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Lecture 4: T Cell Activation And Co-stimulation Flashcards

1
Q

What is specialisation?

A

Responses to distinct microbes are optimised for defence against these microbes

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2
Q

What is cell immunity?

A

When activated T cells respond to different antigens in different ways

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3
Q

Abnormal enhanced T cell function?

A

Observed in autoimmune condition such as multiple sclerosis, insulin dependent diabetes mellitus

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4
Q

Reduced T cell activation?

A

Increased susceptibility of host to infectious microbes and tumours e.g. AIDS, HIV etc

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5
Q

What impairs the immune response?

A

Malnutrition

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6
Q

What do Adjuvants do?

A

Help the development of the immune response Enhance T cell function

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7
Q

What are enhanced T cell function required for?

A

Successful vaccination

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8
Q

What doesn’t innate immunity have?

A

Memory Specialisation

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9
Q

What is innate immunity highly fundamental for?

A

Highly specialised responses to carry out and clear the pathogenic invasion

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10
Q

What are the cells responsible for activating T lymphocytes?

A

Dendritic cells

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11
Q

What are MHC molecules loaded with peptides recognised by?

A

T lymphocytes (specific T cell receptor)

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12
Q

Where does the immune response begin?

A

Lymph nodes

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13
Q

Where can you feel the lymph nodes?

A

Under auxiliary

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14
Q

Where does the dendritic cell migrate towards in the lymph node?

A

Paracortical area [mostly T cells present]

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15
Q

Where does the T cells migrate out from?

A

Efferent lymphatics and out through the subcortical area

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16
Q

Where are B cells located?

A

Germinal centre

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17
Q

Where does naive lymphocytes circulate?

A

Between blood and lymphoid tissue

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18
Q

Where does activation of naive T lymphocytes occur?

A

Secondary lymphoid tissues

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19
Q

What happens in the periphery tissue?

A

T cells can be specialised in killing infected cells T cells that recognises antigen on local APC

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20
Q

What are the phases of adaptive immune responses?

A

Antigen recognition Lymphocyte activation Antigen elimination Contraction Memory

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21
Q

What are the different phases of T cell response?

A

Effector CD4+ T cell Memory CD4+ T cell Effector CD8+ T cell Memory CD8+ T cell

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22
Q

What does effector CD8+ T cell do?

A

Activation of macrophages, B cells and other cells

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23
Q

What does effector CD8+ T cell do?

A

Killing of infected “target cells” Macrophage Activation

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24
Q

What factors determine the cells to divide and become specialised in a function?

A

The strength of signal The cytokines produced by the dendritic cells The number of antigens

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25
What are the phases of B lymphocyte activation?
New protein synthesis Proliferation (clonal expansion) Differentiation Homeostasis
26
What are the stages of lymphocyte activation?
Naive lymphocytes Effector lymphocytes Memory lymphocytes
27
What is naive lymphocytes?
Mature lymphocytes that have not previously encountered antigen Preferential migration to peripheral lymphoid organs
28
What is Effector lymphocytes?
Activate lymphocytes capable of performing functions required to eliminate microbes Cytokine secretion Killing of infected cells
29
What is Memory lymphocytes?
Long-lived, functionally silent cells
30
What are regulatory T cells?
cells that can inhibit the proliferation of other T cells population which cause problem to host body
31
regulatory T cells
Modulate the immune system Maintain tolerance to self-Antigens Prevent autoimmune disease FoxP3, CD4 and CD25 Thymic and inducible
32
What is type 1 immune responses: killing microbes
Pro-inflammatory: neutrophils and macrophages Antibody classes involved in phagocytosis and complement activation Macrophage activation
33
What is type 2 immune responses: defence at epithelium
Allergic inflammation: eosinophils, basophils Antibody classes: IgE and IgG1 (mast cell activation) Expulsion type reactions: diarrhoea, coughing and sneezing)
34
What are TH17?
Aggressive cells that can induce autoimmunity
35
Give examples of regulatory T cells
IL-10 and TGF beta
36
What is TH1 cells l?
Very inflammatory cell which will produce TNF, IL-1, IL-6, MIF and chemokines
37
What are pro inflammatory cytokines?
TNF, IL-1, IL-6, MIF, chemokines
38
What are anti-inflammatory cytokines?
IL-10, IL-1ra, TGF-Beta
39
What are Macrophage activating cytokines?
IFN Gamma
40
What are B cells activating cytokines?
IL-4, IL-5, IL-6
41
What are Eosinophil and/or mast-cell activating cytokines?
IL-3, IL-4, IL-13 and IL-5
42
What are key events in T cell activation?
Antigen recognition TCR recognises MHC molecules Upon recognition of peptide-MHC by TCR, T cell gets activated and becomes proliferated makes clonal expansion and differentiate into memory and effector T cells
43
Where does T cell recognise antigens?
Lymphoid organs and peripheral non-lymphoid toissues
44
What does the activation of T cell squire?
Recognition of antigens displayed on APC, cytokines produced by APC and costimulators
45
What signal 1?
Interaction of MHC peptide with TCR-CD3 complex
46
What is signal 2?
Interaction of CD28 on T cells and members of B7 family on APC
47
What gives signal 1?
Thyroid and dendritic cells
48
What does T cell require to become fully activated?
Signal 2 and conventional APC
49
What does not express B7 molecules?
Thyroid epithelial cells or pancreatic B cells
50
What are the receptors of CD4+ helper T cells?
CD4, TCR, CD3, CD28, LFA-1
51
What is CD4 used for?
Adhesion signal transduction
52
What is TCR used for ?
Antigen recognition
53
What is CD3 and CD28 used for?
Signal transduction
54
What is LFA-1 used for?
Adhesion
55
What are T cells activated by?
T cell receptor
56
What are TCR?
Heterodimers formed by alpha and beta chains
57
What does T cell receptor have?
Short cytoplasmic tail which cannot signal within the cell
58
What are TCR flanked by?
CD3 complex
59
What is CD3 formed by,
Delta, Epsilon and zeta chains which contain ITAM motif —> tyrosine based motif
60
What are MHC class I expressed by?
All cells except RBC
61
What are MHC class I formed by?
Heavy chain and b2m (beta 2 mitoglobulin- keep molecules folded correctly)
62
What are MHC class I molecules recognised by?
CD8+ T cells
63
What are MHC class II expressed by?
Expressed on APC
64
What are MHC class II formed by?
Heterodimer alpha and beta chains
65
What are MHC class II recognised by?
CD4+ T cells
66
What is costimulation?
Crucial second signal that amplifies the TCR initial signal
67
What happens if you have signal 1 + signal 2?
T cell will undergo proliferation, differentiation and effector function
68
What happens in the absence of signal 2?
T cell cord of become anergic
69
What is the role of costimulation?
Maintenance of periphery tolerance Important to prevent autoimmunity
70
What is the function of IL-2?
Autocrine T cell growth factor - produced by T cells and help them to proliferate Important for B cell proliferation [antibody production] and NK cell proliferation [increased cytolytic activity]
71
What do CD4+ helper T cell produce?
Cytokine that stimulate CTL differentiation
72
What does CD4+ helper T cell enhance the ability for f?
APC to stimulate CTL differentiation
73
What does T helper fell express
TCR and CD40L
74
What is double recognition?
One side there will be antigen receptor and on the other side will present antigen to T cell that price the second signal as CD40L bind CD40
75
Is the interaction between TCR and MHC alone sufficient to sustain contact between T cell and APC?
No
76
What strengthens the interaction between T cell and APC
Integrins
77
What does integrin allow?
Prolonged and stable signal of TCR and CD28 on T cells
78
What is the formation of the immunological synapse?
There are various receptors on T cells and Ligands on APC that are dispersed in the plasma membrane of 2 cells before antigen recognition When T cell recognised antigen presented by APC, selected receptors on T cells and their respective ligands are redistributed to a defined area of cell-cell contact forming a synapse The molecules in the central portion of the synapse form the central supramolecular activation cluster (Csmac)
79
What does naive CD8 T cell differentiate into?
Cytotoxic T cells
80
What are the mechanisms involved for the CD8+ T cells?
Perforins Granzymes FAS-FASL
81
What is perforins?
Makes the pores in the membrane
82
What is granzymes?
Serine proteases that are capable of activating caspases
83
What is FAS-Fasl?
Signalling resulting in apoptosis
84
What are the mechanisms of killing of infected cells by CD8+ CTLS
Antigen recognition and conjugate formation CTL Activation CTL granule exocytosis Apoptosis of target cell Granzymes enter the cell via receptor-mediated endocytosis Enter cytoplasm via perforin dependent mechanisms
85
What is CTLA4?
Cytotoxic T cell antigen 4 Member of immunoglobulin superfamily which is expressed on surface of T cell and transmit inhibitory signal to T cells
86
What is the role of CTlA4?
Down modulate T cell response to avoid uncontrolled immune responses
87
What does CTLA-4 guns go?
Same ligand as CD28 with higher affinity and compete with CD28 preventing CD28 from signalling
88
Where is CTLA-4 found?
Surface of T cells and known as CD152 (cluster of differentiation 152)
89
What can the T cell attack be turned on by?
Stimulating the CD28 receptor on T cells
90
What can T cell attack be turned off by?
Stimulating the CTLA-4 receptor - acts as an off switch
91
What is mutation in CTLa4 associated with?
Different autoimmune diseases
92
What are other roles of CTLA4?
Signals to both TCR and CD28 in an inhibitory manner and rips of B7 molecules from APC, induce enzymes to starve the T cells by removing some nutrients
93
What are CD28/CTLA4?
Immune check points - molecules that determine whether an immune response can happen or stop
94
What is an example of cell-cell interaction?
T cell - APC CTL - target cell
95
What is an example of receptor-ligand binding?
TCR - antigen/MHC
96
What is an example of transmembrane signal transduction?
Activation of Lck and zap-70
97
What is an example of generation of second messengers?
1,4,5-IP3 and DAG
98
What is an example of second-messenger effects?
Ca2+ mobilisation and protein kinase C activation
99
What is an example of biochemical pathways?
Phosphatidylinostil pathway and seas pathway
100
What is an example of cellular events?
Secretion of cytolytic granules
101
What is an example of early gene activation?
c-Myc and c Fos
102
What is an example of intermediate gene activation?
Lymphokines, lymphokine receptors and nutrient receptors
103
What is an example of late gene activation?
Gene involved in cell proliferation IL2 and IL-2R alpha
104
What can intracellular signalling be divided into?
Membrane events Cytoplasmic signalling pathways Nuclear transcription of genes
105
What is membrane events?
Recruitment and activation of protein tyrosine kinase into TCR complex Phosphorylation of TCR complex constituents Recruitment of protein tyrosine kinase - zAP-70 and adaptor proteins
106
What is cytokines plasmid signalling pathways?
Lead to activation of effector enzymes such as kinases: ERK, JNK, PKC and the phosphatase calcineurin Enzymes contribute to the activation of transcription factors such as NF-AT, AP-1, NF-kB - enhance gene expression in antigen-stimulated T cells
107
What is nuclear transcription of genes?
Some peptides in which the TCR contact residues are altered and may induce partial T cell responses or inhibit T cell activation by poorly understood biochemical mechanism

Immunology (20 decks)

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