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BPS1101 (402)


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University of Ottawa
Biopharmaceutical sciences
William Ogilvie

TOPIC 9 REVIEW VACCINES What happens when you get sick? - initial symptoms are mild, but you become sicker (may even get a fever). Eventually the symptoms become less intense, and sooner or later the patient is healthy again - what if you could skip the sick part? premise for vaccines! - during infection, microbes try to eat us. Without defences, the microbes win. - We live in a microbial world where the human body is under constant attack, but the immune system defends us - in the case of gangrene, the bacterial infection may take over the body part and it has to be removed How Immune System Works Immune system uses many weapons: - Poisons - defensins - complement - Antibodies - immobilize invaders - selectively destroy invaders - Macrophages - specialized cells to eat foreign cell - specialized cell to kill infected cell Branches of the Immune System Innate immune system provides an immediate response - non-specific response - all cells are targeted - immediate maximum response - innate immune system responds to damage - tissue damage causes the damaged tissue to release of cytokines (signalling chemicals to deal with damage). The cytokines lead to inflammation (redness, swelling) and recruit leukocytes which destroy the invading microbes - inflammation makes for these kinds of cells to have easier access to site requiring action NON-SPECIFIC RESPONSE! Adaptive immune system - Differences from innate immune system: 1) Highly selective (response is selective) - only invading cells are targeted 2) lag-time between exposure and maximum response - 2 3 days - immune system retains a memory of the infection - next time same microbe invades, the response is immediate and strong Antibodies Antibodies are the key recognition devices - Y shaped molecules, have sticky surface which sticks to epitopes (30 atoms wide) - Immune system recognizes tiny part of pathogen - body makes many different antibodies - each antibody is unique (will only stick to specific molecule) - antibody production is random - cannot store large amounts of antibodies therefore you make small amount of many different types - no way to know which microbes will invade - body stores small amounts of as many different antibodies as possible (made randomly) - manufacture large quantities only when needed B cells B cells carry antibodies - each B cell carries a different antibody (Each B cell recognizes 1 epitope) - Body carries many different B cells - dont know in advance which ones are important - store small amounts of each B cell - recognize as many epitopes as possible - immune response triggers replication of specific B cell - amplified B cells target the invaders - after infection, you generate memory cells (some B cells become memory cells) - as you get older, our body contains more memory cells - less than 5% of B cells in a newborn are memory cells - more than 50% of B cells in an adult are memory cells (adults have experienced more infections over time) T cells viruses live inside cells and escape B cells - to get at these, you need T cells! Body makes T cells to destroy viruses - infected cells display parts of viruses - viral protein fragments on MHC receptors - Helper T cells send the kill signal - Killer T cells recognize MHC display on the infected cell and kill the cell - these two kill signals (by helper and killer T cells) provide a failsafe viral infection triggers replication of specific T cells - some T cells become memory cells - memory cells give you immunity - next time microbe invades, you get an immediate and specific immune response - microbes are killed quickly before infection develops nd - because of this, you dont get sick for the 2 infection! most diseases only infect once - how do you get the memory without the sickness? ... VACCINES! History (Getting to Vaccines) Smallpox Smallpox (variola) - had 20 40% mortality rate - smallpox disfigured 70 80% of survivors (if a child had smallpox, likely they would have scars for life) variolation was practised by many cultures - developed in Ancient Egypt and India - realized that if you got sick once, youd never get sick agan - variolation = from the little pustules formed by smallpox on the skin, you collect some pus on the sharp end of a knife and inject it into someone else so they can get a milder form of smallpox and become protected - many kids who had smallpox would die, but if done this way, likely they would get a milder form and not die - brought to England by Lady Montagu - she visited India in the 1600s, and instituted this practice in England Edward Jenner (1749 1823) - he found a safer version of variolation - he noticed that milkmaids (people who worked with cattle) were immune to smallpox in an affected area - the milkmaids would get cowpox, which causes a mild infection (like chickenpox) - after the milkmaids recovered, they had immunity from smallpox- Jenner realized this could be a safe way to protect people from smallpox! - Experiment: inoculated children with cowpox, and after cowpox infection, he exposed them to smallpox virus (which he got from infected smallpox people) - Jenner could the cowpox from a cow named Blossom (hide was kept and is displayed in St Michaels Medical College in England) - children attained immunity in a much safer way - instead of variolation, this was called VACCINATION - it took a while for society to buy into this (approx. 40 years) - Overall - vaccination inoculation with a weaker form of the virus - variolation inoculation with the virus at full strength Vaccination was an incredible success - safer because cowpox is not a human disease, therefore doesnt cause a severe infection - variolation worked but great risk of full-blown case of smallpox - so successful that by 1900, smallpox levels became very low in industrialized countries - smallpox was eradicated by industrialized countries in 1950 - remained endemic in developing countries - people were not vaccinated - World Health Organization initiated in 1966 a program to eradicate smallpox (financed mostly by the US) - tried to vaccinate everyone (new method vaccine gum was developed) - last case of natural smallpox was 1977 - person in Somalia was the last person to get smallpox naturally - Smallpox is currently only found in two places: 1) Centre for Disease Control (Atlanta) 2) Soviet Union kept samples of material (in case US used it as a biological weapon) - if born in an industrialized country before 1972, you got a vaccination s
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