Chapter6- AIDS Flashcards
What does AIDS stand for?
Acquired Immunodeficiency Syndrome
Cause of AIDS
a retrovirus- human immunodeficiency virus
Characteristics of AIDS
profound immunosuppression leading to exposure to opportunistic infections, secondary neoplasms, and neurologic manifestations
Where is AIDS most globally found?
Africa and Asia
Modes of HIV transmission (3)
- Sexual transmission
- Parenteral transmission
- Mother-to-infant transmission
Sexual transmission of HIV
> 75% of cases
enhanced by coexisting STDs
Parenteral transmission of HIV
IV drug abusers
Hemophilias who received factor VIII and IX
Recipients of blood transfusion
How has HIV been eliminated from recipients of blood transfusions?
screening of donated blood and plasma for HIV
purity criteria for factor VIII and factor IX
screenings of donor history
Mother-to-infant transmission
In utero by transplacental spread
during delivery through infected birth canal
breast milk ingestion
How to eliminate risk of HIV in mother-to-infant transmission
antiretroviral therapy
Epidemiology of HIV/AIDS
Men who have sex with men *largest group Heterosexual contacts *globally most common Intravenous drug abusers Hemophiliacs Recipients of blood and blood components HIV infection of newborn
2 forms of HIV
HIV1- common in US Europe Central Africa
HIV2- West Africa and India
Contents of virus core of HIV
major capsid protein p24
2 copies of viral genomic RNA
3 viral enzymes
Major capsid protein p24
most abundant viral antigen
ELISA test used to diagnose HIV infection
3 viral enzymes in HIV viral core
protease
reverse transcriptase
integrase
What protein surrounds the viral core of HIV
matrix protein p17
What studs the viral envelope of HIV molecule
gp120 and gp41
First cells attacked by HIV infection
T cells, DCs, and macrophages to establish itself in lymphoid tissues
(all have CD4)
Process of HIV infection
Attack cells
Active viral replication
More infection of cells
Progression to AIDS
Chemokine Receptors of HIV
R5 strains use CCR5
X4 strains use CXCR4
R5 strains and CCR5 receptor
infect monocyte-macrophage lineage (M-tropic)
homozygous defective copies of CCR5 are resistant to HIV
heterozygous CCR5 causes delayed infection
X4 strain and CXCR4
infects T cells (T-tropic)
generated T cell depletion and impairment
What T cells are infected by HIV Infection?
memory and activated T cells
Why does HIV not infect naive T cells?
naive T cells contain an active form of an enzyme that causes mutations in HIV genome
enzyme- APOBEC3G
How does HIV stimulate cells?
release NFkB which goes to the nucleus and increases HIV DNA transcription
How does T cell depletion occur in HIV?
direct cytopathic effects
kill CD4+ T cells – for a while the immune system can replace them but eventually it can’t keep up
Major abnormalities of Immune Function in AIDS (5)
Lymphopenia Decreased T cell Function in Vivo Altered T cell function in vitro Polyclonal B cell Activation Altered Monocyte or macrophage function
How does lymphopenia occur in AIDS
loss of CD4+ helper T cell
Polyclonal B cell activation in AIDS
poor responses to normal B cell activation signal
Altered monocyte or macrophage function in AIDS
decreased class II HLA expression can't present antigen to T cell
Altered T cell function in vitro in AIDS
decreased IL-2 and IFNy
decreased helper function for B cell antibody production
Macrophages in HIV
HIV-1 can infect and multiply in terminally differentiated non-dividing macrophages
Dendritic Cells in HIV
DCs pick up HIV and present it to the CD4+ cell which causes infection of that CD4+ cell
What receptor on DCs specifically binds HIV and displays it to T cells
lectin-like receptor
Follicular Dendritic cells in HIV
in Lymph nodes
potential reservoirs for HIV
trap HIV virion coated with anti-HIV antibodies but they retain ability to infect CD4+
B cells and HIV
B cell undergoes polyclonal activation
AIDS pts can’t mount antibody response to new antigens
Results of Polyclonal Activation of B cells and HIV (4)
Germinal center B-cell hyperplasia
Bone marrow plasmacytosis
Hyperagammaglobulinemia
Formation of circulating immune complexes
HIV and the brain
Nervous system is a main target for HIV
causes neurologic dysfunction
What does HIV infect in the brain
macrophages and microglial cells
When does Acute Retroviral Syndrome occur?
3-6 weeks after infection, resolves after 2-4 weeks
initial spread of the virus and host response
Symptoms of Acute Retroviral Syndrome (8)
sore throat, myalgias, fever, weight loss, fatigue
rash, diarrhea, vomitting
Where is there continual HIV replication and cell destruction?
lymph nodes and spleen during clinical latency period
number of circulating CD4+ T cells steadily declines
Clinical manifestations during the clinical latency period
oral candidiasis, vaginal candidiasis, herpes zoster, TB
How does HIV evade immune detection? (4)
- Destroys CD4+ T cells
- Antigenic variation (virus is always changing)
- Down-modulation of Class I MHC (not recognized by CTLs)
- Evolve and involve both CCR5 and CXCR4
What accounts for the more rapid decline in CD4+ T cell count?
The evolution from the virus using only CCR5 or CXCR4 to the using both
Typical progression time form HIV to AIDS
7-10 years
Clinical Features of AIDS (7)
Fever Weight loss Diarrhea Generalized Lymphadenopathy Neurologic disease Opportunistic infection Secondary neoplasms
Fungal infections associated with AIDS
pneumoncystis jiroveci, candidiasis, crytococcosis
Viral infections associated with AIDS
JC virus (progressie multifocal leukoencephalopathy) herpes varicella
Neoplasms associated with AIDS
Kaposi sarcoma (HHV8)
EBV - primary lymphoma of brain
HPV- invasive cancer of uterine cervix
Anal Cancer
Highly Active Antiretroviral Therapy
Combination of 3-4 drugs that block different steps of HIV life cycle
Function of HAART (4)
alters HIV infection
alters incidence of opportunistic infection (jiroveci and HHV8)
suppress virus levels below detection
reduce transmission of virus
How does suppressing virus levels in HAART help AIDS
stops loss of CD4+ T
over time slow increase in CD4+
Consequences of HAART
Immune reconstitution inflammatory syndrome
Side Effects
Side Effects of using HAART drug combination (6)
Lipoatrophy (loss of facial fat) Lipoaccumulation (excess fat centrally) Elevated lipids Insulin resistance Peripheral neuropathy Premature cardiovascular, kidney, and liver disease
