immunology of HIV Flashcards
Define Retrovirus
- long term latent infection by integrating genome into host DNA or short term cytopathic effects
- retrovirus reverse transcriptiase copies viral RNA into DNA. DNA integrated into host DNA to form a provirus
Define Acute HIV syndrome
acute illness = 2-6 weeks after initial infection
- -> resembles infectious mononucleosis (headache, fever, rash, swollen lymph nodes)
- -> active virus replication occurs in blood and CSF. Lymphoid organs “seeded” with virus
Seroconversion (produced antibodies to virus) typically occurs 6-9 weeks after exposure to virus
–> window period = patient viremic, but all serologic tests are negative
Define Aids-related complex (ARC)
Subset of patients develop ARC –> persistent fever, nigh sweats, weight loss, chronic diarrhea, inflammatory skin conditions etc
- -> some individuals develop oral candidiasis and or chronic mucocutaneous herpes simplex infection
- -> without treatment, die of AIDS relatively quickly
describe the clinical findings of aids
- recurrent infections with opportunistic pathogens
- tumors –> kaposi’s sarcoma or non-hodgkins lymphoma (both caused by viruses)
- progressive wasting syndrome (cachexia)
- AIDS- induced dementia
- Opportunistic infections –> CD4+ count drops below 200cells/mm cubed
describe the infectious process
Chemokine receptors (CCR’s)
- HIV varients that use CCR5 are called R5 viruses and those prefer CXCR4 called R4. HIV that binds both are called R5X4 virus strains
- many HIV patients tranition from viruses that sue CCR5 (mainly macrophage-tropic) early in the disease to virus that binds CXCR4 (T cell-tropic) late in the disease which causes more damage to CD4+ T cells
- Plasma membrane-expressed gp120 binds to CD4 on nearby cells –> initiates membrane fusion –> passing of HIV genomic material to uninfected cells
- once inside the cell –> viral replication or proviral state exists. (Viral RNA is integrated but no replication occuring)
What triggers pro-viral state to become activated?
Cell activation can trigger virus production because cytokins can trigger activation of transcription factors NFkB and SP1, which are known to bind HIV long terminal repeats (LTR) which control viral gene transcription:
- -> TNF-alpha and IL-2 induces HIV transcription/replication in T cells
- -> IL-1, IL-3, IL-6, TNF-alpha and IFN-gamma induce HIV replication in monocytes and macrophages
drescribe the infected monocytes/macrophages in HIV
Infected monocytes/macrophages not as prone to lysis by HIV as T cells:
- -> may serve as in vivo reservoir for transportation of virus throughout body
- -> macrophage and or virus mediated effects on CNS leads to AIDS dementia complex leading to memory loss
- -> Dementia –> direct virus infection of neurons or destruction of neurons by macrophage-derived cytokines
describe HIV in early in infection
HIV replicates at a very low level:
- -> 1/100 T cells are latently infected
- -> profound immunosuppression due to the destruction of CD4+ T cells
- -> normal individuals - CD4:CD8 = 2, AIDs patients ratio = .5
Describe the killing of T cells during HIV
- Direct lysis by budding HIV
- virus production can interfere with cellular protein synthesis, which leads to cell death
- syncytia formation of infected cells with uninfected cells (cells fuse)
- binding of free gp120 to infected and uninfected T cells –> antibody response –> ADCC
- CTL-medaited destruction of virus-infected cells
describe mechanisms of immunosuppression
T lymphocytes depletion alone can’t account for all the immunosuppression since many T cells remain uninfected
- binding of free gp120 to CD4 of uninfected T cells –> can’t bind class II MHC proteins
- Destruction of follicular dendritic cell network –> alters architecture of lymph nodes and spleen
Why doesn’t immunity not protective
1) HIV integrates DNA into host DNA and remains latent
2) Error-prone reverse transcriptase –> mutations to evade antibodies and CTL’s.
3) The HIV Nef protein downregulates the expression of class I MHC, thus making infected cells invisible to CTL’s. Individuals who are infected with a strain of HIV that has a defective Nef gene do NOT progress to AIDS
4) Seroconverison signals antibody production, but CTL’s are more important in the decline of the virus seen after the initial infection
Define ELISHA
enzyme-linked immunosorbent assay:
- -> utilizes HIV antigens cultured in permissive H-9 cell line
- -> antigens adsorbed to solid phase and patient serum added
- -> followed by secondary antibody conjugated to enzyme such as horseradish peroxidase or alkaline phosphatase
- -> substrate for enzyme added –> color change (might have antibodies to HIV antigens)
High rate of false positives (cross-reactive antibodies to H-9 antigens - multiparous females, patients with autoimmune diseases)
- ELISHA (+) –> test repeated, if still ELISHA (+) –> western blot
Define western blot
Viral antigens separated using SDS-page, transferred to membrane:
- -> membrane incubated with patient serum and enzyme-labeled antihuman immunoglobulin
- -> substrate added –> reaction where the patient antibody has bound
Determines viral proteins to which individual has produced antibodies.
Define PCR
Very sensitive
- detects viral genomes (DNA) integrated into cell DNA –> used to determine whther neonates have been infected
Define RT-PCR
detects free virus in body fluids
- uses reverse transcriptase to convert viral RNA into DNA –> PCR
- used to assess viral loads in adults (since the viral particle contains RNA)
