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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
Q

what is an effector T cell
what are they derived from
are they long/short lived

A

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
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26
Q

what is a MEMORY T cell

are they long or short lived

A
  • have had antigen presented to them & return to resting state
  • are usually long-lived and can be subsequently reactivate
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27
Q

where do naive T lymphocytes migrate

A

preferentially to the peripheral lymph nodes

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28
Q

where do activated/effector T lymphocytes migrate

A

preferentially to inflamed tissues

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29
Q

where do memory T lymphocytes migrate

A

heterogenous: one subset to lymph node, one subset to mucosa and inflamed tissues

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30
Q

what is the frequency of naive T cells responsive to a paticular antigen

A

v low

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31
Q

what is the freq of effector T lymphocytes responsive to a particular antigen

A

high

32
Q

what is th efrequency of memory T cells responsive to a particular antigen

A

low

33
Q

what is the effector function of effector cells

A
  • cytokine secretion

- cytotoxic activity

34
Q

do memory cells have effector functions

A

once they are ACTIVATED they are similar to effector cells

35
Q

how are T cells activated

A
  • naive T cell interacts with an APC
  • results in activation of cell
    proliferation of effector (clonal expansion)
  • release of cytokines/cytotoxic activity
36
Q

what happens when a naive T cell encounters an APC

A
  • it BINDS STRONGLY to the APC, stops migration
37
Q

how quickly does the naive T cell find the antigen

how quickly are effector T cells employed

A
  • 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
Q

how do T cells contact the APC

what is formed

A

an IMMUNOLOGICAL SYNAPSE is formed:

  • TCR is are the core
  • ADHESION molecules STABILISE the interaction
39
Q

what is required to activate T cells

what is this provided by

A

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
Q

what is signal 1 in T cell activation

A

1) TCR/MHC interaction and antigen recogniton

2) INTERACTION OF CO-STIMULATORY MOLECULES

41
Q

which molecules are involved in co-stimulatory molecule interaction

A
  • CD28 co receptor on T CELLS interacts with CD80/86 on APC

- CD80/86 bind to the CD28

42
Q

CD80/86 is also called what

A

B71 and B72 (IN MICE)

43
Q

what is ANERGY

A

a state of unresponsiveness if the second signal (co stimulatory moleucles) is not present

44
Q

interactions in T cell activation are stabilised by what

A

ADHESION molecules eg ICAM-1 binding to LFA-1 on the T cell

45
Q

what happens if both signal 1 and 2 are present

A

SIGNAL TRANSDUCTION: the T cell actiavtes and undergoes clonal expansion

46
Q

why is it important that expression of co stimulators is regulated

A

so T cells respons at the correct TIME and PLACE

47
Q

what is CD80/86 expression induced by

A

microbial products (eg PAMPs) and cytokines (IFN-gamma)

48
Q

what expresses the highest level of co stimuatros

this makes them what

A

DCs

O they are th emost POTENT STIMULATORS of naive T cells

49
Q

what are the 2 modes that DCs can exist in

what has to happen before it can reach the 2nd mode

A

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
Q

what induces DCs to mature

A

cytokines and PAMPs

TNF, IFNgamma, PAMPs

51
Q

why is IL2 important

A

helps clonal expansion and activation of T cells

52
Q

what happens afte rthe synapse is formed

A
  • the kinase :ck is brough into proximity w/ ITAMs on CD3 and the ζζ dimer (zeta zeta) (signal transducing Ag receptor subunits)
53
Q

what is the role of Lck

A

it phsophorylates and ACTIVATES the ITAMs and initiates cell signalling
- signal transduction results in what:
GENE ACTIVATION AND TRANSCRIPTION

54
Q

one activation of the T cell has occured what needs to happen next

A

naive T cell eeds to rapidly proliferate

55
Q

how does IL2 help clonal proliferation

A
  • acts by AUTOCRINE MECHANISM: T cell produces IL2, th eproduced IL2 acts on the same T cell, causing it to proliferate
56
Q

what are the possible outcomes when a T cell comes into contact with an APC

A

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
Q

CTLA-4 is what kind of receptor

A

inhibitory

58
Q

what is PERIPHERAL RESISTANCE

A

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
Q

how can expression of CD28 change through an immune response

A
  • 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
Q

which other cell type can provide CTLA-4
what do they respond to
what is their overall effect

A

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
Q

how might checkpoint inhibitors be used in immunotherapy for cancer

A
  • 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
Q

what could be an unwanted effect of using checkpoint inhibitors

A

we are essentially lowering the threshold for T cell activation O:
inc the risk of patient developing AUTOIMMUNE diseases

63
Q

what are the different types of T cell

A
  • CD4+ (Th1, Th2, Th17, Tregs, Tfh)
  • CD8
  • γδ T cell
  • invariant natural Killer T (iNKT) cells
64
Q

what is the 3rd signal in T cell activation

A
  • 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
Q

during the 3rd signal what do different cytokines in the cytokine env produce
what is each subset induced by

A

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
Q

what is T cell polarisation/differentiation

A
  • 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
Q

what is the effector cytokine for T helper 1 cells

A
  • IFNγ
  • TNFα
  • IL-2
68
Q

what is the effector cytokine for T helper 2 cells

A

IL-4
IL-5
IL-13

69
Q

what is the effector cytokine for T regulatory cells

A

TGFβ

IL-10

70
Q

what is the effector cytokine for T helper 17 cells

A

IL-17

IL-22

71
Q

what is the effector cytokine for T follicular helper cells

A

L-4

IL-21

72
Q

what is the effector function of T regulatory cells

A
  • ANTI-INFLAMMATORY

- Peripheral Tolerance

73
Q

what is the effector function of T helper 1 cells

A

PRO-INFLAMMATORY against INTRACELLULAR PATHOGENS

74
Q

what is the effector function of T helper 17 cells

A

PRO-INFLAMMATORY against BACTERIAL INFECTION

75
Q

what is the effector function of T follicular cells

A

B CELL ACTIVATION IN FOLLICLES, Ig ISOTOPE SWITCHING and AFFINITY MATURATION

76
Q

what is the effector function of T helper 2 cells

A

MAST CELL, EOSINOPHILS AND B CELL ACTIVATION and IgE PRODUCTION (HELMINTHS/TOXINS)

(this is humoral immune response)

77
Q

what is the main surface marker for memory T cells

A

CD45RO

YEAR 2 S2 IMMUNO (14 decks)

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