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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

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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
How long to naive T-cells survive ?
Long lived
26
What do naive T-cells encounter ?
Specific antigens in the form of peptide which are presented by the MHC complex on the surface of the antigen presenting cell
27
Where do T-cells develope?
Thymus
28
What happens when T-cells encounter their specific antigen ?
T-cells proliferate and differentiate into cells that contribute to the removal of antigens (effector T-cells)
29
What are effector T lymphocyes ?
Differentiated cells capable of carrying out their specialised functions in the removal of pathogens
30
What happens to effector T-cells once the immune response is resolved ?
1. Some die off 2. Others remain as memory T-cells
31
What are the T-cell subtypes ?
1. Alpha-Beta T-cell 2. Gamma-delta T-cell
32
What are the two types of alpha-beta TCR ?
1. Cytotoxic T-cell 2. Helper T-cell
33
What is the function of the cytotoxic T-cell ?
1. Express CD8 co-receptor 2. Kills virus infected cells
34
What is the function of the helper T-cell ?
1. Express CD4 2. Activate B-cells and innate immune system
35
What is the percentage of cytotoxic T-cells in the blood ?
20%
36
What is the percentage of helper T-cell in the blood ?
40 %
37
What is the gamma-delta cell ?
1. Expresses CD4 and CD8 2. Non MHC restricted 3. Mucosal defence
38
What percentage of gamma delta clls in the blood ?
1.5 %
39
What do all T-cells express ?
CD3
40
What is the key feature of lymphocytes ?
High specificity
41
What is the toll like receptor structure similar to ?
Fab fragment of antibody
42
What are the regions that a toll like receptor has ?
Variable and constant regions
43
Where is the toll like receptor found ?
Membrane bound
44
What are CD4/8 molecules involved in ?
T-cell selection and lineage fate
45
What are the molecules involved in TCR signalling ?
CD4/8 and CD3
46
What do CD4 T-cells recognise ?
Exogenous antigens
47
What do CD8 T-cells recognise ?
Endogenous antigens
48
What does a particular T-cell receptor recognise ?
Both peptide/MHC and is highly specific for a particualr peptide
49
What does a particular MHC bind ?
Multipe peptides as long as they conform to particular anchor residues
50
What is antigen presenting cells ?
1. Activation of dendritic cells 2. Antigen processing and presentation via MHC
51
What is recognised as being foreign in transplants
MHC
52
What happens when immunoglobulin or toll like recpetor molecules recognise antigens ?
Signals are delivered to the lymphocytes by proteins assoicated with the antigen receptors
53
What are antiboides expressed as ?
Membrane receptors or secreted proteins
54
What do toll like receptors only function as ?
Membrane receptors
55
Do toll like receptors have effector functions ?
No
56
What do antibodies exert effector functions via ?
Fc
57
What types of antigen does immunoglobulin recognise ?
1. Macromolecules (proteins, polysaccharides, lipids, nucleic acids) 2. Small chemicals
58
What is antigen recognition mediated by in the immunoglobulin ?
Variable regions of heavy and light chains of membrane
59
What are the signaling functions mediated by in the immunoglobulin ?
Proteins associated with membrane Ig
60
What are effector functions mediated by in the immunoglobulin ?
Constant regions of secreted Ig
61
What is antigen recognition mediated by in TCR ?
Variable regions of alpha and beta chains
62
What are the domains of a typical TCR specific for ?
A peptide MHC complex
63
Wat is the antigen binding portion of the TCR formed by ?
Valpha and Vbeta domains
64
What does each individual need ?
T-cells capable of recognising any microbial antigen
65
What does the variable domain of both the t-cell receptor alpha and beta chain have ?
Three hypervariable or complementary determinign regions
66
What are T-cells derived from ?
Bone marrow progenitors
67
Where do T-cells develop ?
Thymus
68
What happens to T-cells in the thymus ?
Gene rearrangement
69
What is diGeorge syndrome ?
Have B cells but no T cells
70
How do B and T lymphocytes go through cycles of proliferations and expression of antigen receptor proteins ?
Gene recombination
71
Why do cells that fail to express intact, funtional receptors die by ?
Apoptosis because they do not receive necessary survival signals
72
At the end of lymphocyte maturation what do cells undergo ?
Positive and negative selection
73
What are the steps in lymphocyte maturation ?
1. Commitment 2. Proliferation 3. Pre- B/T antigen receptor expression 4. Proliferation 5. Antigen receptor expression 6. Positive and negative selection
74
What is TCR diversity generated by ?
Gene rearrangement
75
What is rearranged in the thymus for each T-cell to provide a unique TCR ?
Germline DNA
76
What is the function of recombination signal sequences ?
Flank TCR gene segments and ensure correct recombination
77
What are responsible for recombination ?
Recombinase enzymes including recombination activating genes 1 and 2
78
What do RAG enzymes do ?
Recognise RSS sequences - DNA is nicked and unwanted intervening segment is excised
79
What RSS recombinations are allowed to ensure correct joining ?
Only 12/23
80
What is diversity produced by ?
1. Random combinations of V,D and J genes 2. Removal and addition of nucleotides at the V-J or V-D-J
81
What does junctional diversity maximise ?
Variations in the CDR3 regions of the antigen receptor proteins
82
What is CDR3 the site of ?
V-J and V-D-J recombination
83
What is diversity increased by ?
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
What is the result of the random nature of TCR gene rearrangement ?
TCRs generated will be specific for any possible antigen
85
What does the process that ensures the deletion of self-reacitve T-cells avoid ?
The release of self-reactive T-cells from the thymus
86
What are self antigens expressed and under the control of ?
Expressed in the thymic epithelial cells under the control of the AIRE (autoimmune regulator) gene
87
What does positive selection ensure ?
That T-cells recognise peptides in the context of own MHC (Low affinity binding)
88
What does negative selection ensure ?
That T-cells whose TCR binds self antigen with high affinity are deleted
89
Where is the TCR beta first expressed ?
The double negative pre-T cell stage
90
What does the pre-TCR consist of ?
TCR beta chain associated with a protein called pre T alpha
91
Where is the complete T cell receptor expressed ?
In double positive cells
92
What does maturation culminate in ?
The development of CD4+ and CD8+ single positive T-cells
93
What does failure to express antigen receptors lead to ?
Death of the cells by apoptosis
94
Why must T-cells specific for self antigens be deleted ?
To avoid autoimmunity
95
Where are mature naive T-cells exported ?
Into the periphery

Core Concepts in Immunology (22 decks)

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