L15: Immunology of HIV Infections

Question 1

Stages of HIV infections. Describe

Answer 1

1. ) Acute HIV syndrome (2-6 weeks after initial infection)
   - resembles mono infection, period of virus replication in blood and CSF, lymphoid organ seeded with virus
2. ) Asymptomatic infection/latent phase
   - period when HIV nearly undetectable in blood, but is replicated in lymphoid tissue, can be in this phase for up to 10 years
3. ) ARC: AIDS-related complex: (not all pts go through this)
   - period characterized by persistent fevers, night sweats, weight loss, chronic diarrhea, skin conditions, generalized persistent lymphadenopathy, oral candidiasis HSV infections, can die quickly without treatment

4.) AIDS: recurrent infections with opportunistic pathogens, Kaposi’s sarcomas or non-Hodgkins lymphomas, progressive wasting (cachexia) – TNF-alpha, AID-induced dementia, clinically measured with CD4+ count < 200 cells/mm3

Question 2

When do HIV infected pts usually seroconvert?

Answer 2

• 6-9 weeks

Question 3

What is the window period in HIV infected patients?

Answer 3

• Period of time prior to seroconversion when all serologicaly tests are negative, but pt is actually viremic

Question 4

Trigger from latent to active HIV stage?

Answer 4

• Unknown

Question 5

Describe pathogenesis of HIV infection

Answer 5

• HIV virion utilizes chemokine receptors (CCR5/CXCR4) in conjunction with CD4 to access the cell via their gp120 binding to CD4 (gp120 is linked to gp41)
• R5 variants access macrophages and memory T cells via CCR5 and CD4. R4 variants access T cells via CD4 and CXCR4. There are R5X4 variants that can access both
• Once inside cell, viral genome can integrate into cell’s genome using reverse transcriptase. Cell activation via cytokines trigger virus production via activation of NFkB and SP1 TFs
  a. ) TNF-alpha and IL-2 induces this in T cells
  b. ) IL-1, IL-3, IL-6, TNF-alpha, IFN-gamma and GM-CSF induces this in monocytes and macrophages
• Macrophages not as prone to lysis as T cells by virus
• Dementia occurs: virus infection of neurons or destruction via macrophages
• T cells killed via lysis, interference with protein synthesis, syncytia formation with other cells, ADCC, CTL-mediated destruction of virally-infected cells
• Binding free gp120 to CD4 of uninfected T cells, preventing them from binding class II MHC
• Destruction of follicular DC network

Question 6

Why is immunity not protective in HIV infections?

Answer 6

• HIV integrates into DNA, error-prone reverse transcriptase new antigens every days, NEF protein of HIV downregulates class I MHC making infected cells invisible to CTLs

Question 7

What causes death in AIDs pts?

Answer 7

• opportunistic pathogen infections, most frequently Pneumocystis jiroveci (pneumonia)

Question 8

Discuss HIV resistance in some individuals

Answer 8

1. ) small percentage of individuals with truncated CCR5 variant, can be infected with R4 strain
2. ) Gambian/Kenyan sex workers who had potent CTL response

Question 9

Discuss laboratory techniques for diagnosing and monitoring progress of HIV infected pt

Answer 9

1. ) ELISA: detects viral antigens or antibody 6-9 weeks after infection, high false positive d/t x-reactive abs to H-9 cell line
2. ) Western blot: direct detection of viral proteins, again 6-9 weeks after infection
3. ) PCR: detects viral genome integrated into DNA – used in neonates who have been infected from mother
4. ) RT-PCR: detects free virus in body fluids – used to assess viral load in adults

Question 10

An HIV-positive mother delivered a baby. Her physician ordered a laboratory test to determine whether the newborn baby was infected by the virus. From the following, choose the most appropriate test for the physician to have ordered.

1. ELISA test
2. Western blot
3. PCR
4. RT-PCR

Answer 10

• PCR

Question 11

A 24-year old male reports to his physician that he may have been exposed to HIV from a sexual encounter two weeks ago. From the following, choose the most appropriate test for the physician to have ordered.

1. ELISA test
2. Western blot
3. PCR
4. RT-PCR

Answer 11

• RT-PCR

Question 12

A 33-year old mother of two is tested for possible exposure to HIV after sharing a needle at a party eight months ago. She tests positive by the ELISA assay (performed twice), but the Western blot gives a negative result.
What would account for the false-positive result in the ELISA assay?
Other than prior pregnancies and autoimmune diseases, what other circumstances can induce these antibodies?

Answer 12

• Antibodies to the H-9 cell line MHC proteins that contaminate the ELISA assay
• Transfusions and organ/tissue transplantation