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cmb2004 > lecture 4 > Flashcards

lecture 4 Flashcards

1
Q

where do T cells develop?

A

thymus

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2
Q

what does the Pax5 gene do?

A

allow the development of a B lymphocyte to a B cell

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3
Q

what do B cells develop from?

A

haematopoietic stem cells in the bone marrow that express PAX5 transcription factor

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4
Q

what does the development of B cells include?

A
  • rearrangement of genes
  • expression of Ig genes and lymphocyte
  • removal of self reactive cells
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5
Q

what molecule allows early recognition of a B cell?

A

CD19

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6
Q

what happens if an immature B cell bound to self cell surface antigen is removed?

A

negative selection in the bone marrow

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6
Q
A
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7
Q

what happens if a mature B cell that’s bound to foreign antigen is activated?

A
  • B cell leaves bone marrow
  • goes into blood and lymphatics
  • if recognises outside bone marrow it releases the B cell receptor as an antibody
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8
Q

how do activated B cells give rise to plasma and memory cells?

A
  • some cells keep antibody on surface as a receptor which form memory cells as have long life span
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9
Q

what is a pre-B cell receptor?

A

heavy chain with a surrogate light chain

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10
Q

how are pre-B cell receptors formed?

A
  • heavy chain genes rearrange first
  • moves to cell surface with Ig alpha and beta
    -expressed with surrogate light chain
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11
Q

what does the pre-B cell receptor test?

A
  • if the heavy chain can bind to the surrogate light chains
  • if yes, signal dissent once the binding occurs and an actual light chain is produced
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12
Q

what occurs after a pre-B cell receptor is formed?

A
  • light chains rearrange and displace chains associating with the H chain to form IgM BCR
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13
Q

what are immature B cells?

A

B cells which have put together a heavy and light chain

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14
Q

how is the pre-B cell receptor formed?

A
  1. B cell initially doesn’t have BCR as rearranging the heavy chain
  2. preB, at surface, attempts to bind all heavy chain rearrangements- if successful = heavy chain works
  3. if works, signal sent to B cell to arrange light chain to match
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15
Q

what proteins help with signalling machinery?

A

Ig alpha and Ig beta

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16
Q

what is the function of the pre-BCR?

A
  • delivers signal to pre-B cell that H chain is functional
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17
Q

what occurs once this signal is sent?

A
  1. turns off RAG1&2
  2. cell division occurs to replicate enough heavy chain
  3. surrogate light chain expression stops
  4. RAG1&2 turned on again to recombine the light chain sequences
  5. light chain rearrangement starts
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18
Q

what are RAG genes needed for?

A

gene rearrangement

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19
Q

what does each individual B cell express on their light chain?

A

EITHER kappa or lambda

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20
Q

what has a 1 in 3 success rate?

A

rearrangement of genes to produce successful chains

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21
Q

what happens if both the H and L genes fail to rearrange well?

A

cell dies

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22
Q

what occurs following successful H chain rearrangement?

A
  • preB cells that initially fail to generate non productive rearrangements of light chain kappa genes can be ‘rescued’ by up to 10 further rearrangements at same locus
23
Q

what happens if rearrangement at kappa loci doesn’t work?

A

the lambda locus begins to rearrange

24
Q

what expresses membrane IgM only?

A

immature B cells

25
Q

what do immature B cells that bind multivalent self antigens undergo?

A
  1. clonal deletion- cell dies by apoptosis if self reactive BCR
  2. receptor editing- B cell can avoid death if turns back on its RAG genes and try to make another light chain
26
Q

what occurs when a soluble self antigen is bound?

A

cell becomes unresponsive (anergic) - BCR on surface decreases, sneaks out bone marrow as not enough to be killed

27
Q

what happens to cells that don’t express PAX5?

A
  • leave bone marrow quickly with no rearranged receptor
    -enter thymus as thymocytes (on way to becoming T cells)
28
Q

where do T cells originate from?

A

bone marrow stem cells

29
Q

how are T cell developed?

A
  • receptor genes are rearranged once in thymus
  • pre-T receptor is expressed
  • self reactive T cells are eliminated by negative selection
30
Q

what happens if the T cell recognises self MHC molecules which thymus cells are expressing?

A

the T cells are positively selected as can bind the MHC so useful later on

30
Q

what do T cells expressing alpha/beta TCR bind with?

A

self MHC that’s expressed in the thymus

31
Q

what signal do thymocytes require to turn into a T cell?

A

signal from a notch molecule

32
Q

where do activated T cells migrate to?

A

site of infection

33
Q

where do mature T cells migrate to?

A

peripheral lymphoid organs

34
Q

what occurs when developed T cell progenitors migrate to thymus?

A
  • cells continue their development by rearranging their antigen-receptor genes
    -undergo repertoire selection
35
Q

what happens once the precursors develop into thymocytes?

A
  1. rearrange TCR genes (beta first) and express TCR
  2. acquire other markers eg. CD3, CD4, CD8
  3. undergo positive and negative selection while still in thymus
36
Q

what is the thymus?

A
  • bi-lobed organic the anterior mediastinum
  • each lobule has outer cortex and inner medulla
37
Q

what cells are present in the thymus?

A

lymphoid, epithelial, macrophages, dendritic cells

38
Q

how do pre-thymocytes enter the cortex?

A

via blood vessels from bone marrow

39
Q

what occurs once the thymocytes are in the thymus?

A
  1. rearrange TCR beta genes
  2. expressed along with pre-T cell receptor
  3. cells proliferate
  4. TCR alpha genes rearranged
40
Q

what does the surface of T cells express in and out thymus?

A
  • have CD3, 4 & 8 when in thymus
  • once out thymus, have CD4 or CD8
41
Q

what is the function of CD3 complex?

A

-transmits signal to T cell nucleus following TCR recognition of antigen

42
Q

what’s the difference with delta/gamma TCR?

A

-they don’t express CD4 or CD8 markers
-less diverse
-expressed on separate T cell population but most die
-recognise different antigens
-unsure whether undergo positive and negative selection

43
Q

how do T cells become gamma delta T cells?

A

by coming out the thymus - not quite understood by scientists

44
Q

how are both positive and negative cells produced from only negative?

A

-double positive CD4 and 8 undergo positive and negative selection in the thymus to make sure capable of recognising MHC
-results are either cd4+- or cd8+- on surface

45
Q

what might T cells expressing a randomly rearranged alpha/beta recognise?

A
  1. self MHC plus peptide from ‘foreign’ antigen (immunity) - KEEP
  2. recognise self MHC plus peptide from ‘self’ antigen (autoimmunity) - ELIMINATE
  3. not be able to recognise self MHC - ELIMINATE
46
Q

how are T cells positively selected?

A

-occurs when double positive T cells recognise MHC on cortical epithelial cells in thymus
-if doesn’t recognise then apoptosis occurs
-rearrangement gives random TCR repertoire

47
Q

where do positively selected cells move?

A

to the medulla

48
Q

where does positive selection occur?

A

in the cortex by cortical epithelial cells in thymus

49
Q

how are T cells negatively selected?

A

-T cells which recognise self MHC on thymus dendritic checks/ macrophages with high affinity are negatively selected

50
Q

what cells allow negative selection?

A

dendritic cells and macrophages in thymus

51
Q

what happens to cells with no affinity?

A

they die as only cells with affinity are positively selected

52
Q

what is the ultimate goal from positive and negative selection?

A

-a population of T cells with low affinity for self peptide and self MHC
-more likely to have high affinity for self MHC when presenting peptides derived from pathogens

53
Q

what happens to the T cells that survive thymic selection?

A

-express TCR capable of binding self MHC
-depleted of self reactive cells
-exit thymus as mature, single positive T cells

54
Q

what do CD8+ T cells recognise?

A

antigens in association with MHC class I

55
Q

what do CD4+ cells recognise?

A

antigens in association with MHC class II

cmb2004 (11 decks)

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