Immunity to HIV Tutorial Flashcards
How is HIV transmitted?
Majority of transmission in via sexual activity (85%)
Transmission is via exposure to infected blood and body fluid
What are some groups at risk of getting HIV?
sexually active
IV drug users
HCW
Organ recipients
Blood or blood product recipients
Children of infected mothers (breastfeeding)
During what time frame is post-exposure prophylaxis effective?
1 or 2 anti-retrovirals are given as early as possible after exposure
Day 1-2: local replication in mucosal tissues
Day 3: Transport to regional lymph nodes
Day 4: Dissemination throughout lymphoid system
The decline of this lymphocyte is the major driver of pathogenesis and immunodeficiency associated with HIV
CD4 cells (T helper cells)
How does HIV replicate in a host?
Virus integrates into cell DNA —> permanent cell infection and hidden from host immune system
Cell division —> provirus replication with host cell DNA
Virus reactivates and replicates when host cell replicates
How does HIV infect the cell of a host?
Protein on HIV envelope (gp120) attaches to CD4 receptor on host cell
Another protein on HIV envelope (gp41) mediates membrane fusion of HIV and host cell
RNA release from nucleocapsid
Reverse transcription of RNA into DNA
Proviral DNA translocated to nucleus and integrates into host cell genome
Once integrated into host DNA, provirus can remain latent for a long time
What is the initial workup to investigate possibility of HIV infection?
ELISA (detect anti-HIV antibody)
Flow cytometry (measure lymphocyte subsets)
If recent exposure suspected, also add:
- HIV p24 antigen or HIV RNA blood test
What does a positive HIV p24 antigen test indicate about infection?
Pt is either in acute infection or late in disease
What antibody isotope would be expected to be measured on ELISA?
IgM as it is a primary immune response
What does ELISA detect?
The virus itself or antibodies to the virus
What impact does HIV have on natural killer cell and B lymphocytes?
Percentage can increase in later stages because the total number of T cells is reduced
Why is the CD4/CD8 ratio low in early HIV infection? What happens to this ratio in later stages of infection?
Early infection
CD4 cells are lost, CD8 increases in response
Late infection
- Absolute number of CD4 cells continues to fall
Is delayed type hypersensitivity a primary immune response?
No; secondary response mediated by memory T cells that respond to the antigen and create a response
What is the relationship between HIV, delayed-type hypersensitivity, and AIDS?
↓ CD4 —> defective cell-mediated immune response
DTH enhanced by T-cell derived cytokines —> phagocytic and killing processes
Why are antibodies less effective against HIV over time?
HIV mutates rapidly
Rapidly develops resistance to antiviral drugs
Would anti-retrovirals be useful in a patient whose immune system is effectively limiting viral replication?
Yes
Better to use it when the immune system is still intact and prevent it from integrating into host immune cells
This factor generally predicts risk for rapid progression to AIDS and death
Viral load
How can HIV become resistant to anti-retroviral therapies?
Long duration w/o tx can —> time for virus to mutate and have resistances
Drug pressure —> selection of genomes that are resistant
Lack of strict adherence to drug schedule by pt —> lack of sufficient suppression
How can antibodies by effective against HIV?
Bind to HIV proteins expressed on infected cells —> complement fixation
Preventing infection of host cells by blocking HIV proteins from interacting with host receptors
What makes antibodies unable to stop cell to cell HIV spread?
Ab dont have access to intracellular virus and can’t block transfer between cells in close contact
What T cell reacts strongly against HIV? How do they limit HIV replication?
CD8 cells mediate immunity against HIV
Recognize HIV peptides presenting by HLA class I molecules —> killing infected cell presenting the peptide
Can suppress via cytokine release that interferes with host cell infection or blocks HIV gene transcription
