HIV&the immune system

Question 1

where are the most of the pathogens that cause death to the large number of people enter from?

Answer 1

• Mucosal surfaces
• GU
• Rectal
• Oral mucosa

Question 2

what does the initial infection by the HIV show as?

Answer 2

• Clinical mild systemic viral infection

- appears to resolve initially and often mistaken as mild flu like disease

Question 3

What happens during the adaptive immune response?

Answer 3

adaptive response is triggered but the virus is not cleared

Question 4

what happens to the virus over time?

Answer 4

• Over the years, the immune system contains the virus

- gradual loss of CD4 helper cells- virus undergoes lytic replication

Question 5

What is the AIDs first presenting illness?

Answer 5

• opportunistic infections are often first presenting illness of AIDS and generally cause of death
• TB, PCP, Kaposi sarcoma

Question 6

What are the main host cells for the HIV?

Answer 6

CD4 T Cell

Question 7

What are the molecules used for HIV entry?

Answer 7

-gp120

Question 8

What are the main receptors and co-receptors for HIV?

Answer 8

-Main receptor: CD4

Co-receptors : CCR5 and CXCR4

Question 9

What are the normal roles of these co-receptors?

Answer 9

• CCR5- receptor for Rantes, MIP-1alpha

- CXCR4- receptor for SDF-1

Question 10

What are the roles of MIP-1alpha, SDF-1?

Answer 10

-Molecules involved in lymphocytes chemotaxis and HIV supression

Question 11

What is the role of activated CD4 T cells?

Answer 11

-Activated CD4 T cells in the terminal ileum express high levels of CCR5 and primary targets for HIV infection

Question 12

What happens during the primary HIV infection?

Answer 12

-During primary HIV infection effector CD4 T Cells are eliminated rapidly from the gut mucosa owing to high CCR5 expression.

Question 13

Which strains of HIV are transmitted commonly?

Answer 13

HIV strains using CCR5 as their co-receptors are called R5 viruses and are the strains of most commonly transmitted sexually

Question 14

Which receptor does the virus switch to after 5 years?

Answer 14

• Virus use CXCR4 receptor
• known as X4
• Some viruses evolve to use both receptors known as R5X4

Question 15

Explain the 7 steps of HIV infection?

Answer 15

1) Fusion of HIV to the host cell surface
2) HIV RNA reverse transcriptase, integrase and the other viral proteins enter the host cells
3) Viral DNA is formed by reverse transcription
4) Viral DNA is transported across the nucleus and the integrates into the host DNA
5) New viral RNA is used as genomic RNA and to make viral proteins
6) New viral RNA and proteins move to the cell surface and new immature HIV forms
7) The virus matures by protease releasing individual HIV proteins

Question 16

Where does the NRTIs work?

Answer 16

-Reverse transcriptase inhibito (Lamivudine)

Question 17

What are the CD4 T Cell depletion caused by?

Answer 17

• APC cell with HIV virus activates T cell
• Continued stimulation leads to chronic T cell activation
• 3 ways:
  1) Cytopathic effects: Viral replication in the infected CD4+ T cells
• Death of infected cells
  2) Apoptosis- Activation of uninfected CD4+ T cells–> Activation-induced cell death
  3) CTL mediated killing: Expression of HIV peptides on infected CD4+ T cells–> Killing of infected cells by virus- specified CTLs

Question 18

Where are the majority of CD4 T Cells located?

Answer 18

CD4 T cells are in the gut but minority are in the blood

Question 19

What is the consequence of depletion of CD4 T cells in the gut?

Answer 19

-Depletion of CD4 T cells in the gut leads to a loss of control over bacterial commensals and increased translocation of gram negative LPS positive bacteria

Question 20

what happens when the gram negative LPS positive proliferate?

Answer 20

A rise of systemic LPS levels and generalised immune activation- Drives HIV activation