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Immunology-Week 3 & 4 > Autoimmunity/Tolerance > Flashcards

Autoimmunity/Tolerance Flashcards

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1
Q

Describe AIRE

A

AIRE is a transcription factor in mTEC that controls the expression of self-antigens in thymic medullary epithelial cells. Essential for negative selection/self-tolerance.

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2
Q

What happens if AIRE gets deleted or inhibited?

A

Negative selection/self-tolerance does not occur possibly leading to autoimmunity.

Ex. APECED

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3
Q

Describe APECED

A

An AR autoimmune disorder caused by mutations in AIRE gene. Its clinical presentation varies greatly.

Classic Triad:

  1. mucocutaneous candidiasis
  2. adrenal failure
  3. hypoparathyroidism.
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4
Q

What is the fate of CD4 T cells that are self-reactive during negative selection?

A
  1. Apotosis

2. Differentiate into regulatory T cells (“natural Treg”)

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5
Q

What are the lymphocyte markers of Treg T cells?

A
  1. CD3+CD4+CD25high

2. FoxP3+

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6
Q

What cytokines are secreted by Treg?

A

IL-10 & TGF-B

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7
Q

What are the three outcomes of peripheral T lymphocyte (Induced) tolerance?

A
  1. Anergy
  2. Suppression
  3. Deletion/Apotosis
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8
Q

What costimulator molecules are expressed on T cells and APCs, respectively to assist in activation?

A

CD28:B7

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9
Q

What inhibitory molecules are expressed on Treg cells and APCs, respectively, to assist in suppression?

A

CTLA4:B7

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10
Q

What is a monoclonal antibody against CTLA4 to enhance T cell activation and antitumor immunity?

A

Ipilimumab

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11
Q

What drug is CTLA4 agonist that interrupts CD-28 mediated costimulation, causing T cell energy?

A

Abatacept (bind to B7)

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12
Q

What are the components of Abatacept?

A
  1. human CTLA4

2. Fc region of IgG1

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13
Q

What is another name for B7 protein on APCs?

A

CD80/CD86

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14
Q

What cytokines are required to induce peripheral T reg?

A
  1. IL-2

2. TGF-B (allows Fox P3 gene expression of Treg)

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15
Q

What are 3 mechanisms of peripheral T reg in suppression?

A
  1. Production of inhibitory cytokines (IL-10, TGF-B)
  2. Expression of CTLA4
  3. Consumption of IL-2
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16
Q

Describe IPEX

A

An XR disorder caused by mutations in FoxP3 gene.

Classic Triad:

  1. Enteropathy (diarrhea)
  2. Dermatitis (Eczematous rash)
  3. Endocrine disease (diabetes or thyroid-related)
17
Q

What are 2 mechanisms of apoptosis in peripheral T lymphocytes

A
  1. Intrinsic Cell Death: Apoptotic inducing proteins are released from mitochondria (within T cell).
  2. Extrinsic Cell Death: Apoptosis induced by the interaction of FasL (death receptor ligand) and Fas (death receptor) on T cells.
18
Q

Describe ALPS

A

A disorder caused by mutations in Fas/FasL gene leading to defective apoptosis causing chronic accumulation of lymphoid cells.

Clinical presentations:

  1. Enlarged tissues (splenomegaly, hepatomegaly, lymphadenopathy)
  2. Blood cell autoimmunity (hemolytic anemia, thrombocytopenia, neutropenia)
  3. Increased risk for lymphomas
19
Q

What are the three outcomes of Central B Lymphocyte Tolerance?

A
  1. Apoptosis/Deletion
  2. Anergy (reduced receptor expression/signaling)
  3. Receptor Editing
20
Q

What immunoglobulin is produced by Marginal Zone B Cells when they become plasma cells?

A

IgM

21
Q

What is receptor editing?

A

The process in which B cells can go through to become Non-Celf Reactive B cells.

22
Q

What are the three outcomes of Peripheral B Lymphocyte Tolerance?

A
  1. Apoptosis/Deletion
  2. Anergy
  3. Suppression (has inhibitory receptors)
  • Same outcomes as Peripheral T Lymphocyte Tolerance
23
Q

What are three single-gene defects that cause autoimmunity that we have to know?

A
  1. AIRE (APECED)
  2. FOXP3 (IPEX)
  3. FAS (ALPS)
24
Q

What are 2 mechanisms of microbial/environmental-induced autoimmunity?

A
  1. Induction of costimulators on APCs
    - Microbes activate APCs to express costimulator, and APCs present self-antigens instead. This can cause self-reactive T cells to get activated leading to autoimmunity.
  2. Molecular Mimicry
    - Microbial antigens may cross-react with self antigens (mimicry) and initiate self-reactive T cells that attack self tissues.
25
Q

Describe SLE

A

Multi-organ autoimmune disorder caused by defective B and T lymphocyte tolerance due to mutations in many genes. Anti-NUCLEAR antibodies are produced.

  • Predominant in women in childbearing age. due to estrogen.
26
Q

What three factors can lead to loss of self tolerance in SLE?

A
  1. Genetic Mutations (complement deficiency, and others)
  2. Environmental Factors (UV, infection, chemicals)
  3. Hormonal
27
Q

What are examples of anti-NUCLEAR antibodies produced by SLE patients?

A
  1. Ab to dsDNA
  2. Ab to smith nuclear antigen
  3. Ab to phospholipid

Immunology-Week 3 & 4 (11 decks)

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