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Immune system and HIV infection models. Abdessamad Tridane. MTBI summer 2007. HIV PRESENTATION. HIV STRUCTURE. HIV Structure. HIV has just nine genes Three of the HIV genes, called gag, pol and env, contain information needed to make structural proteins for new virus particles.
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Immune system and HIV infection models Abdessamad Tridane MTBI summer 2007
HIV PRESENTATION • HIV STRUCTURE
HIV Structure • HIV has just nine genes • Three of the HIV genes, called gag, pol and env, contain information needed to make structural proteins for new virus particles. • The other six genes, known as tat, rev, nef, vif, vpr and vpu, code for proteins that control the ability of HIV to infect a cell, produce new copies of virus, or cause disease.
Innate Immune system • Dendritic cells • Macrophages • NK-cells • Interferon-producing cells (IPC) • Chemokines • Defensism
Adaptive Immune system • Dendritic cells • Macrophages • B-Lymphocytes • CD4+ Lymphocytes • CD8+ Lymphocytes
Innate Dendritic cells Macrophages NK-cells Interferon-producing cells (IPC) Chemokines …. Adaptive Dendritic cells Macrophages B-Lymphocytes CD4+ Lymphocytes CD8+ Lymphocytes
Importance of the innate Immune System MHC expression NK cell activity Lymphocyte response Innate Immunity Cytokines Anti-microbial responses (Interferon)
Impact of HIV CD4+ T-Cells Reservoir B-cells NK cells Macrophages
Impact of HIV Impact of HIV CD4+ T-Cells Reservoir CD4+ T-Cells Reservoir B-cells B-cells NK cells NK cells Macrophages
HIV Infection Leads to a state of Generalized Immune Activation HIV Induced Immune Activation Increased T- cell turnover (Production and destruction) Increased activation-induced death of T- cells A decline in the size of the CD4+ T Cell pool A state of activation- induced immunodeficiency
CD4+ T-cell Response to HIV • In some individuals, CD4+ T-cell responses remainrelatively normal. • These individuals do not appear to progress to diseaseeven though they are infected. These individuals are termed Long-term non-progressors (LTNP).
CTL Responses To HIV CTL responses are measured by • 51Cr release assay (Killing) • ELISpot (Cytokine release) Antigen specific CD8+ T-cells can be quantified by tetramer staining. (Number of specific cells)
CTL fail to eliminate HIV • Many chronically infected individuals have vigorous HIV-1-specific CTL responses yet they almost always fail to adequately suppress the virus. Why? • Epitope escape? • CTL Exhaustion? • Suboptimal CTL?
Why does the immune response fail to clear HIV? • HIV integrates into the host genome. Therefore, to eliminate HIV, infected cells must be killed. • Host factors can paradoxically enhance HIV replication. Therefore, by responding to HIV, CD4+ T-cells can be destroyed.
Why does the immune response fail to clear HIV? • HIV can mutate and escape immune mediated opposition. • Suboptimal CTL responses can be elicted. • Sugar coating (glycosylation) and folding of gp120 protects against Ab recognition. • Critical binding sites on gp41 are revealed for only a short period of time.
Why does the immune response fail to clear HIV? • APC’s may exhibit altered functions diminishing their ability to elicit immune responses. • Antigen presenting cells can act as trojan horses, spreading HIV to CD4+T-cells as they begin to respond to antigen.
