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UNIVERSITY OF GONDARCOLLEGE OF MEDCINE & HEALTH SCIENCES

SCHOOL OF BIOMEDICAL & LABORATORY SCIENCES

DEPARTMENT OF IMMUNOLOGY & MOLECULAR BIOLOGY

TOPIC: IMMUNITY AGAINST HIV INFECTION

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Prepared by:

Abebe BekeleAlembanch

TsegaAmele work

YilmaFeleke MekonenMelkamu

GetnetEmebet Sahlie

Seble WorkuSetegn EshetieTesfaye AndualemTigist EngdaWondossen

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Acknowledgment We would like to extend our gratitude to Mr. Biniyam Matheous; for his interactive and participatory teaching learning style.

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Out lineIntroduction HIV life cycleComponents of antiviral responseImmune pathogenesis of HIVLiterature reviewConclusion Recommendation Reference

INTRODUCTIONFamily : RetroviridaeSubfamily : LentivirusRNA virus, 120nm in

diameterEnvelope gp160;

gp120 & gp41Icosahedral symmetryNucelocapsid

Outer matrix protein (p17)

Major capsid protein (p24)

Nuclear protein (p7)Diploid RNA with

several copies of reverse transcriptase

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Retroviral Genesgag (group-specific antigen): makes the cone

shape viral capsid.pol (polymerase): codes for viral enzymes

reverse transcriptase, integrase, and viral protease.

env (envelope): makes surface protein gp120 and trans membrane gp41, enabling HIV to fuse to CD4 cells.

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con…

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HIV life cycle

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Component of antiviral response Both humoral and cell-mediated immune

responses partially control the viral production but in

this process they destroy the infected CD4+T

cells, leading to a gradual decline of CD4+ T

cellsInnate Immunity

Antigen presenting cells: Macrophage and Dendritic cells

Other cell types: NK, gamma- delta , NKT cellsSoluble factors: Chemokines

Adaptive Immunity CD4 T helper cells CD8 T cells (CTL)B cells: Neutralizing antibodies

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Cont…

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Pathogenesis of HIV / AIDS Infected T-Cell

HIVVirus

T-CellHIV Infected

T-Cell

New HIVVirus

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Immune pathogenesis of HIVMechanisms

syncytium formationApoptosis Auto immunity

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Literature reviewHIV will mount an effective immune

response to the virus during the first few months of infection. However, over time this response will prove ineffective.

Humeral immunity

Cell mediated immunityBoth are ineffective

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Cont…Mucosal immunity Vs HIV infectionThe study demonstrated that

commercial sex workers were HIV negative after 5 yrs active prostitutions

Associated with the integrity of mucosal immunity.

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Cont..Study indicated that intranasal

administration of DNA vaccine and IL-15 expression plasmid is capable of enhancing the T helper type 1 (Th1) dependent HIV-1-specific cell-mediated immunity, but

It decrease humoral immunity

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Cont…DCs are key regulators of both

adaptive and innate immune responses

According the study, it revealed that the plasma from patients with HIV specifically inhibited DC function.

mediated by elevated apoptotic micro particles.

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Cont…The study confirmed that HIV infection

causes NK cells apoptosis (increase expression of

ki67 and Fas markers in course of infection)Macrophage and monocyte phenotype

change ( alteration of TLR)Causes defect in microbial killing

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Cont..Depot medroxyprogesterone acetate

(DMPA) usage relation to HIV immunity.

Decrease both arms of immunity(interferon (IFN)-gamma, IL-2, IL-4, IL-6, IL-12, TNF alpha and other cytokines)

Mediate up regulation of co-receptors(CXCR4, CCR5)

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Con…In contrast: PA-MSHA activates both

natural and specific immunityNK cells, APCs activates through

TLR More over: serve as adjuvant for

HIV-1 DNA vaccine. Increase Humeral and Cell mediate response

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Cont…cholesterol-25-hydroxylase (CH25H)

recognized that a broadly antiviral interferon stimulated genes

Converts cholesterol in to soluble antiviral agents; inhibits viral replication (attachment)

Animal model shows: CH25H deficient mice more susceptible to HIV-1 infection.

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Conclusion HIV establishes a latent reservoir early in infectionHIV develops mutations to escape immune

responses, HIV depletes functional cells of innate immune

systemHIV depletes CD4 T cells: the “conductor of the

immune orchestra” and blunts immune responsesHIV causes deleterious effects on the entire immune

system resulting in aberrant immune activation

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Recommendation The mechanism of immune response against HIV infection remains incompletely understood, so that

It needs further investigation.So that we post graduate students should take emphasis in this particular researchable area.

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References

Hou J, Liu Y, Shao Y. The MSHA strain of Pseudomonas aeruginosa activated TLR pathway and enhanced HIV-1 DNA vaccine immunoreactivity. PloS one. 2012;7(10):e47724. Epub 2012/10/19.

Poudrier J, Thibodeau V, Roger M. Natural Immunity to HIV: A Delicate Balance between Strength and Control. Clinical & developmental immunology. 2012;2012:875821. Epub 2013/01/11.

And more

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Thank you!!!