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Core Concepts in Immunology > Lecture 11.The T-Cell Receptor and Antigen Recognition by T-Cells > Flashcards

Lecture 11.The T-Cell Receptor and Antigen Recognition by T-Cells Flashcards

1
Q

What is the evolutionary origin of the innate immune system ?

A

Earliest animals - all invertebrates and vertebrates

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2
Q

What is the principal cell in the innate immune system ?

A

Phagocytes

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3
Q

What is the principal effector molecules in the innate immune system ?

A

Complement and cytokines

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4
Q

What is the specificity of the innate immune system ?

A

Broad

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5
Q

What is the speed of the innate immune system ?

A

Rapid

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6
Q

Is the capacity for specific long term memory generation in the innate immune system ?

A

No

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7
Q

What is the evolutionary origin is the adaptive immune system ?

A

Vertebrates only

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8
Q

What is the principal cell in the adaptive immune system ?

A

Lymphocytes (B and T cells )

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9
Q

What are the principal effector molecules in adaptive immune system ?

A

Cytokines and antibody

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10
Q

What is the specificity of the adaptive immune system

A

Highly specific (antigen)

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11
Q

What is the speed of the adaptive immune system ?

A

Slow

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12
Q

What is the capacity for specific long term memory generation ?

A

Yes

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13
Q

What do T-cells recognise ?

A

Small pieces of epitopes of protein antigens

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14
Q

How do proteins get chopped up and how do T cells see them ?

A

Antigens are chopped/processed by antigen presenting cells and then presented to T-cells via MHC molecules

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15
Q

What is the antigen presenting process ?

A
  1. Antibodies bind to epitopes displayed on the surface of antigens
  2. The epitopes recognised by T-cell receptors are often buried
  3. The antigen must first be broken down into peptide fragments
    4.The epitope peptide binds to a self molecule called a MHC
    5.The T-cell receptor binds to a complex of MHC molecule and epitope peptide
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16
Q

What are endogenous antigens presented by ?

A

MHC I

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17
Q

When do T-cells only recognise antigens ?

A

When it is presented to them by antigen presenting cells in the context of MHC

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18
Q

Where do antigen presenting cells capture and present antigens ?

A

Capture in tissues and present in lymph nodes

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19
Q

What is the endogenous antigen processed and presented by ?

A

Class I pathway to CD8 T cells (cytotoxic)

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20
Q

What is the extracellular antigen processed and presented by ?

A

Class II pathway to CD4 T cells (helper)

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21
Q

In a given cell what does each cell express ?

A

The same MHC alleles

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22
Q

What are the phases of an adaptive immune response ?

A
  1. Antigen recognition
  2. Lymphocyte activation
  3. Antigen elimination
  4. Contraction (homeostasis)
  5. Memory
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23
Q

What are naive T-cells ?

A

Mature recirculating T-cells that have not encountered their specific antigen

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24
Q

Where do naive T-cells circulate between ?

A

Lymphoid tissue and blood looking for antigen

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25
Q

How long to naive T-cells survive ?

A

Long lived

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26
Q

What do naive T-cells encounter ?

A

Specific antigens in the form of peptide which are presented by the MHC complex on the surface of the antigen presenting cell

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27
Q

Where do T-cells develope?

A

Thymus

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28
Q

What happens when T-cells encounter their specific antigen ?

A

T-cells proliferate and differentiate into cells that contribute to the removal of antigens (effector T-cells)

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29
Q

What are effector T lymphocyes ?

A

Differentiated cells capable of carrying out their specialised functions in the removal of pathogens

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30
Q

What happens to effector T-cells once the immune response is resolved ?

A
  1. Some die off
  2. Others remain as memory T-cells
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31
Q

What are the T-cell subtypes ?

A
  1. Alpha-Beta T-cell
  2. Gamma-delta T-cell
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32
Q

What are the two types of alpha-beta TCR ?

A
  1. Cytotoxic T-cell
  2. Helper T-cell
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33
Q

What is the function of the cytotoxic T-cell ?

A
  1. Express CD8 co-receptor
  2. Kills virus infected cells
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34
Q

What is the function of the helper T-cell ?

A
  1. Express CD4
  2. Activate B-cells and innate immune system
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35
Q

What is the percentage of cytotoxic T-cells in the blood ?

A

20%

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36
Q

What is the percentage of helper T-cell in the blood ?

A

40 %

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37
Q

What is the gamma-delta cell ?

A
  1. Expresses CD4 and CD8
  2. Non MHC restricted
  3. Mucosal defence
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38
Q

What percentage of gamma delta clls in the blood ?

A

1.5 %

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39
Q

What do all T-cells express ?

A

CD3

40
Q

What is the key feature of lymphocytes ?

A

High specificity

41
Q

What is the toll like receptor structure similar to ?

A

Fab fragment of antibody

42
Q

What are the regions that a toll like receptor has ?

A

Variable and constant regions

43
Q

Where is the toll like receptor found ?

A

Membrane bound

44
Q

What are CD4/8 molecules involved in ?

A

T-cell selection and lineage fate

45
Q

What are the molecules involved in TCR signalling ?

A

CD4/8 and CD3

46
Q

What do CD4 T-cells recognise ?

A

Exogenous antigens

47
Q

What do CD8 T-cells recognise ?

A

Endogenous antigens

48
Q

What does a particular T-cell receptor recognise ?

A

Both peptide/MHC and is highly specific for a particualr peptide

49
Q

What does a particular MHC bind ?

A

Multipe peptides as long as they conform to particular anchor residues

50
Q

What is antigen presenting cells ?

A
  1. Activation of dendritic cells
  2. Antigen processing and presentation via MHC
51
Q

What is recognised as being foreign in transplants

A

MHC

52
Q

What happens when immunoglobulin or toll like recpetor molecules recognise antigens ?

A

Signals are delivered to the lymphocytes by proteins assoicated with the antigen receptors

53
Q

What are antiboides expressed as ?

A

Membrane receptors or secreted proteins

54
Q

What do toll like receptors only function as ?

A

Membrane receptors

55
Q

Do toll like receptors have effector functions ?

A

No

56
Q

What do antibodies exert effector functions via ?

A

Fc

57
Q

What types of antigen does immunoglobulin recognise ?

A
  1. Macromolecules (proteins, polysaccharides, lipids, nucleic acids)
  2. Small chemicals
58
Q

What is antigen recognition mediated by in the immunoglobulin ?

A

Variable regions of heavy and light chains of membrane

59
Q

What are the signaling functions mediated by in the immunoglobulin ?

A

Proteins associated with membrane Ig

60
Q

What are effector functions mediated by in the immunoglobulin ?

A

Constant regions of secreted Ig

61
Q

What is antigen recognition mediated by in TCR ?

A

Variable regions of alpha and beta chains

62
Q

What are the domains of a typical TCR specific for ?

A

A peptide MHC complex

63
Q

Wat is the antigen binding portion of the TCR formed by ?

A

Valpha and Vbeta domains

64
Q

What does each individual need ?

A

T-cells capable of recognising any microbial antigen

65
Q

What does the variable domain of both the t-cell receptor alpha and beta chain have ?

A

Three hypervariable or complementary determinign regions

66
Q

What are T-cells derived from ?

A

Bone marrow progenitors

67
Q

Where do T-cells develop ?

A

Thymus

68
Q

What happens to T-cells in the thymus ?

A

Gene rearrangement

69
Q

What is diGeorge syndrome ?

A

Have B cells but no T cells

70
Q

How do B and T lymphocytes go through cycles of proliferations and expression of antigen receptor proteins ?

A

Gene recombination

71
Q

Why do cells that fail to express intact, funtional receptors die by ?

A

Apoptosis because they do not receive necessary survival signals

72
Q

At the end of lymphocyte maturation what do cells undergo ?

A

Positive and negative selection

73
Q

What are the steps in lymphocyte maturation ?

A
  1. Commitment
  2. Proliferation
  3. Pre- B/T antigen receptor expression
  4. Proliferation
  5. Antigen receptor expression
  6. Positive and negative selection
74
Q

What is TCR diversity generated by ?

A

Gene rearrangement

75
Q

What is rearranged in the thymus for each T-cell to provide a unique TCR ?

A

Germline DNA

76
Q

What is the function of recombination signal sequences ?

A

Flank TCR gene segments and ensure correct recombination

77
Q

What are responsible for recombination ?

A

Recombinase enzymes including recombination activating genes 1 and 2

78
Q

What do RAG enzymes do ?

A

Recognise RSS sequences - DNA is nicked and unwanted intervening segment is excised

79
Q

What RSS recombinations are allowed to ensure correct joining ?

A

Only 12/23

80
Q

What is diversity produced by ?

A
  1. Random combinations of V,D and J genes
  2. Removal and addition of nucleotides at the V-J or V-D-J
81
Q

What does junctional diversity maximise ?

A

Variations in the CDR3 regions of the antigen receptor proteins

82
Q

What is CDR3 the site of ?

A

V-J and V-D-J recombination

83
Q

What is diversity increased by ?

A

The ability of different Ig heavy and light chains or different TCR alpha and beta chains to associate in different cells, forming different receptors

84
Q

What is the result of the random nature of TCR gene rearrangement ?

A

TCRs generated will be specific for any possible antigen

85
Q

What does the process that ensures the deletion of self-reacitve T-cells avoid ?

A

The release of self-reactive T-cells from the thymus

86
Q

What are self antigens expressed and under the control of ?

A

Expressed in the thymic epithelial cells under the control of the AIRE (autoimmune regulator) gene

87
Q

What does positive selection ensure ?

A

That T-cells recognise peptides in the context of own MHC (Low affinity binding)

88
Q

What does negative selection ensure ?

A

That T-cells whose TCR binds self antigen with high affinity are deleted

89
Q

Where is the TCR beta first expressed ?

A

The double negative pre-T cell stage

90
Q

What does the pre-TCR consist of ?

A

TCR beta chain associated with a protein called pre T alpha

91
Q

Where is the complete T cell receptor expressed ?

A

In double positive cells

92
Q

What does maturation culminate in ?

A

The development of CD4+ and CD8+ single positive T-cells

93
Q

What does failure to express antigen receptors lead to ?

A

Death of the cells by apoptosis

94
Q

Why must T-cells specific for self antigens be deleted ?

A

To avoid autoimmunity

95
Q

Where are mature naive T-cells exported ?

A

Into the periphery

Core Concepts in Immunology (22 decks)

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