Download - 15-HIV and AIDS.ppt
Immunodeficiencies 1
HIV and AIDSChapter 15
Self-Test Questions:Intro-A1: allA2: 1 & 2B1: 1 – 3, 5B2: 1, 3, 4B3: allC: 1 - 5D: allE & F: 3G: all
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What causes immunodeficiencies?
1O vs 2O immunodeficiencies
Examples of 1O
LymphaticSCIDDiGeorgesBare lymphocyte (no MHC)Agammaglobulinemia
MyeloidAgranulocytosis e.g., neutropenia
Nude mouse
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What are causes of 2O Immunodeficiencies?-- acquired later in life
Malignancies
Nutritional deficiencies
Stress
Age
Drugs
Infections
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What is the structure of HIV?-- HIV is a ‘retrovirus’
Structure of HIVEnvelope
GP120 receptorInner protein layerCapsidRNART & integrase enzymes
What cells does HIV infect?Host cell ligands
CD4Chemokine receptors
CCR5CXCR4
Target cellsM-tropic: 1O macrophages (CCR5)T-tropic: 1O TH cells (CXCR4)
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What genes are present in the HIV genome?
9 genes, coding for 16 proteins
FunctionsStructuralEnzymaticRegulatory
Precursor proteins
HIV protease
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How does HIV infect cells and replicate?
Infection
Receptor binding & membrane fusion
Capsid entry & dissociation
Release of RNA & enzymes-- Reverse Transcription
Provirus integration in host DNA-- integrase activity
Replication
Provirus activation
Protein and RNA synthesis-- protease activity
Virion self-assembly & buddingMcGraw-Hill
HIV Life Cycle
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How does HIVAffect the immune response?
Has effects on. . .TH – 1O targetB-cellsTc and CTLs
T-cell syncytia
Why do these responses decline?
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How does the immunological response change during the course of an HIV infection?
1. Acute phase
2. Chronic phase
3. AIDS
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What are the clinical categories of an HIV infection?
Clinical PresentationA: typically mild symptoms
B : moderate symptoms
C : severe disease
Immunological Status1: >= 500 TH cells /μl blood
2: 200 – 499 /μl
3: < 200/μl
AIDS diagnosis• HIV+• < 200 TH cells /μl blood• 1 or more AIDS associated diseases
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Clinical course of HIV infection
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Control of viral infections
Antibiotics don’t work
Synthetic drugs-- treat symptoms-- slow viral replication
Anti-HIV therapy – 4 classes
Reverse transcriptase inhibitors1a) nucleotide analogs
e.g., AZT, ddl, ddc, etc1b) non-analog inhibitors
e.g., nevirapine, etc2) protease inhibitors
3) Fuzeon -- newest drug-- fusion inhibitor
Combinational drug therapy (HAART)
McGraw-Hill HIV Treatments
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Why is controlling AIDS in the developing world so difficult?
Genetic variabilityHIV-1 and HIV-2 HIV-1 Clades
Mode of transmissionC&E mainly heterosexual
Weak health care and educational systems
Cost of AIDS drugs
Complexity of drug regimen
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Will there be an AIDS vaccine anytime soon?
Current strategiesDNA vaccinesVector based vaccines
Recent “success” with combined vaccine
ChallengesAntigenic variabilityDifficulty getting CTL and humoral responseDifficulty generating mucosyl-immunity Use of a live-attenuated vaccine is riskyEtc.