cmb2004 > lecture 5 > Flashcards

lecture 5 Flashcards

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1
Q

what is the method of T cell mediated immunity?

A
  1. naive T cells (that have survived +ve and -ve selection) leave the thymus
  2. recirculate via blood/lymphatics through secondary lymphoid tissue
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2
Q

what do naive T cells express?

A

either CD4 or CD8

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3
Q

how do naive T cells become effector/memory T cells?

A

when encounter an antigen

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4
Q

what does contact with a specific antigen and APC lead to?

A

clonal proliferation and differentiation

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5
Q

what do cd8 T cells do?

A

kill infected cells
cytotoxic effect

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6
Q

what do cd4 T cells do?

A

secrete cytokines
helper effector T cells

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7
Q

what happens in the lymphoid tissue?

A
  1. T cells recognise Ag/MHC on APCs
  2. array of APC found, trap and present Ag (in lymph nodes or spleen where T cells go once leave thymus)
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8
Q

what happens following activation of T cells?

A
  • T cell effects leave the areas and migrate to the sites of infection
    -deals with the start site of pathogen entry
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9
Q

how do naive T cells get where they need to be?

A
  1. enter lymph node from blood via high endothelial venules (HEV)
  2. move into T cell area that is rich in dendritic cells and macrophages (APC)
  3. APC present antigen and deliver other activation signals (cytokines)
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10
Q

what are high endothelial venules?

A

distinct compartments in lymph nodes

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11
Q

what happens to T cells that aren’t activated?

A
  • leave lymph node via cortical sinuses into lymphatics
    -reenter circulation
    -recycled for another day
    -short life span so die if cant eventually find an antigen
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12
Q

what happens when the T cells is activated?

A

-proliferation and activation of cells
-actively blocked from leaving that environment, have to expand there
-once expanded to certain level, they leave back to site where antigen is encountered and can deal with antigen

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13
Q

what are cell adhesion molecules (CAM)?

A

-mediate cell interactions
-molecules expressed on surface of T cells (chemokine receptors), binds ligand s (chemokines) expressed or released by other cells
-synthesised by lots of cells
-acts as sign posts fort cells to follow to work out where to go

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14
Q

what occurs with CAMs in close association to other cells?

A

-mediate cell/cell interactions
-hold cells on the APC so assess whether peptide Mac is capable of recepting

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15
Q

what are the different ways CAMs interact?

A

-naive T cell with HEV
-T cell with APC
-effector T cell and target cell

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16
Q

what happens with T cell contact with APC?

A
  1. T cells contact APC using CAMs
  2. TCR scans APC peptide/ MHC complexes
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17
Q

what happens if TCR doesn’t recognise the APC/MHC complex?

A

disengages

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18
Q

what happens if TCR recognises the APC/MHC complex?

A

signal released

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19
Q

how is the signal released?

A

-TCR gets signal through CD3 signalling complex
-causes T cell mediated response

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20
Q

what are occurs after cell contact with APC?

A

-increases affinity of CAM interactions
-T cell divides
-progeny differentiate to effector cells to produce T cell mediated responses

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21
Q

what 2 molecules are important in cell interactions?

A

LFA-1 and ICAM-1

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22
Q

what is the function of LFA-1 and ICAM-1?

A
  1. LFA-1 and ICAM-1 allow cellist stick together while decision is made about accepting
  2. CD4 holds cells together and interacts with class 2
  3. interaction takes place driving signal to alter this
  4. LFA-1 binds to ICAM-1 as a result of initial interactions - allows the two cells to be locked together and allow signalling to occur if correct peptide that TCR recognises
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23
Q

how does co-stimulation of signal 1 occur?

A
  • T cell receive signal through its CD3 complex
    -if TCR is recognising the peptide MHC complex -signal 1
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24
Q

how is signal 2 initiated?

A

-APC express co-stimulatory molecules (B7.1/B7.2 or CD80/CD86) that bind CD28 expressed by naive T cells and delivers signal 2 to the T cell

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25
how is signal 3 delivered?
APCs release cytokines which bind cytokine receptors now unregulated on naive T cells which deliver signal 3
26
what are co-stimulatory molecules expressed on?
APCs only
27
what occurs once activated by the three signals?
-activated T cells now proliferate and express ICOS and CTLA-4 -need inbuilt way of turning off the activated T cells
28
what is the function of ICOS?
binds ICOSL onAPC to induce cytokine secretion by T cells related to CD28
29
what is the function of CTLA-4?
shows stronger binding to B7.1/B7.2 than CD28 acts as an antagonist highly related to CD28
30
what does the binding of CTLA-4 to B7.1/2 on APC do?
delivers a negative signal to the activated T cell dampens down/limits the T cell response
31
what does a mutation in CTLA-4 cause?
-over-responsive immune system -leads to autoimmune disease as T cell responses turned off
32
how are the affects of the mutation reversed?
-the signals are blocked with antibodies -makes T cells more responsive -encourages body to overreact and keep responding to something -stops immune response being turned off by tumours
33
what do these mutations cause?
-type 1 diabetes
34
what are the types of co-stimulatory molecules?
B7.1 (CD80) and B7.2 (CD86)
35
how does the expression of co-stimulatory molecules vary?
-constitutive on mature dendritic cells -inducible on macrophages and B cells
36
what does activation of APC by pathogens induce?
co-stimulation expression so APC can provide signal 2 to activate T cells
37
what is the danger signal?
-binding pathogen associated molecules activates the APC -APC need to present something to T cells but also perceive danger -ensures signal 2 to activate T cell mediated response only occurs during infection
38
what is the response to the danger signal?
-ability to up regulate co-stimulatory molecules as a consequence of pattern recognition receptor engagement
39
what is the purpose of signal 3?
decides what type of T cell/effector is going to be made
40
what is the loop that occurs in signal 3?
the cytokine released from APC that stimulates the T cell to differentiate is also produced by that T cell- perpetuate themselves
41
what T cell does IL-4 produce?
Th2 cells (t helper 2 cells)- mediate activation and maintain immune response
42
what T cell does IL-12 and IFN-gamma produce?
Th1 cells
43
what T cell does TGF-beta and IL-6 produce?
Th17 cells - mediate defensive mechanisms
44
what T cell does IL-6 create?
Tfh cells - T follicular helper cells - development
45
what does TGF-beta form?
T reg cells - control clonal expansion etc.
46
what do APCs express?
MHC class 11 molecules
47
what are the types of APCs?
-dendritic cells -macrophages and B cells
48
what is function of dendritic cells?
-to present antigens -crucial for activation of naive T cells
49
what is the function of macrophages and B cells?
-present antigen in order receive help from effector T cells
50
what are the types of dendritic cell?
1. myeloid (conventional DC2,3) - potent APC, activation of naive T cells 2. plasmacytoid (pDC, DC6)- important in viral infection, secrete several type 1 alpha and beta interferons, express TLR 7 and 9 (sense viral antigens)
51
what is the function of myeloid dendritic cells?
-initiate T cell responses -bone marrow derived -immature form found in epithelia -engulfs by phagocytosis -doesn't express co-stimulatory molecules until activated -migrate to lymph node following danger signal activation -sense danger as have pattern recognition receptors -upregulate B7 if sense danger
52
what occurs after activation of DC?
-mature DC (2,3) found in T cell areas of lymphoid tissues -DC MHC class 1 and 2 will be loaded with peptides from pathogens they encountered in peripheral tissues -levels of co-stimulatory molecules very high -express high levels of adhesion molecules - efficient activators of naive T cells
53
what is the process after activation?
1. immature dendritic cells in peripheral tissues encounter pathogens and are activated by PAMPs 2. DC eats bacteria, chops up and puts on surface in association with class 2 3. move towards lymph nodes 4. cells go to site where needed most 5. b7 molecules on surface 6. DC releases cytokines to produce signal 3
54
what is cross presentation?
some specialised DC (DC 1) take up proteins from outside and instead of presenting on class 2, they present on class 1
55
what is the benefit of cross presentation?
-allows DC to activate naive CD8 T cells -then these CD8 effector cells can kill infected cells that aren't APC so not expressing co-stim
56
what are the features of macrophages?
-function as scavengers/killers of pathogens -highly phagocytic -express MHC class 2 and B7 which increases following T cell help resident in many tissues at peripheral sites -once activated by T cells, secrete many inflammatory cytokines
57
what are the features of B cells?
-poor at phagocytosis -internalise soluble antigens for processing and presentation by BCR-upregulates co-stim on B cells so they become APCs that deliver signal 2 and express class 2 scan deliver signal 1 t to cells and also signal 2 and 3 -found in lymph node presenting to T cells
58
how do B cells act as antigen specific APCs?
-only antigen specific B cell binds the antigen -specific antigen efficiently internalised by receptor mediated endocytosis -high density of specific antigen fragments presented
59
what is a key cytokine in T cell survival ?
IL-2 (interleukin-2)
60
what is the function of IL-2?
-essential for T cell activation -cytokine that T cells make themselves to cause them to proliferate -potent autocrine T cell growth factor
61
how does high affinity for IL2 cause proliferation?
-naive T cells express low affinity of IL2 -once T cells activated they express high affinity IL-2 receptors and secrete IL-2 -IL-2 binding to IL-2R on activated T cells = lots of T cell proliferation
62
what is the function of IL-2?
-allows rapid division of T cells -expands population of antigen specific activated T cells - happens downstream of signals -need to make lots of copies with unique receptor deed to bind to specific peptide -lots of levels of control are in place -target of immunosuppressive drugs eg. cyclosporin
63
once activated, what do T cells differentiate into?
effector T cells -CD8 cells acquire cytotoxic activity (kills cells expressing peptide/MHC class 1 complexes) -CD4 cells function by secreting cytokines, recognise peptide/MHC class 11 complexes
64
what do effector T cells do?
-display effector function when TCR engaged - no longer require stimulation, change expression of adhesion molecules -no longer enter lymph nodes but enter tissues via activated endothelia at sites of infection and inflammation - migrate nowhere needed
65
how are CD8+ T cells activated?
-requires high levels of co-stimulator activity -can be activated directly by infected or cross presenting APC or may require additional help from CD4+ T cells
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