15hiv and aids ppt 4329

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Immunodeficiencies 1

HIV and AIDSChapter 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

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Immunodeficiencies and Cancer 2

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

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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 HIV

EnvelopeGP120 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)

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What genes are present in

the HIV genome?

9 genes, coding for 16 proteins

FunctionsStructural

Enzymatic

Regulatory

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
http://www.marietta.edu/~spilatrs/biol430/animations/McGraw-Hill%20hiv_replication.swfhttp://www.marietta.edu/~spilatrs/biol430/animations/McGraw-Hill%20hiv_replication.swfhttp://www.marietta.edu/~spilatrs/biol430/animations/McGraw-Hill%20hiv_replication.swf

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How does HIV

Affect the immune

response?

Has effects on. . .

TH1O target

B-cells

Tc 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 /l blood

2: 200499 /l

3: < 200/l

AIDS diagnosis HIV+

< 200 TH cells /l 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 dont work

Synthetic drugs-- treat symptoms

-- slow viral replication

Anti-HIV therapy4 classes

Reverse transcriptase inhibitors

1a) nucleotide analogse.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
http://www.marietta.edu/~spilatrs/biol430/animations/McGaw-Hill%20treatment_of_hiv.swfhttp://www.marietta.edu/~spilatrs/biol430/animations/McGaw-Hill%20treatment_of_hiv.swfhttp://www.marietta.edu/~spilatrs/biol430/animations/McGaw-Hill%20treatment_of_hiv.swf

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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 vaccines

Vector based vaccines

Recent success with

combined vaccine

ChallengesAntigenic variability

Difficulty getting CTL

and humoral response

Difficulty generating mucosyl-immunity

Use of a live-attenuated vaccine is risky

Etc.

15hiv and aids ppt 4329

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