HIV Flashcards
Describe the innate immune response upon HIV infection:
–Langerhans cells in vaginal & foreskin epithelia; macrophage, dendritic cells, NK cells in subepithelium, etc.
–The innate immune response plays a role in early virus restriction, shaping adaptive response, but also in virus spread. With virus spread, rapid increase viral load, CD4+ T cell decline; with host immune response, decline in viral load, depletion of CD4+CCR5+ memory cells in mucosa
Describe what happens with the adaptive immune response towards HIV:
- p24 antigen appears, then decreases with seroconversion
- Antibody response to envelope (most) and core antigens
- CD8+ T cells become activated CTLs – detectable throughout infection
- CD4+ T helper response with stimulation of various cytokines (IL-2, IFN-gamma, TNF, etc.) leading to multi-cellular CMI response
When is viral load generally the highest? What brings it down?
Viral load is generally the higest about 3-4 weeks post-exposure. Eventually the load drops off and reaches a viral set point.
Specific antibody against HIV starts a few weeks after exposure. Doesn’t seem to be having a huge effect on suppressing viral load. Onset of generation of CD8 cytotoxic lymphocytes is really what helps bring virus down
What changes are associated with the progressive deterioration of the immune system?
•Impact of viral factors (usage of CCR5 [M-tropic / R5] vs CXCR4 [T-tropic / X4]
Accessory gene function (e.g. deleted nef gene, slower loss),
MHC & co-receptor genotypes,
Th1 to Th2 switch, et al.
Anti-virus specific CD4+ T helper cells:
There are some virus specific CD4+ T cells that are important for initial T and B cell responses and are thought to be required to efficient CD8+ cytotoxic responses.
Problem: these are the cells that HIV likes to take out (HIV loves activated T cells), so these are lost early in infection and can’t help with virus elimination.
Some “elite controller” patients seem to keep more of these around (HIV-1 RNA < 50 c/mL without therapy).
HIV specific CD8+ Cytotoxic T Lymphocytes:
Present in early numbers in HIV infection
Involved in initial control of viremia
Control is strongly associated with HLA (MHC 1) genotype
See a decline associated with progressive CD4 cell loss in most individuals
There is a high binding affinity by TCRs of CD8 cells to MHC I to conserved ______ in HIV
epitopes
Antiviral effect of cytotoxic T lymphocytes:
- Lysis of virus-infected cell before virions are released
- Inhibition of viral replication (IFN-gamma)
- Inhibition of viral entry into surrounding cells (produce MIP-1a, RANTES; block CCR5 usage)
How are CD4+ T cells lost in HIV?
–Direct lysis of cells by HIV
–Virus mediated killing of bystander CD4+ T cells
–Lysis of infected CD4+ T cells by immune response (CTL, ADCC)
–Chronic immune activation – apoptosis
Why can’t we just replace lost CD4 cells?
–Thymic dysfunction
–Bone marrow dysfunction
–Limited ability of T cells to expand in the periphery
Often acute HIV infection will present with ____-like symptoms, such as (list 5):
Mono-like symptoms;
fever, sore throat, swollen lymph nodes, faint rash, mucosal ulcers
If a cell contained HIV virion is lysed, are these virions infectious or not?
No, this cell needs to be enveloped (last step resulting of budding) in order to be infectious
Describe the consequences of the high rate of viral mutation:
Allows changes in HIV proteins and escape from immune control
- Neutralizing antibody (envelope, esp. V3 binding loop)
- CTL epitopes (peptides presented by MHC-I)
- T helper epitopes (peptides presented by MHC-II)
However, some mutations come with a high fitness cost for the virus
Virus with a deleted ____ gene leads to low viral load and slow loss of CD4 T cells in some individual
Nef gene
CCR5 vs. CXCR4 usage affects disease progression - ____ and ____ are associated with rapid loss in CD4 T cells
DM and X4-virus
HIV pathogenesis involves ____ latency but no _____ latency
Has clinical latency but no virological latency
The level of _____ predicts CD4+ T cell loss
Viremia
As CD4+ T cells are lost, immunity to _____ and _____ is lost
immunity to opportunistic pathogens and cancers is lost
Clinical AIDS is a result of the HIV-induced loss of ________
pathogen-specific immunity
_______ is the best predictor of current immunodeficiency
CD4+ T cell number
(but additional predictive power with both this and viral load)
Diagnostic Testing:
Performing an HIV test based on clinical signs or symptoms
Targeted Testing:
Performing an HIV test on subpopulations of persons at higher risk
Screening:
Performing an HIV test for all persons in a defined population
Opt-out screening:
Performing an HIV test after notifying the patient that the test will be done; consent is inferred unless the patient declines
Diagnostic tests for HIV can test for ____, ____, or ____
HIV antibody, virus protein (p24 antigen), or virus
