Lymphopoeisis

Question 1

Lymphocyte production areas

Answer 1

Young fetus: liver and spleen

Late fetus-on: bone marrow

Question 2

General Outline of B cell hematopoeisis

Answer 2

HSC -> CLP (not CMP) -> Pro-B (not T lineage) -> Early Pre-B -> Late Pre-B -> Immature B cells

Question 3

2 Proliferative Steps in B Cell Hematopoeisis

Answer 3

CLP -> ProB and Early Pre-B -> Late Pre-B

Question 4

True B Cells

Answer 4

Actively involved with synthesizing intact Ig, Immature B cells are the first ones

Question 5

2 Cell Surface Markers on Pro-B that Identify As B (and function)

Answer 5

CD19 - costimulatory of B cells

CD45R - phosphatase to maintain signalling pathway

Question 6

2 Rag Activity Steps in B Hematopoeisis

Answer 6

ProB and Early PreB: VDJ of HC to create HC mu

Late PreB and Immature B: VJ of LC to create LC lambda and kappa

Question 7

B Cell Hematopoeisis Checkpoint

Answer 7

Between Early/Late Pre-B. Surrogate LC has to bind to HC expressed on surface and form preBCR which can signal. Extent of preBCR formation dictates clonal proliferation. It also turns off Rag and SL, but as SL decreases, so does preBCR, so Rag turns on again at Late Pre-B/Immature B transition for LC recombination

Question 8

2 Parts of Surrogate LC

Answer 8

VreB - equivalent to V of LC

lambda5 - C of LC

Question 9

Bone Marrow Stroma Proliferative Effects

Answer 9

Release cytokines/other factors which bind to c-kit and IL-7R on Pro-Bs to drive proliferation at low levels. C-kit is lost for PreBs though because it wants preBCR to be the main driver of proliferation

Question 10

2 Differences b/w Immature and Mature B Cells

Answer 10

Just IgM vs. IgM and IgD

Most autoreactive vs. most not

Question 11

2 B Cell Tolerance Mechanisms

Answer 11

Self Ags exposed, if react strongly just undergo clonal deletion/death, if react weakly undergo receptor editing to salvage - turn LC recomb back on until it either dies or is no longer self reactive

Question 12

3 Types of B Cells

Answer 12

B-1: Fetal/neonatal, first line of defense good at responding to common bacterial pathogens but can cause leukemias
B-2: Normal Bs
Marginal Zone (MZ) Bs: in white pulp of spleen, good at responding very quickly to common Ags on bloodborne pathogens (1st line of defense there)

Question 13

3 Steps of T Cell Development and Location

Answer 13

Commitment - rearrangement/expression of TCR - subcapsular region
TCR Pos/Neg Selection - TCR repertoire established - cortex
Maturation - produce functional CD4/8 Ts - medulla

Question 14

2.4 Cellular Components of Thymus

Answer 14

Thymocytes - developing T cells
Stroma which produce necessary signals: Nonlymphoid (fibroblasts, epithelial, pos selection) and lymphoid (dendritic cells neg selection, macs)

Question 15

Hassall’s Corpuscles

Answer 15

In thymus to get rid of dead/dying cells

Question 16

DiGeorge Syndrome

Answer 16

Thymic aplasia, don’t ever develop it so you don’t get T cell production really

Question 17

T Cell Development, CD4/8 Containing Aspects, and Proliferation

Answer 17

Proliferate from precursors to double negs in subcapsular
Proliferate to double pos for R selection in cortex
Heavily selected against so numbers drop to medulla and only CD4+ or CD8+

Question 18

2 Effects of IL-7

Answer 18

Stimulates bone marrow precursor cell to Tc (and also can stimulate that to a TCRgamma/delta) during commitment

Question 19

TCR Recombination

Answer 19

Gamma and beta on different chroms, just need to recombine VJ
Alpha/delta on same chrom, either no alpha rearragement or it deletes delta

Question 20

3 TCR alpha/beta and gamma/delta differences

Answer 20

More adaptive vs. innate
More numerous vs. less
Peripheral lymphoid tissues vs. GI/resp

Question 21

Beta Selection

Answer 21

Ensures a lot more alpha/beta by only needing one rearragement (beta) and then undergoing second round of intense proliferation with a productive arragement

Question 22

X-Linked Severe Combined Immunodeficiency Disease (X-SCID)

Answer 22

Failed IL-7 signaling gives shitty cytokine R gammac sub, necessary for IL Rs including IL-2, and so no T or NK cells

Question 23

3 Important Aspects of Commitment

Answer 23

IL-7 dependent expansion of precursor cells
Rearragement of TCR beta/gamma/delta genes
Second wave of expansion for Ts w/ TCRbeta mediated by pre-TCR (beta selection)

Question 24

Positive and Negative Selection in General

Answer 24

Positive: only Ts which bind MHC can live or else death by neglect
Negative: Ts that bind too strongly killed.
Together get only weakly bound, self tolerant Ts

Question 25

CD4/CD8 Selection

Answer 25

Exposed to epithelial MHCs. If weakly recognizes MHC II, Th-POK produced to cause CD4>CD8. If weakly recognizes MHC I, no Th-POK produced and CD8>CD4. If no binding, death by neglect. If strong binding (later against DC-presented self Ags), negative selection and death.

Question 26

2 Sources of Negative Selection

Answer 26

DCs/Macs presenting broken down self peptides
Thymic medullary epithelial cells expressing autoimmune regulator (AIRE), a transcriptional activator which produces tons of tissue-specific prots like insulin

Question 27

MHC Restriction

Answer 27

Result of positive selection - if that CD doesn’t bind, it’s not gonna be that kind of mature cell

Question 28

Bare Lymphocyte Syndrome

Answer 28

Lack of MHC II expression on thymic epithelial cells and APC, so no positive selection and no mature CD4+ Ts for generalized immunosuppression

Question 29

Treg Function

Answer 29

To inhibit autoreactive Ts that escape neg selection via inhibitory cytokines (IL-10, TGFbeta) and inhibitory Rs (CTLA4)

Question 30

Treg Production

Answer 30

Stimulated by *IL-2R and depend on transcription factor Foxp3

Question 31

X-Linked Autoimmune Immunodeficient Syndrome

Answer 31

Foxp3 gene mutation so no Tregs and multiorgan inflammatory infiltrates cause wasting away

Question 32

4 Aspects of Thymocyte Maturation

Answer 32

Express only CD4 or 8
Increase TCR
Acquire functional potential (CTL or cytokine secretion)
Acquire homing Rs necessary to leave thymus and enter tissues