Presentation on theme: "Immune Responses to HIV"— Presentation transcript:
1 Immune Responses to HIV Zoran Galic Ph.D.Division of Hematology/OncologyDavid Geffen School of Medicine UCLAAugust 19, 2014
2 Innate vs adaptive immunity In response to pathogens, vertebrate immune systems use two interconnected systems:Innate immunityAdaptive immunity
3 The major cells of innate immunity Big eaters/Always hungryAntigen Presenting Cells (APCs)Proteins eaten by APCs are broken down to small pieces (peptides),which are loaded on special receptors (MHCs) and transported to thecell surface. Peptide+MHC complex can be recognized by a T cell and that interaction can lead to an adaptive immune response.
5 HIV induces strong cellular and humoral immune responses CTL-cytotoxic T lymphocytes (CD8 killer T cells)
6 Why is HIV not cleared by the immune system? High mutation rate of HIVHIV latencyCompromised immune function, primarily through the lossof CD4 T helper cells
7 CD4 T cells are depleted in the course of HIV infection
8 Why are CD4 T cells depleted during the course of HIV infection? HIV-infected CD4 T cells are targeted by the immune responseCD4 T cells are lost due to immune exhaustion
9 Innate immune system vs HIV Innate responses against HIVRapid and first line of defense against the virusAlert and activate the adaptive immune responseRelease pro-inflammatory signalsClearance of infected cellsInternalize and process the virus to present to T cells to initiate the adaptive responseHIV counter-attackThe virus can infect members of the innate immune systemInnate cells can act as depot and effectively transmit virusInhibition of function via viral factor release and/or improper immune signals
10 CD4 T cells vs HIV CD4 T cells responses against HIV Orchestrate adaptive immune responseActivated by innate immune systemFacilitate CD8 T cell (killer) andB cell activationProvide signals and growth factors for proper immune responsesHIV counter-attackInfects CD4 T cellsCauses depletion of the CD4T cell population and thereby removes the “brains” of the immune responseUses surviving CD4 T cellsas a reservoir (latent HIV)
11 B cells vs HIV B cell responses against HIV Directed by CD4 T cell to make antibodies against HIVAntibodies neutralize the virus to prevent spreadHIV counter-attackVirus mutates at a very high rateLoss of CD4 T cells results in:Increase in numbers ofimmature B cellsExhaustionDecreased memory
12 CD8 T cells vs HIV CD8 T cells responses against HIV Killer arm of the immune systemSeek, identify and destroy infected cellsControl virus in the initial months of infectionHIV counter-attackVirus mutates and escapesChronic inflammation leadsto exhaustionLack of CD4 T cells:Insufficient signals toactivate more killer cellsDefective memoryImpaired function
13 Closing CommentsAPCs, B cells, CD4 and CD8 T cells work together to fight infectionHIV perturbs APC function, and kills CD4 T cellsThis allows secondary “opportunistic” infections to occur,leading to disease/deathVaccines have the potential to halt HIV infection, but thus faran efficacious vaccine strategy has proven elusiveA vaccine approach that takes into account all aspects of the immuneresponse will likely have the best chance of success
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