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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
What is the action of Th1 cells?
interact with **macrophages** - phacotyose intracellular bacteria
26
What is the action of Th2 cells?
interact with antigen-specigic **B cells** - antibody production
27
What is the action of Th2 cells?
interact with antigen-specigic **B cells** - antibody production
28
What are CTLps?
cytotoxic lymphocyte precursor - naive T cell
29
Do CTLps express an IL-2 receptor?
no
30
Which cells do CTLps require for activation and proliferation?
Th1 helper T cells (CD4)
31
What are the stages of cytotoxic T cells inducing apoptosis?
* 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 f**ocus 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
32
What happens in a) early apoptosis and b) late apoptosis?
* a) chromatin condenses * b) nucleus very condensed, mitochondria visible, cell loses much of cytoplasm and membrane
33
What are 3 types of granules released by cytotoxic T cells?
perforin granzyme granulysin
34
What is the action of perforin?
polymerises to form pore of target cell
35
What is the action of granzyme?
serine proteases, activate apoptosis in cytoplasm
36
What is the action of granulysin?
induce apoptosis
37
What are the 2 pathways of apoptotic cell death?
granule exocytosis pathway + FAS pathway
38
What is the granule exocytosis pathway of cell death?
perforin -> granzymes -> cascades
39
What is the FAS pathway of cell death?
interaction -> expression of Fas ligand on T cell - binding initiates cascades -> apoptosis
40
What happens after CTL have dissociated with the target cell?
CTL are re-used
41
What are 3 cytokines released by cytotoxic T lymphocytes (CD8)?
IFN-γ, TFN α and TNF β
42
What is the function of each of the 3 main cytokines released by CTLs?
* IFN-γ - inhibits viral replicatin and activates macrophages * TNF α - synergises with IFN-γ * TNF β - synergises with IFN-γ
43
What does the type of T helper cell that is activated depend upon?
the environment e.g. APC and cytokines
44
What signal corresponds to developing into Th1 cell?
IL-12
45
What signal corresponds to developing into Th2 cell?
IL-4
46
Which MHC class do Th1+2 correspond to?
MHC II
47
What is the role of Th1 cells and which cytokine does this involve?
Th1 activate macrophages in a regulated and coordinated manner, involved in opsonisation and phagocytosis - involves IFN-γ
48
What is the role of T helper 2 cells and which 2 cytokines does this involve?
TH2 coordinate mast cell degranulation involving IL-4 release IL-5 -> eosinophil activation Also activate B cells using IL-4
49
What is coordinated by T helper cells?
coordinate immune responses to infections with intracellular pathogens
50
What are 3 cytokines which inhibit macrophage activation?
* IL-10 * IL-4 * IL-13
51
Which cells mediate the delayed type hypersensitivity (DTH) reaction?
Mainly inflammatory **CD4+ Th1 cells**
52
How do memory CD4+ Th1 cells mediate the delayed type hypersensitivity reaction?
release inflammatory cytokines that affect blood vessels (TNF-β), recruit chemokines and activate macrophages (IFN-γ)
53
What is the primary role of the delayed type hypersensitivity reaction?
defence against intracellular pathogens
54
What are 4 key DTH inducers?
1. intracellular parasites (e.g. Leishmania) 2. intracellular bacteria (e.g. mycobacteria) 3. intracellular fungi (candida) 4. intracellular viruses (herpes simplex)
55
What is the result of the DTH if the source of hte antigen is not eradicated?
chronic stimulation resulting in granuloma formation
56
What is the result if the antigen in DTH is not a microbe?
DTH produces tissue injury without protection - hypersensitivity
57
What are the 2 phases of the DTH response?
1. Sensitisation phase 2. Effector phase
58
What is the appearance of the tuberculin-type delayed hypersensitivity reaction?
red firm swelling of the skin
59
When is the maximal reaction in tuberculin-type hypersensitivity?
48-72h after challenge
60
What can be found histologically after the tuberculin test due to DTH?
dense dermal infiltrate of leukocytes and macrophages
61
How do B cells present antigen on their surface?
Ig binds specific antigen; Ig-antigen complex is internalised, processed and antigenic peptides are presented on B cell surface with **MHC II**
62
How do T cells interact with B cells presenting antigen on their surface?
T helper cells with specific TCR recognise antigen-MHC complex
63
What happens subsequent to TCR on T helper cells recognising antigen-MHC compelx on B cells?
* 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
What are the key actions of CD8 T cells?
cytotoxic - bind via Fas ligands to virus infected cells, release cytotoxic effector molecules (perforin, granzymes, granulysin, Fas ligand)
65
Which type of MHC class is recognised by CD8 cells?
MHC class I
66
What are 3 cytokines released by CD8 cells?
1. IFN-gamma 2. TNF-beta 3. TNF-alpha
67
What is the key action of Th1 cells?
bind via CD40 ligand to macrophages, release cytkines, activate the macrophages
68
What are 5 molecules released by Th1 cells to active macrophages?
1. IFN-gamma 2. GM-CSF 3. TNF-alpha 4. CD40 ligand 5. Fas ligand
69
What are 5 molecules released by Th1 cells to active macrophages?
1. IFN-gamma 2. GM-CSF 3. TNF-alpha 4. CD40 ligand 5. Fas ligand
70
What i the key action of Th2 cells?
bind via CD40 ligand to antigen-specific B cells + activate B cell
71
What are 4 B-cell activating effector molecules?
1. IL-4 2. IL-5 3. IL-15 4. CD40 ligand
72
What are 3 outcomes of T cell recognition of antigenic peptides + activation?
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
What are 2 cytokines involved in macrophage activation?
1. IFN-γ 2. TNF-α
74
What are 5 cytokines involved in the DTH reaction?
1. IL-2 2. IFN-γ 3. TNF-α 4. IL-3 5. GM-CSF
75
Which cytokine is key for help for CD8 cells?
IL-2
76
Which cytokine is important for down-regulation of Th2 responses?
IFN-γ
77
What are 3 cytokines involved in B cell proliferation?
1. IL-2 2. IL-4 3. IL-5
78
What are 5 cytokines involve in B cell differntiation and Ig class switching?
1. IL-2 2. IL-4 3. IL-5 4. IFN-γ 5. TGF-β
79
What are 3 cytokines involved in downregulation of Th1 responses?
1. IL-4 2. TGF-β 3. IL-10
80
Where do some T cells differentiate into regulatory cells?
in thymus or peripheral tissue
81
What is the action of regulatory T cells?
inhibit the activation of naive and effector T cells by ***CONTACT*-DEPENDENT INHIBITION** or by ***CYTOKINE*-MEDIATED INHIBITION**
82
Which 2 cytokines are critical in cytokine mediated inhibition of T cell responses by T regulatory cells?
IL-10, TGF-beta
83
What is immunological memory?
adaptive immune response in which the immune system remembers subsequent enounters with the same pathogen - faster and stronger immune response
84
Do T cells undergo isotype switching or affinity maturation?
no
85
What allows T cells to differentiate from naive memory cells?
* no CD45RA expression unlike naive T cells * chemokine receptor CCR7 expression allows further subdivision of memory T cells (effector vs central)
86
What are the 2 key types of T memory cells and how are they distinguished?
1. effector memory T cells - CCR7 negative, CD45RA negative 2. central memory T cells - CCR7 positive, CD45RA negative
87
What are the roles of T effector memory vs T central memory cells?
* TEM: display immediate effector function * TCM: lack immediate effector function, differentiate into CCR7 effector cells after secondary stimulation
88
How does the role of live parasites and the 2 types of memory T cells differ?
* CM T cells are maintained in the absence of live parasites * EM T cells require the presence of live paraistes
89
What happens to EM T cells on re infection with a parasite?
home immediately to infected lesion sites and produce effector cytokines
90
What happens to CM T cells on re infection with a parasite?
must first pass throguh a phase of activation and differentiation to generate effector cells
91
Why is a balance of both subsets of CM and EM T memory cells required?
most effective protection provided when both are genearted and maintained

OPHTH Immunology (8 decks)

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