T Cell Receptors & MHC - Diebel Flashcards

1
Q

Th1 CD4+ T Cells:

Polarized by?
Master gene regulator?
Effector cytokines?

A

Polarized by: IL-12, IL-18, IFN-gamma

Master Gene regulator: T-bet

Effector cytokines: IFN-gamma and TNF

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2
Q

Th1 functions

A
  • Cell mediated immunity
  • IFN gamma polarized macs into M1, activates, and attracts them.
  • inflammation
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3
Q

Th2 CD4+ T cells:

Polarized by?
Master gene regulator?
Effector cytokines?

A

Polarized by: IL-4

MGR: GATA3

Effector cytokines: IL-4, IL-5, IL-13

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4
Q

Th2 functions

A

-IL-4 and IL-13 polarize macs into M2 (for healing) , activates, and attracts them.

IL-4 and IL-5 attract eosinophils

Allergic and anti-helminth responses

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5
Q

Th17 CD4+ T cell

Polarized by?
Master gene regulator?
Effector cytokines?

A

Polarized by: IL-1, IL-6, IL-23, TGF-beta

MGR: ROR-gamma-t

Effector cytokines: IL-17, IL-22

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6
Q

Th17 Function

A

-IL-17 and IL-22 attract and activate multiple inflammatory cells

More intense than Th1
**Th17 are in mucosal surfaces
Th1 are in tissues/under skin

-implicated in autoimmune diseases (yikes)

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7
Q

Tfh CD4+ T cells

Polarized by?
Master gene regulator?
Effector cytokines?

A

Polarized by: IL-6, IL-21

MGR: Bcl-6

Effector cytokines: IL-4, IL21

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8
Q

Tfh Functions:

A

B cell help in germinal centers

Help B cells that have regonized antigen become activated and differentiate into plasma cells

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9
Q

Treg CD4+ T cells

Polarized by?
Master gene regulator?
Effector cytokines?

A

Polarized by: IL-2, TGF-beta

MGR: FOXP3

Effector cytokines: IL-10, TGF-beta

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10
Q

Treg Function

A

Suppress Th1, Th2, Th17, Tfh by contact and soluble factors like IL-10 and TGF-beta

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11
Q

CD8+ Killer T cells

A

Once activated (in lymph nodes), they scout for surface antigens out in the periphery that can bind their surface receptor –> kill the cell

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12
Q

CD8+ kills cell in two ways:

A
  1. Activated Fas receptor on target cell –> starts apoptosis pathway
  2. Secretes granzymes and perforins which trigger apoptosis and poke holes in membrane, respectively.
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13
Q

CD8+ cell need help from what to get activated?

A

Th1!

IL-2 for driving proliferation

IFN-gamma to drive activation

Thanks Th1 :)

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14
Q

Positive Selection:

A
  • Want to select a T cell witha TcR with intermediate affinity to MHC molecules.
    It needs to recognize MHC molecules to get selected to become mature
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15
Q

Negative Selection

A
  • TcR should NOT bind to self antigens

- if they do they get killed. (sucks to suck)

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16
Q

When do APCs express their surface molecules?

DCs:

Macs:

B cells:

A

DC: ALWAYS expressing MHC II molecules and B7/other costimulartory molecules

Macs: need to be ACTIVATED by phagocytosis to express MHC II and any costimulatory molecules

B cells: Always express MHC II
- need to be activated by antigen binding Ab to express costimulatory molecule

17
Q

TcR structure

A

2 chains- Alpha and beta (or gamma and delta)

  • Each alpha and beta has a constant and variable portion.
  • Receptor made out of V, D, and J regions of T CELL genes

***BOTH chains have transmembrane domains

18
Q

What does CD3 do?

A

associated with TCR and transduces TCR signals for T cell.

19
Q

CD4+ and APC immunological synapse

CD4+ —–> APC

A

CD4+ ————> APC

CD2    ----------> LFA-3
TCR/CD3------> MHC II 
CD4    ----------> MHC II 
CD28  -----------> CD80/86 (B7-1/2)
LFA-1   -----------> ICAM-1
20
Q

CD8+ and APC immunological synapse

CD8+ —–> APC

A

CD8+ ————> APC

CD2    ----------> LFA-3
TCR/CD3------> MHC I 
CD8    ----------> MHC I 
CD28  -----------> CD80/86 (B7-1/2)
LFA-1   -----------> ICAM-1
21
Q

Alpha chain (like the light chain)

A

Encoded by V, J, and C gene segments

rearrangement –> VJ combo attached to SINGLE C segment

22
Q

Beta chain (like heavy chain)

A

Encoded by V,D,J and C gene segments

Rearrangement –> VDJ combo attached to one of two C gene segments

23
Q

TCR rearrangement is basically the same as Ab stuff we learned:

What is different?

A

Same: Use RAGs to put together VDJ, do some somatic mutation by TdT and putting some nucleotides in the junction parts.

Different: NO somatic hypermutations.

24
Q

T Cell Selection, they must:

A
  1. Not recognize self
  2. Not recognize free antigen
  3. Recognize antigenic peptide plus self MHC
25
Q

How many different MHC I and MHC II can one person express?

A

6 different MHC I

12 different MHC II

26
Q

MHC I

A

Has alpha chain that is membrane bound and is 3 domains long, 1 beta to interact with the alpha ==6 different possibilities.

Subclasses: A, B , C

27
Q

MHC II

A

Alpha part has 2 subunits
Beta has 2 subunits
Both are membrane bound

Subclasses: DP, DQ, DR

28
Q

MHC Polymorphisms

A

Many known alleles for each classical Class I and Class II locus

  • Most are in cleft region (antigenic binding site)
  • Makes us each individual
29
Q

HLA-B27 polymorphism

A

Ankylosing spondylitis (90x more likely)

also: psoriasis, IBD, Reiter’s syndrome

30
Q

HLA-DR2

A

Narcolepsy (130x more likely)

Also: MS, hay fever, SLE

31
Q

HLA-A3/B14

A

Hemochromatosis (90x)

32
Q

HLA-DQ2/GQ8

A

Celiac disease

33
Q

HLA-DR3

A

Diabetes mellitus type I

Grave’s Disease

34
Q

HLA-DR4

A

Rheumatoid arthritis

Diabetes mellitus type I

35
Q

HLA-B53

A

GOOD!

Protection against childhood malaria