HIV Flashcards

1
Q

CD4 cells are targeted for infection by HIV. How are CD4 cells lost during HIV infection?

A

HIV-induced cell lysis, apoptosis, CD8-mediated killing

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2
Q

What serves as a long-term reservoir for HIV?

A

Memory T cells in which proviral DNA is integrated into host chromosomes

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3
Q

What is meant by pre-integration latency?

A

Inactive CD4 cells result in a nonproductive HIV infection. In these cases, proviral DNA has not integrated into the genome, but may if the cell is activated. Inactive CD4 cells serve as short-term HIV reservoirs.

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4
Q

True/False. Dendritic cells can be productively infected by HIV.

A

True. Dendritic cells have CD4 and CCR5 receptors that HIV can bind and enter the cell.

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5
Q

What is the role of dendritic cells in the establishment of an HIV infection?

A

Dendritic cells have a DC-SIGN receptor to which HIV can bind. The DC stores the HIV in an endocytic vesicle and transports the virus to lymph nodes where it is released near CD4 T cells.

Alternatively, dendritic cells can ingest HIV and present peptides through MHC II to CD4 T cells which activates HIV gene expression.

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6
Q

HIV is capable of infecting monocytes and macrophages. Why are these cells more resistant to HIV-induced cell lysis? How do these cells contribute to infection?

A

Monocytes express less CD4 on their surface than T cells are more resistant to lysis. This also means that the cells persist and release the virus for longer periods of time. Monocytes are short-term reservoirs for HIV.

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7
Q

Why can HIV not be completely resolved with ART?

A

HIV exists in a post-integration latency state in memory CD4 T cells. In this state, there is not productive infection. As such, there is no target for ART.

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8
Q

What are HIV virus particles that bind CCR5 chemokine receptors called?

A

R5 viruses

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9
Q

What are HIV virus particles that bind CRCX4 chemokine receptors called?

A

X4 viruses

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10
Q

How does the presence of R5 and X4 viruses change throughout infection?

A

R5 viruses are predominantly present in the early stages of infection and are responsible for the majority of viral transmission. As infection progresses, more X4 viruses become present.

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11
Q

True/False. Host immune response and ART select for resistant HIV mutants that maintain infection.

A

True. Immune response and ART place selective pressure for mutants that are resistant.

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12
Q

True/False. During clinical latency no viral particles are synthesized and the infection is latent.

A

False. Clinical latency does not equal infection latency. HIV virus is still actively producing an infection, however, there are no clinical symptoms of disease.

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13
Q

What is the role of B cells in HIV infection?

A

Follicular dendritic cells in lymph nodes present HIV antigens to B cells, resulting in activation. Activated B cells secrete cytokines, which enhances viral replication in CD4 T cells. CD4 T cells migrate to lymph nodes for T-dependent immune responses and become infected with the virus.

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14
Q

How does the number of CD4 T cells vary throughout HIV infection?

A

During early infection, there is a significant drop in CD4 T cell numbers. As the infection progresses, CD4 T cell numbers increase slightly except in GALT. CD4 T cell counts then decrease with chronic infection over years.

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15
Q

What is the viral set point?

A

This is the viral load that can be managed by the immune system. The lower the set point, the better managed the infection and the longer it will take for progression to AIDS.

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16
Q

What is the role of CD8 T cells in HIV infection?

A

CD8 T cells produce cytokines that block viral binding to receptors, however, this may activate transcription factors in T cells that enhance HIV replication.

CD8 T cells also eliminate infected CD4 T cells, but this leads to immunosuppression, increased HIV infection, and decreased CD8 T cell numbers.

Some HLA types of MHC I receptors are associated with slower infection progression.

17
Q

Neutralizing antibodies are produced against HIV. Why then is the virus not prevented from infecting cells?

A

Initial antibodies respond to gp120/gp41 and are non-neutralizing. Neutralizing antibodies are not produced until several weeks after infection and only prevent infection of new cells.

18
Q

What are the clinical stages of HIV infection?

A

Asymptomatic; Early Symptomatic (AIDS-Related Complex); AIDS; Advanced HIV Infection

19
Q

What are the immunological stages of HIV infection?

A

Stage 0 (before positive test);
Stage 1 (>500 CD4 T cells);
Stage 2 (200-499 CD4 T cells);
Stage 3 (AIDS, <200 CD4 T cells)

20
Q

What symptoms are associated with acute HIV syndrome?

A

Mono or flu-like symptoms - fatigue, lymphadenopathy, sore throat, headache, myalgia

21
Q

What symptoms are present during clinical latency?

A

Generally asymptomatic with generalized lymphadenopathy

22
Q

What symptoms are present during Early Symptomatic/AIDS-Related Complex infection?

A

Nonspecific symptoms - low-grade fever, fatigue, weight loss, malaise, diarrhea

Increased susceptibility to opportunistic and other infections

23
Q

When does HIV progress to AIDS?

A

CD4 T cell count below 200 cells/uL of blood

24
Q

What are some AIDS-defining illnesses?

A

Hairy leukoplakia, Candidiasis, Kaposi’s sarcoma, Pneumonia, CMV, Cryptosporidiosis

25
Q

What is an important reservoir for HIV in the CNS?

A

Microglial cells

26
Q

What is HIV-associated dementia (HAD)?

A

Occurs very late in infection - includes attention & concentration impairment, memory deficits, mental slowing, slow and jerky movements, behavior and mood changes

27
Q

What are Long-Term Non-Progressors and Elite Controllers? What is the difference between each?

A

Long-term non-progressors maintain a low viral load for an extended period of time resulting in prolonged time before AIDS.

Elite controllers maintain an undetectable viral load for an extended time. These individuals are even better at managing HIV than long-term non-progressors.

28
Q

What HLA types are better at inducing a CD8 T cell response to conserved epitopes?

A

HLA-B5701 & HLA-B27

29
Q

Why is it best to mount an immune response or develop ART that target conserved regions of the HIV genome?

A

These regions are generally present in most HIV mutants. Even if sections of the region are mutated, these mutants are generally less infections.