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Microbiology and Immunology > T Cell development and generation and of repertoire diversity > Flashcards

T Cell development and generation and of repertoire diversity Flashcards

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Biology 101 flashcards
1
Q

What are the stages of haematopoesis?

A

Commitment
Proliferation
Selection
Differentiation in distinct subpopulations

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2
Q

What progenitor do lymphocytes (B and T cells) come from?

A

Common lymphoid progenitor which commits into B or T cell lineage (forming pro B or pro T cell)

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3
Q

What happens in the proliferation stage of haematopoesis?

A

Pro B or pro T cell proliferates intensely after receptor rearrangement before selection

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4
Q

What happens in the selection stage of haematopoesis?

A

Types of receptors on specific cells selected

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5
Q

What drives the commitment of precursor in T or B cells?

A

c-KIT

IL7 and IL3 cytokines later needed to T cell lineage

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6
Q

What are the 3 cells that a common lymphoid progenitor commited to T cell lineage forms?

A

alpha beta or gamma delta t cell from pro t cell

some t cells progenitor may branch out earlier before becoming a pro T cell instead into iINNATE LYMPHOID CELLS which accumulate in cells

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7
Q

What factors control the development from a T cell precursor into a pro-T cell?

A

Notch 1 and GATA 3

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8
Q

Describe the process of T cell maturation/development?

A

Stem cell reprecursor move early from bone marrow to thymus and becomes pro-lymphocyte

Pro-lymphocyte becomes committed T cell lineage due to notch signals from thymic stroma into pre-lymphocyte in T lineage.

Notch signals activates transcription factor GATA 3 for commitment of T cell and rearrangement of T cell receptor.

Once receptor has developed, T cell proliferate intensely.

Thymic selection occurs and T cell can leave thymus untl activated by antigen where it can carry out effector function

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9
Q

Where do pro-lymphocytes becomes committed to T cell lineage?

A

In the thymus

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10
Q

What are the 2 regions of the thymus?

A

Cortex (darker)

Medulla (lighter)

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11
Q

What cells are in the thymus?

A

network of epithelial cells and lymphocytes

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12
Q

Why does the thymus not increase in size during intense proliferation of T cells?

A

Many T cells fails negative selection due to rearrangement of T cell receptor

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13
Q

How do you know which stage a T cell is in in its development?

A

Changes in surface receptors indicate level of development

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14
Q

Describe the change in surface receptors of T cell during its development/maturation process?

A

T cell progenitors (committed to T cell lineage in thymus) express CD2 and Thy1 so far DON’T EXPRESS NORMAL MARKERS OF T CELLS FOUND IN PERIPHERY (SUCH AS CD3, CD8, CD4) so currently double negative T cells

Rearrangement of T cells receptor on thymocyte as it becomes a pro T cell to express both CD4 and CD8 (double positive)

Later stages and selection causes single positive T cells (loses one of receptors)

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15
Q

What is a t cell receptor?

A

Heterodimer - 2 transmembrane polypeptide chains covalently linked by disulfide bonds (either an alpha and beta or a gamma and delta)

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16
Q

What are the regions on a TCR?

A

N terminal variable domain (V)
Constant domain (C)
Hydrophobic transmembrane region
Short signalling cytoplasmic region

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17
Q

What varies in the V region of TCRs?

A

Short amino acid chains that are variable between receptors

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18
Q

What does the variable region of TCRs form?

A

Complementary determining regions (CDRs) forming the MHC binding site (aka antigen binding site)

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19
Q

Compare similarities and differences structurally between immunoglobulins and TCRs?

A

TCR made of alpha and beta chain
Ig made of heavy and light chain

Both have 3 CDRs (one for each chain)

TCR has one V and one C domain on each chain
Ig has one V domain and 3-4 C domains on heavy chain and one V domain and one C domain on light chain

Somatic mutation, secreted form and isotope switching only in Ig’s

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20
Q

What components make up a TCR signalling complex?

A

TCR and CD3 and zeta chain

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21
Q

How is the TCR signalling complex formed?

A

C regions of TCR have cysteine residues which are charged amino acids. They bring the chains together and also bind to CD3 and zeta chain (receptor interacts with accessory molecules) forming signalling complex.

Once MHC peptide binds to TCR, transduction of signal takes place (downstream signals)

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22
Q

Which type of peptides do T cell recognise?

A

short LINEAR peptides (not full confirmational peptides) , so must be cleaves and processed and presented on MHC

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23
Q

What peptides do CD4 T cell recongise? and why

A

Peptides from extracellular spaces since these are the peptides expressed on MHC class 2 which CD4 recongises

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24
Q

What peptides do CD8 T cell recognise?

A

Peptides from intracellular spaces since these are he peptides presented on MHC class 1 which CD8 recognises

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25
Q

What is the molecular principle of MHC restriction?

A

MHC also interacts with TCR independent of peptide showing TCR is functional (which is why during selection they are made sure to bind to self MHC)

26
Q

What is MHC?

A

Major histocompatibility complex

27
Q

What is the MHC found in humans?

A

HLA (human leukocyte antigen)

28
Q

What peptides do MHC class 1 present?

A

Peptide antigen derived from pathogens that replicate inside the cell e.g viruses

29
Q

What peptides do MHC class 2 present?

A

Peptides from pathogens and antigens that are present outside the cell taken up by endocytic vesicles of phagocytic cells

30
Q

What binding site is present on the conserved region of MHC class 2?

A

CD4 binding site

31
Q

What binding site is present on the conserved region of MHC class 1?

A

CD8 binding site

32
Q

Which part of the TCR does CD4 or CD8 depending on MHC class bind to?

A

Conserved domain

33
Q

Why are there many different MHCs?

A

MHC molecules are polymorphic and polygenic (many genes and many variants of each gene)

34
Q

Define polymorphic

A

Multiple variants of each gene

35
Q

Define polygenic

A

Several different MHC class 1 and class 2 genes

36
Q

How many peptides can bind to MHC?

A

Only one at a time but can bind diff peptides (due to high level of diversity)

37
Q

When do MHC molecules acquire the peptide they present?

A

Whilst being assembled inside the cell

38
Q

How do peptides bind to MHC molecules?

A

Peptides have similar structural features that promote binding

39
Q

What other molecule apart from pathogenic peptide does MHC present?

A

Self peptides

40
Q

Which cells express MHC class 1?

A

All body cells apart from erthyrocytes

41
Q

What is the pathway of antigen processing and presentation on top of MHC class 2?

A

Phagocytosis (dendritic cells and macrophages)

Internalised protein is processed in endosomal/lysosomal vesicles

Synthesis and transport of MHC class 2 molecules via golgi to vesicles to endosomes

MHC class 2 release CLIP molecules and exchanges for peptide molecule - association of MHC class 2 and processed peptide (peptide has affinity to binding groove)

Expression of peptide MHC complex on cell surface

42
Q

What are the simplified steps of TCR rearrangment?

A

Germ line alpha chain DNA (contains multiple V, J etc… variants)
Rearranged alpha chain DNA made (variants selected)
+
Germ line beta chain DNA
Rearranged beta chain DNA made

Rearrnaged beta chain and alpha chain form alpha beta heterodimer (TCR)

43
Q

How are T cells produced with many different TCRs (diverse reportire) with specificities?

A

Variable domains made from combination of a group of sequences in the germ line
Choose which D and J fragments then binds to form rearranged product

44
Q

How many TCRs does each T cell have?

A

Only one TCR so specific to one antigen

45
Q

Are TCRs secreted?

A

No, immunoglobulins are

46
Q

When does a T cell become an effector T cell?

A

When it finds a complimenatry foreign antigen

47
Q

Why is it unlikely that a T cell will bind to a self antigen

A

Due to randomness of process of selection in rearrangment of germ line genes (VDJ reassortment)

48
Q

Which enzyme rearranges gene segments (VDJ)?

A

Rag 1 and Rag 2

49
Q

Apart from alpha beta receptors, what other TCRs are made from gene reassortment?

A

gamma delta

50
Q

What order does gene reassortment go in?

A

V fist, then J and last C(constant) to join it all together

51
Q

Does alpha or beta chain have a D segment?

A

Beta chain

52
Q

Does the biosynthesis of TCRs mediated by Rag 1 and Rag 2 (for gene reassortment) require antigens?

A

No this is antigen independent

53
Q

Does TCRalpha or TCRbeta o through gene reassortment first? and what happens to the other

A

TCR beta

TCR alpha rearrangement is halted

54
Q

How much gene reassortment has to happen to produce a TCR?

A

Repeated multiple times until productive rearrangment made

55
Q

What is junctional diversity?

A

Nucleotides made be added or removed during gene reassortment creating new sequences at junctions

56
Q

What mediates junctional diversity?

A

TdT terminal deoxynucleotidyl transferase

57
Q

Why is junctional diversity important?

A

another source of diversity in TCRs

58
Q

What happens to the beta chain until alpha chain is also made?

A

Beta chain is exported with temporary alpha chain(pre-TCR) to cell surface to signal completion of beta chain rearrangement after which alpha chain rearrangment finishes

59
Q

What is the point of pe-TCR?

A

Beta selection

Pre-TCR signals suppression of RAG genes temporarily - no more rearrangement by allelic exclusion ensuring only one TCR beta is expressed

60
Q

What happens after succesfull pre-TCR signalling step by step?

A

Further beta chain rearrangement stopped
Induce expression of CD4 and CD8
Initiate alpha chain rearrangement

61
Q

What are the 2 ways diversity is given to TCRs?

A

Gene reassortment and junctional diversity

Microbiology and Immunology (31 decks)

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