Pathogenesis of HIV

Question 1

what and when is first peak of Sx

Answer 1

• maybe mono Sx

- around week 6-8 - viral spike

Question 2

what is stable level of CD4

Answer 2

set-point - varies for people

Question 3

when do constitutionsal Sx occur

Answer 3

CD 500

Question 4

when do opportunisitic infections begin

Answer 4

CD 200

Question 5

def. AIDS

Answer 5

1. presence of HIV and

2. presence of opp. infection or CD

Question 6

3 function of CD4

Answer 6

1. help activate macrophages
2. activate B cells
3. activate NK cells

Question 7

HIV structure

Answer 7

enveloped RNA virus

Question 8

what is HIV surface protein

Answer 8

gp120

Question 9

what does gp120 interact with (2)

Answer 9

CD4-r

coreceptor - CCR5 or CXCR4

Question 10

what cells have receptors that HIV can bind to

Answer 10

CD4+ T -cells, monocytes, macrophages

Question 11

what happens in people with no CCR5

Answer 11

can’t get HIV

Question 12

what causes lack of CCR5

Answer 12

32bp mutation - mostly northern europeans

- must be homozygous

Question 13

what happens in tetanus vaccine in people with HIV

Answer 13

get increased viral load

Question 14

what dramatically increase HIV load

Answer 14

inflamm. cytokines - IL1, TNF, !L-6

Question 15

what is special about HIV to give it wide population differences

Answer 15

1. high rep. rate (bill/day)
2. high error rate
3. many mutations - lots of variance

Question 16

what are 2 main changes to CD4

Answer 16

1. less cells

2. defective cells

Question 17

2 general hypothoses about why kills CD4

Answer 17

1. direct killing

2. indirect killing

Question 18

why does direct killing not explain everything

Answer 18

when look at pool of CD4 cells that die, only small # have infection

Question 19

what supports indirect hypo

Answer 19

when look at cells ex vivo not infected they are apoping

Question 20

**3 possible indirect mechs

Answer 20

1. immune activation causes proliferation and then apoptosis
2. some virus proteins cause activation or cause cells to apoptose
3. lipopolysaccharide(LPS) translocating into the blood may cause activation

Question 21

2 ways CD4 cells are dyfunctional

Answer 21

1. can’t prolif to antigens

2. Can’t produce IL-2 to make themselves grow

Question 22

what does HIV ABs indicate

Answer 22

have disease, but can’t get rid of - same thing in HepC, but in HepB it means you are immune

Question 23

2 ways to detect HIV

Answer 23

1. direct detection

2. detect ABs

Question 24

4 ways of direct detection

Answer 24

1. culture or isolate virus from blood or lymph (expensive)
2. detect presence of DNA or RNA in plasma via PCR (standard)
3. detect DNA in cells (not standardized)
4. detect presence of HIV protein in blood (p24) assay- only good for high levels

Question 25

how are HIV ABs testes (main test)

Answer 25

immunoflroueced ELIZA

Question 26

what is back up to ELIZA to lower false positives

Answer 26

western blot assay

Question 27

what is limitation to using ELIZA test

Answer 27

need HIV ABs which take a few weeks to develop

Question 28

what should be done if acute HIV and need a test

Answer 28

1. HIV viral load assay | 2. more sensitive p24 assay

Question 29

manifestation of HIV

Answer 29

1. more opp. infections | 2. increased tumor and viral related cancers (HPV, HHV8, lymphoma -EBV)