Lymphocyte differentiation in central lymphoid organs

Question 1

where do lymphocytes originate from

Answer 1

pluripotent hematopoietic stem cells of bone marrow

Question 2

what happens to the lympocytes that differentiate in bone marrow, and those that go to thymus

Answer 2

B cells
T cells

Question 3

what kind of lymphoid organs are Bone marrow nd thymus

Answer 3

central/primary

Question 4

what is antigen independant differentiation

Answer 4

immature lymphocytes build their receptors for antigen (become immunocompetent)

Question 5

what kind of genes do germline DNA NOT contain

Answer 5

• doesn’t contain ready made genes for variable parts of Igs + TCR chains
• has numerous tandemly arranged gene fragments. the random combos produces the genes for variable parts

Question 6

What is VDJ recombination

Answer 6

cutting and joining together DNA fragments

Question 7

WHat is the light Ig chain and TCR chain made from
what is the heavy chain and TCR β chain made from

Answer 7

• 2 fragments: V + J (respectively)
• 3 fragments: V, D + J (respectively)

Question 8

How is additional diversity created

Answer 8

enxyme: terminal deoxynucleotidyl transferase (Tdt)

inserts single random nucleotides btw fragments

Question 9

Red bone marrow + location

Answer 9

main hematopoietic organ (except in embryo + foetus)

Located in spongy bones, filling spaces btw bone trabeculae

Question 10

what is the stroma of the bone marrow

Answer 10

(connective tissue from mesynchymal cells)
- provides microenvironment for blood cell differentiation

• formed by stromal/ reticular cells cos the fibres prod by them form 3D network

Question 11

what do hematopoietic stem cells give rise to

Answer 11

lymphoid stem cell / common lymphoid progenitor

Question 12

some lymphoid stem cells become pro B cells which poliferate and differnetiate. what the most imp elemt of B cell differentiation

Answer 12

become immunocompetent (building antigen receptor)

Question 13

Pro B cells will rearrange heavy chain genes - D J then VDJ. What is allelic exclusion

Answer 13

if first rearrangement successful,

the cell will use only the rearranged chromosome and will not touch its homologue.

Question 14

why does first rearrangement become unsuccessful. what happens after

Answer 14

• if frameshift / early stop codon obtained
• cell then tries to rearrange 2nd chromosome, if fail again then it will commit apoptosis

Question 15

what happens to successful pro B cells

Answer 15

They synthesize class mu heavy chain. It remains in the
cytoplasm

Question 16

What do Pre B cells rearrange
what happens with failure

Answer 16

VJ of light chain gens starting with Kappa. success leads to allelic exclusion.

• failure: homologous chromosome rearranged.
• if both kappa attempts fail, lambda genes tried

Question 17

what happens when cells acquires light chain

Answer 17

it expresses IgM receptor on its surface and becomes
an immature B cell. It is immunocompetent.

Question 18

Immature B cells are checked for eventual
reaction of their IgM receptor with a normal
tissue component called what

Answer 18

autoantigen

Question 19

B lymphocytes that react with autoantigens are called what

Answer 19

self reactive / autoreactive

Question 20

what do autoreactive cells do. what is the proccess called

Answer 20

Receptor editing - the cells receive a signal to correct
themselves. They reactivate their V(D)J
recombination machinery and attempt to
produce other, better antibody chains.

Question 21

what happens when B cell gets good Ig receptor

Answer 21

allowed to leave the bone marrow for the
periphery.

Question 22

what happens to B cells that fail in getting Ig receptor

Answer 22

undergo apoptosis = negative selection (ridding self reactive lymphocytes)

Question 23

where is the thymus located

Answer 23

cranially from the heart and behind the
sternum. It is composed of two identical lobes.

Question 24

what is the tthymus divided into

Answer 24

cortex (subcapsule) +medulla.
Border btw them is = cortico-medullary junction.

Question 25

how do the t lymphocytes develop in thymus

Answer 25

same as B proliferation, differentiation, apoptosis

Question 26

cells in the stroma of thymus

Answer 26

hematopoietic (thymocytes) + stromal cells provides microenvironment for differentiation

Question 27

what are the 2 tyoes of stromal cells and their location

Answer 27

- thymic epithelial cells (cortex + medulla) - dendritic cells + macrophages (medulla) They can be antigen presenting cells

Question 28

structure of dendritic cells

Answer 28

. branch-like projections, . related to mononuclear phagocytes . originate from bone marrow.

Question 29

are the stromal cells antigen presetign

Answer 29

yes they express MHC class 1 + 2

Question 30

thymocyte path

Answer 30

. travel in bloodstream . enters thymus via cortico- medullary junction . then migrates to outer cortex . then moves to medulla to mature

Question 31

what receptor do lymphoid progenitors express

Answer 31

Notch receptor some stromal cells express notch ligand which allows progenitor to become T cell

Question 32

wha happens when Notch receptor not present / over reactive. conclusion?

Answer 32

1. no T cells made , B cells will differentiate in thymus 2. no B cells, abnormal T cells in bone marrow ** shows that lymphoid progenitors become B cells by default and need a Notch signal to become T cells.

Question 33

why are thymocytes called double negative

Answer 33

they express neither CD4 nor CD8

Question 34

Where do thymocytes proliferate. how do they develop

Answer 34

- proliferates while migrating to outer cortex - They express Tdt and start V(D)J recombination to produce TCR. **same as B cells, success in rearrangement leads to allelic exclusion, 1 unsuccessful attempt prompts rearrangment on homologous chromosome, and double failure triggers apoptosis.

Question 35

where are β chain genes are rearranged.

Answer 35

outer cortex thymocyte migrates back to cortico medullary junction + rearranges α chain genes.

Question 36

What happens to thymocytes after successful VDJ recombination

Answer 36

- inner cortex thymocytes express TCR2 and CD3 on their surface - They also express both CD4 and CD8 and therefore are called double positive

Question 37

What is positive selection in thymocytes

Answer 37

- TCR must prove its functionality by recognizing MHC presented by cortical thymic epithelial cells. - Thymocytes that fail to bind MHC + peptide die by apoptosis. Only those that bind MHC survive.

Question 38

why does B cells not hv positive selection

Answer 38

step is absent in B cells because they have no MHC restriction (B cell receptors do not check if the antigen was presented by MHC).

Question 39

why do thymocytes hv to be double positive. what does positive selection test

Answer 39

- because they cannot “know” beforehand which class of MHC is better recognized by their TCR. - Positive selection tests the reaction of TCR with both MHC-I and MHC-II. So, the thymocyte preference for class I or II MHC becomes known.

Question 40

how are thymocytes single positive

Answer 40

Thymocytes recognizing MHC-I + peptide will not need CD4 and stop expressing it. Those recognizing MHC-II + peptide stop expressing CD8.

Question 41

to be useful where do t cells bind to how can restricion for self MHC be tested

Answer 41

- foreign peptide on self MHC - tested only on MHC + self peptide, because only self antigens are available in the thymus.

Question 42

what is negative selection in thymosytes

Answer 42

function is to eliminate self-reactive T cells which are very dangerous. ( those best during positive selection must die now)

Question 43

* what does negative selection involve?

Answer 43

TCRs that bind self peptide + MHC moderately, will bind toforeign peptide + MHC strongly. dendritic cells present self peptides + MHC to thymocytes + induce apoptosis in those that react strongly.

Question 44

what does T helper 17 cells do

Answer 44

pro inflammatory - prod interlukin 17 defense against extracellular pathogens, particularly at the mucosal and epithelial barriers, abnormal activation can lead to autoimmune diseases

Question 45

what do regulatory T cells do

Answer 45

maintain tolerance to self- antigens, and prevent autoimmune disease.

Question 46

do thymocytes hv receptor editing and what happens next in their development after bypassing apoptois

Answer 46

no single positive medullary thymocytes that survive leave the thymus as immunocompetent, mature T cells. - They go to peripheral lymphoid tissues to take part in immune response.

Question 47

qhat happens to thymus after fast prenatal growth

Answer 47

thymus involutes ( reduce in mass) can do this as t cells hv very long life spans

Question 48

in early childhood the peripheral lymphoid organs are populated by mature incompetent T cells that persist in later years. what do this. what does this mean for later life

Answer 48

Guarantees efficient immune response even without new reinforcements from the thymus. * Removal of thymus (thymectomy) has little effect in adults. In healthy organisms even the involuted thymus has active parts so produces new T cells till advanced age.