Lecture 14&15: HIV symposium

Question 1

How does immune deficiency cause illness

Answer 1

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.

Question 2

Which immune system effectors are responsible for antigen specific cytotoxicity

Answer 2

CD8 lymphocytes 
K lymphocytes (antibody dependent)

Question 3

Which immune system component is responsible for non antigen specific cytotoxicity

Answer 3

Natural killer cells

Question 4

Which immune system component is responsible for inflammation and phagocytosis

Answer 4

neutrophils

Question 5

Which immune system component is responsible for inflammation and phagocytosis

Answer 5

neutrophils

Question 6

Which immune system component is responsible for producing cytokines to mediate immune regulation

Answer 6

CD4 T lymphocytes

Question 7

What does HIV do to a cell once inside

Answer 7

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.

Question 8

Describe the 3 steps of HIV first entering the CD4 cell and what proteins it recognises

Answer 8

1. HIV’s surface molecule glycoprotein 120 binds directly to CD4 receptor on juvenile and mature helper T cell.
2. After binding, the CD4 undergoes a conformational change bringing HIV membrane in contact with chemokine receptor CCR5/cxcr4 on CD4 T lymphocytes.
3. This enables membrane to fuse and release the protein capsid covering RNA

Question 9

How does immune system get rid of HIV infected cells

Answer 9

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

Question 10

Why is the loss of functional CD4 t lymphocytes due to HIV so bad

Answer 10

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.

Question 11

Which of the two strains of HIV is the majority and from what animal did it come from

Answer 11

HIV 1 (majority) and HIV 2 (only in some african populations). Entered human populations from primates.

Question 12

What are some signs of Aquired ImmunoDeficiency Syndrome (AIDS) that marked HIV infection in people with healthy history

Answer 12

Thrush on soft palate and back of throat, cancer of lymphoid vessels, toxoplasma parasite damage

Question 13

Describe what happens to the viral RNA in the capsid once in the cell that leads to production of viral proteins

Answer 13

4. Capsid is dissolved by enzymes in the cell which releases RNA
5. Virion Reverse transcriptase makes viral DNA copy of the RNA
6. Enzyme RNAseH disconnects the DNA from the RNA
7. Integrase opens host DNA and integrates viral DNA into the host genome, downstream of a transcription factor.
8. Viral proteins are made from host cell normal gene expression

Question 14

What do HIV enzymes target

Answer 14

The enzymes Reverse transcriptase, Integrase and protease

Question 15

Describe what happens after virus proteins (RNA in capsid, enzymes around outside) assemble in the cell

Answer 15

9. Virus buds off and and T cell protease folds other virus enzymes to allow them to work efficiently

Question 16

How is HIV transmitted and what is the highest risk

Answer 16

Through blood transfusion, needle sharing, mother to child transmission, sexual exposure

Question 17

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

Answer 17

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

Question 18

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)

Answer 18

1. 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
2. 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.
3. When CD4 count is very low, Virus load rapidly increases in the late stage HIV

Question 19

What is CD4 cell count used and what are the benchmarks of risk

Answer 19

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

Question 20

How is HIV managed

Answer 20

1. Treat people as quickly as possible
2. Maintain health to increase CD4 counts: exercise, sleep, eat, reduce smoking, alcohol, optimism
3. Stopping HIV replication through drugs that target enzymes: 3 drugs at least 2 different targets to prevent virus mutation
4. Preventing/ reducing transmission of HIV

Question 21

What are Latently infected helper T cells - ones that die off slowly

Answer 21

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

Question 22

Why do people taking HIV medicines need to take them everyday

Answer 22

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

Question 23

What happens to CD4 count after successful treatment

Answer 23

CD4 cell count will rise over 4-5 years and then plateau at healthy amount while Virus load drops to undetectable levels