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IHO Week 3 - WLB > T-cell Receptors and MHC Complex - Diebel > Flashcards

T-cell Receptors and MHC Complex - Diebel Flashcards

1
Q

What are the 6 different kinds of T-cells that are important for immune function?

A
  • Th1
  • Th2
  • Th17
  • <span>T</span>reg
  • TFH
  • CD8+
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2
Q

What do most helper T-cells begin as?

A

Undifferentiated precursor Th0

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3
Q

What are the main determinants of the precursor T-cell’s ultimate progeny?

A
  • Previous experience of the Dendritic cell that presents the correct antigen
    • conditions in the periphery
    • what TLR was engaged
    • what cytokines/chemokines predominated
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4
Q

What surface proteins (CD molecules) are important in the interaction between the Dendritic Cell when it presents the MHC Class II antigen to a T-cell?

A
  • Dendritic cell
    • MHC Class II receptor
    • CD 80/86 (B7)
    • other costimulatory molecules
  • T-cell
    • CD4 (interacts with MHC II)
    • CD3
    • CD 28 (interacts with CD 80/86)
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5
Q

What cytokines produced by the APC polarize Th0 to become Th1?

A
  • IL-12
  • IL-18
  • IFN-gamma
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6
Q

What is the master transcriptional regulator of Th1 cells?

A

T-bet

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7
Q

What effector cytokines do Th1 cells make?

A
  • Lymphokines
    • IFN-gamma
    • TNF-beta
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8
Q

What are the main functions of Th1 cells?

A
  • cell-mediated immunity
  • inflammatory response
  • IFN-gamma release:
    • polarizes macrophages to activate into M1 “Angry” macrophages and attract them to the site of infection
    • pro-inflammatory
    • chemotactic agent
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9
Q

What cytokines produced by the APC polarize Th0 to become Th17?

A
  • TGF-beta
  • IL-1
  • IL-6
  • IL-23
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10
Q

What is the master transcriptional regulator for Th17 cells?

A

ROR-gamma-t

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11
Q

What effector cytokines do Th17 cells make?

A
  • IL-17
  • IL-22
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12
Q

What are the main functions of Th17 cells?

A
  • Biggest role in maintaining the integrity of mucosal surfaces
  • IL-17 and IL-22 attracts and activates multiple inflammatory cells
    • aggressively proinflammatory
    • activation of M1 Angry macrophages at the site of infection
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13
Q

What cytokines produced by the APC polarize Th0 to become Th2?

A
  • IL-4
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14
Q

What is the master transcriptional regulator of Th2 cells?

A

GATA3

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15
Q

What effector cytokines do Th2 cells make?

A
  • IL-4
  • IL-5
  • IL-13
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16
Q

What are the main functions of Th2 cells?

A
  • IL-4 and IL-13 polarize macrophages into M2 Healing/Repair macrophages, activates/attracts them
  • IL-4 and IL-5 attract eosinophils
  • Allergic and anti-helminth responses
  • Also give rise to Th2-like follicular helper T cells (Tfh) → lymphoid follicles → release IL-4 → B-cell switch from naïve IgM/IgD → IgE
17
Q

What cytokines produced by the APC polarize Th0 to become Treg?

A
  • IL-2
  • TGF-beta
18
Q

What is the master transcriptional regulator for Treg cells?

19
Q

What effector cytokines do Treg cells make?

A
  • IL-10
  • TGF-beta
20
Q

What are the main functions of Treg cells?

A
  • Suppress the activation and function of Th0, Th1, Th2, Th17, and Tfh by contact and soluble factors
    • IL-10 & TGF-beta
21
Q

What cytokines produced by the APC polarize Th0 to become TFH?

A
  • IL-6
  • IL-21
22
Q

What is the master transcriptional regulator of Tfh cells?

23
Q

What effector cytokines do Tfh cells make?

A
  • IL-4
  • IL-21
24
Q

What are the main functions of Tfh cells?

A
  • Migrate into the follicles (germinal centers) of the cortex
    • help B cells that have recognized the antigen become activated and differentiate into antibody-secreting plasma cells
    • cytokines direct the B cells to switch from secreting IgM to IgG, IgA, or IgE
25
How are Cytotoxic CD8+ T cells activated?
* Activated in the lymph nodes after contact with an antigen-bearing Dendritic Cell * Require help from Th1 for activation * IL-2 * IFN-gamma
26
What are the two ways a Cytotoxic CD8+ T-cell gives the target the "kiss of death" or a lethal hit?
* Engage death receptor = Fas (CD95) * CD8+ T-cells have Fas ligan (CD95L) * cross-linked Fas acitvates latent apoptosis pathway * Secrete the contents of "lytic granules" = granzymes, perforins, & selective proteases that trigger apoptosis
27
What are the three things that a T-cell must do for successful T-cell Selection?
1. **Not recognize "self"**: cannot bind so firmly to a self structure that the T-cell becomes activated (this would be autoimmunity) 2. **Not recognize free antigen** (which is antibody's job) 3. **Recognize antigenic peptide plus self MHC** (This repertoire is selected within the thymus.)
28
What T cells survive the positive selection process?
* T-cells that have the appropriate (intermediate) affinity co-receptor * T cells have successfully rearranged their TCRα locus and are capable of recognizing peptide-MHC complexes with appropriate affinity
29
What T cells survive the negative selection process?
T cells that do not bind too strongly to self-antigens expressed on MHC molecules
30
What is the process of T cell maturation within the cortex? (hint: 3 main steps)
* FIRST: Lymphoid pre-cursor cells develop a functional pre-TCR with an invariant alpha chain and a functional beta chain * SECOND: Positive selection checks that T cells have successfully rearranged their TCRα locus and are capable of recognizing peptide-MHC complexes with appropriate affinity. * THIRD: Negative selection in the medulla then obliterates T cells that bind too strongly to self-antigens expressed on MHC molecules. * These selection processes allow for tolerance of self by the immune system. * Typical T-cells that leave the thymus (via the corticomedullarly junction) are self-restricted, self-tolerant, and singly positive.
31
What is the medical significance of MHC polymorphisms?
* Polymorphism * gives us our unique identity * permits the recognition of self vs. non-self * is an impediment to organ transplant * affects the ability to make an immune response * affects the resistance or susceptibility to infectious diseases * affects the susceptibility to autoimmune disease & allergies
32
Where are most of the polymorphisms in Class I and II MHCs?
Cleft region | (antigenic binding site)
33
What are 6 HLA genes that have been linked to specific diseases?
* HLA-B27 → ankylosing spondylitis, psoriasis, IBD, Reiter's syndrome * HLA-DR2 → narcolepsy, MS, hay fever, SLE * HLA-A3/B14 → hemochromatosis * HLA-DQ2/GQ8 → celiac disease * HLA-DR3 → DM Type I, Grave's disease * HLA-DR4 → RA, DM Type I
34
What HLA gene has been associated with protection against childhood malaria?
HLA-B53
35
What molecular interactions take place at the immunological synapse between CD4+ T cells and antigen presenting cells?
* TCR/CD3 → MHC Class II * CD4 → MHC Class II * CD 28 → CD80 or CD 86 (B7) * LFA-1 → ICAM-1 * CD2 → LFA-3
36
What molecular interactions take place at the immunological synapse between CD8+ T cells and antigen presenting cells?
* TCR/CD3 → MHC Class I * CD8 → MHC Class I * CD28 → CD80 or CD86 (B7) * LFA-1 → ICAM-1 * CD2 → LFA-3

IHO Week 3 - WLB (10 decks)

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