Lecture 14/15 T Cell Development Positive and Negative Selection Flashcards Preview

Medical Immunology Bios 443/843 > Lecture 14/15 T Cell Development Positive and Negative Selection > Flashcards

Flashcards in Lecture 14/15 T Cell Development Positive and Negative Selection Deck (40):
1

Where does Class II processing Occur?

In acidic endosomes with Cathepsins S and L being the most important in proteolytic cleavage of peptides.

2

CLIP

Class II associated invariant chain peptide prevents other peptides from binding class II.

3

Why is invariant chain important?

Invariant chain prevents premature binding of peptides to Class II; binds to alpha and beta chains w/clip

4

What enzyme cleaves Invariant chain?

Cathepsin S

5

Class I (exogenous or endogenous)

endogenous

6

Class II (exogenous or endogenous)

exogenous

7

Invariant chain (Ii) (exogenous or endogenous)

exogenous; Ii binds to MHC II and keeps peptides from binding prematurely

8

Lysosomal hydrolases (exogenous or endogenous)

exogenous; endosome and lysosome fuse;

9

TAP1/TAP2 (exogenous or endogenous)

endogenous (associated with Class I only)

10

Transport of vesicles from the ER to the golgi (exogenous or endogenous)

Both Class I and Class II MHC are made in the ER; both MHC II and I are both processed by the golgi

11

Proteosomes (exogenous or endogenous)

MHC I; endogenous

12

phagocytosis (exogenous or endogenous)

exogenous

13

calnexin (exogenous or endogenous)

endogenous Chaperone for MHC I stabilizes class I

14

CLIP (exogenous or endogenous)

exogenous MHC II; associated with invariant chain

15

Tapasin (exogenous or endogenous)

endogenous

16

In what organ to T Cells mature?

Thymus. Thymocytes originate from the bone marrow

17

What are the two different T cell lineages?

ab vs gd

18

EBF, E2A and Pax 5 are the important transcription factors for a progenitor cell to commit to B cell development. What transcription factor is important for T cell commitment?

Notch-1

19

Thymic Cortex

contains cortical epithelial cells; immature thymocytes

20

Thymic medulla

contain medullary epithelial cells; mature thymocytes

21

Nude mouse

Defect in cortical epithelium, so thymus doesn't develop

22

SCID

Severe combined immunodeficiency caused by defect in genes that encode for RAG1/2; VDJ recombination can not occur.

23

DN1

Express CD44 and Kit (Reacts w/SCF)

24

DN2

Express CD44 and now CD25, begin to rearrange b chain of TCR (Db to Jb) become CD44'˚

25

DN3

CD44'˚, Kit'˚, CD25 continue to rearrange b chain (Vb to DJb) and pair with preTalpha

26

DN4

CD44-, CD25-, Pre-T Cell receptor complex w CD3 allows cells to proliferate and to block further b-chain rearrangement.

27

Where does positive selection occur?

Deep cortex; with interaction with thymic cortical epithelial cells expressing MHC interact with DP cells- positive selection takes place.

28

What is the first checkpoint in thymocyte development?

B chain rearrangement; preTalpha signaling; and CD4/CD8 at double negative

29

Positive Selection

Takes place in the Cortext; double positive thymocytes receive survial signals after interacting with specialized APCs in the thymus - Thymic epithelial cells

30

Positive Selection and Thymic environment

T cells are positively selected based on the MHC expressed by Thymic epithelial cells

31

Where does positive selection occur?

By Thymic cortical epithelial cells in the Cortex

32

3 Hypotheses to Explain Transition to single positive thymocytes

1) CD4 or CD8 is turned off randomly, no relation to TCR
2) Interaction between TCR, MHC I, and CD8 instructs cell to differentiate into CD8+ Class I restricted T cell. (and vice versa)
3) Interaction between TCR, MHC II and CD4 in a continuous signal instructs cell to differentiate into CD4+ class II restricted T cell, cell with CD8 gets an interrupted TCR signal and survives with IL-7 signals

33

Where does negative selection occur?

In the medulla, bone marrow derived DCs and Macrophages are the most effective in mediating negative selection; cells that react strongly with self MHC: self peptide combinations are deleted during negative selection; results in tolerance

34

Where do thymocytes become single positive?

Post-positive selection in the cortex.

35

How does tolerance in the periphery occur?

Negative selection in secondary lymphoid organs, regulation by Treg,

36

AIRE

Autoimmune Regulator; a transcription factor that induces the expression of many tissue specific proteins in the medulla on medullary thymic epithelial cells; mutations in AIRE lead to autoimmune disease against a variety of organ-APECED

37

What role does Macrophages play in thymocyte apoptosis?

Macrophages phagocytose thymocytes that have experienced apoptosis.

38

Scid/scid mouse

lack recombination machinery, cannot produce T Cell receptor

39

Nu/nu mouse

lack thymus or thymic epithelial cells, cannot produce T Cells.

40

Where are DN thymocytes found?

Subcapsular region

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