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Case 7: HIV > Immunology > Flashcards

Immunology Flashcards

1
Q

Draw the immunological synapse of dendritic cell & CD4+ T cell

A

Notes

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2
Q

Discuss T cell activation & consequences of an incomplete synapse

A

T cell activation depends on the environment.
If there are an complete immunological synapse, T cell becomes activated & have a Th1 or Th2 response
Th2 if B cell presents
If the immunological synapse is incomplete the T cell dies or anergic

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3
Q

List the 3 antiviral/Th1 cytokines

A

INF-alpha & - beta
IL-12

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4
Q

Where does antibodies come from

A

Secreted from B cell receptors

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5
Q

What is the 4 functions of antibodies

A

Opsonisation
Complement
Ab dependent cellular cytotoxicity
Neutralization

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6
Q

2 ways a HIV infection be prevented

A

By a neutralizing antibody
Prevent infection/toxic particles to bind to cell receptor at the site of entry

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7
Q

What neutralizing antibody is the most optimal response

A

IgA, IgG

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8
Q

How to make antibodies

A
  1. Gene of B cell receptor
  2. Chopped up finely
  3. Recombination & junctional diversity
  4. B cell mature in 3 days
  5. T cell presentation for somatic hypermutation & class switching
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9
Q

Can you make antibodies for HIV before you acquire an infection

A

Yes, antibodies are made randomly

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10
Q

Can you make neutralizing antibodies w/o acquiring HIV

A

No, neutralizing antibodies require T cell presentation but can be passively transferred from mother to child

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11
Q

How is the virus transmission prevented

A

If there is neutralizing antibodies & antiviral factors

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12
Q

What is the 8 steps of an effective anti-viral immune response

A
  1. Virus can not be transmitted because mucosal is covered with/ neutralizing antibodies & specific anti-viral factors
  2. If the virus is transmitted & manages to infect & enter a cell, the cell will sense it through innate PRR molecule inside the cell (anti-viral toll like receptors, 3,7,8 & 9)
  3. If the PR molecule is unregulated the infected cell will start producing interferons & prepare for death
  4. Interferons will prime APC in the environment to present to CD4+ T cells in a Th1 manner
  5. CD4+ T cells will activate via Th1 cytokines CD8+ T cells to kill virally infected cells
  6. At cells that escape CD8+ T cell killing or down regulate MHC 1 will be killed by NK cell
  7. Generation of memory cells
  8. Resolution by up regulation of anti-inflammatory markers like TGF-beta (angiogenesis & healing) & IL-10 (Dow regulates lymphocytes & APC interactions)
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13
Q

3 ways how an infected cell prepare for self death

A

Up regulating:
1. Own internal antiviral proteins- restriction enzymes
2. FAS
3. MHC 1

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14
Q

State 2 instances when a NK cell get activated

A
  1. MHC 1 down regulation
  2. Activating signals overwhelm inhibitory signals
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15
Q

List 6 ways how virus escape from getting killed

A
  1. Rapid mutation causing poor recognition
  2. Inactivate TLR signaling by sequestering signaling molecule
  3. Prevent interferons secretion
  4. Prevent MHC class 1 up regulation (stop host cell from dying)
  5. Prevent MHC class 2 up regulation (stop CD4 T cell response)
  6. Prevent up regulation of second signals (CD4 T cell die)
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16
Q

What happens when an infection becomes chronic

A

It causes non-specific activation of immune response leading to immune exhaustion & CD4/8+ T cell apoptosis

17
Q

With what 4 things are chronic viral infections associated with

A
  1. Increased risk of Ca
  2. Inappropriate immunological response
  3. Increased risk of infection w/ other pathogens
  4. Non-specific immunological responses associated with loss of tolerance
18
Q

What is HIV’s tropism

A

CD4+ cells

19
Q

What happens when CD4+ T cell response is lost

A

Whole immune system dysfunction as it directs the Th1 & 2 response
Th1-intracellular pathogens & Th2-increase risk of bacterial & fungal infections w/ non-specific Ab production

20
Q

Why does non-specific B cells get produced

A

Due to B cell hyper stimulation & B cell response dysfunction as Ab opsonise that increase the risk of HIV uptake by dendritic cells & monocytes making Ab deleterious

21
Q

What 3 cells does HIV infect & why

A

Macrophages
Dendritic cells
T cells
CCR5/CXCR4 receptors

22
Q

Where does viral transmission occur

A

At the mucosal surfaces predominantly of vagina, penis & rectum

23
Q

What is the 4 protective mechanisms of the vagina against infections

A

Low pH
Thick epithelium & mucous layer
Innate immune defense
Adaptive immune defense

24
Q

What factors increase the risk of HIV transmission in the vagina

A

Change in epithelium
Cervical ectopy & dryness (dry sex)
Abnormal flora & increase T cells (STI, immunocompromised)

25
Q

What is the first cells being infected with/ HIV

A

Dendritic cells & macrophages that moves to lymph nodes & infect other cells or remain dormant

26
Q

What happens when activated CD4+ T cells get infected in the gut

A

They die & forms gaps in GIT mucosa & allows pathogens to move to bloodstream & activated PRR causing more inflammation

27
Q

List the 3 reasons for CD4+ T cell depletion

A
  1. Infected & pop
  2. Killed by CD8+ T cells/NK cells
  3. Becomes overexcited & exhausted
28
Q

What is leaky gut & what does it cause

A

Leaky guts is when there is gaps in mucosa of GIT & allows small particles to pass causing non-specific activation of CD4/8+ T cell response causing severe inflammation

29
Q

What is an elite controller

A

Manage to suppress viral replication w/o drugs

30
Q

What is a long term non-progressor

A

Maintain immune function w/ high viraemia

31
Q

What is the “cure” for HIV

A

A bone marrow transplant of a Caucasian person w/ lack of CCR5

32
Q

What is a sterilizing cure vaccine

A

Wipes out all HIV from the body

33
Q

What is a functional cure for HIV

A

Viral load remains suppressed despite patient stopping ARV treatment

34
Q

What is prophylactic vaccine & the problems associated (HHI)

A

Prevent acquiring HIV
Problems:
Highly mutable
Heavily glycosylated - Ab can’t bind
Infection is not sterility

35
Q

What is 2 things a successful prophylactic vaccine require

A

Neutralising antibodies (IgA)
Against conserved sites

36
Q

What is a therapeutic vaccine & problem w/ development

A

Assist w/ antiviral immune response in patients that already have infection
Problem method of delivery

37
Q

What is the problem w/ latency

A

HIV sleeps w/i CD4+ T cell & quiescent & stable
It hides from immune response/medication, making the cure difficult

38
Q

3 other modalities to prevent & cure HIV

A
  1. Protect site of infection
  2. Shock & kill HIV out of hiding places to be targeted
  3. Gene editing to eliminate HIV

Case 7: HIV (6 decks)

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