for proteins to move from the pathogen to the host. These proteins are often used to shut down host defenses.

An evasion strategy used by several pathogens to avoid the innate immune system is to hide within the cells of their host (also called intracellular pathogenesis). Here, a pathogen spends most of its life-cycle inside host cells, where it is shielded from direct contact with immune cells, antibodies and complement. Some examples of intracellular pathogens include viruses, the food poisoning bacterium Salmonella and the eukaryotic parasites that cause malaria (Plasmodium falciparum) and leishmaniasis (Leishmania spp.). Other bacteria, such as Mycobacterium tuberculosis, live inside a protective capsule that prevents lysis by complement.[123] Many pathogens secrete compounds that diminish or misdirect the host's immune response. Some bacteria form biofilms to protect themselves from the cells and proteins of the immune system. Such biofilms are present in many successful infections, e.g., the chronic Pseudomonas aeruginosa and Burkholderia cenocepacia infections characteristic of cystic fibrosis. Other bacteria generate surface proteins that bind to antibodies, rendering them ineffective; examples include Streptococcus (protein G), Staphylococcus aureus (protein A), and Peptostreptococcus magnus (protein L).

The mechanisms used to evade the adaptive immune system are more complicated. The simplest approach is to rapidly change non-essential epitopes (amino acids and/or sugars) on the surface of the pathogen, while keeping essential epitopes concealed. This is called antigenic variation. An example is HIV, which mutates rapidly, so the proteins on its viral envelope that are essential for entry into its host target cell are constantly changing. These frequent changes in antigens may explain the failures of vaccines directed at this virus. The parasite Trypanosoma brucei uses a similar strategy, constantly switching one type of surface protein for another, allowing it to stay one step ahead of the antibody response. Masking antigens with host molecules is another common strategy for avoiding detection by the immune system. In HIV, the envelope that covers the viron is formed from the outermost membrane of the host cell; such "self-cloaked" viruses make it difficult for the immune system to identify them as "non-self" structures.

History of immunology


Paul EhrlichImmunology is a science that examines the structure and function of the immune system. It originates from medicine and early studies on the causes of immunity to disease. The earliest known mention of immunity was during the plague of Athens in 430 BC. Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. In the 18th century, Pierre-Louis Moreau de Maupertuis made experiments with scorpion venom and observed that certain dogs and mice were immune to this venom.[130] This and other observations of acquired immunity was later exploited by Louis Pasteur in his development of vaccination and his proposed germ theory of disease.[131] Pasteur's theory was in direct opposition to contemporary theories of disease, such as the miasma theory. It was not until Robert Koch's 1891 proofs, for which he was awarded a Nobel Prize in 1905, that microorganisms were confirmed as the cause of infectious disease.[132] Viruses were confirmed as human pathogens in 1901, with the discovery of the yellow fever virus by Walter Reed.

Immunology made a great advance towards the end of the 19th century, through rapid developments, in the study of humoral immunity and cellular immunity. Particularly important was the work of Paul Ehrlich, who proposed the side-chain theory to explain the specificity of the antigen-antibody reaction; his contributions to the understanding of humoral immunity were recognized by the award of a Nobel Prize in 1908, which was jointly awarded to the founder of cellular immunology, Elie Metchnikoff