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Department
Immunology
Course
IMM250H1
Professor
All Professors
Semester
Winter

Description
APRIL 2 , IMM430 TUTORIAL – next Tuesday, same time of class – overview post-midterm lectures SAME FORMAT – SHORT ANSWER QUESTIONS 10 marks per pre-midtedrm lecture; 20 marks per post- midterm lecture RESEARCH ARTICLE – STUART BERGER – REVIEW THE ABSTRACTS STUDENT PRESENTATION: GLYCEROL MONOLAURATE PREVENTS MUCOSAL SIV TRANSMISSION Protective immunity against HIV-1 HIV Protective immunity – different meanings to different people - Exposed to HIV, not infected – almost all vaccines allow little bit of infection, which gets aborted - Controlling immunity – infected by HIV but immune response is able to control virus – do not go on to develop immune suppression – have good health - Transmission – may or may not be able to transmit – not able to transmit the virus to someone else - More virus – more likely to develop immunosuppression – to transmit to sexual partner Many areas in Sub-Saharan Africa – rate is decreasing Prevalence = what percentage of people in particular population have HIV? If prevalence goes down, either cured of HIV or deaths due to HIV Incidence of new cases is what is desired to go down Prevalence wanted to stay the same; then able to age naturally with HIV Prevalence stays the same, but incidence stays at zero HIV – risk of transmission 20% - mother’s chances of passing to baby 0.1% - single sexual contact of getting HIV Determinant in infected partner – what happens in blood doesn’t mirror what’s going on in genital tract But if viral load low in the blood, generally low in genital tract Viral load in infected person is important determinant of whether transmitted to sexual partner or not Virus is enveloped – RNA virus RNA into DNA by reverse transcriptase HIV virus genetics HIV2 originated in West Africa – where sooty mangabeys are SIV transmitted into humans, became HIV 1 and 2 HIV 1 more transmissible Within same individual – diversity generated quickly – even if 100% identifal when injected, get 5% diversity due to error-prone In untreated primate – make billion viruses a day Majority of viruses unable to infect cell – mutations occurred where critical of virus – but enough are functional to case disease – if put evolutionary pressur on virus (either by medication or) virus can adapt and escape can mutate and escape by generating mutations in key areas, so targeted by immune response or medication HIV binds – CD4; CCR5 and CCR5 – HIV has primary and co-receptor – almost all primary viruses – newly transmitted viruses use CCR5 – Fusion of virus Virus that uses CCR5 – almost everyone, when fisrt infected, get CCR5 With more advanced infection, virus can change over time – can bind to different co-receptor CXCR4 High levels of virus in bloodstream – comes down as immune system kicks in – Low level of virus – CD4 count declines over time – once peripheral blood CD4 count comes down – at a sufficiently low level, called AIDS – T helper cells so dysfunctional so get braod-based infection Coincident – viral load goes up Times that are most infectious are up to 12 weeks, and at 11 years – in the former, within firt month or two or infection, being sexually active, may have other STI that enhance transmission – viral load 2 or 3 logs higher than traditional HIV tests negative – Traditional ELISA test relies on antibody – there is a period of time where have virus and no antibody response Images of gut – small intestine should have lymphoid tissue in the gut – Peyer’s Patches – yellow patches are the immune inductive sites of gut, the Peyer’s patches In HIV, the lymphoid tissue wiped out – Full of activated CD4 T cells – so rapid replication in guts so they are wiped out in early acute phase Alpha 4 beta 7 – mucosal integrin – take dendritic cells form Pey’ers patch from gut – show T cell – take dendritic cells from lymph nodes – CD8 PP – stimulated by dendritic cell from Peyer’s patch – DC from gut or mucosla surface make CD8 cells they prime express alpha 5 beta 7 Alpha 4 beta 7 binds HIV well – ineracts with envelope of virus – thethers virus a little while the virus looks around for CD$ CCR5 Cells more susceptible if express this integrin Damage gut – leaky gut – full of bacteria – bacteria break through mucosal barrier if damage mucosal enough – leaking into bloodstream, which lcan generate immunodeficiency and pathogenesis – most of damage done not due to direct deaeth – due to secondary mechanisms Humoral immunity – HIV – IgG response to HIV is ubiquitous – once infected – means that do not get protected by antibodies – affected chronically despite having antibodies – most people are good at having neutralizing antibodies against their own virus – looking at antibody over time – antibodies today good at neutralizing virus six months ago; bad at neutralizing virus today – HIV antibody responses – CONS Do not generally neutralize well Conformational masking – to do with entropy – antibody doesn’t want to be in right conformational form to neutralize virus – Glycan shield – Lots of antibodies against non-functional virus – DECOY Dead, defective virus – so immune response directed against what doesn’t matter Do make good neutralizing antibodies but virus escapes quickly – PROS – some antibodies are quite good at targeting conserved areas of virus and viruses isolated from people – talking about some of the traditional ones – always talking about six antibodies – cool ways to screen antibodies – Two cons – those antibodies do not correlate with better health; and often the people who have those antibodies have progressive disease – how do you make a vaccine induced antibodies? Not make vaccine induced antibodies against infection – make one specific monoclonal antibody – never been attempted with vaccine High throughput screening – Passive immunization – only model of sterile protection Only way that have been shown that sterile protection – take cocktail of antibodies – do not work well if have HIV – gives sterile protection – protects well against virus with physiologically relevant virus in primate model – question is – if someone is high-risk – cannot be giving large doses of monoclonal antibodies – maybe useful aftedr mother to child – some narrow therapeutic opportunities CTL –
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