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Body Defence > Adaptive Immune Response - T Cells > Flashcards

Adaptive Immune Response - T Cells Flashcards

1
Q

When are T cells induced into the immune response?

A

After inflammatory and innate response starts to control pathogens

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2
Q

Why do virally infected cells need to be removed? (2)

A
  • Stop virus creating more virus particles

- Stop infection of neighbouring cells

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3
Q

What does the first green bell curve in a viral infection graph represent?

A

Innate production of interferons (IFN)

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4
Q

What does the second blue bell curve in the viral infection graph represent?

A

Innate NK-mediated killing

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5
Q

What does the final red curve that starts increasing from 2 days into viral infection a viral infection graph show?

A

Adaptive B cell and T cell responses

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6
Q

When does virus load remain constant? (2)

A
  • During innate production of interferons

- During innte NK mediated killing

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7
Q

When does virus load start decreasing?

A

During adaptive B cell and T cell response

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8
Q

Where are T lymphocytes produced?

A

Bone marrow

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9
Q

Where do T lymphocytes mature?

A

Thymus

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10
Q

What happens to T lymphocytes in the thymus?

A
  • Thymic education
  • Learn to distinguish self from non self
  • Only respond to foreign antigens
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11
Q

What is the result of errors in thymic education?

A

Autoimmunity

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12
Q

What type of mechanisms are in place to prevent errors in thymic education and subsequent autoimmunity?

A

Peripheral

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13
Q

What happens to T lymphocytes after thymic education?

A

Enter circulation as non self reactive T cells

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14
Q

What do T lymphocytes do in circulation?

A

Work with B cells to provide different types of immune response

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15
Q

What is the type of immunity T lymphocytes provide alongside B cells governed by? (2)

A
  • Innate factors microorganism alerts

- Signals macrophages give to other cells

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16
Q

Label the lymph node diragram

A

See Morgan lecture and histology lecture

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17
Q

What is the main type of antigen presenting cell? (APC)

A

Dendritic cell

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18
Q

What do dendritic cells do? (2)

A
  • Process big antigens into small fragments to present to MHC molecules
  • Interact with other cells to produce cytokines
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19
Q

What is the purpose of the dendrites on dendritic cells while they are precursors taking up antigens?

A

Project out to grab microbe fragments, pull them inside to capture antigen

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20
Q

What can dendrites do on dendritic cells to increase capture of antigens even when no overt infection/inflammation?

A

Extend processes through tight epithelia junctions

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21
Q

What properties of dendritic cells make them ideal for their function? (2)

A
  • Large surface area

- Multiple dendrites

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22
Q

Why do dendritic cells have a high surface area?

A

Numerous cytoplasmic processes

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23
Q

Why do dendritic cells need to have a high surface area?

A

Need contact with a large number of surrounding cells e.g T cells, NK cells, neutrophils, epithelial cells

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24
Q

Where dendritic precursors found?

A

Bone marrow

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25
Q

What do dendritic precursors do before infection?

A
  • Migrate from bone marrow through bloodstream to non lymphoid tissue
  • Immature state
  • Take up fragments of microbes
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26
Q

What 3 ways do dendritic precursors before infection take up fragments of microbes in tissues?

A
  • Phagocytosis
  • Pinocytosis
  • Endocytosis
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27
Q

What is pinocytosis?

A

Small particles suspended in extracellular fluid are brought into the cell by the budding of small vesicles from the cell membrane

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28
Q

What do dendritic precursors do during pathogen invasion? (8)

A
  • Migrate to lymphoid tissue through chemotaxis
  • On the way:
    1) Differentiate and become active - no more antigen capturing
    2) Process antigens into smaller fragments
    3) Secrete pro inflammatory cytokines
  • To cross epithelium of afferent lymphatic vessels, become round veiled cells, losing dendrites
  • Reach subcapsular sinus of lymph nodes, regain dendrites to become interdigitating dendritic cell
  • Move to T cell zone
  • Present antigens to MHC molecules on T (and B) cells
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29
Q

What is the purpose of the dendrites on dendritic cells when they are presenting antigens?

A

Lymphocytes crawl over dendrites looking for microbial antigens

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30
Q

Why do immune system cells look similar?

A

Genes encoding them sit close together on chromosomes

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31
Q

What do all immune system cells show in terms of structure?

A
  • Homogeneity

- Conservatism

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32
Q

Where do antigens bind to T cells?

A

Immunoglobulin like antigen receptor (T cell receptor - TCR)

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33
Q

Where is the TCR found on a T cell?

A

Cell surface at proximal end of molecule

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34
Q

How can the TCR recognise antigens? (2)

A
  • Small peptide antigen fragments

- Presented by MHC molecules

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35
Q

What does MHC stand for?

A

Major histocompatibility complex

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36
Q

What are MHC molecules often referred to in humans?

A

Human Leukocyte Antigens (HLA)

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37
Q

What are the two classes of MHC molecule?

A

Class I

Class II

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38
Q

What are MHC molecules expressed as?

A

Co-dominants

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39
Q

What does it mean that MHC molecules are expressed as co-dominants?

A

Each individual can express 2 different forms of each product (maternal and paternal)

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40
Q

How many different MHC class I molecules and class II molecules can each individual express?

A

6 of each class

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41
Q

What creates diversity in the varieties of MHC molecules? (2)

A
  • Many different regions of the MHC complex code for different varieties of class I and II
  • MHC molecules expressed as co-dominants
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42
Q

Why is it important for there to be a huge diversity in the number of MHC molecules?

A

So many different types of antigen fragments can be presented to T cells

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43
Q

What are MHC molecules expressed by?

A

Antigen presenting cells

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44
Q

What regions code for MHC class I molecules? (3)

A
  • B
  • C
  • A
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45
Q

What regions code for MHC class II molecules? (3)

A
  • DP
  • DQ
  • DR
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46
Q

What MHC molecule subtype does the DP region code for?

A

DP alpha beta

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47
Q

What MHC molecule subtype does the DQ region code for?

A

DQ alpha beta

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48
Q

What MHC molecule subtype does the DR region code for?

A

DR alpha beta

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49
Q

What MHC molecule subtype does the B region code for?

A

HLA-B

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50
Q

What MHC molecule subtype does the C region code for?

A

HLA-C

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51
Q

What MHC molecule subtype does the A region code for?

A

HLA-A

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52
Q

What does the TCR not bind to?

A

Free floating/soluble antigens

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53
Q

What size of peptide fragments do MHC class I molecules present?

A

6-16 amino acid residues

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54
Q

What type of cells express MHC class I molecules? Give 3 exceptions.

A

All nucleated cells except

  • Neurones
  • Sperm cells
  • Certain placenta cells
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55
Q

What type of cells express MHC class II molecules? Give 3 examples.

A

Antigen presenting cells

  • Dendritic cells
  • B cells
  • Macrophages
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56
Q

What size of peptide fragments do MHC class II molecules present?

A

Larger - 30+ amino acid residues

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57
Q

What are the 2 types of antigen?

A
  • Endogenous

- Exogenous

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58
Q

What are endogenous antigens? (2)

A
  • Synthesised within cells

- Self/non self

59
Q

Give an example of an endogenous antigen

A

Virus

60
Q

What class of MHC presents endogenous antigens?

A

Class I

61
Q

What are exogenous antigens? (2)

A
  • From outside the cell

- Self/non self

62
Q

Give 2 examples of endogenous antigens

A
  • Bacteria

- Toxins

63
Q

What class of MHC presents exogenous antigens?

A

Class II

64
Q

Why do 2 different classes of MHC present the different types of antigens?

A

Ensures efficiency - different antigen sources handled differently, different T cells activated

65
Q

What are the 2 main types of T lymphocyte?

A
  • T helper cells

- T cytotoxic cell (TCL)

66
Q

What are the 2 types of T helper cell?

A
  • Th1

- Th2

67
Q

Aside from T helper cells and TCLs, what are some other T cell types? (2)

A
  • T regulatory cells

- Th17 (effector memory T cell)

68
Q

What do T helper 1 cells do?

A

Help macrophages

69
Q

What do T helper 2 cells do?

A

Help B cells

70
Q

What type of co-receptor do both T helper cell types have?

A

CD4

71
Q

What does CD stand for in T cells?

A

Cluster of differentiation

72
Q

What is a cluster of differentiation (CD)?

A

Cell surface molecules expressed on immune system cells

73
Q

What are clusters of differentiation (CD)s used for?

A

Cell identification for phenotyping - identifying presence/proportion of various populations

74
Q

What type of antigen do both T helper cell types recognise and as such what MHC class presents to them?

A

Exogenous

Class II MHC

75
Q

What type of co-receptor do T regulatory and Th17 cells have?

A

CD4

76
Q

What type of antigen do both T regulatory and Th17 cells recognise and as such what MHC class presents to them?

A

Exogenous

Class II MHC

77
Q

What type of co-receptor do T cytotoxic cells have?

A

CD8

78
Q

What type of antigen do T cytotoxic cells have recognise and as such what MHC class presents to them?

A

Endogenous

Class I MHC

79
Q

Explain the MHC class I antigen processing and presentation of endogenous antigens (10)

A
  • Production of protein in cytosol
  • Ubiquitinated and unfolded to give characteristics
  • Cytosolic linear protein degraded in proteosome into fragments (8-10 peptides)
  • Trafficked into ER through TAP
  • ER produces MHC class I molecules
  • Stabilised by beta 2 molecule
  • Peptide - class I complexes assembled
  • Triggered for export through exocytosis
  • Surface expression of peptide-class I complexes
  • Presented to T cell
80
Q

Explain the MHC class II antigen processing and presentation of exogenous antigens (9)

A
  • Extracellular protein uptake into vesicular APC compartments
  • Internalised proteins processed in endosomal/lysosomal vesicles
  • Enzymes chop proteins into 12-20 amino acid peptide chains
  • Class II synthesised in ER at same time as class I
  • But blocked by CLIP chain from binding
  • Class II MHC molecules transported to endosomes in exocytic vesciles
  • DM takes off CLIP to allow binding
  • Fuse with processed peptides in vesicles
  • Exocytosis: peptide MHC complexes expressed on cell surface
81
Q

What is CLIP protein?

A

Class II-associated invariant chain peptide

82
Q

What is the purpose of CLIP protein?

A

Stops class II MHC molecules binding to anything (e.g class I MHC/self antigens) before full synthesis and transport to endo/lyosomes

83
Q

What two signals does T cell activation require?

A
  • Signal 1: antigen-specific

- Signal 2: co-stimulation

84
Q

What is signal 1 in T cell activation?

A

Antigen specific signal where MHC molecules present peptides to TCR

85
Q

What is signal 2 in T cell activation?

A

Co-stimulation where CD28 on a T cell is stimulated by B7 on APC (two types: CD86+CD80)

86
Q

Where does co-stimulation happen on a T cell?

A

Synapse between APC and T cell

87
Q

What are the 3 stages of T helper cell activation? (3)

A
  • Recognition
  • Proliferation
  • Differentiation
88
Q

What do T helper cells start producing after recognition to drive proliferation?

A
  • IL2

- IL2 receptors

89
Q

What is IL2 and IL2 receptors specific to in T cells?

A

Peptide derived from pathogen

90
Q

What cytokines are produced by Th1 cells? (3)

A
  • IFN gamma
  • TNF
  • IL-2
91
Q

What cytokines are produced by Th2 cells? (3)

A
  • IL-4
  • IL-5
  • IL-10
92
Q

What effect does cytokine IFN gamma have? (3)

A
  • Macrophage activation
  • Increased MHC expression
  • Nk cell activation
93
Q

What type of bacteria and viruses do Th1 cells act on?

A

Intracellular

94
Q

What type of bacteria, viruses and parasites do Th2 cells act on?

A

Extracellular

95
Q

What effect does cytokine TNF have? (3)

A
  • Macrophage activation
  • Neutrophil activation
  • Kills tumour cells
96
Q

What effect does cytokine IL-2 have? (2)

A
  • T cell growth

- CTL growth and activation

97
Q

What is the immune response of Th1 cells like in comparison to Th2 cells?

A

Very damaging - lots of macrophages and phagocytic activity

98
Q

What response needs dampening to reduce tissue damage in immunopathology?

A

Th1 response

99
Q

How can viruses be processed by both class I and class II MHC molecules?

A
  • Viral proteins made in cells: endogenous antigens

- Viral debris outside of cell: exogenous antigen

100
Q

What effects does cytokine IL-4 have? (4)

A
  • B cell activation
  • Switch factor for IgE
  • Mast cell generation
  • Differentiation of naive T cells to Th2 cells = positive feedback loop
101
Q

What effects does cytokine IL-5 have? (3)

A
  • IgA synthesis
  • B cell growth
  • Eosinophil activation
102
Q

What effects does cytokine IL-10 have? (3)

A
  • Inhibits macrophage activation
  • Activates B cells
  • Stimulates Th2 cells
103
Q

What does the Th2 helper cell being less destructive than the Th1 response mean?

A

If we can divert response here, less immunopathology

104
Q

Why is the Th2 response less destructive than the Th1 response? (2)

A
  • Antibody mediated

- Inhibits macrophage activity

105
Q

Explain how a naive CD4 cell is activated to become a CD4 Th2 cell (3)

A
  • Antigen uptake and processing by dendritic cells
  • Migration to local lymph nodes
  • Dendritic cell presents peptides to naive CD4+ T cell in groove of class II MHC molecule
106
Q

What are dendritic cells known as in the skin?

A

Langerhan’s cells

107
Q

How are Langerhan’s cells a specialised form of dendritic cells? (2)

A
  • Can activate “virgin” T cells

- Not seeking to be activated through presenting antigen

108
Q

What do dendritic cells condition with T helper cells?

A

What type the naive CD4 cell becomes - different type of immunity

109
Q

Explain the process leading to B cell: T cell collaboration (4)

A
  • B cells internalise and process antigen
  • After binding to surface immunoglobulin
  • B cells activated b/c antigen binding
  • B cells and T cells migrate into “follicles”
110
Q

Explain what B cell: T cell collaboration leads to from a Th2 cell (2)

A
  • CD40L (ligand) expression

- IL-4 release

111
Q

What is B cell: T cell collaboration?

A

B cells present antigen on MHC class II to CD4 Th2 cells

112
Q

How does B cell: T cell collaboration lead to further B cell activation?

A
  • Il-4 release causes B cell differentiation into plasma cells producing specific antibodies
  • CD40 ligand binds to CD40 on B cells - further activation
113
Q

Explain the natural history of the CD4 Th1 response (4)

A
  • Dendritic cells produce IL-12
  • Conditions naive CD4 cell to become CD4 Th1 cell
  • Leaves lymph node
  • CD40L/CD40 interaction between Th1 cell and macrophages = macrophage activation
114
Q

What do cytoxic CD8+ T cells do?

A

Kill target cells at infection sites

115
Q

What two signals are needed to activate a CD8 T cell?

A
  • Signal 1: MHC class I/TCR

- Signal 2: B7 costimulation

116
Q

What 2 substances are released by CD8 T cells as part of their effector function?

A
  • Cytokines

- Cytotoxic granules

117
Q

What do cytokines do when released by CD8 T cells?

A

Alter behaviour of target cell to make it more susceptible to being killed by T cell

118
Q

What do cytotoxins do when released by CD8 T cells?

A

Kill target cell by apoptosis

119
Q

What are the 2 types of cell death?

A
  • Necrosis

- Apoptosis

120
Q

What is necrosis caused by?

A

Physical/chemical injury

121
Q

Give an example of necrosis in the immune response

A

Phagocytosis

122
Q

What is apoptosis?

A

Programmed cell death

123
Q

What is activated to carry out apoptosis?

A

Endogenous endonucleases

124
Q

What is the mechanism of apoptosis?

A

DNA fragmentation in 200bp multiples

125
Q

What signal is not required for armed effector CD8+ T cells to respond to target cells to kill them?

A

B7 co-stimulation signal 2

126
Q

What signal is required for armed effector CD8+ T cells to respond to target cells to kill them?

A

Signal 1: MHC class I/TCR of target cells bearing specific antigen

127
Q

How do CD8+ T cells prevent collateral tissue damage in cytotoxic granule release?

A

Highly polarised release aligned along immune synapse

128
Q

What do cytotoxic granules released by CD8+ T cells contain? (2)

A
  • Perforin

- Granzymes

129
Q

What is the function of perforin?

A
  • Produces ion channels in target cell membrane

- Causes osmotic lysis

130
Q

What does perforin allow to enter target cells?

A

Granzymes also in cytoxic granules to enter target cell

131
Q

What is the function of granzymes? (3)

A
  • Cleave proteins in virus
  • Shut down viral protein production
  • Causes apoptosis of target cell
132
Q

What type of chemical are granzymes?

A

Serine proteases

133
Q

What cytokine do CD8+ T cells secrete primarily to kill cells?

A

TNF alpha

134
Q

What effect does TNF alpha cytokine released by CD8+ T cells have? (3)

A
  • Interacts with receptors on target cell to initiate apoptosis
  • Increased expression of MHC Class I and Class II molecules
  • Activates eosinophils/neutrophils/macrophages
135
Q

What two types of target cell do cytotoxic T cells target?

A
  • Tumour cells

- Virally infected cells

136
Q

What does TNF stand for?

A

Tumour necrosis factor

137
Q

What cell interactions aid in CD8+ T cell destruction of infected cells?

A

Fas/FasL interaction

138
Q

Explain the Fas/Fas L interaction (2)

A
  • Activated CD8+ T cells express FasL on target cell surface

- Binds to Fas receptor on target cell

139
Q

What does the Fas/FasL interaction lead to?

A

Pulls together signalling molecules activating caspase cascade = target cell apoptosis

140
Q

Explain the structure of an MHC Class I molecule (3)

A
  • Alpha (heavy chain)
  • In non covalent complex
  • With beta 2 microglobulin
141
Q

Explain the structure of an MHC Class II molecule

A

2 MHC encoded polymorphic chains (alpha and beta)

142
Q

Summarise the MHC class I antigen presenting process

A

Cytosolic proteins are proteolytically degraded in the proteasome

143
Q

Summarise the MHC class II antigen presenting process

A

Extracellular proteins are internalised into endosomes

Body Defence (11 decks)

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