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Lecture 5: T Cell Mediated Immunity Flashcards

1
Q

What are target cells?

A

The cells on which effector T cells act

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2
Q

What does CD8 T cell recognise?

A

Pathogen peptide presented by MHC class I molecules

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3
Q

What is he function of CD8 cytotoxic T cells?

A

Kill Virus-infected cells

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4
Q

What are the pathogens targeted for CD8 cytotoxic T cells?

A

Viruses e.g. Influenza, rabies and vaccinia Some intracellular bacteria

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5
Q

What is the function of CD4 TH1 cells?

A

Activate infected macrophages, provide help to B cells for antibody production

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6
Q

What are pathogens targeted by CD4 TH1 cells ?

A

Microbes that persist in Macrophage vesicles (e.g. mycobacteria, Listeria leishmania, Donovani Pneumocystis) Extracellular Bacteria

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7
Q

What is the function of CD4 TH2 cells?

A

Provide help to B cells for antibody production, especially switching to IgE

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8
Q

What are the pathogens targeted by CD4TH2 cells?

A

Helminth parasites

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9
Q

What is the function of CD4 TH17 cells?

A

Enhance neutrophil response

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10
Q

What are the pathogens targeted for CD4 TH17 cells?

A

Extracellular Bacteria e.g. salmonella enterica

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11
Q

What is the function of CD4 regulatory T cells?

A

Suppress T cell responses

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12
Q

What is the most highly organised lymphoid tissues?

A

Thymus Lymph nodes

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13
Q

What is the most common cell type in lymphoid tissue?

A

Lymphocytes

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14
Q

Where are lymphocytes formed from?

A

Stem cells in bone marrow

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15
Q

Where does T lymphocytes mature?

A

Thymus

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16
Q

Where does B lymphocytes mature?

A

Bone marrow

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17
Q

How does lymphocytes and lymph return to blood?

A

Thoracic duct

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18
Q

Where does naive Lymphocytes enter lymph nodes from?

A

Blood

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19
Q

How does the antigen from site of infection reach lymph nodes?

A

Lymphatics

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20
Q

Where does B cells start to proliferate?

A

Primary lymphoid follicle

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21
Q

What is the Germinal centre?

A

B cells proliferate and produce antibodies

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22
Q

What is the paracortical area?

A

Where T cells accumulate

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23
Q

Where does the immature dendritic cell reside?

A

Peripheral tissues

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24
Q

Where does dendritic cells migrate to via lymphatic vessels?

A

Regional lymph nodes

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25
What are Antigen presenting cells?
Dendritic cells Macrophages B lymphocytes
26
What is Antigen uptake of DC?
Macropinocytosis and phagocytosis by tissue dendritic cells
27
What is the MHC expression of DC?
Low on tissue dendritic cells High on dendritic cells in lymphoid tissues
28
What is co-stimulator delivery of Dendritic cells?
Constitutive by mature, non-phagocytic lymphoid dendritic cells
29
What are antigens presented by DC
Peptide Viral antigens Allergens
30
What is the location of DC?
Ubiquitous throughout the body
31
What is the Antigen uptake of macrophages?
Phagocytosis
32
What is the MHC expression of macrophages?
Inducible by Bacteria and cytokines (- to +++)
33
What is the co-stimulator delivery of macrophages?
Inducible (- to +++)
34
What is the antigens presented by macrophages?
Particulate Antigens Intracellular and Extracellular pathogens
35
What are the location of macrophages?
Lymphoid tissue. Connective tissue Body cavities
36
What is the Antigen uptake of B cells?
Antigen-specific receptor (Ig)
37
What is the MHC expression of B cells?
Constitutive increases on activation (+++ to +++)
38
What is the costimulatory delivery of B cells ?
Inducible (- to +++)
39
What are the antigens presented by B cells?
Soluble antigens Toxins Viruses
40
What is the location of B cells?
Lymphoid tissue | Peripheral blood
41
How does B cells internalise specific soluble molecules?
Cell-surface immunoglobulin
42
Process of B cells
Antigen specific B cells bind to antigen Specific Antigen efficiently internalised by receptor-mediated endocytosis High density of specific antigen fragments presented
43
How do T cells enter the lymph node cortex?
From blood via high endothelial Venules
44
What happens to T cells not activated by Antigen presented by dendritic cells?
Exit lymph node via the cortical sinuses
45
What happens to T cells activated by Antigen presented by dendritic cells?
Proliferate and lose ability to exit lymph node
46
What happens to T cells that have been activated?
Differentiate to effector cells and exit the lymph node
47
Small resting lymphocytes
Cell is quite small Very little cytoplasm Most of the Cell is occupied by nucleus DNA is very condensed > transcriptionally silent
48
Lymphoblast
The cytoplasm is relatively small DNA is less compressed T cells become transcriptionally active
49
Effector and B and T cell
Cell become bigger Cytoplasm is bigger. Endoplasmjc reticulum present B cells are transcriptionally and translationally active
50
What do Effector T cells produce ?
Large amounts of cytokines
51
What is the clonal selection hypothesis?
Each lymphocyte bears a single type of receptor with unique specificity Interaction between foreign molecule and lymphocyte receptor lead to lymphocyte activation. Differentiated effector cells derived from activated lymphocytes bear receptors of identical specificity to parental cell from which that lymphocyte was derived. Lymphocyte bearing receptors specific for ubiquitious self molecules are deleted and are absent from mature lymphocytes
52
What is the structure of TCR?
Alpha and beta chains linked by a disulphide bond One Antigen binding site TCR are never secreted N terminal region is responsible for binding of antigen [variable region ]
53
Antibodies and epitopes
Antibodies bind to epitopes displayed on surface of antigens. The epitopes recognised by T cell receptors are often buried The Antigen must first be broken down into peptide fragments The epitope peptide binds to a self molecule, an MHC molecule The T cell receptor binds to a complex of MHC molecule and epitope peptide
54
What does APC express
MHC class II molecules and I-Cam
55
What do T cell express ?
CD4 (can bind to MHC II), TCR an LFA-1
56
What happens when T cell and APC are in close vicinity?
Weak interaction occurs between integrin (LFA-1 and ICAM-1)
57
What does the change in LFA-1 stabilise ?
Association between Antigen-Specific T cell and APC
58
What are the 3 chains the IL-2 receptor is composed of?
Alpha. Beta. Gama
59
What receptors do Resting T cell express?
Beta and gamma chain only Bind IL-2 with moderate affinity (T cell responds to very high concentration of IL-2)
60
What happens when there is association of alpha chain to beta and gamma heterodimer?
Creates a receptor with increased affinity for IL-2 - cells respond to very low concentration of IL-2
61
What does IL-2 induce?
T cell proliferation
62
What does binding of IL-2 to its receptor signal?
T cell to enter cell cycle
63
What does CTLA-4 lack?
ITIM motifs
64
What does CTlA-4 do?
Inhibit T cell activation Compete with CD28 for interaction with B7 molecules expressed by APC
65
What is essential for limiting proliferative response ?
CTLA-4 binding to B7 molecules
66
Where does signal 2 only take place in ?
Inflammatory context - cause recruitment of macrophages and neutrophils
67
What is signal 2?
CD80/86 on APC interact with their receptor CD28 on T cell to generate activating signals
68
What is signal 3?
Secretion of cytokines by APC Delivers all the necessary information for T cell to fully understand the type of pathogen the host is dealing with
69
TGF - beta —> FoxP3
T reg cells
70
TGF-beta IL-6 > ROR Gamma T
TH17 cells
71
IFN Gamma (IL-12) > T-bet
TH1 cells
72
IL-4 > GATA-3
TH2 cells
73
How does CTL kill?
CTL recognises and binds Virus-infected Cell. CTL programs target for death, induce DNA fragmentation. CTL migrate to new target. Target cell dies by apoptosis
74
What promote the response of B cells ?
TH1 and TH2
75
What does TH1 help to eradicate?
Infections by microbes that can survive or replicate within marcrophages
76
What does TH2 help to control?
Infects by Extracellular parasites particularly helminths by promoting responses mediated by eosionophils, mast cells and IgE
77
What are TH17 responses typically induced by?
Extracellular Bacteria and Fungi Amplify neutrophilic response
78
What do most CD8 cytotoxic T cell release?
Cytokines; IFN Gamma, TNF alpha, LT alpha
79
What does IFN Gamma inhibit?
Viral replication directly. Activate macrophages
80
What does perforin do?
Aids in delivering contents of granules into the cytoplasm of target cells
81
What is the function of Granzymes?
Serine proteases which activate apoptosis once in the cytoplasm of target cell
82
What is the function of Granulysin?
Antimicrobial actions and can induce apoptosis
83
What is the function of IFN-Gamma and CD40 ligand?
Activated macrophages to destroy engulfed bacteria
84
What is the function of Fas ligand and LT alpha?
Kills chronically infected cells, releasing bacteria to be destroyed by fresh macrophages
85
What is the function of IL-2?
Induce T cell proliferation, increasing number of effector cells
86
What is the function of IL-3 + GM-CSF?
Induces Macrophage Differentiation In bone marrow
87
What is the function of TNF-alpha and LT-beta?
Activates endothelium to induce Macrophage binding and exit from blood vessel at site of infection
88
What is the function of CCL2?
Causes macrophages to accumulate at the site of infection
89
How does T cell enter lymph node cortex from blood?
High endothelial venue (HEV) | Through interaction that are not antigen-specific but are governed by cell-adhesion molecules

Immunology (20 decks)

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