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Immunology > Lec 1 Final > Flashcards

Lec 1 Final Flashcards

1
Q

What is immunologic tolerance?

A

The unresponsiveness of the immune system to an antigen (tolerogen)

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2
Q

Why is immunologic tolerance particularly important when dealing with self-antigens?

A

It protects against autoimmunity (autoimmune diseases).

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3
Q

What are the types of immunologic tolerance?

A

1- Central tolerance
2- Peripheral tolerance

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4
Q

How are self-antigens presented to the immune system?

A

1- locally in the primary lymphoid organs
2- Imported after their capture from the periphery.

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5
Q

When is peripheral tolerance used?

A

Peripheral tolerance is used when the self-antigen is not presented in the primary lymphoid organ or when the self-antigen is expressed only in adult life.

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6
Q

What happens to self-reactive lymphocytes in peripheral tolerance?

A

1- apoptosis (programmed cell death)
2- anergic (unresponsive)
3- actively suppressed by regulatory T (Treg) cells.

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7
Q

How does sequestration of self-antigens in immune-privileged areas prevent immune responses?

A

By keeping self-antigens away from the immune system

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8
Q

Where does negative selection occur in the thymus?

A

1- Double-positive (DP) T cells ➡️ Cortex
2- Single-positive (SP) T cells ➡️ Medulla.

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9
Q

What happens if a thymocyte’s T cell receptor (TCR) recognizes a self-antigen-HLA complex on an antigen-presenting cell with STRONG SIGNAL

A

It leads to clonal deletion.

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10
Q

What happens if a thymocyte’s T cell receptor (TCR) recognizes a self-antigen-HLA complex on an antigen-presenting cell with WEAKER SIGNAL

A

formation of regulatory T (Treg) cells, which are released to the periphery and mediate peripheral tolerance.

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11
Q

What are the pathways of programmed cell death (apoptosis) ?

A

The intrinsic (mitochondrial) pathway - The extrinsic (death receptor) pathway

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12
Q

The intrinsic (mitochondrial) pathway is related to . . . ?

A

Central tolerance

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13
Q

The extrinsic (death receptor) pathway is related to . . . ?

A

Peripheral tolerance

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14
Q

The intrinsic (mitochondrial) pathway is regulated by . . . ?

A

Bcl-2 family proteins, such as Bim

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15
Q

Explain the process of the intrinsic (mitochondrial) pathway

A

Bcl-2 family proteins, such as Bim will oligomerize and insert into the outer mitochondrial membrane, leading to the leakage of mitochondrial cytochrome c. This activates caspase-9, which then causes fragmentation of cellular DNA and cell death.

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16
Q

Explain the process of the the extrinsic (death receptor) pathway

A

It involves the binding of the Fas ligand (FasL) to the Fas (CD95) receptor, which activates caspase-8 and eventually leads to apoptosis.

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17
Q

What is co-stimulation in T cell activation?

A

Co-stimulation involves the binding of CD28 on T cells to B7-1 (CD80) and B7-2 (CD86) on antigen-presenting cells (APCs).

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18
Q

How does anergy occur?

A

1- blockage of TCR-induced signal transduction
2- Ubiquitination
3- Activation of inhibitor receptors of the CD28 family, including CTLA-4 and PD-1.

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19
Q

How does CTLA-4 function in T cell tolerance?

A

1- competing with CD28
2- endocytosis of the corresponding B7 molecule.

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20
Q

How does PD-1 function in T cell tolerance?

A

By phosphatase activity that inactivates immune receptors.

21
Q

What are Treg cells?

A

Treg cells are CD4+ T cells that suppress immune responses.

22
Q

What are the characteristic features of Treg cells?

A

1- Express high levels of the IL-2 receptor α chain (CD25)
2- FoxP3 transcription factor.

23
Q

Name the divisions of Treg cells based on their mode of formation?

A

1- Thymic Treg (tTreg) cells
2- Peripheral Treg (pTreg) cells.

24
Q

peripheral Treg (pTreg) cells known as … ?

A

Known as adaptive or inducible Tregs

25
Q

Factors that enhance regulatory T cell (Treg) formation include

A

IL-2 - TGF-β - Retinoic acid

26
Q

How Treg cells, through CTLA-4, can reduce the responsiveness of antigen-presenting cells (APCs) to T cells ?

A

Treg cells reduce the amount of B7 on APCs and thus decrease their responsiveness to T cells

27
Q

What is the function of IL-10 ?

A

Inhibit the formation of IL-12 (and thus IFNγ), MHC class II molecules as well as costimulators

28
Q

The portal of entry for tolerogenicity is within the intradermal ( T or F )

A

False

29
Q

Adjuvants are present in immunogenicity ( T or F )

A

True

30
Q

Where does central tolerance occur in B cell development?

A

Central tolerance occurs in the bone marrow.

31
Q

What happens if immature B cell is highly self-reactive (strong signal)

A

Receptor editing

32
Q

What happens if the editing attempts of a self-reactive B cell fail?

A

Apoptosis

33
Q

What happens if a self-reactive B cell receives a weak signal?

A

Anergy

34
Q

What is the inhibitory receptor in the peripheral tolerance of B cells?

A

CD22, FcγRIIB

35
Q

What are the two types of autoimmune diseases?

A

Autoimmune diseases can be either systemic or organ-specific.

36
Q

Give an example of a systemic autoimmune disease.

A

Systemic lupus erythematosus (SLE)

37
Q

Provide examples of organ-specific autoimmune diseases.

A

Myasthenia gravis, type 1 diabetes, and multiple sclerosis.

38
Q

Which gene is associated with ankylosing spondylitis?

A

The MHC gene HLA-B27

39
Q

How does deficiency in complement proteins contribute to autoimmunity?

A

Deficiency in complement proteins can reduce immune complex clearance and lead to lupus-like autoimmune diseases.

40
Q

Which autoimmune diseases are associated with CD25 gene variants?

A

Multiple sclerosis and type 1diabetes

41
Q

Which autoimmune diseases are associated with IL-23R?

A

Psoriasis or Crohn’s disease

42
Q

What is the role of the AIRE protein in autoimmunity?

A

The AIRE protein is involved in the expression of peripheral self-antigens in the thymus.

42
Q

What are some characteristics of single gene defects in autoimmunity?

A

1- clearer pathogenic mechanisms
2- higher penetrance
3- less interplay with the environment to cause diseases.

43
Q

Defects in AIRE protein will lead to ?

A

Autoimmune polyendocrine syndrome type 1 (APS1)

44
Q

What is the significance of autoantibodies against IL-17 in APS1 patients?

A

Autoantibodies against IL-17 in APS1 patients make them susceptible to fungal infections.

45
Q

Defects in Fas/FasL will lead to ?

A

Autoimmune lymphoproliferative syndrome (ALPS)

45
Q

Defects in CTLA-4 will lead to ?

A

Systemic inflammatory diseases

46
Q

Defects in IL-10R will lead to ?

A

Colitis

47
Q

Rheumatic fever is an example of ?

A

Molecular mimicry

Immunology (2 decks)

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