Adaptive Ag Recognition

Question 1

B cell receptor describe.

Answer 1

BCR is composed of four chains two heavy chains and two light chains.
Has no signaling within the receptor itself, they use ITAMs (Igalpha and Ig beta).

Question 2

What is the TCR composed of?

Answer 2

Composed of alpha nad beta chain heterodimer.

CD3 is the invariant protein that ensures signal transduction. The TCR complex is TCR and CD3 proteins.

Question 3

What are the three genes found on BCRs?

Answer 3

Heavy chain and two light chains kappa and lambda

Question 4

What is combinatorial diversity?

Answer 4

Multiple germ line genes that produces a large amount of receptors creating diversity.
Starts with heavy chain locus and recombines the genes V-J for TCR and VDJ for BCR.

Question 5

TCR B and D are analogous to BCR _____.

Answer 5

Heavy chains

Question 6

TCR a and y are analogous to BCR _____.

Answer 6

Light chains (K and L)

Question 7

Describe combinatorial diversity.

Answer 7

Germ line DNA gets somatically recombined at random.
First a “J” is randomly chosen and second a “D”
Then this JD is randomly added with a V. RASS shows RAG-1 and RAG-2 where to cut and are responsible for combining VDJ. TdT catalyze insertion of N and P nucleotides. This creates random unique sequences and is major source of diversity.

Question 8

Significance of frameshifts in Junctional diversity?

Answer 8

Frameshifts can triple the diversity that is generated by VDJ and DJ joining. Diversity from this is generated in the hyper variable region.

Question 9

What chains are made first in BCR and TCR?

Answer 9

Beta chain in TCR and Heavy chain in BCR

Question 10

Light chain/ A chain combinational diveristy?

Answer 10

VJ rearrangement no D.
Uses RSS RAG and TdT.
TdT is not up regulated it uses left over TdT

Question 11

What is the second type of combinatorial diversity?

Answer 11

After both receptor chains have been made successfully the heavy and light are combined randomly, can be mom mom, mom dad, dad dad. A and B combine as well giving extra layer of diversity.

Question 12

overview of lymphocyte maturation?

Answer 12

Stem cell —> prolymphocyte —> Pre-lymphocyte (expresses pre Ag receptors) —-> immature lymphocyte —> lymphocyte subset (distinct T and B subsets) —> mature lymphocytes

NO Ag until immature lymphocyte stage and it is exposed to self Ag.

Question 13

Importance of stromal cells?

Answer 13

Stromal cells express adhesion molecules and cytokines within bone marrow!
They provide IL-7
Stem cell factor and Kit lead to proliferation of early pro B cells.
Stromal cells also look for self reaction.

Question 14

Surface markers for Pro-B?

Answer 14

CD43+
CD19+. **
CD10+

Located in bone marrow, no Ag, Unrecombined Germline DNA due to making the enzymes needed for recombination.

Question 15

What is a Pre-B cell? Markers and location?

Answer 15

Has a heavy chain recombined VDJ and Mu on surface with a surrogate light chain to hold heavy chain in place for interaction with stromal cells.
B220 and CD43+ surface markers, located in bone marrow no Ag

Question 16

Describe Immature B cell.

Answer 16

It has a recombined H chain and K or lambda genes.
Expresses Membrane IgM, surface markers are IgM and CD43+.
Negative selection occurs and receptor editing. After tested against self it moves to spleen and gets tested more.

Question 17

What happens if B cell reacts to self?

Answer 17

If it strongly responds its deleted. If it responds to soluble it becomes anergic and moves to periphery. Also can undergo receptor editing!
it re expresses proteins and makes a second light chain, lambda, it re expresses RAG for rearrangement and gets a second try. If it is not self reactive it undergoes positive selection and survive. Important for development of central tolerance!

Question 18

Describe alternative splicing of heavy chain.

Answer 18

Both IgM and IgD are expressed simultaneously.

Question 19

What is the co b receptor?

Answer 19

CD19, CD81 and CR2(CD21) found on mature naive B cells

BCR markers are IgM IgD and Igalpha and Igbeta.

Question 20

What is AIRE?

Answer 20

Self protein to see if T cells respond to self within the thymus

Question 21

Describe the Pro T cell.

Answer 21

TdT is expressed, the TCR is un-recombined and has surface markers of CD44+ CD25+and C-kit. Located in thymus no Ag.

Question 22

Describe Pre-T cell.

Answer 22

Recombined B chain with a surrogate alpha chain.(Surrogate alpha chain makes this “Pre”) RAG expression
Kit CD44+ CD25+ located in thymus and no AG

Question 23

Double positive T cell.

Answer 23

RAG expression, Recombined beta alpha chain genes, membrane alpha beta TCR expresses CD4+ CD8+ CD3+. Located in thymus and responses to positive and negative selection.

Question 24

Single positive immature T cell.

Answer 24

Recombined beta and alpha chain genes, membrane alpha beta TCR, located in thymus no AG

Question 25

Mature Naive T cell.

Answer 25

Recombined beta and alpha chains, membrane alpha beta TCR, expresses CD4 or CD8 and TCR with CD3. Periphery location and activation to Ag

Question 26

Where are double positive T cells found

Answer 26

Throughout cortex and especially at the corticomedullary junction

Question 27

Where is class I HLA found?

Answer 27

Everywhere. On all nucleated cells.

Question 28

What do T-reg cells express?

Answer 28

CTLA-4 and CD25

Transcription factor FOXP3 allows for this expression