HIV - Immunology COPY Flashcards
HIV INITIAL INFECTION
i) what does initial infection with HIV-1 result in clinically? what is it often mistaken for?
ii) what continues to happen after symptoms have initially?
iii) which type of cells rise sharply? what effect does this have on viral load?
i) initial infection with HIV-1 results in clinically mild systemic viral infection
- often mistaken for mild flu like disease
ii) mucosal infection continues to develop
iii) HIV specific CD8 T cells rise sharply and reduce viral load
HIV INFECTION OVER TIME
i) what cells is there a gradual loss of? what does the virus do in these cells?
ii) what eventually happens to the immune system and what consequently develops?
iii) what is often the first presenting illness of AIDS? give three examples
iv) which immune cells are a primary target for HIV?
i) gradual loss of CD4 T helper cells where the virus undergoes lytic replication
ii) eventually loss of Th cells weaknes the immune response and opportunistic infections occur
iii) first presenting symptom of AIDS is usually opportunistic infections
- eg TB, PCP, kaposi sarcoma
iv) CD4 T cells
HIV INFECTION OF CD4 CELLS
i) what does HIV use to dock on a CD4 cell? which two other co-receptors on CD4 cell may also be used?
ii) what happens once the virus has docked?
iii) what type of virus is HIV? what mechnaism does it use to infect the host cell? which drugs may target this?
iv) what happens once viral DNA has been transcribed? which enzyme allows it to mature? what is the end product?
i) HIV uses gp120 molecule to dock to CD4 receptor on T cell
- can also bind co-R on T cell = CCR5 and CXCR4
ii) once virus has docked it fuses with the host cell and releases its viral genome
iii) HIV is an RNA virus so needs reverse transcriptase to transcribe viral DNA
- nucleoside rev transcrip inhibitors can target this
iv) once viral DNA is transcribed a new viral particule is made and it buds off from the host cell taking some cell mem with it
- proteases allow maturation
- end product is a new mature HIV virion
HIV IN THE GUT
i) what molecule does HIV use to enter cell?
ii) what is the normal role of CCR5 and CXCR4? in what situation are they normally upregulated? what does this mean in HIV?
iii) which CD4 T cells in the gut express high levels of CCR5? what does this mean about susceptibility of these cells to HIV infection?
iv) what happens to these cells during primary HIV infection?
v) name three important roles of these cells in the gut
i) gp120
ii) CCR5 > receptor for rantes and MIP-1 alpha
CXCR4 > receptor for SDF-1
- all involved in lymphocyte chemotaxis and HIV supression
- normally upregulated in infection to help fight it
- increases vulnerability in HIV
iii) lamina propria and intraepithelial CD4 cells in the gut express high levels of CCR5
- these cells are primary targets for HIV infection
iv) during primary HIV infections these cells are rapidly eliminated from the gut mucosa
v) important roles of lam prop and intra ep CD4 T cells
- prev of invasive infection
- killing of infected epithelial cells
- immune regulation
HIV AND CCR5
i) what phase of HIV infection is CCR5 co receptor used?
ii) what are strains of the HIV virus using this co -receptor called? how are they most commonly transmitted?
iii) how many years into infection do most viruses start to use CXCR4? what are the viruses that use this co-R called?
iv) what does the use of CXCR4 do?
i) HIV uses CCR5 in early stages of infection
ii) use of CCR5 = R5 viruses
- most commonly sexually transmitted
iii) after about five years into infection virus start to use CXCR4 > then called X4
iv) CXCR4 use widens the target spectrum
CD4 INFECTION AND CELL DEATH
i) what type of cell death is induced by viral replication in the CD4 cell?
ii) what type of cell death is due to CD T cell activation?
iii) expression of what on CD4 cells will induce death by cytotoxic T cells?
i) viral replication > cytopathic effects > death
ii) activation > activation induced cell death (apop)
iii) expression of HIV peptides causes death by cytotoxic T cells
TIME COURSE OF HIV INFECTION
i) at initial infection - what happens to CD4 count and viral load? which cells respond?
ii) which cells become depleted first? which cells then become depleted? what happens to viral load at this point? after how long does this happen?
i) initial infection - low CD4 cells and high viral load
- then CD8 cells respond and reduce viral load
ii) CD4 cells are depleted first then CD8
- then viral load increases
- happens in the late phase (years)
HIV INFECTION AND THE GUT
i) by what type of infection is HIV usually transmitted? what do pathogens that enter the body this way usually a cause of?
ii) name the three main transmission routes
iii) what % of CD4 cells are found in the gut? what happens when HIV infects these?
iv) what do lamina propria CD4 T cells express high levels of?
i) mucosal infection
- usually cause death of large groups
ii) main transmission routes - GU, rectal, oral mucosa
iii) 60% CD4 cells are in the gut > depleted on HIV infec
iv) lamina propria CD4 cells express high levels of CCR5
HIV INFECTION IN THE GUT 2
i) what does depletion of CD4 cells in the gut cause? how long does this take to happen?
ii) what does this lead to translocation of? what is seen systemically?
iii) what does this cause in relation to the immune system?
iv) what does immune activation drive?
v) why is HIV and TB a bad combination?
i) CD4 depletion int he gut leads to loss of control of bacterial commensals > happens in weeks of infection
ii) leads to translocation of LPS and rise in systemic LPS
iii) generalised immune activation and TNF production
iv) immune activation drives inflam cytokines such as TNF which drive HIV recplication and CCR5 upregulation (as it is used to combat HIV)
v) HIV and TB is bad because TB patients depend on TNF for granuloma formation
- TNF drives HIV replication (worsens HIV and controls TB)
