T CELLS AND ADAPTIVE Flashcards
1
Q
What is cell mediated immunity?
A
Defense against intracellular microbes –> needed when pathogens resist the antimicrobial activities of pathogens
2
Q
What stimulates the ability of macrophages to kill ingested phagocytes?
A
- T cells
3
Q
What are 3 functions of T cells?
A
- ACTIVATION of phagocytes
- KILLING of infected cells
- HELP for B cells
4
Q
Do naive T cells have effector functions??
A
NO! only effector T cells. Naive T cells must first be activated
5
Q
What happens once naive T cells recognise antigen in the peripheri?
A
- Proliferation of T cells and differentiation into effector T cells and memory T cells is INITIATED
6
Q
What are the GENERAL steps for T cell activation and where does it occur?
A
Naive T cells recognise MHC: peptide on professional APC
- Lymph node
- T cells produce IL-2 cytokine and also have IL-2 receptor (thus autocrine signalling)
- IL-2 binding causes T cell proliferation
- Differentiates into effector T cells and memory T cells and goes out into peripheri
7
Q
Do ALL T cells go into effector organs/tissues?
A
- NO! Some T cells stay in lymph nodes
- Eradicate infected cells OR give signals to B cells –> antibody
8
Q
Where do naive T lymphocytes travel and what do they do?
A
- Constantly circulate through peripheral lymphoid organs to FIND ANTIGENS matching their receptor
9
Q
What are the 5 different factors (general) needed on T cells to recongise the ligands on APCs and allow for activation of T cells?
A
- TCR
- CD4/CD8 coreceptor molecules
- Adhesion molecules
- Costimulator molecule binding to costimulatory receptor on naive T cell
- Cytokines to amplify T cell response
10
Q
What recognises both complexes of peptide antigen and MHC on APCs? (signal 1)?
A
- TCR + CD4/CD8 coreceptor
11
Q
Do the TCR alpha and beta chain both take part in atnigen recognition?
A
- YES!
12
Q
Where do the CD4/CD8 coreceptors recosgnise the class I/II MHC?
A
- At a site DIFFERENT to the peptide binding cleft
13
Q
Which T cell surface molecule does signal transduction by TCR complex?
A
- CD3 (x3) + zeta chain
- Transmits the biochemical signals
14
Q
Do CD3 and zeta proteins stay the same or different in different T cells?
A
- Stay the SAME (invariant)
15
Q
What is the role of adhesion molecules in T cell responses?
A
- Recognise their specific ligands and STABILISE binding of T cells to APC (DC)
- Bc. T cells usually bind with low affinity so adhesion molecules allow there to be time for signalling interaction to occur. E.g. integrins (LFA-1) –> APC ligand —> iCAM-1
16
Q
What does ‘costimulator’ mean?
A
- Molecules that provide stimuli to T cells that function together with antigen’
e. g. CD80 and CD86 (B7 molecules) (APCs express this and increases expression with microbe detection)
17
Q
Which receptor on T cells recognises CD80 and CD86 (B7) molecules?
A
CD28 receptor which is essential for naive T cell activation
18
Q
What would occur without CD28:CD80/86 ?
A
NOTHING
- No activation–> anitgen recognition by TCR would not be enough for T Cell activation
19
Q
What does costimulation ensure?
A
- Makes sure T cells aren’t activated by random substances that are not harmful (autoreactivity)
20
Q
Where is the CD40L (ligand) present?
A
- ACTIVATED T CELLS
`
21
Q
Where is CD40 present and what does it do?
A
- Present on APCs (e.g. Dendritic Cells)
- Makes APCs ‘better’ at stimulating T cells
22
Q
Do the CD40 ligand/CD40 directly enhance T cell activation?
A
- NO
23
Q
What happens when CD40L on T cells binds to CD40 on APCs?
A
- Causes the APC to express MORE CD80 (B7) costimulators + secrete cytokines (IL-12)–> Enhances T cell differentiation
24
Q
What do Adjuvants do?
A
- They are products of microbes sometimes and induce expression of costimlators (APCs)–> stimulate APCs to secrete cytokines
25
What are the inhibitory receptors of T cells?
- CTLA-4
| - PP-1
26
What does CTLA-4 recognise?
- CD80 and CD86 (B71 and 2) on APCs
27
What do the inhibitory receptors of T cells (CTLA-4 and PP1 do?
- Induced in activated T cells and terminate responsiveness of T cells
- Evolved to PREVENT immune responses against SELF antigens
28
What does the activation of CD8 T cells require?
- Class I MHC
- Costimulation
- CD4+ T cells (Helper)
29
What does the differentiation of T (CD8) cells into active T cells + memory cells require?
- CD4 T cells --> can produce cytokines or membrane molecules to help activate CD8T cells
30
What level of protein synthesis do proteins have?
LOW
31
Which 3 biochem processes does antigen recognition involve?
Activation of enzymes
Adaptor protein recruitment
Production of transcription factors
32
When are the biochem pathways activated?
When TCR complexes + coreceptor are brought together by binding to mhc:peptide complex
33
Do the proteins come together with cell-cell contact?
YES! TCR complex, CD4/CD8 coreceptors, CD28 come together to form the PERIPHERAL RING
34
What is required for optimal induction of activating signals in T cell?
Redistribution of signalling and adhesion molecules
35
What is the immune synapse?
Region of contact b/w APC and T cell (including redistributed proteins
36
What is CD69?
Marker of T cell activation (cell migration)
37
What does IL-2 do?
- Promote T cell survival signal and proliferation
38
What does CTLA-4 do?
Inhibits immune responses
39
What is cFos?
- Transcription factor involved in expression of the naive T cell
40
Which protein kinase does CD4 and CD8 coreceptors facilitate signalling through?
- Lck
41
What are ITAMs found on and what are they critical for?
- Immunoreceptor Tyrosine Based Activation Motif
- critical for signalling
- CD3 + zeta chain contain these
42
What contains the ITAMs?
CD3 and zeta chain
43
What is Lck brought near the TCR by?
- CD4/CD8 molecules
44
What are the 4 major signalling pathways linked to the zeta chain and phosphorylated ZAP70?
1. Calcium-NFAT pathway
2. Ras/Rac-MAPK pathway
3. PKCtheta-NF-kappa B pathway
4. PI3K pathway
45
What is NFAT?
- Transcription factor inactive when phosphorylated in resting T cells
46
What does NFAT activation and nuclear translocation depend on?
- Ca2+ ions in cytosol
47
What is the calcium NFAT-pathway iniitated by ?
- ZAP70 and activation of phospholipase C
48
What does activation of transcription factors in T cells lead to and what are the transcription factors?
- NFAT
- AP-1
- NF-kappaB
- Activation of TFs in T cells leads to stimulation of transcription and cytokines, cytokine receptors, cell cycle inducers, effector molecules like CD40 ligand
49
Which general metabolic changes occur when T Cell are activated?
- INCREASE in glucose uptake, increase in amino acid synthesis, + building blocks for organelles
50
Which type of T cell secretes IL-2 in response to antigens and costimulators?
- CD4+ T cells
51
What happens after CD4 T cells secrete IL-2?
- Increase in the expression of high affinity Il-2 receptor
| - So T cells can respond and bind to Il-2 receptor
52
What is the structure of the Il-2 receptor and which cells excpress it/in what form?
- 3 chain molecule
| - Naive T cells express LOW AFFINITY complex (2 chains )
53
How does activation of T cells by antigens and costimulaotrs change the structure and thus function of the IL-2 receptor?
- Allows third chain of Il-2R to be made
| - Il-2R can now bind to Il-2 strognly
54
Why are so many CD8 T cells made compared to CD4+ T cells?
- CD8 T cells have effector functions that kill infected cells DIRECTLY (so is needed to kill large numbers of infected cells)
- CD4 T cells secrete cytokines to HELP other T cells
55
What are the CD4+ T cell subtypes?-
Th1, Th2, Th17, Treg
- migrate from peripheral lymphoid organs to the site of infection --> cytokines then RECRUIT OTHER LEUKOCYTES --> destroy infectious agent
56
When is CD40L transcribed?
- In response to antigen recogition and costimulation
57
What do the T cells that stay in the lymph nodes and migrate to lymph follicles do?
- Help B cells produce antibodies
58
What does the CD40L bind to?
- CD40 receptor on MACROPHAGES, B cells, and DCs
| - These cells are stimulated from CD40L:CD40R interaction
59
Which two cytokines have an effect in keeping Memory T cells alive after infection has gone?
- IL-7 (via upregulation of Bcl2) and Il-15
60
Where can memory T cells be found?
```
Lymphoid organs (central memory cells--> RAPID clonal expansion)
Peripheral tissues (mucosa and skin--> effector memory cells)
Circulation
```
61
where are T cell responses primarily inititated?-
- In secondary lymphoid organs (lymph node and spleen)
62
Where is the effector T cell phase mainly?
- In peripheral tissue at sites of infection
63
Where do naive T cells circulate before encountering DCs in lymph organ?
-Between blood and secondary lymph organs
64
Which 3 families of proteins control T cell migration (naive and effector) ?
- Selectins
- Integrins
- Chemokines
- These regulate migration of ALL leukocytes
65
Which adhesion molecule and chemokine receptor does a naive T cell express?-
- L-selectin (CD 62L)
| - CCR7 receptor
66
Which strucutre do naive T cells migrate to the lymph nodes via?
- HEV
67
What do HEVs do in lymph node?
- Have endothelial cells that express carb ligands --> bind to L-selectin
- Display chemokines only recognised by CCR7
68
What is the process of naive T cell migration?
- Naive T cells in blood (L-selectin rolling interactions with HEV)
- Chemokines can bind to CCR7 on T cells --> intracellular signals
- LFA-1 gets activated on naive T cell
- Increased binding affinity of integrin to ICAM-1
- Increased adhesion of T cells (so they slow down)
- T cells EXIT through endothelial junctions and retained in lymph node
- Goes to T cell zone of stroma (lymph node)
69
Do effector T cells express CCR7 or L-selectin?
NO! Hence don't get drawn to lymph node
70
Is the migration of activated T cells controlled by the same factors as in leykocyte migration?
- YES
71
What do activated T cells epxress a lot of?
- Glycoprotein ligands --> E and P selectins + integrins LFA-1 and VLA-4
72
In T cell migration, what do TNF-alpha and IL-1 act on endothelial cells to increase?
- Act on endothelial cells to INCREASE E, P selectins + ligands for integrins like ICAM1, VCAM-1 (Vascular cell adhesion molecule)
73
Does effector T cells migrating to the infection site (homing of effector T cells) depend on antigen recognition?
- NO!!
- It depends on adhesion molecules and chemokines
(BUT lymphocytes that recognise antigens are preferentially retained at this site )
74
Can any effector T cell in blood enter any site of infection?
- YES!
| - To maximise chances that effector T cells will happen to recognise antigen and help with infection
75
Can any effector T cell be REACTIVATED from ANY host cell displaying peptide:MHC?
- YES! (but not the same for naive T cells)
76
What is expressed on lymphocytes that determines specificity and diversity?
- Antigen recepotrs generated via VDJ recombination
77
What is the clonal selection theory?
one cell-one antibody
- after exposure to a microbe, antigen specific clone "selected" and then proliferates
- Immune response SPECIFIC to that antigen occurs
78
What is clonal expansion?
- Lymphocytes proliferate after activation generating army of clones with a SINGLE SPECIFICITY
79
What is specialisation?
- Tailored responses for effective elimination of specific pathogen
80
What is the contraction of homeostasis?
- The decline of the immune response from apoptosis of lymphocytes AFTER pathogen is elminated
- Homeostasis settled with memory cells
81
Why do we need two types of adaptive immunity?
- Because certain antigens are important for SOME pathogens and not others
e. g. Cholera needs the adaptive immune system
- Bacteria has flagella which innate immune system will recognise BUT won't work because it is the toxin the bacteria secretes that does damage
- SO adaptive response needed to PRODUCE ANTIBODIES TO NEUTRALISE TOXIN
82
Can antibodies block infections from occuring in the first place?
- YES!
| - Can bind to virus infected cell
83
A combination of ___ and _____ activates DCs:
A combination of PRRs and CYTOKINES will activate DCs
84
Why do DCs and T cells BOTH express CCR7?
- So they can MIGRATE to lymph node and come into contact at T cell zone --> adaptive immune response generated
85
What is T cell priming?
- Where the T cell meets the CORRECT/MATCHING DC with peptide
86
What is the role of adaptor proteins such as SH2 and SH3?
- LINK receptors to COMMON signalling pathways in cell
| - mediate protein-protein interactions
87
What is signal 1 for T cell activation?
- Antigen recognition
88
Is signal 1 (Antigen recognition) sufficient for activation of a T cell?
No! (Well technically it is sufficient and not necessary)
| - need signal 2
89
`Can TCR induce signals and why?
- NO
| - Small cytoplasmic domains
90
What does ITAM stand for?
- Immunoreceptor Tyrosine based Activation Motif
91
What is the advantage of CD4/CD8 domains interacting with MHC?
- Coreceptor can be in close proximity to TCR complex
92
What is the function of Lck?
- Interacts with the large cytoplasmic tails of CD4 + CD8
| - Lck phosphorylates ITAMs and creates docking sites
93
What are the 3 parts of signalling?
1. MEMBRANE PROXIMAL EVENTS (Tyrosine is phosphorylated--> activates enzymes--> creates docking sites for adaptor proteins
2. COMMON BIOCHEMICAL SIGNALLING PATHWAYS (Enzymes + 2nd messengers amplify the cell surface signal and transduce signals)
3. TRANSCRIPTION FACTORS ACTIVATED
94
What is the generalised pathway for TCR: peptide recognition/signalling?
TCR recognises peptide: MHC
- CD4/CD8 interacts with MHC in a PEPTIDE INDEPENDENT WAY
- Lck comes into CLOSE PROXIMITY with TCR complex AND phosphorylates tyrosines in ITAMs of CD3 and zeta chains
- ZAP70 (tyrosine K) binds to phosphorylated tyrosines on CD3 and zeta chains which ACTIVATED ZAP70--> proteins phosphorylated--> adaptor proteins + enzymes go into signalling pathway --> 2nd messengers made and TFs activated -- > ACTIVATED T CELL TURNS ON NUMBER OF GENES
95
What does LFA-1 on a T cell bind to?
- ICAM-1 on APC
96
What is signal 2 for T cell activation?
- B7 molecules (CD80 and CD86) on DC
| and CD28 on T cell
97
What is LFA-1 LOW AFFINITY on?
- Naive T cell BEFORE antigen recognition
98
If DC is presenting self MHC: peptide then there is no:
No costimulatory signal
99
What do microbes cause the expression of?
- Costimulatory molecules
| - Signal 2 --> CD28 on T cell is confirming that there is a threat
100
Which 4 things must occur for T cell activation to be SUCCESSFUL?
- Antigen recognition (TCR and peptide: MHC)
- Signal transduction (TCR complex + CD4/CD8 coreceptor)
- ADHESION---> Stabilises T cell-APC interaction (LFA-1 and ICAM1)
- Costimulatory signals (signal transduction via CD28 (T cell) binding to CD80 (DC)
101
which genes are transcribed from signalling pathways?-
- Cell cycle proteins e.g. c-Fos
- Molecules important for effector functions e.g. CD40L
- Molecules that regulate immune response e..g CTLA-4
- Cytokines like IL-2
102
Without IL-2 expression, what DON'T you have?
- No clonal expansion
103
What occurs in T cell activation in terms of IL-2 expression?
- Increased expression of Il-2R alpha chain
- Causes Il-2 to bind with HIGH AFFINITY to IL-2R
- Leads to PROLIFERATION AND SURVIVAL
104
What is the function of CTLA-4?
- Binds to CD80/CD86 (on DC) which leads to DECREASED costimulation, decreased IL-2 expression and decreased proliferation
105
What additional help do CD8 T cells need to be activated?
- Cross presentation
| - Present class II to MHC then class I
106
What does it mean if a T cell becomes anergic?
- Lack of a reaction
| - only requires one instead of 2 signals
107
DO CD4 T cells get activated in close proximity to CD8 T cells?-
YES!
| - So CD4+ helper T cells can Secrete Il-2 which stimulates CD8 T cells
108
How does CD4 T cell help CD8? (2 reasons)
1. Secretes Il-2 (allows CD8 T cell to proliferate more)
| 2. Sends signals to DC to INCREASE costimulators on surface to activate CD8 T cells)
109
What activation in migration are chemokines involved in?
- integrin activation
- Integrin goes from low affinity--> high affintiy
- Also chemotaxis
110
What are integrins important for?
- Stable adhesion of leukocytes to endothelial cells (LFA-1) --> has multiple adhesion functions
111
What is selectin?
- 'A naive T cell home-in molecule'
| - Gets the naive T cell into lymph node
112
Do activated helper T cells differentiate into any type of cell to eliminate a microbe?
- NO! The one that BEST eliminates the pathogen is selected --> e.g. either Th1, Th2, Th17 cells
113
What are CD4+ T helper cells involved with in general?
- intracell (phagocytosed) and EXTRACELLULAR bacteria
| - MHC II presents it CD4+ T cells recognise it --> macroophages and B cells activated --> INFLAMMATION (in general)
114
What are the 3 signals that DCs give to naive T cells?
signal 1: Antigen recognitiopn (TCR recognition of peptide:MHC)
Signal 2: Costimulation signal CD28 (T cell) with CD80/CD86 (B7) proteins on activated DCs
SIgnal 3: Cytokines--> diffrerentiation of helper T cells
115
What do cytokines allow T cells to do?
- Differentiate into various helper T cells
116
`What happens when flagella on microbes is detected? (what PRRS, what cytokine secreted etc)
TLR5 (flagella) and TLR-4 (LPS) activated
- DC recognises it--> secretes IL-12
- STAT 4 and STAT1 (TFs) ACTIVATED
- Th1 cells formed
117
In basic terms what is Th1 responsible for?
- Intracellular microbes
118
In basic terms what is Th2 responsible for?
- Helminths
119
In basic terms what is Th17 responsible for?
- Extracellular fungi and bacteria
120
What is a T0 cell?
- AN ACTIVATED T cell but not differentiated
121
Which cytokine does Th1 secrete, what does it act on (target), which host is it defending and what role does it have in the disease?
- Cytokine: IFN-gamma
- Target cell: Macrophage (paracrine signalling)
- Host defense: intracellular pathogen
- Role in disease is autoimmune diseases and CHRONIC inflammation
122
Which cytokines does Th2 secrete, what is its target cell, which host is it defending, and what role does it play in disease?
- Cytokine: IL-4, Il-5, IL-13
- Target cell: Eosinophils
- Defense: Parasites
- Role in disease : Allergy
123
Which cytokines does Th17 secrete. what is the target cell the cytokines act on, what is the host defense and what role does it play in disease?
- Cytokines: Il-17, IL-22
- Target cell: Neutrophils
- Defense: Extracellular fungi
- Role in disease: Autoimmunity
124
Are T cell cytokines produced all the time?
- NO! Only produced when needed
125
What does it mean when we say T cells and cytokines exhibit pleiotropy?
- That each cell has multiple biological actions
126
What does it mean when we say T cell cytokines are redundant?
MULTIPLE cytokines share the SAME activity
127
What does IL-2 cause?
- T cell activation (via autocrine signalling) and proliferation
128
What does IFN-gamma cause?
- Activation of macrophages
| - from CD4+ CD8+ and NK cells
129
What does IL-5 cause?
- Activation of eosinophils
| - from CD4+ T cells, mast cells, innate lymphoid cells
130
What does IL-4 cause?
- B cell switches--> IgE
| - from CD4T cells and mast cells
131
What does Il-17 cause?***
- Stimulates ACUTE inflammation
- Promotes production of antimicrobial peptides
- from CD4 T cells, and other cells
(not sure what other cells)
132
What does IL-22 cause?
- Maintains epithelial barrier
- Increased barrier integrity
- Promotes the production of antimicrobial peptides
- From CD4+ T cell, NK cells, innate lymphoid cells
133
What does TGF-beta cause?
- Inhibits T cell activation
- Differentiation of Treg cells
- from CD4+ T cells and other cells
134
What are 3 examples of intracellular microbes (ones that evade killing in phagolysosome-not viruses) rthat Th1 cells will work against?
- Leishmania
- TB
- Protozoa
- Lysteria (food borne)
135
For a T0 cell to differentiate into a Th1 cell, which two cytokines does it need to be exposed to and what isthe process?
- IL-12 and INF-gamma
- Intacellular microbes cause DCs and macrophages to secrete IL-12 + NK cells secrete IFN-gamma
- Th1 cell produced
136
Is INF-gamma produced by other Th1 cells?
- YES! Later in the immune response
137
What is the Th1 cell effector function?
- Secretes IFN-gamma --> activates macrophages (classical macrophage activation) ---> makes macrophages BETTER killers of microbes
- Complement activation (opsonisation and phagocytosis)
138
Do CTLs work with Th1 cells sometimes to fight infection?
- YES!
- Th1 cells aren't always on their own e.g. those that escape into the cytosol following phagocytosis
- Th1 cells ACTIVATE macrophages to BETTER kill microbes and CTLs KILL infected macrophages
139
Which cytokines does Th2 secrete?
Il-4, Il-5, IL-13 , acts on parasites like helminths and acts on eosinophils
140
Which cytokine do you need for differentiation T0 cells to Th2 cells?-
- IL-4 secreted by ILC2 and NKT cells (natural killer T cells), and mast and eosinophils
- IL-4 also acts on B cells for IgE production
141
Which cytokines do you need for the differention of T0 cells to Th17 cells ?
- Il-1
- IL-6
- IL-23
- TGF-beta
- These then cause differentiation to Th17 which then secretes IL-22 and IL-17
142
Which Th2 cell cytokines are involved in intestinal mucus secretion and peristalsis (weep and sweep response) ?
- IL-4 and IL-13 (weep-mucus and sweep response)
143
What role do the cytokines IL-4 and IL-13 have with macrophages?
- They ALTERNATIVELY activate macrophages --> M2 macrophages -antiinflammatory
144
Are M2 macrophages inflammatory or antiinflammaotry?
- Antiinflammatory
145
Which cytokine is involved in antobody production and mast cell degranulation (Th2) ?
- IL-4
146
Which Th2 cytokine activates eosinophils?
- Il-5
147
What does Eosinophil activation result from?
- Crosslinking of FceRs by IgE + IL-5 (Th2 cells)
148
What is the Th1/Th2 paradigm?
- There must be a balance between Th1 and Th2 responses
149
In terms of the Th1/Th2 paradigm, what does a strogner Th1 cell response mean?
- There will be a weaker Th2 response
| - TH1 cytokines will INHIBIT Th2 differentiation via IFN-gamma
150
What do Th1 cells inhibit the Th2 differentiation with ?
- IFN-gamma
151
What do Th2 cells inhibit the Th1 cell response with (cytokine)?
Il-4 at the developmental level
152
What are M1 macrophages?
- Proinflammatory
| - Dangerous cells (lots of chemokines, cytokines and lysosomal enzymes)
153
What are M2 macropohges and which cytokine inihibits the M1 macrophage?
- Antiinflammatory
| - IL-10 and TGF-beta inhibit inflammation and IL-4 and Il-13 (Th2) inhibit M1 macrophage activation
154
Is the Th1/Th2 balance affected by both environmental and genetic factors?
- YES! e.g. high or low fibre diet and UV
155
What are the effects of Th1 cells causing pathology?
- Chronic inflammation will occur
- Activation of M1 and pro inflammatory cytokines
e. g. Inflammatory bowel disease (autoimmune disease)
- tH CELLS, CTL and B cells involved
156
What happens when Th2 cells go bad?
- Asthma, anaphylaxis, allergic rhinitis
- Reexposure to allergen = mast cell degranulation, histamine release and cytokine production
- IgE binds to the Fc receptor on mast cell
157
What are Treg cells important in?
- Regulation of balance between Th1/Th2 cells
| - Secrete TGF-beta to suppress differentiation and proliferation of Th1 and Th2 cells
158
What are three examples of conditions that Th17 cells work against?
- Staph aureus
- Pneumoniae (klebsiella pnemoniae)
- Candida albicans (thrush)
159
Which 4 cytokines drive the differentiation of T cells?
- IL-1
- IL-6
- IL-23
- TGF-beta
These switch on RORy + STAT 3 : T0--> Th17
160
What does IL-17 do?
- INDIRECTLY attracts neutrophil to site of infection
| - Acts on other cells and induces them to secrete pro inflammatory cytokines and chemokines to INCREASE inflammation
161
What does IL-22 do?
- Acts on endothelial cells to enhance integrity of epithelial barriers
162
What do IL-17 and IL-22 act together to do?
- Promote the production of antimicrobial peptides =DEFENSINS (Cause microbe to lyse)
163
What are 3 exmaples og conditions that CTL try to eliminate?
- Cytosolic microbes (Influenza and ebola)
| - Tumor cells (melanoma)
164
Which cytokine is needed to help CD8 T cells to activate and differentiate?
- IL-2 needed
165
What are the CD8 T cell effector functions?
-Perforin and granzymes in CTL granules
166
When do CTLs become activated?
- After recognition of peptide:MHC on target cells (immune synapse forms)
167
What does perforin do?
- Pokes pores in target cell membrane and vesicle membrane
- Allows GRANZYME B to enter
- GRANZYME B activates caspases --> APOPTOSIS
168
What is an effector funcion of CD8 T cells ?
- Can secrete IFN-gamma --> upregulates MHC class I expression (more likely CD8 T cell will recognise)
- inhibit viral replication
169
What does IFN-gamm cause for Th1 differentiation andf macrophages?
- Increases Th1 differentiation (intracellular microbes)
| - Increases Macrophage activation (become better killers)
170
Do CTLs, Igs and Th1 cells all cooperate in viral infections?
- YES!
- Antibodies work to neutralise virus (prevents entry in cells)
- CTLs KILL viral cells
- Th1 cells result in CTL differentiation and HELP B cells prosduce neutralising Igs
