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YEAR 2 S2 IMMUNO > Theme 4 - 4a (T cell activation pt 1) > Flashcards

Theme 4 - 4a (T cell activation pt 1) Flashcards

1
Q

what are the differences between the innate and adaptive immune system

A
  • adaptive immune system changes in exposure to antigens
  • the cells of adaptive immune system (B and T cells) recognise SPECIFIC antigens whereas cells of INNATE recognise PAMPs
  • vaccines trigger response from the ADAPTIVE system as it has memory
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2
Q

what does PAMPs stand for

A

pathogen associated molecular patterns

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3
Q

what is the key cell of humoral immunity

how is it different to cell mediated immunity?

A

B cells (producing antibodies- soluble factors that circulate blood and can enter mucosal tissues)

cell mediated immunity uses direct secretion of CYTOKINES and uses cell cell contact

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4
Q

what is adaptive immunity

A

an immune response that becomes MORE POWERFUL following repeated encounters with the same antigen

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5
Q

what are the 3 advantages of using HIGHLY SPECIFIC ANTIGEN receptors

A

1) pathogens that don’t have PAMPs can be recognised
2) responses can be HIGHLY SPECIFIC for the pathogen
3) the SPECIFICITY of the response allows for IMMUNOLOGICAL MEMORY

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6
Q

what are the 2 ways specific immunity can be achieved?

A

1) natural exposure eg chickenpox

2) or ARTIFICIALLY via VACCINATION

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7
Q

what microbe does humoral immunity target

A

extracellular microbes

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8
Q

what are the responding lymphocytes in humoral immunity

A

B lymphocytes

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9
Q

what is the effector mechanism of humoral immunity

A

secreted antidbody

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10
Q

what is the function of humoral immunity

A

block infecions and eliminate extracellular microbes

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11
Q

what are the micorbes targeted in cell mediated immunity

A
  • phagocytosed microbes in MACROPHAGES

- INTRACELLULAR microbes eg viruses replicating within infected cell

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12
Q

what are the responding lymphocytes in cell mediated immunity

A
  • Helper T lymphocytes

- Cytotoxic T lymphocytes

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13
Q

what is the effector mechanism of cell mediated immunity

A
  • activated macrophages and killing the infected cell (cytotoxic T cells)
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14
Q

what is the function of cell mediated immunity

A
  • eliminate phagocytosed microbes

- kill infected cells and eliminate reservoirs of infection

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15
Q

what is produced in humoral immunity

A
  • the production of ANTIGEN-SPECIFIC antibodies by B cells
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16
Q

what is produced in cell-mediated (T cell mediated) immunity

A

generation of ANTIGEN SPECIFIC cytotoxic T cells also known as CTL (cytotoxic T lymphocytes)

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17
Q

how does humoral immunity req to help it

A

req CD4+ T cells to help activate B cells, induce memory and antibody production

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18
Q

T cell mediated immunity is what

A

also referred to as cell mediated immunity but it also includes NK cells and macrophages

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19
Q

why is it v important that T cell activation is highly regulated

A

to prevent INFLAMMATORY DISEASE and AUTOIMMUNITY eg rheumatoid arthiritis

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20
Q

what kind of foreign organism/particle etc may enter the body, but that we DO NOT want to have an immune response to

A
  • dust/particles in the air (we should not respond to it due to the sheer amount)
  • natural MICROBIOTA (responding to this may cause inflammation in the GI tract)
  • food (we dont want to respond to this)
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21
Q

where does T cell maturation and selection occur

what does positive selection ensure

A

iin the thymus, where only self Ag is present

- positive selection ensures ADEQUATE RECOGNITION of MHC presented Ags

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22
Q

what are the 4 possible fates of an immature T cell

A

1) it becomes able to WEAKLY recognise class I MHC and peptide O becomes a mature CD8+ T cell (it is POSITIVELY SELECTED)
2) it becomes able to WEAKLY recognise class II MHC and peptide O becomes a mature CD8+ T cell (it is positively selected)
3) it is UNABLE to recognise MHC and peptide (failur eof positive selection, dies by APOPTOSIS)
4) STRONG recognition of either MHC class I or II and peptide O it is NEGATIVELY selected and dies via APOPTOSIS

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23
Q

what is central tolerance

why is it called ‘central’ tolerance

A

a process of negative selction whereby any T cells that SELF RECOGNISE or are not able to recognise ANYTHING die by apoptosis
- it occurs in the CENTRAL LYMPHOID ORGANS

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24
Q

what is a naive T cell

A
  • have not been stimulated by ANTIGEN since leaving the thymus
  • circulate blood and lymph nodes
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25
what is an effector T cell what are they derived from are they long/short lived
have specialised functions e.g. secretion of cytokines or lysis of target cells - effector cells derive from naïve or memory cells - are short-lived, in an activated state but require further stimulation for full function
26
what is a MEMORY T cell | are they long or short lived
- have had antigen presented to them & return to resting state - are usually long-lived and can be subsequently reactivate
27
where do naive T lymphocytes migrate
preferentially to the peripheral lymph nodes
28
where do activated/effector T lymphocytes migrate
preferentially to inflamed tissues
29
where do memory T lymphocytes migrate
heterogenous: one subset to lymph node, one subset to mucosa and inflamed tissues
30
what is the frequency of naive T cells responsive to a paticular antigen
v low
31
what is the freq of effector T lymphocytes responsive to a particular antigen
high
32
what is th efrequency of memory T cells responsive to a particular antigen
low
33
what is the effector function of effector cells
- cytokine secretion | - cytotoxic activity
34
do memory cells have effector functions
once they are ACTIVATED they are similar to effector cells
35
how are T cells activated
- naive T cell interacts with an APC - results in activation of cell proliferation of effector (clonal expansion) - release of cytokines/cytotoxic activity
36
what happens when a naive T cell encounters an APC
- it BINDS STRONGLY to the APC, stops migration
37
how quickly does the naive T cell find the antigen | how quickly are effector T cells employed
- within 2 days most antigen specific T cells have been trapped by antigen SPECIFIC T cells - within 4/5 days EFFECTOR T cells start migarting out of the lymph node
38
how do T cells contact the APC | what is formed
an IMMUNOLOGICAL SYNAPSE is formed: - TCR is are the core - ADHESION molecules STABILISE the interaction
39
what is required to activate T cells | what is this provided by
the SECOND SIGNAL: - provided the same APC that presents the antigen - an antigen that req a RESPONSE from the T cell will produce a PRO INFLAMMATORY ENVIRONMENT using CO-STIMULATORY MOLECULES
40
what is signal 1 in T cell activation
1) TCR/MHC interaction and antigen recogniton | 2) INTERACTION OF CO-STIMULATORY MOLECULES
41
which molecules are involved in co-stimulatory molecule interaction
- CD28 co receptor on T CELLS interacts with CD80/86 on APC | - CD80/86 bind to the CD28
42
CD80/86 is also called what
B71 and B72 (IN MICE)
43
what is ANERGY
a state of unresponsiveness if the second signal (co stimulatory moleucles) is not present
44
interactions in T cell activation are stabilised by what
ADHESION molecules eg ICAM-1 binding to LFA-1 on the T cell
45
what happens if both signal 1 and 2 are present
SIGNAL TRANSDUCTION: the T cell actiavtes and undergoes clonal expansion
46
why is it important that expression of co stimulators is regulated
so T cells respons at the correct TIME and PLACE
47
what is CD80/86 expression induced by
microbial products (eg PAMPs) and cytokines (IFN-gamma)
48
what expresses the highest level of co stimuatros | this makes them what
DCs | O they are th emost POTENT STIMULATORS of naive T cells
49
what are the 2 modes that DCs can exist in | what has to happen before it can reach the 2nd mode
1) Ag uptake mode (NOT v MOBILE, highly phagocytic O good at uptaking) 2) Ag presentation mode (present Ag, v motile, move to lymph node, express HIGH LEVELS OF MHC, inc expression of CD80/86) DC must MATURE
50
what induces DCs to mature
cytokines and PAMPs | TNF, IFNgamma, PAMPs
51
why is IL2 important
helps clonal expansion and activation of T cells
52
what happens afte rthe synapse is formed
- the kinase :ck is brough into proximity w/ ITAMs on CD3 and the ζζ dimer (zeta zeta) (signal transducing Ag receptor subunits)
53
what is the role of Lck
it phsophorylates and ACTIVATES the ITAMs and initiates cell signalling - signal transduction results in what: GENE ACTIVATION AND TRANSCRIPTION
54
one activation of the T cell has occured what needs to happen next
naive T cell eeds to rapidly proliferate
55
how does IL2 help clonal proliferation
- acts by AUTOCRINE MECHANISM: T cell produces IL2, th eproduced IL2 acts on the same T cell, causing it to proliferate
56
what are the possible outcomes when a T cell comes into contact with an APC
1) APC presents peptide recognised by T cell BUT THERE ARE NO CO STIMULATORY molecules O the T cell goes into ANERGY/ undergoes apoptosis 2) APC presenting peptide is recognised by T cell, CO STIMULATORY moleucles ARE present O the T cell PROLIFERATES (CLONAL EXPANSION) leads to effector function 3) the T cell expresses CTLA-4 which can engage CD80/86 INSTEAD of CD28 - this has an INHIBITORY effect - can induce anergy/APOPTOSIS and PERIPHERAL TOLERANCE
57
CTLA-4 is what kind of receptor
inhibitory
58
what is PERIPHERAL RESISTANCE
the T cell expresses CTLA-4 which can engage CD80/86 INSTEAD of CD28 - this has an INHIBITORY effect - can induce anergy/APOPTOSIS and PERIPHERAL TOLERANCE
59
how can expression of CD28 change through an immune response
- at the beginning there might be a lot of CD28 expressed - as it progresses, in order to SLOW the intensity of the immune response CD28 will be reduced and CTLA-4 will INCREASED (inhib)
60
which other cell type can provide CTLA-4 what do they respond to what is their overall effect
T regulatory cells (a type of CD4+ T helper cell) when these develop in thymus, they are made to RESPOND TO SELF TISSUES and when they are activated, they SUPRESS THE IMMUNE SYSTEM
61
how might checkpoint inhibitors be used in immunotherapy for cancer
- they BLOCK the activity of CTLA-4 (inhibit the inhibitor) | O you are ALLOWING the T cell to become activated O we can use the imune system against cancerous growth
62
what could be an unwanted effect of using checkpoint inhibitors
we are essentially lowering the threshold for T cell activation O: inc the risk of patient developing AUTOIMMUNE diseases
63
what are the different types of T cell
- CD4+ (Th1, Th2, Th17, Tregs, Tfh) - CD8 - γδ T cell - invariant natural Killer T (iNKT) cells
64
what is the 3rd signal in T cell activation
- CYTOKINES - directs T cell DIFFERENTIATION into DIFFERENT SUBSETS - cytokines are made BY THE SAME APC that provided MHCII/Ag and co stimulation by other cells to create CYTOKINE ENVIRONMENT
65
during the 3rd signal what do different cytokines in the cytokine env produce what is each subset induced by
different cytokines produce DIFFERENT TYPE OF EFFECTOR CD4 (Th) cell - each ach subset is induced by the types of microbes that subset is best able to combat
66
what is T cell polarisation/differentiation
- Different cytokines in the cytokine environment produces a different type of effector CD4 (Th) cell - each subset is induced by the types of microbes that subset is best able to combat - each subset has different functions
67
what is the effector cytokine for T helper 1 cells
- IFNγ - TNFα - IL-2
68
what is the effector cytokine for T helper 2 cells
IL-4 IL-5 IL-13
69
what is the effector cytokine for T regulatory cells
TGFβ | IL-10
70
what is the effector cytokine for T helper 17 cells
IL-17 | IL-22
71
what is the effector cytokine for T follicular helper cells
L-4 | IL-21
72
what is the effector function of T regulatory cells
- ANTI-INFLAMMATORY | - Peripheral Tolerance
73
what is the effector function of T helper 1 cells
PRO-INFLAMMATORY against INTRACELLULAR PATHOGENS
74
what is the effector function of T helper 17 cells
PRO-INFLAMMATORY against BACTERIAL INFECTION
75
what is the effector function of T follicular cells
B CELL ACTIVATION IN FOLLICLES, Ig ISOTOPE SWITCHING and AFFINITY MATURATION
76
what is the effector function of T helper 2 cells
MAST CELL, EOSINOPHILS AND B CELL ACTIVATION and IgE PRODUCTION (HELMINTHS/TOXINS) (this is humoral immune response)
77
what is the main surface marker for memory T cells
CD45RO

YEAR 2 S2 IMMUNO (14 decks)

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