HIV and AIDS

Chapter 15

Self-Test Questions:
Intro-A1: all A2: 1 & 2 B1: 1 3, 5 B2: 1, 3, 4 B3: all C: 1 - 5 D: all E & F: 3 G: all

Immunodeficiencies

What causes immunodeficiencies?

1O vs 2O immunodeficiencies Examples of 1O
Lymphatic SCID DiGeorges Bare lymphocyte (no MHC) Agammaglobulinemia Myeloid Agranulocytosis e.g., neutropenia

Nude mouse

Immunodeficiencies and Cancer

What are causes of 2O Immunodeficiencies?

-- acquired later in life
Malignancies
Nutritional deficiencies Stress

Age
Drugs Infections

Immunodeficiencies and Cancer

What is the structure of HIV?

-- HIV is a retrovirus Structure of HIV Envelope GP120 receptor Inner protein layer Capsid RNA RT & integrase enzymes

What cells does HIV infect?

Host cell ligands
CD4 Chemokine receptors CCR5 CXCR4

Target cells M-tropic: 1O macrophages (CCR5) T-tropic: 1O TH cells (CXCR4)

Immunodeficiencies and Cancer

What genes are present in the HIV genome?

9 genes, coding for 16 proteins

Functions
Structural Enzymatic Regulatory

Precursor proteins HIV protease

Immunodeficiencies and Cancer

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 & budding
McGraw-Hill HIV Life Cycle

Immunodeficiencies and Cancer

How does HIV Affect the immune response?

Has effects on. . . TH 1O target B-cells Tc and CTLs

Why do these responses decline?

T-cell syncytia

Immunodeficiencies and Cancer

How does the immunological response change during the course of an HIV infection?
1. Acute phase 2. Chronic phase

3. AIDS

Immunodeficiencies and Cancer

What are the clinical categories of an HIV infection?

Clinical Presentation
A: typically mild symptoms B : moderate symptoms C : severe disease

Immunological Status
1: >= 500 TH cells /l blood 2: 200 499 /l 3: < 200/l

AIDS diagnosis
HIV+ < 200 TH cells /l blood 1 or more AIDS associated diseases

Immunodeficiencies and Cancer

Clinical course of HIV infection

Immunodeficiencies and Cancer

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Control of viral infections

Antibiotics dont work

Synthetic drugs
-- treat symptoms -- slow viral replication

Anti-HIV therapy 4 classes

Reverse transcriptase inhibitors 1a) nucleotide analogs e.g., AZT, ddl, ddc, etc 1b) non-analog inhibitors e.g., nevirapine, etc 2) protease inhibitors

3) Fuzeon -- newest drug -- fusion inhibitor

Combinational drug therapy (HAART)

McGraw-Hill HIV Treatments

Immunodeficiencies and Cancer

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Why is controlling AIDS in the developing world so difficult?

Genetic variability
HIV-1 and HIV-2 HIV-1 Clades

Mode of transmission
C&E mainly heterosexual

Weak health care and educational systems Cost of AIDS drugs

Complexity of drug regimen

Immunodeficiencies and Cancer

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Will there be an AIDS vaccine anytime soon?

Current strategies
DNA vaccines Vector based vaccines Recent success with combined vaccine

Challenges
Antigenic variability Difficulty getting CTL and humoral response Difficulty generating mucosyl-immunity Use of a live-attenuated vaccine is risky Etc.

Immunodeficiencies and Cancer

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