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PATH 415 > T Lymphocytes > Flashcards

T Lymphocytes Flashcards

1
Q

What are the basic characteristics of TCR?

A
  1. Are membrane receptors & not secreted
  2. Responsible for specific Ag recognition in the adaptive immune system
  3. Distinguish & bind to a large number of Ags
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2
Q

What is the structure of TCR?

A
  1. Consist of alpha and beta chain, recognize Ag
  2. Each chain contains a V and C region
  3. TCR Complex = TCR + CD3 complex
    - TCR cytoplasmic tails are too short hence require CD3 for signal transduction (CD3 chains have long cytoplasmic tails)
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3
Q

What is the purpose of VDJ recombination?

A

Different VDJ combinations result in different specificities, allowing lymphocyte diversity

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4
Q

CD4 T cells recognize what class of MHC?

A

Class II

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5
Q

CD8 T cells recognize what class of MHC?

A

Class I

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6
Q

What is TCR binding specific for?

A

Peptide and MHC

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7
Q

How many kinds of peptide-MHC complexes on APC are T cells specific for?

A

1 - Monogamy relationship

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8
Q

Define the functions of the key accessory molecules of T lymphocytes and their corresponding ligands.

A
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9
Q

What is a T cell accessory molecule?

A

Participates in Ag responses but are not the receptors for Ag

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10
Q

What is the function of CD3?

A

Signal transduction by TCR complex

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11
Q

What is the function of CD4?

A

Signal transduction

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12
Q

What is the ligand for CD4 and where is the ligand expressed on?

A

Class II MHC
Expressed on APCs

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13
Q

What is the function of CD8?

A

Signal transduction

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14
Q

What is the ligand for CD8 and where is it expressed on?

A

Class I MHC
Expressed on APCs, CTL target cells

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15
Q

What is the function of CD28?

A

Costimulation of naive T cells

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16
Q

What is the ligand for CD28 and where is it expressed on?

A

B7-1/B7-2
Expressed on APCs

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17
Q

*What is the function of CTLA-4?

A

Negative regulator of T cell activation

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18
Q

What is the ligand for CTLA-4 and where is it expressed on?

A

B7-1/B7-2
Expressed on APCs

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19
Q

What is the function of CD-2?

A

Signal transduction & ADHESION

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20
Q

What is the ligand for CD-2 and where is it expressed on?

A

LFA-3
Hematopoietic & non-hematopoietic cells

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21
Q

What is the function of LFA-1?

A

Adhesion

22
Q

What is the ligand for LFA-1 and where is it expressed on?

A

ICAM-1
APCs, Endothelium

23
Q

What is the function of VLA-4?

A

Adhesion

24
Q

What is the ligand for VLA-4 and where is it expressed on?

A

VCAM-1 and fibronectin

Endothelium

25
Q

Where are the co-stimulators in T cell activation found?

A

APC surface

26
Q

What is the function of costimulators?

A

Provides stimulus (2nd signal) for activation of naive T cells, in addition to Ag recognition (1st) signal)

27
Q

What are the co-stimulators in T cell activation?

A

B7-1 (CD80) and B7-2 (CD86) molecules:
1. Best defined co-stimulator on APC
2. Bind to CD28 (expressed on all T cells)

28
Q

Can resting APCs activate naive T cells?

A

No

29
Q

When are cytokines produced? What is the function of cytokines?

A

Produced during innate immune responses to microbes and induces expression of co-stimulator on APC

30
Q

*What is the co-stimulation requirement?

A

Ensures that naive T cells are activated fully by microbial Ag, not by harmless substances

31
Q

What does CD40 ligand bind to?

A

CD40 ligand (CD40L) binds to CD40 on APC

32
Q

What happens when CD40L (CD154) binds to CD40?

A

APC expresses more B7 co-stimulator & secretes cytokines (ex. IL-2) that enhance T cell differentiation.

CD40L-CD40 interaction allows APC to better stimulate T cells

33
Q

What is required for the sustained expression of CD40L?

A

B7-CD28 as well as Ag

B7 and CD40 pathways stimulate each other

34
Q

What is the clinical relevance of costimulation?

A
  1. RA Therapy - blocks B7:CD28 unwanted response
  2. Abs blocking CD40:CD40L - reduce/prevent graft rejection in transplant recipients
  3. Tumour therapy - enhances co-stimulator expression
  4. CTLA-4 is induced in activated T cells and binds B7 on APC which is critical for limiting & terminating immune responses
    - a deletion in the gene will result in excessive lymphocyte expansion & autoimmune disease
35
Q

What is the first signal in T cell activation?

A

Ag recognition by TCR

36
Q

What is the second signal in T cell activation?

A

Interactions of T cell accessory molecules with their ligands on APC

37
Q

What determines the outcome of T cell activation?

A

Duration and affinity of TCR-Ag interaction

38
Q

What are the different subsets of T cells and what kind of effector cells do they differentiate into? State the functions of these effector cells.

A

Naive CD4 becomes T helper cell (Th cell)
- Produce cytokines
- Promote Ab production (HUMORAL IMMUNITY) or macrophage killing of ingested microbes (CELL MEDIATED IMMUNITY)

Naive CD8 becomes cytotoxic T-lymphocyte (CTL)
- Directly kill cells harboring microbes (virus/bacteria) in the cell cytoplasm

39
Q

How does cytotoxic T lymphocytes cause a cell to undergo apoptosis?

A
  1. Requires contact with target cell
  2. Deliver PERFORIN and GRANZYME B into the target cll
  3. Granzyme B triggers an enzymatic chain reaction inside the target cell that causes the cell to commit suicide by apoptosis
40
Q

What does T helper 17 (Th17) secrete?

A

IL-17 as key cytokine

41
Q

What are the effector functions of Th17?

A
  1. Host defence against some bacteria and fungal infections
  2. Promote recruitment of neutrophils & monocytes
42
Q

Where do regulatory T cells develop? What are their functions?

A

Develop in the thymus (major) or peripheral lymphoid organs

Functions:
1. Block activation of potentially harmful lymphocytes specific for self Ags
2. Control autoimmunity, allergic & inflammatory reactions and responses to infectious agents and tumors

43
Q

Is the development of T cell subsets a random process? What is it regulated by?

A
  1. Development of Th1, Th2, Th17 and Tregulatory subsets is NOT a random process
  2. Regulated by the stimuli that naive CD4+ T cells receive when encountering microbial Ag (via initial innate response)
44
Q

What is the development stimulus for the different T cell subsets?

A

Th1 - IL-12 & IFN-gamma
Th2 - IL4
Th17 - IL-6, IL-1beta, IL-23, TGF-beta
Tregulatory - IL-2 & TGF-beta

45
Q

What are the cytokines produced by the different T cell subsets?

A

Th1 - IFN-gamma
Th2 - IL4
Th17 - IL-17 & IL-22
Tregulatory - IL-10 & TGF-beta

46
Q

What are the effector functions of the different T cell subtypes?

A

Th1
- Host defence against intracellular microbes
- Inflammation

Th2
- Defend against extracellular microbes
- Stimulate B cells

Th17
- Host defence against infections
- In tissue inflammation during autoimmunity: MS, RA, IBD

Tregulatory
- maintenance of self-tolerance

47
Q

What happens after infection is cleared?

A
  1. Proliferated cells are deprived of survival signals (Ag, CD28, IL-2)
  2. Cells die by apoptosis
  3. T cell response subsides within 1-2 weeks
  4. Only surviving memory lymphocytes remain
48
Q

What does CTLA-4 stand for?

A

cytotoxic T-lymphocyte associated protein 4

49
Q

Which has higher affinity for B7-1 and B7-2, CTLA-4 or CD28?

A

CTLA-4

50
Q

What does Ipilimumab do?

A

Blocks CTLA-4 for unresectable/metastatic melanoma

PATH 415 (10 decks)

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