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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
Q

How are Cytotoxic CD8+ T cells activated?

A
  • Activated in the lymph nodes after contact with an antigen-bearing Dendritic Cell
  • Require help from Th1 for activation
    • IL-2
    • IFN-gamma
26
Q

What are the two ways a Cytotoxic CD8+ T-cell gives the target the “kiss of death” or a lethal hit?

A
  • 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
Q

What are the three things that a T-cell must do for successful T-cell Selection?

A
  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
Q

What T cells survive the positive selection process?

A
  • 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
Q

What T cells survive the negative selection process?

A

T cells that do not bind too strongly to self-antigens expressed on MHC molecules

30
Q

What is the process of T cell maturation within the cortex?

(hint: 3 main steps)

A
  • 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
Q

What is the medical significance of MHC polymorphisms?

A
  • 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
Q

Where are most of the polymorphisms in Class I and II MHCs?

A

Cleft region

(antigenic binding site)

33
Q

What are 6 HLA genes that have been linked to specific diseases?

A
  • 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
Q

What HLA gene has been associated with protection against childhood malaria?

35
Q

What molecular interactions take place at the immunological synapse between CD4+ T cells and antigen presenting cells?

A
  • TCR/CD3 → MHC Class II
  • CD4 → MHC Class II
  • CD 28 → CD80 or CD 86 (B7)
  • LFA-1 → ICAM-1
  • CD2 → LFA-3
36
Q

What molecular interactions take place at the immunological synapse between CD8+ T cells and antigen presenting cells?

A
  • 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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