Immunology - HIV infection Flashcards

1
Q

Using which enzyme does HIV replicate inside cells?

A

Reverse Transcriptase

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2
Q

How many genes are inside the HIV genome?

A

9 genes that encode 15 proteins

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3
Q

What is the role of reverse transcriptase in HIV?

A

Converts RNA into DNA which can be incorporated into host cells’ genes

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4
Q

What are the two key glycoproteins encoded by the HIV virus?

A

gp120 (initial binding)
gp41( conformational change)

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5
Q

Which cell of the immune system is particularly affected by HIV?

A

CD4+ T cells

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6
Q

Recall the receptor and co-receptors for HIV on CD4+ T cells

A

CD4 receptors
CCR5 CXCR4 coreceptors

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7
Q

In people who have natural immunity to HIV, what antibodies may be present in serum?

A

Anti-gp120 and anti-gp41 (Nt) antibodies

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8
Q

How does HIV infection affect CD8+ T cells?

A

by affecting the function of CD4+ T-cells and antigen presenting cells that are required for proper CD8+ T-cell maturation, HIV is able to decrease the circulating pool of effector and memory CD8+ T-cells that are able to combat viral infection

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9
Q

How does HIV infection affect monocytes and dendritic cells?

A

Not activated by CD4+ T cells and so cannot prime naive CD8+ T cells

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10
Q

How does HIV affect immunological memory (2)?

A

CD4+ T cell memory is lost

CD8 memory cell not activated by antigen-presenting cell

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11
Q

Why is there so much variation/mutation in HIV infection?

A

lacks proof-reading mechanisms from cellular DNA polymerases

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12
Q

Why is HIV mutation within the host problematic (3)?

A

Escape from neutralising antibodies.

Escape from HIV-1-specific T cells.

Resistance and escape from antiretroviral drugs.

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13
Q

Recall the 7 steps of the HIV life cycle

A
  1. Attachment/Entry
  2. Reverse Transcription and DNA Synthesis
  3. Integration
  4. Viral Transcription
  5. Viral Protein Synthesis
  6. Assembly of Virus and Release of Virus
  7. Maturation
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14
Q

Which drug classes are capable of inhibiting the action of reverse transcriptase in HIV infection?

A
  1. Nucleoside analogues reverse transcriptase inhibitors
  2. Non-nucleotide reverse transcriptases inhbitors
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15
Q

Which class of HIV drugs can prevent integration of viral DNA?

A

Integrase inhibitors

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16
Q

Which HIV drugs can prevent modification of translated viral proteins?

A

Protease inhibitors

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17
Q

What is the median time of infection with HIV to AIDS development?

A

8-10 years

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18
Q

What does it mean if someone is an HIV exposed seronegative individual?

A

Partner of individual with HIV who remains uninfected

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19
Q

What are the 3 major markers used to monitor HIV?

A

CD8
CD4
Plasma viral load

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20
Q

What is long-term nonprogression of HIV?

A

individuals who are infected with HIV, but control the infection without antiretroviral therapy (ART).

individuals who have been living with HIV for at least 7 to 12 years and have stable CD4+

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21
Q

How can HIV be diagnosed (2)?

A

anti-HIV antibodies (ELISA) - screening test

Western Blot = Confirmatory test

22
Q

How are CD4+ T cell levels measured in HIV infection?

A

Flow cytometry

23
Q

What are the two methods of testing for ARV resistance?

A

Phenotypic = viral replication is measured in cell cultures under selective pressure of increasing concentrations of antiretroviral drugs (compared to wildtype)
Genotypic = mutations detected by sequencing amplified HIV genome (limited to sequencing RT and P)

24
Q

Which drugs make up a HAART regimen?

A

Three or more ART drugs

25
When should HAART treatment be initiated?
Immediately on diagnosis
26
Give 3 examples of NRTI HIV drugs
Zidovudine Lamivudine Emtricitabine
27
Recall 2 examples of protease inhibitor HIV drugs
Indinavir saquinavir
28
What class of drugs are dolutegravir & raltegravir?
Integrase inhibitor
29
Which drugs make up the HAART regimen initially?
2 NRTIs + PI
30
What CD4 count defines AIDS?
\<200 cells/ mm3
31
Which drugs make up the atripla pill?
Emtricitabine + tenofovir + efavirenz
32
Which ARV is best to use in pregnancy?
Zidovudine
33
How can CD8+ T cells prevent HIV entry into cells?
Producing chemokines MIP-1A, MIP-1b and RANTES which block co receptors Macrophage Inflammatory Protein-1 Alpha
34
does HAART elimiate HIV from body?
no - there's a reservoir in CD4+ T cells
35
4 ways of preventing HIV spread?
Male circumcision (APCs in foreskin at a high density) Condoms PrEP (Truvada) TasP (Treatment as Prevention – if on treatment, cannot transmit infection; i.e. U=U)
36
what type of virus is HIV
HIV is a retrovirus, which means it carries single-stranded RNA contains reverse transcriptase
37
whats gag protein
major structural protein (of HIV-1
38
what is the 1st line screeening test for HIV and what is the confirmational test
Anti-HIV antibodies (ELISA) – screening test Anti-HIV antibodies (Western Blot) – confirmation test
39
whats a non-neutralising atibody seen in the adpative immune response to HIV?
anti-p24
40
what predits disease progression?
initial viral burdern (set point)
41
who are rapid progressors & elite controllers?
Rapid progressors (10%) will take 2-3 years to develop AIDS (these are mainly seen in Africa) Elite Controllers (EC) can suppress the viral replication
42
what does a positive test require?
A positive test requires the patient to have SEROCONVERTED (i.e. started to produce Ab) This happens after ~10 weeks incubation period
43
what type of drug is efiraverz? what effect does it have on amplodipine
non NRTI also a P450 inducer amlodipine wont work as well
44
3 outcomes of HAART
increases CD4 T cell count controls viral replication improvement in host defences
45
4 limitations of HAART
doesn’t eradicate latent HIV-1; fails to restore HIV-specific T-cell responses; high pill burden; adherence; threat of drug resistance
46
other than T lymphocytes, what cell type is primarily infected by HIV?
macrophages
47
a mutation in what cell surface receptor may confer immunity from HIV?
CCR5 ## Footnote HIV is made up of two main viral envelope proteins: gp120 - This receptor is responsible for initial binding to CD4 and a co-receptor, such as the CCR5 receptor. gp41 - Binding of gp120 exposes gp41. gp41 then leads to fusion with the host cell membrane and viral entry into the cell. Mutations in the CCR5 receptor confer immunity against HIV as the virus cannot enter cells to replicate.
48
outline the effects on HIV on the immune system
activated infected CD4 helper T cells die/anergised therefore monocytea and dendritic cells arent activated and cant prime naive CD8 T cell CD8 T cell and B cell responses lost as a consequence CD4 T cell memory also lost CTLs kill infected monocytes and dendritic cells
49
give an example of a NNRTI
efavirenz
50
give an example of a fusion inhibitor
enfuviritide
51
gve an example of an attachment inhibitor
maraviroc