2-HIV

Question 1

HIV

general

Answer 1

causes AIDS (acquired immunodef syndrome)
-profound immunosupp so lots of infections, malignancies, wasting/CNS degen

Question 2

retrovirus

Answer 2

long term latent infectio by integrating genome into host DNA
OR short term cytopathic effects

reverse transcriptase copies viral RNA into DNa to integrate = provirus

Question 3

types of HIV

Answer 3

HIV 1 and 2 known to infect people in US, 1 more prevalent
-2 is more in west africa

Question 4

acute HIV syndrome

Answer 4

2-6 weeks after initial infection, stage 1
-resembles infectious mononucleosis so headache, fever, rash, swollen lymph nodes, sore throat
-active virus replication in blood and CSF so lymphoid organs seeded with virus

Question 5

seroconversion

Answer 5

point where Ab can be detected 6-9 weeks after exposure
-window period when viremic so virus is in blood but serologic tests negative so no Ab

Question 6

asymptomatic infection

Answer 6

latent phase, stage 2
-HIV nearly undetectable in blood but still replicating in lymphoid tissues
-can be up for 10 years but still seropos

Question 7

aids related complex

ARC

Answer 7

a subset of AIDS pts with persistent fevers, night sweats, weight loss, chronic diarrhea, inflamm skin, persist generalized lymphadenopathy

maybe oral candidiasis or chronic mucocutaneous herpes

will die quickly without treat

Question 8

AIDS clinical findings

Answer 8

1. recurrent infections, CD4 drops <200
2. tumors- kaposi sarcoma or non hodgkins lymphoma
3. progressie wasting syndrome, cachexia
4. AIDS induced dementia

Question 9

transmission of HIV

Answer 9

1. sexual contact
2. inoculation with infected blood
3. vertical transmission from mother to child

Question 10

infection process

general

Answer 10

1. virus (gp120) binds CD4
2. chemokine receptor bind
3. gp41 fusion peptide inserts into T cell
4. viral and T cell membranes fuse
5. inside cell either enter viral replication or proviral/dormant state

Question 11

chemokine receptors

Answer 11

HIV uses CCR5 and CXCR4
-R5 viruses = macros and memory T cells
-R4 viruses= T cells

can start early in disease with R5 then transition to R4

Question 12

cytokines with HIV

Answer 12

1. TNF-a and IL-2 induce HIV transcription/replication in T
2. IL1/3/6, TNF-a, IFN-y, GM-CSF induce HIV rep in monocytes/macros

in general trigger transcription factors NFkB and SP1

Question 13

infected monocytes/macros

Answer 13

since not as prone to lysis at T cells may serve as in vivo reservoir to transport thru body
-macros derived cytokines will cause AIDS dementia complex = memory loss

Question 14

killing T cells

Answer 14

via
1. direct lysis by budding HIV
2. virus prod interfere with protein syn so cell death
3. syncytia form of infected cells with uninfect
4. binding of gp120 to infected and uninfect T cells > Ab resp > ADCC
5. CTL mediated destructino of virus infected cells

Question 15

immunosuppression

Answer 15

T lymph destruction + destruc of follicular dendritic cell network + gp120 prevents binding class II MHC

Question 16

why immunity not protective

Answer 16

1. HIV integrates into DNA so latent
2. error prone reverse transcriptase so mutations to evade Abs and CTLs
3. HIV Nef protein downreg class I MHC so CTLs not bind
4. seroconversion signals Ab prod but CTL more important after intial infection

Question 17

causes of death

Answer 17

from infection by protozoan, bacterial, viral opportunistic pathogens
OR
malignancies like kaposi sarcoma or lymphoma

fatal pneumonia from pneumocystis jiroveci most freq COD

Question 18

obstacles to vaccine develop

Answer 18

1. genetic diveristy of HIV strains
2. lack of good animal model
3. transmission of HIV within cells instead of free viral particles
4. viral progression in face of immune resp

Question 19

HIV resistant indivs

Answer 19

CCR5 variants are seroneg after repeat exposure but can still be infected by R4 strain

also if have potent CTL resp

Question 20

ELISA

Answer 20

screening tech using HIV antigens cultured in H9 cell line
-antigens absorbed to solid phase and pt serum added then secondary antibody conj to enz

if color change then pos, repeat test, then do western blot to confirm

Question 21

pros/cons ELISA

Answer 21

-high false pos rate bc cross reacts with Ab to H9 antigens
-reasonable cost
-screen large numbers of samples
-configured to detect viral antigens

Question 22

western blot

Answer 22

viral antigen sep using SDS PAGE then transfer to membrane incubated with pt serum + antihuman immunoglobulin
-add substrate and see if rxn where pt Ab bound

aka detrmines viral proteins that have Abs

Question 23

PCR

Answer 23

very sensitive but only detects viral genome DNA integrated so use for neonates

RT-PCR will detect free virus in body fluids so assess viral load in adults