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Immunology > Lecture 4: T Cell Activation And Co-stimulation > Flashcards

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
Q

What are the phases of B lymphocyte activation?

A

New protein synthesis Proliferation (clonal expansion) Differentiation Homeostasis

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26
Q

What are the stages of lymphocyte activation?

A

Naive lymphocytes Effector lymphocytes Memory lymphocytes

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27
Q

What is naive lymphocytes?

A

Mature lymphocytes that have not previously encountered antigen Preferential migration to peripheral lymphoid organs

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28
Q

What is Effector lymphocytes?

A

Activate lymphocytes capable of performing functions required to eliminate microbes Cytokine secretion Killing of infected cells

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29
Q

What is Memory lymphocytes?

A

Long-lived, functionally silent cells

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30
Q

What are regulatory T cells?

A

cells that can inhibit the proliferation of other T cells population which cause problem to host body

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31
Q

regulatory T cells

A

Modulate the immune system Maintain tolerance to self-Antigens Prevent autoimmune disease FoxP3, CD4 and CD25 Thymic and inducible

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32
Q

What is type 1 immune responses: killing microbes

A

Pro-inflammatory: neutrophils and macrophages Antibody classes involved in phagocytosis and complement activation Macrophage activation

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33
Q

What is type 2 immune responses: defence at epithelium

A

Allergic inflammation: eosinophils, basophils Antibody classes: IgE and IgG1 (mast cell activation) Expulsion type reactions: diarrhoea, coughing and sneezing)

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34
Q

What are TH17?

A

Aggressive cells that can induce autoimmunity

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35
Q

Give examples of regulatory T cells

A

IL-10 and TGF beta

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36
Q

What is TH1 cells l?

A

Very inflammatory cell which will produce TNF, IL-1, IL-6, MIF and chemokines

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37
Q

What are pro inflammatory cytokines?

A

TNF, IL-1, IL-6, MIF, chemokines

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38
Q

What are anti-inflammatory cytokines?

A

IL-10, IL-1ra, TGF-Beta

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39
Q

What are Macrophage activating cytokines?

A

IFN Gamma

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40
Q

What are B cells activating cytokines?

A

IL-4, IL-5, IL-6

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41
Q

What are Eosinophil and/or mast-cell activating cytokines?

A

IL-3, IL-4, IL-13 and IL-5

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42
Q

What are key events in T cell activation?

A

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

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43
Q

Where does T cell recognise antigens?

A

Lymphoid organs and peripheral non-lymphoid toissues

44
Q

What does the activation of T cell squire?

A

Recognition of antigens displayed on APC, cytokines produced by APC and costimulators

45
Q

What signal 1?

A

Interaction of MHC peptide with TCR-CD3 complex

46
Q

What is signal 2?

A

Interaction of CD28 on T cells and members of B7 family on APC

47
Q

What gives signal 1?

A

Thyroid and dendritic cells

48
Q

What does T cell require to become fully activated?

A

Signal 2 and conventional APC

49
Q

What does not express B7 molecules?

A

Thyroid epithelial cells or pancreatic B cells

50
Q

What are the receptors of CD4+ helper T cells?

A

CD4, TCR, CD3, CD28, LFA-1

51
Q

What is CD4 used for?

A

Adhesion signal transduction

52
Q

What is TCR used for ?

A

Antigen recognition

53
Q

What is CD3 and CD28 used for?

A

Signal transduction

54
Q

What is LFA-1 used for?

A

Adhesion

55
Q

What are T cells activated by?

A

T cell receptor

56
Q

What are TCR?

A

Heterodimers formed by alpha and beta chains

57
Q

What does T cell receptor have?

A

Short cytoplasmic tail which cannot signal within the cell

58
Q

What are TCR flanked by?

A

CD3 complex

59
Q

What is CD3 formed by,

A

Delta, Epsilon and zeta chains which contain ITAM motif —> tyrosine based motif

60
Q

What are MHC class I expressed by?

A

All cells except RBC

61
Q

What are MHC class I formed by?

A

Heavy chain and b2m (beta 2 mitoglobulin- keep molecules folded correctly)

62
Q

What are MHC class I molecules recognised by?

A

CD8+ T cells

63
Q

What are MHC class II expressed by?

A

Expressed on APC

64
Q

What are MHC class II formed by?

A

Heterodimer alpha and beta chains

65
Q

What are MHC class II recognised by?

A

CD4+ T cells

66
Q

What is costimulation?

A

Crucial second signal that amplifies the TCR initial signal

67
Q

What happens if you have signal 1 + signal 2?

A

T cell will undergo proliferation, differentiation and effector function

68
Q

What happens in the absence of signal 2?

A

T cell cord of become anergic

69
Q

What is the role of costimulation?

A

Maintenance of periphery tolerance Important to prevent autoimmunity

70
Q

What is the function of IL-2?

A

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
Q

What do CD4+ helper T cell produce?

A

Cytokine that stimulate CTL differentiation

72
Q

What does CD4+ helper T cell enhance the ability for f?

A

APC to stimulate CTL differentiation

73
Q

What does T helper fell express

A

TCR and CD40L

74
Q

What is double recognition?

A

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
Q

Is the interaction between TCR and MHC alone sufficient to sustain contact between T cell and APC?

A

No

76
Q

What strengthens the interaction between T cell and APC

A

Integrins

77
Q

What does integrin allow?

A

Prolonged and stable signal of TCR and CD28 on T cells

78
Q

What is the formation of the immunological synapse?

A

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
Q

What does naive CD8 T cell differentiate into?

A

Cytotoxic T cells

80
Q

What are the mechanisms involved for the CD8+ T cells?

A

Perforins Granzymes FAS-FASL

81
Q

What is perforins?

A

Makes the pores in the membrane

82
Q

What is granzymes?

A

Serine proteases that are capable of activating caspases

83
Q

What is FAS-Fasl?

A

Signalling resulting in apoptosis

84
Q

What are the mechanisms of killing of infected cells by CD8+ CTLS

A

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
Q

What is CTLA4?

A

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
Q

What is the role of CTlA4?

A

Down modulate T cell response to avoid uncontrolled immune responses

87
Q

What does CTLA-4 guns go?

A

Same ligand as CD28 with higher affinity and compete with CD28 preventing CD28 from signalling

88
Q

Where is CTLA-4 found?

A

Surface of T cells and known as CD152 (cluster of differentiation 152)

89
Q

What can the T cell attack be turned on by?

A

Stimulating the CD28 receptor on T cells

90
Q

What can T cell attack be turned off by?

A

Stimulating the CTLA-4 receptor - acts as an off switch

91
Q

What is mutation in CTLa4 associated with?

A

Different autoimmune diseases

92
Q

What are other roles of CTLA4?

A

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
Q

What are CD28/CTLA4?

A

Immune check points - molecules that determine whether an immune response can happen or stop

94
Q

What is an example of cell-cell interaction?

A

T cell - APC CTL - target cell

95
Q

What is an example of receptor-ligand binding?

A

TCR - antigen/MHC

96
Q

What is an example of transmembrane signal transduction?

A

Activation of Lck and zap-70

97
Q

What is an example of generation of second messengers?

A

1,4,5-IP3 and DAG

98
Q

What is an example of second-messenger effects?

A

Ca2+ mobilisation and protein kinase C activation

99
Q

What is an example of biochemical pathways?

A

Phosphatidylinostil pathway and seas pathway

100
Q

What is an example of cellular events?

A

Secretion of cytolytic granules

101
Q

What is an example of early gene activation?

A

c-Myc and c Fos

102
Q

What is an example of intermediate gene activation?

A

Lymphokines, lymphokine receptors and nutrient receptors

103
Q

What is an example of late gene activation?

A

Gene involved in cell proliferation IL2 and IL-2R alpha

104
Q

What can intracellular signalling be divided into?

A

Membrane events Cytoplasmic signalling pathways Nuclear transcription of genes

105
Q

What is membrane events?

A

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
Q

What is cytokines plasmid signalling pathways?

A

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
Q

What is nuclear transcription of genes?

A

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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