Immunology of AIDS (complete) Flashcards Preview

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Flashcards in Immunology of AIDS (complete) Deck (29):
1

What is the difference between "HIV-seropositive" and "AIDS"?

S+: if a pt has Ab to HIV (first way to detect infection)

AIDS: symptoms of opportunistic infections or Kaposi's sarcoma, their Th (CD4+) cells are <200/microL of blood

2

What is the virus that causes AIDS?

HIV-1

3

What is HIV-1's classification?

- A nontransforming retrovirus
- RNA virus that carries no oncogene

4

What is the origin of the AIDS virus?

Simian Immunodeficiency Virus (SIV)

Thought that HIV evolved from SIV in DRC

5

What is the approximate number of HIV cases in the US?

1.1 million

6

What is the approximate number of HIV cases in the world?

35 million

7

What is the rate of change in incidence?

16%

8

Discuss the pathogenesis of AIDS. Include target cells types, mode of entry of virus, mode of exit, and latency vs productive infection

- After first exposure => high blood virus levels, peak at 6 weeks
- loss of CD4 cells in gut => increased gut permeability => systemic spread
- Ab peaks @ 9 wks, falls to almost 0 but at steady state
- DCs w/ HIV = Trojan horse, go to lymph nodes
- HIV gp120 bind to CD4 on Th cells => cause host cell CCR-5 binding as coreceptor
- CCR-5 binds => conf change of gp41 => exposes hydrophobic region that melts T cell membrane
- Th cell and virus fuse => vRNA and reverse transcriptase injected into cell => vDNA production
- W/ viral integrase, vDNA inserts at random break of host DNA => latent virus

9

What is the role of Tfh cells in persistence of HIV latency?

- They are able to suppress viral replication
- Can't eliminate the virus DNA from their nuclei

10

What is the role of Tfh cells in persistence of active HIV infection?

- If the Tfh cell w/ viral DNA is activated by its correct Ag => a clone of virus-producing cells
- Accompanied w/ or leads to dysregulation o f B cells

11

What are the types of infections seen in patients w/ AIDS?

1) Viral infection
2) Fungal infection
3) Protozoan infection
4) OIs of intracellular bacteria

12

What is the immunological basis for the spectrum of infection types seen in patients w/ AIDS?

- Virus targets T-cell mediated immunity
- More infections occur that require this

13

What are the possible reasons for which the total number of CD4 cells in patients w/ AIDS decline?

- When infected w/ HIV, you have to replace your CD4 cells OFTEN
- Simple exhaustion => decreased ability to produce more
- This is when CD4s decline... => opportunistic infections w/ a weak immune system

14

What are the reasons for apparent ineffectiveness of Ab in HIV infection?

- When virus is replicating => gp120/gp41 made early => inserted into plasma membrane of host
- Helps w/ fusion of infected cell to nearby uninfected CD4 cells
- Can spread w/o an extracellular phase
- Abs can't attack w/o extracellular presence

- Abs bind to virus but can't block attachment to/infection of Th cells
- Neutralizing epitopes on virus are shielded by carb --- if pt makes neutralizing Ab, virus mutates, escapes

15

Define "long term survivors" in HIV infection. Discuss

- Those who survived longer than other in the time before the first HIV drug, pre-1987
- Homozygous for 32-base pair deletion for CCR5 (chemokine, HIV coreceptor)
- 10% frequency in caucasians

16

Define "elite controllers" in HIV infection. Discuss

- Infected w/ HIV but didn't progress to AIDS
- 2/3 have HLA-B57 allele
- They just make effective CTL to HIV peptides presented at HLA-B57
- More HIV-specific CTL#s = better prognosis

17

Describe the laboratory diagnosis of AIDS

- Test for Ab to HIV
- Measured by ELISA (can have false+) => confirmed w/ Western blot analysis --- must bind to gp120/41 to be true positive

Also:
- Small amounts of RNA can be detected w/ PCR

18

What are the prospects of AIDS vaccine development?

Broad neutralizing Ab!!

- can block infection by almost all HIV strains/mutant forms
- Trying to find a vaccine that can produce that
- People (LTS) develop this Ab after having the disease for 20 years

19

What are the problems of AIDS vaccine development?

- Kind of like the flu vaccine
- Epitopes/virus is always changing => how do you make a vaccine with that?

As Cohen says: an HIV vaccine would neutralize today's virus but not tomorrow's

20

What are the three things that happen after HIV infects Tn cells?

HIV-infected T cells:

1) Die rapidly
2) Become persistent virus-producers
3) Enter latency

21

Why do HIV-infected T cells die rapidly?

- Viruses try to bud
- But it tears so many holes in membrane => cells dies

22

What is the standard antiretroviral therapy for patients w/ HIV?

- 2 NRTIs
- 1 drug from a different class (usually NNRTI)

23

What are two drugs that target reverse transcriptase?

1) Nucleosides (NRTI)
2) Non-nucleosides (NNRTI)

24

What are NRTIs?

- Competitive inhibitors of reverse transcriptase
- Chain terminators!

25

What are NNRTIs?

- Bind a hydrophobic pocket on reverse transcriptase => changes conformation => changes activity of catalytic site
- Escape common to these types of drugs

26

What is the target for protease inhibitors?

- The gag, pol, and env proteins
- These are made by cleaving a larger polyprotein using a viral protease

27

What is Enfuviritide?

- a fusion inhibitor
- binds to part og gp41 => can't change conformations => no cell entry/fusion

28

What is maraviroc?

- A CCR5 antagonist
- Blocks viral entry into CD4 cells
- Binds to transmembrane part of CCR5 => changes conformation of external receptor
- Can't bind to gp120

29

What is Raltegravir?

- Integrase inhibitor
- Used in pts w/ reverse transcriptase inhibitor-resistant strains of HIV