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OPHTH Immunology > Effector T-lymphocytes > Flashcards

Effector T-lymphocytes Flashcards

1
Q

What type of pathogens are detected + eliminated by T cells?

A

intracellular pathogens + altered cells i.e. tumour cells

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2
Q

Which forms of pathogen do CD4+ and CD8+ T cells respond to respectively?

A
  • CD4: phagocytes with ingested microbes, antigens in vesicles
  • CD8: infected cell with microbes in cytoplasm
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3
Q

What are 2 principle functions of CD4+ T cells?

A
  1. Cytokine secretion -> activates macrophages which kill ingested microbes (+ leads to inflammation)
  2. secrete IFN-γ, IL-2, TNF-β
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4
Q

What are the 2 cytokines released by CD4+ T cells?

A
  1. IFN-γ
  2. IL-2
  3. TNF-β
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5
Q

What are 2 primary functions of CD8+ T cells?

A
  1. killing of infected cell
  2. secrete granules
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6
Q

Where do naive T lymphocytes get activated?

A

secondary lymphoid organs (recirculate in blood -> lymph -> lymphoid organs)

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7
Q

Where do naive T lymphocytes enter lymph nodes?

A

high endothliel venules (HEV) - specialised areas in post-capillary venules

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8
Q

What type of T cells can enter non-lymphoid tissue?

A

effector cells only - not naive T cells, as they have to have undergone differentiation process in response to antigen

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9
Q

What is the role of APCs and MHC class II?

A

lead to activation of T cells into effector cells

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10
Q

What are the 3 steps of the role of dendritic cells in T lymphocytes?

A
  1. immature DC take up antigen (innate immunity) in the peripheral tissue
  2. immature DC activated - leave tissue - migrate to secondary lymphoid tissue
  3. in LN DC matures, expresses high levels of peptide/MHC complexes and costimulatory molecules - leads to more efficient APC
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11
Q

What are the 2 possible steps of initial activation of naive T cells after monitoring for antigens presenting by APC?

A
  • T cells enter HEV in cortex
  • monitor for antigens presented by APC:
  • 1) encounter -> proliferation and differentiation into effector cells
  • 2) non-encounter -> leave lymph nodes
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12
Q

What 2 things are required for T cell activation?

A

antigen AND costimulatory molecules
(only exception is superantigens e.g. TSST-1 - can activate without costimulation)

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13
Q

What is an example of a costimulatory molecule for T cell activation with antigen?

A

CD28 (requires CD80 or CD86 ligand)

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14
Q

What are the 2 ligands that CD28 costimulatory molecule may require to active T cells?

A
  1. CD80
  2. CD86
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15
Q

What is the result of lack of co-stimulation of T cells?

A

unresponsive T cells and tolerance in peripheral T cells

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16
Q

What happens after recognition and costimulation of T lymphocytes by antigen?

A

proliferation/differentiation -> effector function

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17
Q

What 2 things are secreted by T cells in response to antigen recognition? What is its function?

A

IL-2 and IL-2 receptor - required for proliferation

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18
Q

What is the action of IL-2 secreted by T-cells in response to antigen recognition?

A

direct response: autocrine action, leading to cell activation and multiplication

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19
Q

What is the result of effector T cells following autocrine response to IL-2?

A

apoptosis - destroy infected target cells

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20
Q

How dependent are effector T cells on costimulation?

A

less dependent on co-stimulation

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21
Q

Which type of T cells has the highest affinity receptor to IL-2?

A
  • activated cell - high affinity receptor (β + γ + α chains) AND secretion
  • resting T cells have moderate affinity receptor only ((IL-2Rβ + γ chains)
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22
Q

What is the effect of IL-2 and its receptor binding to T cells?

A

signals the T cell to enter the cell, which induces proliferation

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23
Q

What is the definition of effector T cells?

A

have encountered antigen, proliferated and differentiated into cells that participate in the host defence

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24
Q

What are the 2 key types of CD4 T effector cells?

A
  • Th1
  • Th2
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25
Q

What is the action of Th1 cells?

A

interact with macrophages - phacotyose intracellular bacteria

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26
Q

What is the action of Th2 cells?

A

interact with antigen-specigic B cells - antibody production

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27
Q

What is the action of Th2 cells?

A

interact with antigen-specigic B cells - antibody production

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28
Q

What are CTLps?

A

cytotoxic lymphocyte precursor - naive T cell

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29
Q

Do CTLps express an IL-2 receptor?

A

no

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30
Q

Which cells do CTLps require for activation and proliferation?

A

Th1 helper T cells (CD4)

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31
Q

What are the stages of cytotoxic T cells inducing apoptosis?

A
  • TCRs bind to specific antigenic peptide:self-MHC complexes -> TCRs and their coreceptors cluster to the site of cell-cell contact
  • clustering of TCRs signals reorientation of cytoskeleton - POLARIZES the effector cell to focus the release of effector molecules at the site of contact with target cell
  • CTLs contain lytic granules which contain cytotoxic molecules
  • In the polarized T cells, secretory apparatus becomes aligned toward target cell -> content of the lytic granules secreted
  • The lytic granules induce APOPTOSIS
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32
Q

What happens in a) early apoptosis and b) late apoptosis?

A
  • a) chromatin condenses
  • b) nucleus very condensed, mitochondria visible, cell loses much of cytoplasm and membrane
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33
Q

What are 3 types of granules released by cytotoxic T cells?

A

perforin
granzyme
granulysin

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34
Q

What is the action of perforin?

A

polymerises to form pore of target cell

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35
Q

What is the action of granzyme?

A

serine proteases, activate apoptosis in cytoplasm

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36
Q

What is the action of granulysin?

A

induce apoptosis

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37
Q

What are the 2 pathways of apoptotic cell death?

A

granule exocytosis pathway + FAS pathway

38
Q

What is the granule exocytosis pathway of cell death?

A

perforin -> granzymes -> cascades

39
Q

What is the FAS pathway of cell death?

A

interaction -> expression of Fas ligand on T cell - binding initiates cascades -> apoptosis

40
Q

What happens after CTL have dissociated with the target cell?

A

CTL are re-used

41
Q

What are 3 cytokines released by cytotoxic T lymphocytes (CD8)?

A

IFN-γ, TFN α and TNF β

42
Q

What is the function of each of the 3 main cytokines released by CTLs?

A
  • IFN-γ - inhibits viral replicatin and activates macrophages
  • TNF α - synergises with IFN-γ
  • TNF β - synergises with IFN-γ
43
Q

What does the type of T helper cell that is activated depend upon?

A

the environment e.g. APC and cytokines

44
Q

What signal corresponds to developing into Th1 cell?

A

IL-12

45
Q

What signal corresponds to developing into Th2 cell?

A

IL-4

46
Q

Which MHC class do Th1+2 correspond to?

A

MHC II

47
Q

What is the role of Th1 cells and which cytokine does this involve?

A

Th1 activate macrophages in a regulated and coordinated manner, involved in opsonisation and phagocytosis - involves IFN-γ

48
Q

What is the role of T helper 2 cells and which 2 cytokines does this involve?

A

TH2 coordinate mast cell degranulation involving IL-4
release IL-5 -> eosinophil activation
Also activate B cells using IL-4

49
Q

What is coordinated by T helper cells?

A

coordinate immune responses to infections with intracellular pathogens

50
Q

What are 3 cytokines which inhibit macrophage activation?

A
  • IL-10
  • IL-4
  • IL-13
51
Q

Which cells mediate the delayed type hypersensitivity (DTH) reaction?

A

Mainly inflammatory CD4+ Th1 cells

52
Q

How do memory CD4+ Th1 cells mediate the delayed type hypersensitivity reaction?

A

release inflammatory cytokines that affect blood vessels (TNF-β), recruit chemokines and activate macrophages (IFN-γ)

53
Q

What is the primary role of the delayed type hypersensitivity reaction?

A

defence against intracellular pathogens

54
Q

What are 4 key DTH inducers?

A
  1. intracellular parasites (e.g. Leishmania)
  2. intracellular bacteria (e.g. mycobacteria)
  3. intracellular fungi (candida)
  4. intracellular viruses (herpes simplex)
55
Q

What is the result of the DTH if the source of hte antigen is not eradicated?

A

chronic stimulation resulting in granuloma formation

56
Q

What is the result if the antigen in DTH is not a microbe?

A

DTH produces tissue injury without protection - hypersensitivity

57
Q

What are the 2 phases of the DTH response?

A
  1. Sensitisation phase
  2. Effector phase
58
Q

What is the appearance of the tuberculin-type delayed hypersensitivity reaction?

A

red firm swelling of the skin

59
Q

When is the maximal reaction in tuberculin-type hypersensitivity?

A

48-72h after challenge

60
Q

What can be found histologically after the tuberculin test due to DTH?

A

dense dermal infiltrate of leukocytes and macrophages

61
Q

How do B cells present antigen on their surface?

A

Ig binds specific antigen; Ig-antigen complex is internalised, processed and antigenic peptides are presented on B cell surface with MHC II

62
Q

How do T cells interact with B cells presenting antigen on their surface?

A

T helper cells with specific TCR recognise antigen-MHC complex

63
Q

What happens subsequent to TCR on T helper cells recognising antigen-MHC compelx on B cells?

A
  • T-B interactions trigger expression of CD40 ligand on T cells; this interacts with CD40 expressed by B cells
  • T cells secrete cytokines and B cells express cytokine receptors
  • activated B cell differentiates into antibody secreting plasma cell
64
Q

What are the key actions of CD8 T cells?

A

cytotoxic - bind via Fas ligands to virus infected cells, release cytotoxic effector molecules (perforin, granzymes, granulysin, Fas ligand)

65
Q

Which type of MHC class is recognised by CD8 cells?

A

MHC class I

66
Q

What are 3 cytokines released by CD8 cells?

A
  1. IFN-gamma
  2. TNF-beta
  3. TNF-alpha
67
Q

What is the key action of Th1 cells?

A

bind via CD40 ligand to macrophages, release cytkines, activate the macrophages

68
Q

What are 5 molecules released by Th1 cells to active macrophages?

A
  1. IFN-gamma
  2. GM-CSF
  3. TNF-alpha
  4. CD40 ligand
  5. Fas ligand
69
Q

What are 5 molecules released by Th1 cells to active macrophages?

A
  1. IFN-gamma
  2. GM-CSF
  3. TNF-alpha
  4. CD40 ligand
  5. Fas ligand
70
Q

What i the key action of Th2 cells?

A

bind via CD40 ligand to antigen-specific B cells + activate B cell

71
Q

What are 4 B-cell activating effector molecules?

A
  1. IL-4
  2. IL-5
  3. IL-15
  4. CD40 ligand
72
Q

What are 3 outcomes of T cell recognition of antigenic peptides + activation?

A
  1. clearance of pathogen - antigenic peptide derived from foreign pathogen
  2. autoimmunity - antigenic peptide derived from self protein
  3. rejection (transplants) - antigenic peptide derived from self protein of transplant donor
73
Q

What are 2 cytokines involved in macrophage activation?

A
  1. IFN-γ
  2. TNF-α
74
Q

What are 5 cytokines involved in the DTH reaction?

A
  1. IL-2
  2. IFN-γ
  3. TNF-α
  4. IL-3
  5. GM-CSF
75
Q

Which cytokine is key for help for CD8 cells?

A

IL-2

76
Q

Which cytokine is important for down-regulation of Th2 responses?

A

IFN-γ

77
Q

What are 3 cytokines involved in B cell proliferation?

A
  1. IL-2
  2. IL-4
  3. IL-5
78
Q

What are 5 cytokines involve in B cell differntiation and Ig class switching?

A
  1. IL-2
  2. IL-4
  3. IL-5
  4. IFN-γ
  5. TGF-β
79
Q

What are 3 cytokines involved in downregulation of Th1 responses?

A
  1. IL-4
  2. TGF-β
  3. IL-10
80
Q

Where do some T cells differentiate into regulatory cells?

A

in thymus or peripheral tissue

81
Q

What is the action of regulatory T cells?

A

inhibit the activation of naive and effector T cells by CONTACT-DEPENDENT INHIBITION or
by CYTOKINE-MEDIATED INHIBITION

82
Q

Which 2 cytokines are critical in cytokine mediated inhibition of T cell responses by T regulatory cells?

A

IL-10, TGF-beta

83
Q

What is immunological memory?

A

adaptive immune response in which the immune system remembers subsequent enounters with the same pathogen - faster and stronger immune response

84
Q

Do T cells undergo isotype switching or affinity maturation?

A

no

85
Q

What allows T cells to differentiate from naive memory cells?

A
  • no CD45RA expression unlike naive T cells
  • chemokine receptor CCR7 expression allows further subdivision of memory T cells (effector vs central)
86
Q

What are the 2 key types of T memory cells and how are they distinguished?

A
  1. effector memory T cells - CCR7 negative, CD45RA negative
  2. central memory T cells - CCR7 positive, CD45RA negative
87
Q

What are the roles of T effector memory vs T central memory cells?

A
  • TEM: display immediate effector function
  • TCM: lack immediate effector function, differentiate into CCR7 effector cells after secondary stimulation
88
Q

How does the role of live parasites and the 2 types of memory T cells differ?

A
  • CM T cells are maintained in the absence of live parasites
  • EM T cells require the presence of live paraistes
89
Q

What happens to EM T cells on re infection with a parasite?

A

home immediately to infected lesion sites and produce effector cytokines

90
Q

What happens to CM T cells on re infection with a parasite?

A

must first pass throguh a phase of activation and differentiation to generate effector cells

91
Q

Why is a balance of both subsets of CM and EM T memory cells required?

A

most effective protection provided when both are genearted and maintained

OPHTH Immunology (8 decks)

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