L04 Flashcards by Hafsa Niaz

what is expressed when the cells stay in the bone marrow

Pax5

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what are the B cell-specific markers

CD45 then CD19

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what is negative selection

removal of self reactive cells

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what are the steps of making B cells

B cell precursor rearranges its immunoglobulin genes leading to generation of B cell receptors in the bone marrow

immature B cell bound to self cell-surface antigen is removed from repertoire (negative selection in the bone marrow

mature B cell bound to foreign Ag is activated leading to migration of B cells through the circulatory system to lymphoid organs and B-cell activation.

activated B cells give rise to plasma cells and memory cells (antibody secretion and memory cells in bone marrow and lymphoid tissue)

if B cells do not encounter Ag or see self Ag they die

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what happens to pre-B cells before becoming immature B cells

H chain genes rearrange first (μ chain) moves to cell surface with Ig alpha and Ig beta and expressed with surrogate light chain (product of V preB and λ5 genes)

—> pre-B cell receptor (pBCR)

then light chains rearrange, and displace
V preB and λ5 chains (associating with H chain)

—>IgM BCR

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when does D to Jh rearrangement happen

early pro-B cell

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in what cells does heavy chain rearrangement stop and light chain gene rearrangement progress

Large pre-B cell

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in what cells does light chain rearrangement stop

immature B cells

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what does pre-BCR

Delivers signal to pre-B cell that H chain looks functional
no Ag required yet

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what are the features of pre-BCR signal

Turns off RAG-1, RAG-2 genes

5 - 6 rounds of cell division

Surrogate light chain expression stops

RAG-1 and RAG-2 turned on again

L chain rearrangement starts

(RAG genes needed for gene rearrangement)

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what is the most commonly expressed light chain in humans

kappa

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what are the stages between stem cells and mature B cells

Stem cell

early pro-B cell

Late pro-B cells

large pre-B cell

small pre-B cell

immature B cell

mature B cell

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when does Vh to DJh take place

late pro-B cell

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when does V kappa to J kappa take place

from Large pre-B cell, small pre-B cell to immature B cell

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when does V lambda to J lambda happen

Small pre-B cell to immature B cell

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what happens when productive or nonproductive joining take place

check slide 9

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what is the success rate of each rearrangement

1 in 3

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what happens when pre-B cells that fail to generate non-productive re-arrangements of light chain kappa genes

they can be “rescued” by up to 10 further
rearrangements at the same locus, (as there are 5 Jk genes on each chromosome). If after all these attempts and still out of frame, then lambda locus will begin to rearrange

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when are RAG 1 and 2 off

large pre-B cell

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what is the function of RAG 1 and 2

lymphoid specific recombinase

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what is the function of TdT

N-nucleotide

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what is the function of lambda 5 and VpreB

surrogate light-chain components

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what is the function of Ig alpha, Ig beta, SD45R, and Btk

signal transduction

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what do immature B cells only express

IgM

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what do immature B cells that bind multivalent self-antigen undergo

either clonal deletion: cell dies by apoptosis or receptor editing: further light chain gene rearrangements of variable regions (get another chance)

what happens when immature B cells bind soluble self-antigen

cell becomes unresponsive

when is the heavy chain rearrangement done

Large pre-B cells

what is the surrogate light chain the product of

V preB and lambda 5 genes

how are the levels of μ and δ in anergic B cells

normal δ low μ

Activated B cells in the periphery can develop into?

plasma cells, memory B cells

What is the fate of a pre-B cell with non productive re-arrangements of light chain genes?

They have up to 5 attempts on each kappa locus (= no. of J kappa genes) and then another four (no. of J lambda genes) on each lambda locus

what are the 2 types of T cell genes

alpha and beta delta and gamma

what are the types of alpha and beta T cells

CD4+ or CD8+

what is the first round of selection and what does it eliminate

positive selection eliminates alpha and beta T cells that do not bind to self MHC

what is the second round of selection and what does it eliminate

negative selection T cells that interact strongly with self antigen are eliminated

what do the alpha and beta T cells in the thymus develop into

thymocytes

what are the steps in developing thymocytes

1) re-arrange TCR genes (β first) and express TCR -firstly, they rearrange TCRβ genes (similar to H chain in BCR) -expressed along with pre-T cell receptor -cells proliferate and then re-arrange TCR alpha genes 2) acquire other markers e.g. CD3, CD4, CD8 3) undergo positive and negative selection

what are the features of the thymus

bi-lobed organ in anterior mediastinum each lobe divided into many lobules each lobule has outer cortex and inner medulla

what cells are there in the thymus

lymphoid cells epithelial cells macrophages and dendritic cells

whare does the first round of T cell selection happen in the thymus

the cortex

whare does the second round of T cell selection happen in the thymus

the medulla

T cells express TCR with CD3 and both CD4 and CD8 and then peripheral T cells express either CD4 or CD8

true

what are the components of the CD3 complex

γ,δ,ε chains ζ (zeta) chain dimer)

what does the CD3 complex do

transmits signal to T cell nucleus following TCR recognition of p/MHC

What is more diverse - gamma/delta TCR or alpha/beta TCR

alpha/beta

Are alpha/beta and gamma/delta expressed on the same T-cell population?

What percent of gamma-delta TCR is in circulation?

1-5%

Where is gamma-delta TCR found?

epithelial tissues at mucosal surfaces

Do alpha-beta and gamma-delta recognise the same antigents?

Do gamma/delta TCR express CD4 or CD8?

What is a 'double-negative' thymocyte?

CD3-4-8- (T cell not expressing any)

What are the products of 'double-negative' thymocyte?

CD3+4-8- (export+selection in periphery) and large active 'double-positive' thymocytes (CD3+,pTalpha:beta+,CD4+, CD8+)

What is the product of 'double-positive' large active thymocyte

Small resting 'double-positive' thymocytes

What are the products of small resting 'double-positive' thymocytes?

small resting 'single-positive' thymocytes

What are the three possibilities that T cells expressing randomly arranged alpha-beta TCRs may engage in?

- recognise self MHC & "foreign" Ag = immunity - recognise self MHC & "self" Ag = autoimmunity - unable to recognise self-MHC

What are the criteria for positive selection?

recognise self MHC & self peptide

What cells undergo positive selection?

double-positive T cells

Where does positive selection occur?

cortical epithelial cells in thymus

What happens if cells are not recognised?

Apoptosis

What percent of T-cells are capable of recognising own MHC?

1-2%

Where do the positively selected cells move?

Medulla

Where does the negative selection of T cells occur?

thymic dendritic cells/Mq with high affinity

What causes to T cell apoptosis?

TCR binding to MHC/self-peptide with high affinity

Why do T cells undergo apoptosis if they have high affinity?

Could induce autoimmunity

What is the ultimate goal of TCR affinity for selection?

a population of T cells with low affinity for self peptide + self MHC

What percent of T cells that survive thymic selection?

less than 5%

What are the properties of T cells that survive thymic selection?

- express TCR capable of binding self MHC - depleted of self-reactive cells

What do CD8+T cells recognise?

Ag in association with MHC class I

What do CD4+T cells recognise?

Ag in association with MHC class II

What are the origin of thymocytes

HPC - bone marrow

Process of elimination of self-reactive T cells?

Negative

Site of T cell development and body location?

Thymus

Gene segments for alpha and beta chains that get re-arranged?

VJ, VDJ

Cells other than thymocytes present in the thymus are?

epithelial cells, APC

Alpha or beta genes rearranged first?

Beta

What is the pre-TCR?

a protein bound to rearranged TCRb that checks the assembly of b chain

What does the CD3 molecule do and why is it important?

Multi-component signalling part of TCR; leads to T cell activation following peptide/MHC antigen binding

Do gamma delta T cells normally express CD4/CD8?

What is positive and negative selection of T cells?

TCR must recognize self MHC alleles in thymic cortex = +ve selection, then if a T cells TCR binds self MHC and peptide too strongly in thymic medulla will die (-ve selection)

If a T cell recognises peptide and MHC I which marker does it have on the surface?

CD8

Are the criteria for positive and negative selection of immature T cells the same?

They are similar. They both involve ability to recognise self MHC molecules, but the affinity of TCR for peptide/MHC forms the basis of the differences