15hiv and Aids Ppt 4329
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Transcript of 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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Immunodeficiencies and Cancer 3
What are causes of 2O Immunodeficiencies?-- acquired later in life
Malignancies
Nutritional deficiencies
Stress
Age
Drugs
Infections
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Immunodeficiencies and Cancer 4
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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Immunodeficiencies and Cancer 5
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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Immunodeficiencies and Cancer 6
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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Immunodeficiencies and Cancer 7
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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Immunodeficiencies and Cancer 8
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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Immunodeficiencies and Cancer 9
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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Immunodeficiencies and Cancer 10
Clinical course of HIV infection
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Immunodeficiencies and Cancer 11
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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Immunodeficiencies and Cancer 12
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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Immunodeficiencies and Cancer 13
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.