Lecture 14&15: HIV symposium Flashcards
How does immune deficiency cause illness
Overtime there is depletion of T cells - assymptomatic HIV infection, later leading to people becoming susceptible to illnesses which usually don’t affect most people.
-There is also chronic immune system activation/ inflammation leading to increased risk of bone loss, CVD, neurological deficits etc.
Which immune system effectors are responsible for antigen specific cytotoxicity
CD8 lymphocytes K lymphocytes (antibody dependent)
Which immune system component is responsible for non antigen specific cytotoxicity
Natural killer cells
Which immune system component is responsible for inflammation and phagocytosis
neutrophils
Which immune system component is responsible for inflammation and phagocytosis
neutrophils
Which immune system component is responsible for producing cytokines to mediate immune regulation
CD4 T lymphocytes
What does HIV do to a cell once inside
RNA from HIV gets reverse transcripted into DNA which is integrated into host cells DNA. Viral genes are then expressed into making new viruses which bud off and infect other CD4 cells.
Describe the 3 steps of HIV first entering the CD4 cell and what proteins it recognises
- HIV’s surface molecule glycoprotein 120 binds directly to CD4 receptor on juvenile and mature helper T cell.
- After binding, the CD4 undergoes a conformational change bringing HIV membrane in contact with chemokine receptor CCR5/cxcr4 on CD4 T lymphocytes.
- This enables membrane to fuse and release the protein capsid covering RNA
How does immune system get rid of HIV infected cells
HIV infected CD4 T lymphocytes will present viral antigens on their class 1 MHC which is recieved by the CD8 t cell with correct receptor. This leads to killing of these infected cells
Why is the loss of functional CD4 t lymphocytes due to HIV so bad
CD4 T cells produce the cytokines that play a central part in the regulation of phagocytosis and inflammation, the clonal activation of CD8, CD4 and B cell populations -> therefore antibody and cytotoxic effector cells, and bringing about systemic changes which increase chance of survival.
Which of the two strains of HIV is the majority and from what animal did it come from
HIV 1 (majority) and HIV 2 (only in some african populations). Entered human populations from primates.
What are some signs of Aquired ImmunoDeficiency Syndrome (AIDS) that marked HIV infection in people with healthy history
Thrush on soft palate and back of throat, cancer of lymphoid vessels, toxoplasma parasite damage
Describe what happens to the viral RNA in the capsid once in the cell that leads to production of viral proteins
- Capsid is dissolved by enzymes in the cell which releases RNA
- Virion Reverse transcriptase makes viral DNA copy of the RNA
- Enzyme RNAseH disconnects the DNA from the RNA
- Integrase opens host DNA and integrates viral DNA into the host genome, downstream of a transcription factor.
- Viral proteins are made from host cell normal gene expression
What do HIV enzymes target
The enzymes Reverse transcriptase, Integrase and protease
Describe what happens after virus proteins (RNA in capsid, enzymes around outside) assemble in the cell
- Virus buds off and and T cell protease folds other virus enzymes to allow them to work efficiently
How is HIV transmitted and what is the highest risk
Through blood transfusion, needle sharing, mother to child transmission, sexual exposure
Why are there larger proportions of HIV infection in men who have sex with men and what lead to changins increase and decrease of these numbers
Through the reduced use of condoms there was increased risk of STI transference. At first there was an increase before education and then as treatment improved it has increased again
Describe the timeline of HIV infection in comparing CD4 count and HIVirus load: The 3 stages
(average duration from infection to risk of AIDs 6-8 years)
- At the beginning of infection HIV load rises rapidly and for the next weeks is the Seroconversion illness- flu like illness where CD4 count takes a dive
- This goes away and CD4 count rises and for years is the Asymptomatic HIV infection where CD4 cell count is declining while fighting equilibrium with the virus load.
- When CD4 count is very low, Virus load rapidly increases in the late stage HIV
What is CD4 cell count used and what are the benchmarks of risk
CD4 cell count is used to measure risk of illness before starting treatment
CD4<500 risk of illness
CD4<200 greater risk of illness
CD4<50 usually sick
How is HIV managed
- Treat people as quickly as possible
- Maintain health to increase CD4 counts: exercise, sleep, eat, reduce smoking, alcohol, optimism
- Stopping HIV replication through drugs that target enzymes: 3 drugs at least 2 different targets to prevent virus mutation
- Preventing/ reducing transmission of HIV
What are Latently infected helper T cells - ones that die off slowly
These are helper T cells that have had the intergrase make a mistake and put the DNA in the wrong place and makes them not susceptible to anti intergrase drugs but the HIV is dormant in them
Why do people taking HIV medicines need to take them everyday
The virus will come back and if there is low levels of medicine in the blood it can allow the virus to mutate and gain resistance
What happens to CD4 count after successful treatment
CD4 cell count will rise over 4-5 years and then plateau at healthy amount while Virus load drops to undetectable levels
