Adaptive Immune Response - T Cells Flashcards
(143 cards)
1
Q
When are T cells induced into the immune response?
A
After inflammatory and innate response starts to control pathogens
2
Q
Why do virally infected cells need to be removed? (2)
A
- Stop virus creating more virus particles
- Stop infection of neighbouring cells
3
Q
What does the first green bell curve in a viral infection graph represent?
A
Innate production of interferons (IFN)
4
Q
What does the second blue bell curve in the viral infection graph represent?
A
Innate NK-mediated killing
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
6
Q
When does virus load remain constant? (2)
A
- During innate production of interferons
- During innte NK mediated killing
7
Q
When does virus load start decreasing?
A
During adaptive B cell and T cell response
8
Q
Where are T lymphocytes produced?
A
Bone marrow
9
Q
Where do T lymphocytes mature?
A
Thymus
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
11
Q
What is the result of errors in thymic education?
A
Autoimmunity
12
Q
What type of mechanisms are in place to prevent errors in thymic education and subsequent autoimmunity?
A
Peripheral
13
Q
What happens to T lymphocytes after thymic education?
A
Enter circulation as non self reactive T cells
14
Q
What do T lymphocytes do in circulation?
A
Work with B cells to provide different types of immune response
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
16
Q
Label the lymph node diragram
A
See Morgan lecture and histology lecture
17
Q
What is the main type of antigen presenting cell? (APC)
A
Dendritic cell
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
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
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
21
Q
What properties of dendritic cells make them ideal for their function? (2)
A
- Large surface area
- Multiple dendrites
22
Q
Why do dendritic cells have a high surface area?
A
Numerous cytoplasmic processes
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
24
Q
Where dendritic precursors found?
A
Bone marrow
25
What do dendritic precursors do before infection?
- Migrate from bone marrow through bloodstream to non lymphoid tissue
- Immature state
- Take up fragments of microbes
26
What 3 ways do dendritic precursors before infection take up fragments of microbes in tissues?
- Phagocytosis
- Pinocytosis
- Endocytosis
27
What is pinocytosis?
Small particles suspended in extracellular fluid are brought into the cell by the budding of small vesicles from the cell membrane
28
What do dendritic precursors do during pathogen invasion? (8)
- 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
29
What is the purpose of the dendrites on dendritic cells when they are presenting antigens?
Lymphocytes crawl over dendrites looking for microbial antigens
30
Why do immune system cells look similar?
Genes encoding them sit close together on chromosomes
31
What do all immune system cells show in terms of structure?
- Homogeneity
| - Conservatism
32
Where do antigens bind to T cells?
Immunoglobulin like antigen receptor (T cell receptor - TCR)
33
Where is the TCR found on a T cell?
Cell surface at proximal end of molecule
34
How can the TCR recognise antigens? (2)
- Small peptide antigen fragments
| - Presented by MHC molecules
35
What does MHC stand for?
Major histocompatibility complex
36
What are MHC molecules often referred to in humans?
Human Leukocyte Antigens (HLA)
37
What are the two classes of MHC molecule?
Class I
| Class II
38
What are MHC molecules expressed as?
Co-dominants
39
What does it mean that MHC molecules are expressed as co-dominants?
Each individual can express 2 different forms of each product (maternal and paternal)
40
How many different MHC class I molecules and class II molecules can each individual express?
6 of each class
41
What creates diversity in the varieties of MHC molecules? (2)
- Many different regions of the MHC complex code for different varieties of class I and II
- MHC molecules expressed as co-dominants
42
Why is it important for there to be a huge diversity in the number of MHC molecules?
So many different types of antigen fragments can be presented to T cells
43
What are MHC molecules expressed by?
Antigen presenting cells
44
What regions code for MHC class I molecules? (3)
- B
- C
- A
45
What regions code for MHC class II molecules? (3)
- DP
- DQ
- DR
46
What MHC molecule subtype does the DP region code for?
DP alpha beta
47
What MHC molecule subtype does the DQ region code for?
DQ alpha beta
48
What MHC molecule subtype does the DR region code for?
DR alpha beta
49
What MHC molecule subtype does the B region code for?
HLA-B
50
What MHC molecule subtype does the C region code for?
HLA-C
51
What MHC molecule subtype does the A region code for?
HLA-A
52
What does the TCR not bind to?
Free floating/soluble antigens
53
What size of peptide fragments do MHC class I molecules present?
6-16 amino acid residues
54
What type of cells express MHC class I molecules? Give 3 exceptions.
All nucleated cells except
- Neurones
- Sperm cells
- Certain placenta cells
55
What type of cells express MHC class II molecules? Give 3 examples.
Antigen presenting cells
- Dendritic cells
- B cells
- Macrophages
56
What size of peptide fragments do MHC class II molecules present?
Larger - 30+ amino acid residues
57
What are the 2 types of antigen?
- Endogenous
| - Exogenous
58
What are endogenous antigens? (2)
- Synthesised within cells
| - Self/non self
59
Give an example of an endogenous antigen
Virus
60
What class of MHC presents endogenous antigens?
Class I
61
What are exogenous antigens? (2)
- From outside the cell
| - Self/non self
62
Give 2 examples of endogenous antigens
- Bacteria
| - Toxins
63
What class of MHC presents exogenous antigens?
Class II
64
Why do 2 different classes of MHC present the different types of antigens?
Ensures efficiency - different antigen sources handled differently, different T cells activated
65
What are the 2 main types of T lymphocyte?
- T helper cells
| - T cytotoxic cell (TCL)
66
What are the 2 types of T helper cell?
- Th1
| - Th2
67
Aside from T helper cells and TCLs, what are some other T cell types? (2)
- T regulatory cells
| - Th17 (effector memory T cell)
68
What do T helper 1 cells do?
Help macrophages
69
What do T helper 2 cells do?
Help B cells
70
What type of co-receptor do both T helper cell types have?
CD4
71
What does CD stand for in T cells?
Cluster of differentiation
72
What is a cluster of differentiation (CD)?
Cell surface molecules expressed on immune system cells
73
What are clusters of differentiation (CD)s used for?
Cell identification for phenotyping - identifying presence/proportion of various populations
74
What type of antigen do both T helper cell types recognise and as such what MHC class presents to them?
Exogenous
| Class II MHC
75
What type of co-receptor do T regulatory and Th17 cells have?
CD4
76
What type of antigen do both T regulatory and Th17 cells recognise and as such what MHC class presents to them?
Exogenous
| Class II MHC
77
What type of co-receptor do T cytotoxic cells have?
CD8
78
What type of antigen do T cytotoxic cells have recognise and as such what MHC class presents to them?
Endogenous
| Class I MHC
79
Explain the MHC class I antigen processing and presentation of endogenous antigens (10)
- 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
Explain the MHC class II antigen processing and presentation of exogenous antigens (9)
- 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
What is CLIP protein?
Class II-associated invariant chain peptide
82
What is the purpose of CLIP protein?
Stops class II MHC molecules binding to anything (e.g class I MHC/self antigens) before full synthesis and transport to endo/lyosomes
83
What two signals does T cell activation require?
- Signal 1: antigen-specific
| - Signal 2: co-stimulation
84
What is signal 1 in T cell activation?
Antigen specific signal where MHC molecules present peptides to TCR
85
What is signal 2 in T cell activation?
Co-stimulation where CD28 on a T cell is stimulated by B7 on APC (two types: CD86+CD80)
86
Where does co-stimulation happen on a T cell?
Synapse between APC and T cell
87
What are the 3 stages of T helper cell activation? (3)
- Recognition
- Proliferation
- Differentiation
88
What do T helper cells start producing after recognition to drive proliferation?
- IL2
| - IL2 receptors
89
What is IL2 and IL2 receptors specific to in T cells?
Peptide derived from pathogen
90
What cytokines are produced by Th1 cells? (3)
- IFN gamma
- TNF
- IL-2
91
What cytokines are produced by Th2 cells? (3)
- IL-4
- IL-5
- IL-10
92
What effect does cytokine IFN gamma have? (3)
- Macrophage activation
- Increased MHC expression
- Nk cell activation
93
What type of bacteria and viruses do Th1 cells act on?
Intracellular
94
What type of bacteria, viruses and parasites do Th2 cells act on?
Extracellular
95
What effect does cytokine TNF have? (3)
- Macrophage activation
- Neutrophil activation
- Kills tumour cells
96
What effect does cytokine IL-2 have? (2)
- T cell growth
| - CTL growth and activation
97
What is the immune response of Th1 cells like in comparison to Th2 cells?
Very damaging - lots of macrophages and phagocytic activity
98
What response needs dampening to reduce tissue damage in immunopathology?
Th1 response
99
How can viruses be processed by both class I and class II MHC molecules?
- Viral proteins made in cells: endogenous antigens
| - Viral debris outside of cell: exogenous antigen
100
What effects does cytokine IL-4 have? (4)
- B cell activation
- Switch factor for IgE
- Mast cell generation
- Differentiation of naive T cells to Th2 cells = positive feedback loop
101
What effects does cytokine IL-5 have? (3)
- IgA synthesis
- B cell growth
- Eosinophil activation
102
What effects does cytokine IL-10 have? (3)
- Inhibits macrophage activation
- Activates B cells
- Stimulates Th2 cells
103
What does the Th2 helper cell being less destructive than the Th1 response mean?
If we can divert response here, less immunopathology
104
Why is the Th2 response less destructive than the Th1 response? (2)
- Antibody mediated
| - Inhibits macrophage activity
105
Explain how a naive CD4 cell is activated to become a CD4 Th2 cell (3)
- 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
What are dendritic cells known as in the skin?
Langerhan's cells
107
How are Langerhan's cells a specialised form of dendritic cells? (2)
- Can activate "virgin" T cells
| - Not seeking to be activated through presenting antigen
108
What do dendritic cells condition with T helper cells?
What type the naive CD4 cell becomes - different type of immunity
109
Explain the process leading to B cell: T cell collaboration (4)
- 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
Explain what B cell: T cell collaboration leads to from a Th2 cell (2)
- CD40L (ligand) expression
| - IL-4 release
111
What is B cell: T cell collaboration?
B cells present antigen on MHC class II to CD4 Th2 cells
112
How does B cell: T cell collaboration lead to further B cell activation?
- Il-4 release causes B cell differentiation into plasma cells producing specific antibodies
- CD40 ligand binds to CD40 on B cells - further activation
113
Explain the natural history of the CD4 Th1 response (4)
- 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
What do cytoxic CD8+ T cells do?
Kill target cells at infection sites
115
What two signals are needed to activate a CD8 T cell?
- Signal 1: MHC class I/TCR
| - Signal 2: B7 costimulation
116
What 2 substances are released by CD8 T cells as part of their effector function?
- Cytokines
| - Cytotoxic granules
117
What do cytokines do when released by CD8 T cells?
Alter behaviour of target cell to make it more susceptible to being killed by T cell
118
What do cytotoxins do when released by CD8 T cells?
Kill target cell by apoptosis
119
What are the 2 types of cell death?
- Necrosis
| - Apoptosis
120
What is necrosis caused by?
Physical/chemical injury
121
Give an example of necrosis in the immune response
Phagocytosis
122
What is apoptosis?
Programmed cell death
123
What is activated to carry out apoptosis?
Endogenous endonucleases
124
What is the mechanism of apoptosis?
DNA fragmentation in 200bp multiples
125
What signal is not required for armed effector CD8+ T cells to respond to target cells to kill them?
B7 co-stimulation signal 2
126
What signal is required for armed effector CD8+ T cells to respond to target cells to kill them?
Signal 1: MHC class I/TCR of target cells bearing specific antigen
127
How do CD8+ T cells prevent collateral tissue damage in cytotoxic granule release?
Highly polarised release aligned along immune synapse
128
What do cytotoxic granules released by CD8+ T cells contain? (2)
- Perforin
| - Granzymes
129
What is the function of perforin?
- Produces ion channels in target cell membrane
| - Causes osmotic lysis
130
What does perforin allow to enter target cells?
Granzymes also in cytoxic granules to enter target cell
131
What is the function of granzymes? (3)
- Cleave proteins in virus
- Shut down viral protein production
- Causes apoptosis of target cell
132
What type of chemical are granzymes?
Serine proteases
133
What cytokine do CD8+ T cells secrete primarily to kill cells?
TNF alpha
134
What effect does TNF alpha cytokine released by CD8+ T cells have? (3)
- Interacts with receptors on target cell to initiate apoptosis
- Increased expression of MHC Class I and Class II molecules
- Activates eosinophils/neutrophils/macrophages
135
What two types of target cell do cytotoxic T cells target?
- Tumour cells
| - Virally infected cells
136
What does TNF stand for?
Tumour necrosis factor
137
What cell interactions aid in CD8+ T cell destruction of infected cells?
Fas/FasL interaction
138
Explain the Fas/Fas L interaction (2)
- Activated CD8+ T cells express FasL on target cell surface
| - Binds to Fas receptor on target cell
139
What does the Fas/FasL interaction lead to?
Pulls together signalling molecules activating caspase cascade = target cell apoptosis
140
Explain the structure of an MHC Class I molecule (3)
- Alpha (heavy chain)
- In non covalent complex
- With beta 2 microglobulin
141
Explain the structure of an MHC Class II molecule
2 MHC encoded polymorphic chains (alpha and beta)
142
Summarise the MHC class I antigen presenting process
Cytosolic proteins are proteolytically degraded in the proteasome
143
Summarise the MHC class II antigen presenting process
Extracellular proteins are internalised into endosomes
