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Immunology > Lymphocyte development > Flashcards

Lymphocyte development Flashcards

1
Q

B cell development occurs in the ___ and is antigen ___

A

Bone marrow, independent

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2
Q

What are the 5 stages of B cell maturation?

A
  1. Pre-pro-B cell
  2. Pro-B cell
  3. Pre-B cell
  4. Immature B cell
  5. Mature B cell
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3
Q

What is pre-pro-B cell stage expressing/ whats going on with the genes

A

Expressing B220+

Ig genes are in germ line configuration

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4
Q

Pro-B cell - what happens to the genes? What proteins are expressed?

A

Heavy chain rearrangement
-D to J first, then V to D

Lambda5 and VpreB are expressed

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5
Q

What occurs at the pre-B cell stage? what is it called at this stage?

A

express the heavy chain with a surrogate light chain, along with Ig-alpha and Ig-beta

Called the pre-BCR

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6
Q

The pre-BCR receives a signal causing which 4 things?

A
  1. Downregulate TdT and RAGs (transient)
  2. Proliferate
  3. Rearrange light chain
  4. Prevent rearranging of second heavy chain (allelic exclusion)
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7
Q

What occurs at the immature B cell stage

A

Light chain is assembled with heavy chain into the final IgM immunoglobulin molecule which is then expressed on the cell surface

Clonal deletion occurs

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8
Q

What is clonal deletion?

A

autoreactive BCR are identified in the bone marrow and many of these cells eliminated by apoptosis

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9
Q

What is central tolerance

A

product of clonal deletion is central tolerance, meaning most of the remaining cells do not react to self

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10
Q

What is receptor editing?

A

autoreactive B cells can reattempt to rearrange light chain segments
- remaining V to J segments on the other chromosome

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11
Q

What are anergic B cells

A

Autoreactive B cells that escape the bone marrow but remain unresponsive to antigen

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12
Q

What is peripheral tolerance

A

B cells that are autoreactive encounter antigen in the periphery and are deleted by apoptosis

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13
Q

Mature B cells - characteristics

A

Express both IgM and IgD

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14
Q

Plamsa cells

A

Following antigen stimulation mature B cells become plasma cells

No longer proliferates but produces copious amounts of antibody

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15
Q

What do BCRs signal through ?

A

Ig alpha and Ig beta

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16
Q

What do Ig alpha and Ig beta have on them

A

immunoreceptor tyrosine based activation motifs (ITAMS)

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17
Q

Describe the 4 steps of BCR signalling

A
  1. BCR crosslinks by binding antigen
  2. Crosslinking brings the src family kinases together which phosphorylate the ITAMs
  3. Phosphorylated ITAMs act as a docking site for Syk kinases
  4. Syk kinases phosphorylate molecules that recruit compoenets of several signalling pathways
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18
Q

What occurs during T-dependent B cell stimulation?

A
  1. BCR binds antigen, brings it in
  2. presents antigen to Th cell via class II MHC
  3. Stimulated through CD40/CD40L signals
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19
Q

What are the two types of T independent B cell stimulation?

A
  1. Type 1 = bacterial products like LPS

2. Type 2 = highly repetitive molecules like cell wall polysaccharides

20
Q

How do Type 1 elements signal?

A

By binding to both the BCR and the TLR

21
Q

How do Type 2 elements signal?

A

By crosslinking BCR and CD21

-only activate mature B cells

22
Q

Acute stress can lead to a rapid loss of :

A

cortical thymocytes

23
Q

Coritcal thymocytes also decrease during:

A

pregnancy and aging

24
Q

Hematopoietic precursor cells are attracted to the thymus from ___ by ___

A

Bone marrow by chemokines

25
Q

Development in the thymus of mature T cells is dependent on which factor?

A

Notch ligand

26
Q

What secretes notch ligand

A

thymic epithelial cells

27
Q

how long does thymic development take?

A

1-3 weeks

28
Q

What are developing T cells in the thymus called?

A

Thymocytes

29
Q

Precursor T cells are attracted to the thymus by

A

chemotkines

30
Q

In the thymic cortex, the Double negatives expresses what cytokines and receptors and which enzyme

A

Thy-1

TdT

IL-2 and IL-2R which lead to autocrine proliferation of T cells

31
Q

What increases TCR diversity in the DN cells?

A

TdT inserting nucleotides at the D and J junction sites

P nucleotide addition

32
Q

How are gamma delta T cells produced?

A

Double-negative cells that productively rearrange gamma and delta chain gene segments develop into CD3+CD4+CD8+ gamma/delta T cells that are exported to the periphery in small numbers

33
Q

What is stimulation through the pre-TCR of alpha beta t cells called?

A 
Beta selection 
(basically is positive selection)
34
Q

What is the pre-TCR composed of?

A

successfully rearranged ß chain expressed with a surrogate alpha chain called the pre-T alpha chain

35
Q

What 4 signals are transmitted through binding of the pre-TCR?

A
  1. Allelic exclusion (halt further ß chain rearrangement)
  2. Proliferate
  3. Upregulate and express CD4 and CD8
  4. Stop proliferation and begin alpha chain rearrangements
36
Q

What do they cells become following ß selection?

A

The alpha beta T cells now become CD4+CD8+ or “double-positive” cells.

37
Q

What are the three models that describe how DP t cells become single positives ?

A
  1. Instructive model
  2. Stochastic model
  3. Kinetic signalling model
38
Q

instructive model

A

multiple interactions between the TCR, CD4 or CD8 co-receptors and class I or II MHC molecules instruct the cell through different signals to differentiate along one pathway

39
Q

Stochastic model

A

one coreceptor is shut-off randomly, independent of interactions with the TCR

40
Q

Kinetic signalling model

A

strong TCR signaling throughout the development favor CD4 expression while weak TCR signaling or interrupted signaling favor CD8 expression

41
Q

What are 4 factors involved in positive selection

A
  1. involves a physical interaction between immature thymocytes and epithelial cells in the thymic cortex
  2. believed that this interaction results in a protective signal which prevents death by apoptosis
  3. only thymocytes with receptors for self-MHC survive
  4. cells become single positives, i.e. express one of CD4 or CD8
42
Q

What are 3 factors involved in negative selection

A
  1. thymocytes which survive positive selection physically interact with dendritic cells and macrophages in the thymic medulla. Some cells will have low affinity TCR for self MHC/self antigen while others will have high affinity receptors
  2. thymocytes with high affinity TCR for self MHC/self antigen die by apoptosis
  3. the remaining thymocytes are self-tolerant
43
Q

What are 3 facts about gamma delta t cells

A
  1. are a small population of double negative T cells which are predominant in the skin, intestinal
    epithelium and pulmonary epithelium
  2. are not restricted in activity by self MHC
  3. remain fixed within tissue sites where they are thought to act as a first line of defense against
    infections and cancers
44
Q

Stimulation of T cells through the TCR is done in collaboration with?

A

CD3

45
Q

Explain the steps in TCR signalling

A
  1. Binding to the TCR causes CD45 to remove the inhibiting phosphate on lck kinase
  2. lck kinase now phosphorylates ITAMs on the CD3
  3. Phosphorylated ITAMs act as a docking site for ZAP-70
  4. ZAP-70 binds and is phosphorylated by lck
  5. ZAP-70 can now phosphorylate other factors in cell signalling

Immunology (19 decks)

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