Lymphocyte differentiation in central lymphoid organs Flashcards

1
Q

where do lymphocytes originate from

A

pluripotent hematopoietic stem cells of bone marrow

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2
Q

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

A

B cells
T cells

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3
Q

what kind of lymphoid organs are Bone marrow nd thymus

A

central/primary

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4
Q

what is antigen independant differentiation

A

immature lymphocytes build their receptors for antigen (become immunocompetent)

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5
Q

what kind of genes do germline DNA NOT contain

A
  • 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
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6
Q

What is VDJ recombination

A

cutting and joining together DNA fragments

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7
Q

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

A
  • 2 fragments: V + J (respectively)
  • 3 fragments: V, D + J (respectively)
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8
Q

How is additional diversity created

A

enxyme: terminal deoxynucleotidyl transferase (Tdt)

inserts single random nucleotides btw fragments

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9
Q

Red bone marrow + location

A

main hematopoietic organ (except in embryo + foetus)

Located in spongy bones, filling spaces btw bone trabeculae

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10
Q

what is the stroma of the bone marrow

A

(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
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11
Q

what do hematopoietic stem cells give rise to

A

lymphoid stem cell / common lymphoid progenitor

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12
Q

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

A

become immunocompetent (building antigen receptor)

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13
Q

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

A

if first rearrangement successful,

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

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14
Q

why does first rearrangement become unsuccessful. what happens after

A
  • if frameshift / early stop codon obtained
  • cell then tries to rearrange 2nd chromosome, if fail again then it will commit apoptosis
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15
Q

what happens to successful pro B cells

A

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

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16
Q

What do Pre B cells rearrange
what happens with failure

A

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
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17
Q

what happens when cells acquires light chain

A

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

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18
Q

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

A

autoantigen

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19
Q

B lymphocytes that react with autoantigens are called what

A

self reactive / autoreactive

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20
Q

what do autoreactive cells do. what is the proccess called

A

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.

21
Q

what happens when B cell gets good Ig receptor

A

allowed to leave the bone marrow for the
periphery.

22
Q

what happens to B cells that fail in getting Ig receptor

A

undergo apoptosis = negative selection (ridding self reactive lymphocytes)

23
Q

where is the thymus located

A

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

24
Q

what is the tthymus divided into

A

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

25
Q

how do the t lymphocytes develop in thymus

A

same as B

proliferation, differentiation, apoptosis

26
Q

cells in the stroma of thymus

A

hematopoietic (thymocytes) + stromal cells

provides microenvironment for differentiation

27
Q

what are the 2 tyoes of stromal cells and their location

A
  • thymic epithelial cells (cortex + medulla)
  • dendritic cells + macrophages (medulla)

They can be antigen presenting cells

28
Q

structure of dendritic cells

A

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

29
Q

are the stromal cells antigen presetign

A

yes

they express MHC class 1 + 2

30
Q

thymocyte path

A

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

31
Q

what receptor do lymphoid progenitors express

A

Notch receptor

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

32
Q

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

A
  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.

33
Q

why are thymocytes called double negative

A

they express neither CD4 nor CD8

34
Q

Where do thymocytes proliferate. how do they develop

A
  • 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.

35
Q

where are β chain genes are rearranged.

A

outer cortex

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

36
Q

What happens to thymocytes after successful VDJ recombination

A
  • inner cortex thymocytes express TCR2 and CD3 on
    their surface
  • They also express both CD4 and CD8 and
    therefore are called double positive
37
Q

What is positive selection in thymocytes

A
  • 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.
38
Q

why does B cells not hv positive selection

A

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).

39
Q

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

A
  • 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.
40
Q

how are thymocytes single positive

A

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

Those recognizing MHC-II + peptide stop
expressing CD8.

41
Q

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

A
  • foreign peptide on self MHC
  • tested only on MHC + self peptide, because only self antigens are available in the thymus.
42
Q

what is negative selection in thymosytes

A

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

43
Q
  • what does negative selection involve?
A

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.

44
Q

what does T helper 17 cells do

A

pro inflammatory - prod interlukin 17

defense against extracellular pathogens, particularly at the mucosal and epithelial barriers,

abnormal activation can lead to autoimmune diseases

45
Q

what do regulatory T cells do

A

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

46
Q

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

A

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.

47
Q

qhat happens to thymus after fast prenatal growth

A

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

48
Q

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

A

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.