HIV infection Flashcards by RK Splendid

which infectious disease is the biggest killer globally?

HIV

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which cells does hIV-1 infect?

immune system cells

hence why it cuases immuno deficieincy and aids

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what are thee characteristcs of HIV molecule?

HIV has an Icosahedral structure (20-faced tr).
- Genome is diploid, (+) ssRNA genome.
- Contains 9 genes

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the HIV env genes codes for which proteins?

gp120 - surface protein

gp41 - transmembrane protein

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the HIV gag genes codes for which proteins?

p17 - matrix protein

p24 - caspid protein

p9,p7 - inside capsids

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list the targets for the HIV-1 pathogen ?

CD4+ T helper cells (& CD4+ Monocytes) - main targets

infected, killed or disabled by HIV1

can also affect cd4+ dendritic cells

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which of our immune cells/components are responsible for fighting HIV-1?

antibodies (B cells) to prevent infection and neutralize virus (opsonisation)

and sufficient CD8+ T cells (CTL) to eliminate (kill) latently infected cells.

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the immune system fails to control HIV-1 infection ?

Because hiv-1 targets the CD4 t cells.

depletion of the cd4 cells means;

less/no activation of immune response (cd4 cells activate, cd8, apc, & B cells)
less response to the HIV-1 antigens for example;

mitogen, allo antigen, recall antigen, HIV-specific

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how does HIV1 enter target cells?

CD4 molecule/Ag

most also use

1b. co-receptor molecules (CCR5 and CXCR4)

possibly
2. other co-receptors; chemokine receptors

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when does Mother to child hiv transmission occur?

before or during birth or via breast milk.

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how does hiv infection via std occur?

how do other immune cells get infected?

The virus enters through mucosal surfaces.

Increased by factors which damage such surfaces.

Infects CD4+ cells, but also DC in the mucosa

may bind to and carry the virus from the site of infection to the LYMPH NODES

where other immune cells become infected.

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describie the timeline of natural immunity in resposne to hiv infection ?

Mobilised within hours of infection

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what does natural immunity in resposne to hiv infection involve?

Inflammation.
Non-specific activation of macrophages.
Non-specific activation of NK cells and complement.
Release of cytokines and chemokines.
Stimulation of pDCs via toll-like receptors.

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what doe s acquired immunity to HIV involve?

Productio of antibodies;

Neutralising antibodies
- Anti-gp120 and anti-gp41
Non neutroalising antibodies
- anti-p24 gag IgG

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what is the state of the HIV molecule post opsonisation with antibodies?

HIV remains infectious even when coated with antibodies

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what is the role of the CD4+ T cells normally?

ORCHESTRATORS

White blood cells that orchestrate the immune response, signalling other cells in the immune system to perform their special functions

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what does CD4 cell do upon detection of HIV?

detects processed antigen - especially Gag p24 (peptides) - USING

class II MHC/HLA molecules.

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whic immune cells can;

prevent infection by blocking entry of HIV virus into CD4+ T cells?

by which mechanism?

CD8+ T cells

Secrete soluble cytokines and chemokines

such as MIP-1a, MIP-1b, and RANTES

these are able to prevent infection by blocking entry of virus into CD4+ T cells

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cd8 t cells recognise antigens via?

MHC/HLA class 1 molecule

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what is the role of cd8 t cells ?

White blood cells that kill cells infected with HIV or other viruses, or transformed by cancer (CTL). Also able to suppress viral replication

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what are the dfferences between MHC1 and MHC2 molecules?

MHC1:
1 transmembrane segment
a1,a2,a3 chain
b2 microglobulin unit

MHC2:
2 transmembrane segments
a1,a2 chain and b1b2 chain

how does hiv prevent cd8 cell activation

mainly through;

CD4 cells - killing/inactivating
Monocytes/dendritic cells

Activated infected CD4+ helper T cells die and are lost
Infected CD4+ T cells are also disabled (ANERGISED) by the virus
MO/DC are not activated by the CD4+ T cells and can not prime naïve CD8+ CTL
CD4+ T cell memory is lost

CD8+ T cell and B cell responses are diminished without help

Infected MO/DC are killed by virus or CTL
Defect in antigen presentation
Failure to activate memory CTL*

list Chemokines & CAF relased by cd8 upon activation?

MIP-1a
MIP-1b
RANTES

list cytokines relased by cd8 upon activation?

IFNg

TNFa

how do cd8 cells cause cell death/lysis?

Release of: 1. Perforin - binds to target cells and forms pores 2. Granzymes - induce programmed cell death (apoptosis) in the target cell 3. Fas/FasL - ligation of Fas with FasL results in the activation of a caspase cascade that initiates apoptosis

why can HIV accumulate many mutations and numerous variants or quasispecies.?

High error rates of: i) RT ii) RNA polymerase II i) Reverse Transcriptase lacks the proof reading mechanisms so genomes of retroviruses are copied into DNA with low fidelity. ii) Transcription of DNA into RNA copies is also of low fidelity

how has hiv escaped immune destruction all this while?

Many mutations and numerous variants or quasispecies Escape from neutralising antibodies. Escape from HIV-1-specific T cells. Resistance and escape from antiretroviral drugs

list the 7 steps in hiv life cycle?

1. Attachment/Entry 2. Reverse Transcription & DNA Synthesis 3. Integration 4. Viral Transcription 5. Viral Protein Synthesis 6. Assembly of Virus & Release of Virus 7. Maturation

HAART involves which regime?

HAART = 2NRTIs + PI (or NNRTI)

how do nrti work?

prevent viral rna conversion into cDNA - complementary DNA preventing incorporation in human dna

how do protease inhibitors work?

prevent maturation and budding of viral proteins

list some hiv therapies that prevent Attachment | getting in?

Attachment inhibitors fusion inhibitors

what is complementary DNA ?

is DNA synthesized from a single-stranded RNA eg mrna

what is the role of Integrase Inhibitors?

prevent integration and transcription ; Viral DNA joins host DNA and copy production

what is the role of protease Inhibitors?

prevent Viral protease cleaving viral proteins

what is Median time from infection with HIV to development of AIDS in 1. normally infected 2. rapid progressors? 3. Long term non Progressors

1. 8-10 years 2. 2-3 years 3. no symptoms after 10 years.

at what point is a diagnosis of AIDS made?

CD4 count < 200

what % of hiv do the following make up? 1. normally infected 2. rapid progressors? 3. Long term non Progressors

1. normally infected 85% 2. rapid progressors? 10% 3. Long term non Progressors <5%

list some characteristics of Long term non Progressors in HIV infection?

Normal, Stable CD4 | Vigorous CD4 and CD8 anti-HIV responses

which HIV types Increase optimism that some forms of protective immunity may indeed exist in HIV-1 infection.?

exposed seronegatives Long term non Progressors

list some Host genetic factors that are Possible mechanisms of long-term nonprogression with HIV infection?

Slow progressor HLA profile Heterozygosity for 32-bp deletion in chemokine receptor CCR5 Mannose binding lectin alleles Tumor necrosis factor c2 microsatellite alleles Gc vitamin D-binding factor alleles

list some Host immune response factors that are Possible mechanisms of long-term nonprogression with HIV infection?

Effective CTL & HTL responses Secretion of CD8 antiviral factor Secretion of chemokines that block HIV entry co-receptors CCR5 (e.g., MIP-1a, MIP-1b, and RANTES) and CXCR4 (e.g., SDF-1) Secretion of IL-16 Effective humoral immune response Maintenance of functional lymphoid tissue architecture

list some Virologic factors that are Possible mechanisms of long-term nonprogression with HIV infection?

Infection with attenuated strains of HIV

how can HIV-1 be detected?

1. Anti-HIV antibody - (ELISA) -> screening - western blot -> confirmatory 2. HIV RNA (Viral load) - (More Sensitive) (PCR)

How are CD4 T cell counts monitored?

flow cytometry

which cell surface markers can be detected by flow cytometry?

- anti-human CD3 - anti-human CD4 - anti-human CD8 - anti-human CD19 - anti-human CD56

list the 2 forms of HIV-1 Resistance Testing?

Phenotypic: cell cultures . increasing concentrations of antiretroviral drugs Genotypic: Mutations determined by direct sequencing of the amplified HIV genome

what is the Effect of HAART on VLoad and CD4 counts ?

suppressed viral load increased CD4 count; Initial CD4 rise – memory T-cells redistributed Later CD4 rise is thymic naïve T-cells

when is HAART given?

All symptomatic patients All CD4 <200 cells/ml START: CD4 200-350 cells/ml

list some Limitations & Complications of HAART regimens

``` Effective HAART does not eradicate latent HIV-1 in the host Fails to restore HIV-specific T-cell responses the threat of drug resistance Significant Toxicities High pill burden Adherence problems Quality of life issues Cost ```

Permanent control of latently infected cells by ___ may prevent progression to AIDS?

CD8/CTL

An effective vaccine must elicit _____ and ____?

potent antibodies and CTL/CD8