Immunology Notes

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Western University
Microbiology and Immunology
Microbiology and Immunology 3300B
Rodney Dekoter

Immunology NotesNov 1012 Humans and pathogens have coevolved The JC virus has successfully coevolved with us It has infected 90 of all humans The initial infection is in the GI tract and is largely asymptomatic The virus persists in the GI for the life of the patient without symptoms There is pathology only in immunosuppressed patients JC virus is an old human pathogen and has infected humans since at least 200000 years ago It establishes a latent infection It is able to avoid immunity without compromising host health because it has had lots of time to adapt to our bodies Ebola virus has not undergone coevolution with us Infection is rare and it is highly lethal Persontoperson transmission is rare due to rapid death of infected patients The virus is easily spread Persistentlatent infections do not occur It is a new human pathogen 1976 and was probably zoonotic bats Its rarity and severity has offered few opportunities for coevolution Malaria is humanities oldest plague It is transmitted persontoperson through mosquitoes Malaria avoids an immune response by avoiding entering the spleen There has been coevolution between malaria plasmodium species and humansmammals The first human strain of it appeared 7 mya when hominoids diverged from chimps Humans have evolved protective mutations that help reduce the risk of getting malaria but malaria has also evolved to become more virulent In areas of the world where most people have blood type O there are more cases of malariaHIVEvidence for human evolution Some people have evolved protective alleles that are resistant to HIV When MHC I and II of these people were sequenced it was found they have the protective alleles HLAA and HLADRB101 Selection for these protective alleles is occurring throughout evolution Hostpathogen evolutionseeking balance The host wants to minimize loss of fitness by selecting successful MHC haplotypes selecting resistance genes and selection of less virulent pathogen strains The pathogen wants to maximize reproductive success by ensuring host survival at least until transmitted avoiding immunity and modulation of virulence To be a pathogen you must 1 Be able to survive in the human body pH temperature 2 Be able to avoid or modulate the immune response to allow your own survival As such most microorganisms are not pathogens and most pathogens have immuneavoidance mechanisms Avoiding innate immunitypreventing opsonisation Lyme disease borellia coats its surface with factor H through binding with exotoxin CspA on the bacteria Factor H is a complementinhibitory protein that inhibits complement deposition evades complement and antibody binding Syphilis treponema coats its surface with host proteins through nonspecific binding to charged lipids in the bacterial membrane This allows it to hide its antigens and cell surface from antibodies and complement Streptococcus produces proteins A and G that bind to IgG via the Fc domain This prevents opsonisation phagocytosis and complement activation Avoiding innate immunityshutting down TLRs Brucella produces the exotoxin TcpB and UTI E coli produces the exotoxin TcpC These exotoxins contain TIR domains which bind to MyD88 This inhibits TLR signalling by preventing MyD88TLR association Avoiding innate immunitypreventing GPCR signalling Whooping cough shuts down G protein coupling receptors GPCRs The pertussis toxin chemically modifies G preventing GDP to GTP exchange GPCR bound to ligand cannot bind to G protein in the GDP form so this signalling pathway is shut down Activation of integrins cant happen if G protein is shut down and as a result immune cells cant enter into the infected tissue Even if neutrophils manage to find the pertussis toxin it will still avoid being destroyed by preventing oxidative burst from occurring in the phagolysosome Avoiding innate immunitydisrupting phagocytosis Normally when a pathogen is phagocytosed Rac2 induces assembly of NADP oxidase in the membrane which leads to the generation of O2 and
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