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20-25 - Lecture 20 Humans and Pathogens have Co-Evolved...

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Lecture 20 Humans and Pathogens have Co-Evolved Successfully co-evolved= JC virus: Has infected 90% of all humans; initial infection is in GI tract and is largely asymptomatic; virus persists in GI for life of patient, without symptoms; pathology only in immunosuppressed patients (HIV/transplant); shed virus through urine and feces; most common pathogen but largely unknown; managed to optimize its biology while unaffecting us Old human pathogen (infecting humans at least since our speciation in Africa about 200 000 years ago); establishes a latent infection; able to avoid immunity without compromising host health; many opportunities to adapt to our body; ale to affect large numbers of people and has mechanisms to evade our immune system No co-evolution= Ebola: Infection is rare; highly lethal (50-100% mortality); person-to-person transmission is rare (due to rapid death of infected patients; virus is actually easily spread); persistent/latent infections do NOT occur; not a chance to continue to see environment because its very lethal Zoonotic (bats?); new human pathogen (1976); rarity and severity has offered few opportunities for co-evolution; lethality prevents transmission Malaria= humanities oldest plague We also involve in response to pathogens Malaria transmitted by mosquitoes; blood borne; lives in RBCs (become anemic); malaria evades immune response by avoiding spleen (where macrophages are) Malaria’s Fingerprints on our genome A lot of evolution of malaria coincides with our evolution New species of malaria occurs around the same time as ABO blood types (hominid group O mutation from A) Protective mutations arise (sickle cell disease=protective against malaria); Hb S; Hb c; G6PD; thalassemia; HbE; membranopathies When humans develop agriculture= increase in malaria Northern latitudes= type A Eastern Europe/Western Asia= Type B South America/Africa= Type O; high prevalence of malaria here too HIV: Evidence for Human Evolution Sex workers in Kenya were long-term not infected by HIV→ sequence MHCI/II→ identification of protective alleles: HLA-A2 6802 and HLA-DRB1*01 (resistant to HIV) HIV: oldest confirmed case (HIV-1)=1959 Suspected species “jump”: 1931 (HIV-1); 1940 and 1945 (HIV-2 A and B) Host-Pathogen Evolution= seeking balance Host: Minimize loss of fitness= select successful MHC haplotypes; selecting resistance genes; “selection” los less-virulent pathogen strains (may persist longer) Pathogen: Maximize reproductive success= host survival (at least until transmitted); avoid immunity; modulation of virulence To be a pathogen you must: 1. Be able to survive in the human body (pH, temperature etc) 2. Be able to avoid or modulate the immune response to allow your own survival As such: A) most microorganisms are NOT pathogens (most are killed by immune system); and B) most pathogens have immune-avoidance mechanisms Avoiding Innate Immunity: Preventing Opsonization Lyme disease (Borellia):
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