Virology A9: Immunity In Hiv/aids

Front 1

What proteins are expressed by HIV?

Back 1

1) gp120 env
2) gp 41 env
3) p24 gag
4) p17 gag
5) Reverse transcriptase
6) ssRNA (HIV-1)

Front 2

How long is HIV's gene?

Back 2

10 KB

Front 3

HIV:

1) How does it attach to cells?
2) What is the cell receptor?
3) What is required for infection of the cell?

Back 3

1) gp120 envelope protein
2) CD4
3) Chemokine receptors - CCR5, heptahelical receptors for macrophages and T cells

CXCR4 (T cells)

Front 4

R5 chemokine receptors:

1) What are they also known as?
2) When do they predominate?
3) What kind of strains resist HIV infection?
4) What cells are these chemokines found on?

Back 4

1) M-tropic
2) Early in infection
3) Delta CCR5 resistant to infection
4) Macrophages, T cells

Front 5

CXCR4 strains:

1) What are these also known as?
2) When are they found?
3) What kind of cells are these chemokines found on?

Back 5

1) T-tropic
2) Late stage infection
3) T-cells

Front 6

Describe the steps in HIV invading a CD4 T cell.

Back 6

1) gp120 envelope binds CD4 cell
2) Conformational change
3) gp120 binds CCR-5
4) gp41 causes membrane penetration
5) membrane fusion

Front 7

What cells are infected by HIV?

Back 7

1) CD4+ cells - helper T cells, macrophages, dendritic cells.

2) Stem cells, T cell precursors

3) NK cells (do not express CD4)

4) Mucosal epithelial cells (do not express CD4)

Front 8

What marker do most infected CD4 lymphocytes co-express? Cells expressing this are considered as..?

Back 8

CD45RO marker, considered activated or memory helper T lymphocytes

Front 9

Which cells (and where) are most frequently infected with HIV? Why?

Back 9

Memory CD4+ T cells in the gut - majority of CD4 cells in the body are in the gut.

Front 10

How do NK cells get infected with HIV although they don't express CD4?

Back 10

Alpha4Beta7 adhesion protein

Front 11

1) Do mucosal epithelial cells express CD4?
2) Are they infected with HIV?
3) What strains and how?

Back 11

1) NO - MUCOSAL EPITHELIAL CELLS DO NOT EXPRESS CD4

2) YES

3) CXCR4-tropic (T tropic) through GALACTOSYLCERAMIDE receptor AND CXCR4 co-receptor.

Front 12

1) What are the two ways macrophages can get infected by HIV?
2) Which strain attacks macrophages, and when?
3) Is the virus cytotoxic to the macrophage?

Back 12

1) HIV gp120 binds to CD4 receptor, or antibody opsonization marks virus for phagocytosis by macrophage

2) Macrophage tropic (CCR5), EARLY in infection (macrophages get attacked first early in infection)

3) No - non-proliferating mature macrophages keep HIV reproduction going on without being killed off. Virus reservoir, which is why you can't really cure HIV

Front 13

1) What is the major HIV infected cell type in the CNS?
2) What receptors does it express?
3) How does it help HIV replication?
4) What do infected cells release?

Back 13

1) Microglia
2) CD4, CCR5, CXCR4
3) They produce the new virus, may be reservoir
4) Neurotoxins - by end of HIV disease, most cells in the brain will be infected

Front 14

1) Which HIV strains infect microglia? Through what receptors and which co-receptors? What disease does this result in?

2) Which HIV strains infect astroglia? Through what receptors? What disease does this result in?

Back 14

1) HIV-1 M-tropic - CD4+ receptor, R5, R3 co-receptor. HIV-1 encephalitis

2) HIV-1 T-tropic - CD4- receptor, X4 co-receptor. HIV-1 encephalopathy

Front 15

Primary infection:

1) What is the doubling time, and when is peak viremia?
2) Each infected cell seeds how many other cells?
3) When does the viral load drop?

Asymptomatic phase:

1b) What is it also known as?
2b) How many virus particles are made and eliminated daily?
3b) How many CD4+ T cells are made and eliminated daily?
4b) What is going on overall with viral and T cell levels?

Back 15

1) 10 hours, peak viremia @ 21 days
2) 20 infected cells
3) When immune response kicks in

1b) Latency
2b) ~10^10
3b) 10^9
4b) virus replication and elimination are very nearly in equilibrium


1b) Latency
2b) 10^10
3b) 10^9
4b) Virus replication/elimination nearly in equilibrium

Front 16

Viral reservoir:

1) How many T cells sustain HIV-1 infection?
2) What is the status of these T cells?
3) What is the size of the latent HIV-1 reservoir like?

Back 16

1) 10^6
2) Productively infected, activated T cells
3) Similar

Front 17

Half lives for virus in:

1) Plasma
2) Productively infected activated T-cell
3) Latently infected resting CD4+ T cell cell

Back 17

1) 1-2 hrs
2) 1.5 days
3) 6-12 months

Front 18

1) What happens during clinical latency?
2) What triggers the provirus to start proliferating?
3) What happens after T cell replication is started?

Back 18

1) Provirus is in latent infection, or low-level infection
2) Other microbial infections stimulate release of cytokines, TNF
3) Extensive viral replication and CD4+ cell LYSIS - full blown AIDS and destruction of lymphoid tissue, depletion of CD4+ T-cells

Front 19

What are the 4 major HIV reservoirs and how long does the virus remain in them?

Back 19

1) Resting CD4+ memory T cells with integrated provirus - months - years as long as they're not activated

2) Monocytes/macrophages - ~2 weeks

3) Follicular dendritic cells (trapped virions) - months to years, virus is trapped on surface and not ingested

4) Astrocytes/parenchymal microglia

Front 20

What kind of virions are found on follicular dendritic cells? What does this indicate?

Back 20

Multiple, genetically diverse replication competent viral particles, indicating that virus is mutating all the time and becoming a different strain

Front 21

Humoral response to HIV:

1) Are in vivo antibodies to gp120 and gp41 effective?
2) Does humoral response eliminate the infection/prevent evolution of AIDS?
3) Is HIV envelope immunogenic? Why?
4) What do its antigens display?
5) What is the constant site for mutation in HIV? Why is an antibody ineffective?

Back 21

1) Antibodies not effective against envelope proteins in vivo. Only in vitro.
2) Humoral response does NOT eliminate infection/prevent evolution
3) HIV envelope poorly immunogenic - heavily glycosylated, hides the protein part
4) High antigenic variability
5) gp120 is site for constant mutation. Will mutate before antibody will be effective

Front 22

Cell mediated response to HIV:

1) What do CD8+ T cells recognize?
2) What do CD8+ T cells release that help fight HIV?
3) What can cell mediated responses do against HIV infection?

Back 22

1) gag, env, nef, pol - major epitopes
2) Chemokines that block CXCR4 receptors
3) Can block infection of new cells, reduce viral replication

Front 23

What viral antigen is detected in the blood first? When does it first appear in the blood? When is antibody made and when does the viral load start dropping because of it?

Back 23

p24 - 10 days. Antibody made ~3 weeks, free virus starts dropping

Front 24

In terms of time:

1) When are antibodies to HIV envelope made? What pattern do they have?

2) HIV-specific CTL

3) When are antibodies to p24 made? When do they peak?

4) Viremia?

Back 24

1) ~3 weeks, stay high.
2) Peaks at 8 weeks, stays high, but lower than antibodies, primarily responsible for getting viral load down
3) ~3 weeks, lower than HIV-specific CTL, drops towards end
4) Peaks ~8 weeks, comes back down during latent phase, creeps up around 2-3 years when you progress towards AIDS

Front 25

How does CTL response correlate to prognosis for a HIV patient?

Who has the worst response?

Back 25

1) Weak CTL -> rapid progression
2) Moderate CTL -> moderate progression
3) Strong CTL -> slow progression

People with strongest CTL response show slowest progression. People who are immunocompromised or children have weakest response and worst prognosis.

Front 26

1) What effect does HIV have on immune system cells overall?
2) Is gp120 recognized by antibody?
3) Why does HIV mutate at a rapid rate? What does this affect?
4) How does virus affect MHC?
5) How is infection of monocytes/macrophages different?

Back 26

1) Infects immune effector T cells and macrophages
2) No - it's so heavily glycosylated
3) Error-prone RT - affects envelope proteins, antigenic drift of gp120
4) Downregulates MHC-I, interferes with T cell recognition
5) Not cytotoxic to monocytes/macrophages - they are RESERVOIRS

Front 27

Towards the end of HIV progression, what two things pop up?

Back 27

Constitutional symptoms, opportunistic disease

Front 28

What 5 things that cause T cell depletion in AIDS?

Back 28

1) HIV replication, cell lysis
2) Formation of syncytia
3) T-cell killing of HIV infected T cells
4) Intracellular accumulation of viral DNA
5) Infection of stem cells, reduced production of T cell precursors

Front 29

Syncytia:

1) What are they?
2) Which strains form them?
3) How are they formed?

Back 29

1) Multinucleated lymphocyte giant cell - useless
2) R4 strains
3) gp120 expressed on productively infected cells binds to CD4 of uninfected T cells

Front 30

Death of infected T cells by lysis is termed?

Back 30

Cytopathic effect

Front 31

What happens during T cell killing of HIV-infected T cells?

Back 31

Infected CD4+ cells express HIV peptides, HIV-specific CTL kills it

Front 32

What would you see in the terminal ileum in a healthy patient? AIDS infected?

Back 32

Healthy patient - lymphoid aggregates
AIDS infected - lymphoid aggregates vanish

Front 33

What are the 4 main immunological abnormalities in HIV/AIDS?

Back 33

1) CD4 T cells decline in # and function
2) Chronic immune activation - as CD4 cells fall, get more mild diseases, immune system always activated and causes resting CD4 cells with provirus with them to activate and multiply
3) Cytokine dysregulation - increased production of inflammatory cytokines (IL-1, IL-6, TNF), decreased production of TH1 cytokines (IL-2, IL-12, IFNgamma)
4) Failure of B cell immunity (no activation from CD4)

Front 34

What is the most obviously impaired immunological abnormality in HIV/AIDS?

Back 34

Decreased production of IL-2.

Front 35

What is seen in the marrow of a HIV patient?

Back 35

Hyperplasia with plasmacytosis - plasymacytosis = tons of antibodies being made because of chronic immune activation in HIV/AIDS

Front 36

What happens to the total # of:

1) Total blood lymphocytes
2) Total T cells
3) Ratio of CD8:CD4
4) CD4+ T cells
5) B lymphocytes

Back 36

1) Down - CD4+ makes up most of blood lymphocytes
2) Down
3) Usually 1:2, but at the end as CD4 killed of, end up with more CD8
4) Down
5) Normal or increased because of chronic immune activation

Front 37

What happens to:

1) Delayed hypersensitivity - what type of hypersensitivity is this?
2) Response to mitogens
3) IL-2 production
4) Primary antibody response
5) Serum IgG/IgA

Back 37

1) Type 4 - T cell mediated. Contact sensitivity, tuberculin sensitivity, granulomatous sensitivity
2) Down
3) Down
4) Normal, then low later because CD4s are disappearing
5) Very increased because of chronic activation, then way lowered

Front 38

What are the five steps of lymph node pathology in AIDS infection?

Back 38

1) Follicular hyperplasia due to immune activation
2) Severe follicular involution
3) Lymphocyte depletion
4) Atrophy
5) Lymphocyte depletion in spleen, thymus

Front 39

What is one of the earliest signs of HIV infection?

Back 39

Follicular hyperplasia b/c of constant immune activation

Front 40

1) When does viral load peak?
2) When does the viral load fall to low levels?
3) When do antibodies to HIV become detectable?
4) CD4+ cell count - when do they begin to deplete? What is AIDS defined by?

Back 40

1) 2 weeks following infection
2) ~2 months
3) 2 weeks - 2 months
4) Months to years after infection. <200 cells/ul

Front 41

CD4+ T cell numbers:

1) >500/ul means?
2) 200-499/ul?
3) <200/ul?

Back 41

1) acute HIV infection, asymptomatic phase or persistent generalized lypmhadenopathy
2) symptomatic but not AIDS defining
3) AIDS defining

Front 42

Predictors of control:

1) HLA B27 and B57 - what are they associated with?

2) CCR5delta32 polymorphism

3) Strong CTL response

Back 42

1) Low viral load, prolonged asymptomatic phase

2) Reduced disease progression

3) Reduced disease progression

Front 43

Dental therapy of HIV/AIDS patients at UNLV:

1) CD4 200-350/mm^3, asymptomatic, no Hx Ols
2) CD4 <200/mm^3, asymptomatic, no Ol prophy, not neutropenic, low viral load
3) CD4 150-200 mm^3, symptomatic, neutropenic, Hx Ols or has high viral load
4) CD4 <150/mm^3, or PMN <500 mm^3

Back 43

1) provide all dental services
2) no restrictions, consider antibiotics
3) restrict tx to alleviate pain, caries, infections, xerostomia, antibiotics if neutropenic
4) do not treat in open clinic, restrict treatment to alleviate pain, caries, infections, xerostomia. Requires antibiotics

Front 44

Immunizations:

1) Influenza
2) Pneumococcal
3) Hep B
4) dTAP
5) HPV
6) MMR
7) Varicella
8) Hep A
9) Meningococcal

Back 44

1) 1 dose/yr
2) 1 dose
3) 3 doses
4) Sub 1 dose of Tdap for Td booster, boost with Td every 10 years
5) Optional
6) DO NOT ADMINISTER
7) DO NOT ADMINISTER
8) 2 doses
9) 1 or more doses