[EXAM 2] Lecture 5 (T-cell- Mediated Immunity) Flashcards

(77 cards)

1
Q

What are the two stages of T cell mediated immunity?

A
  1. ) T-cell activation (T-cell priming)

2. ) Differentiation into effector T-cells

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2
Q

What are the different types of lymphocytes?

A
Natural Killer cell
CD8 Cytotoxic T cell 
B cell 
Regulatory T cell
CD4 Helper T cell
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3
Q

Where do T cell interact with pathogen antigen?

A

in secondary lymphoid tissue , not the site where infection occurs

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4
Q

What do Myeloid dendritic cells do?

A

capture antigen at the site of infection and bring it to the secondary lymphoid tissue, present antigen to naive T cells

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5
Q

What is the first defense mechanism against damage to skin?

A

draining lymph nodes send signals

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6
Q

What is initially used to fight off infection in the blood??

A

spleen

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7
Q

What makes up the associated mucosal secondary lymphoid tissue?

A

mucosal tissue

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8
Q

Where do T cells reside in the lymph node?

A

paracortical area

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9
Q

What components fill the cortex of the lymph node?

A

primary lymphoid follicle
secondary lymphoid follicle (mostly B cells)
germinal center

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10
Q

What cells are in the medullary cords of lymph node?

A

macrophages and plasma cells

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11
Q

Where is MHCII located in peripheral tissue?

A

in endocytic vesicles

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12
Q

When does MHCII leave the endocytic vesicle?

A

as the mature dendritic cell enters the T cell area of the lymph node MHCII is located on the cell surface

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13
Q

Why does dendritic processes increase surface area?

A

increase surface area for T-cell interaction

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14
Q

What role do dendritic cells play in regard to T cells?

A

activate naive T cells

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15
Q

What role do macrophages play in lymph nodes?

A

They remove pathogens and breakdown products from afferent lymph arriving from the site of infection (prevents infection from entering the blood stream)

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16
Q

What are the different fomrs of antigen presentation by dendritic cells?

A
  1. ) receptor-mediated endocytosis of bacteria (MHC class II and CD4 T cell)
  2. ) macropinocytosis of bacteria or viruses (MHC class II and CD4 T cell)
  3. ) viral infection (MHC Class I and CD8 T cell)
  4. ) cross-presentation of exogenous viral antigens (MHC class I and CD8 T cell)
  5. ) Transfer of viral antigens from infected dendritic cell to resident dendritic cell (MHC class I and CD8 T cells)
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17
Q

What is the cross-presentation of exogenous viral antigens?

A

the antigen is not processed and presented to the CD8 T cell

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18
Q

What cells are only capable of activating naive CD8 T- cells?

A

dendritic cells

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19
Q

What cells activate CD4 T cells?

A

macrophages

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20
Q

What receptors are expressed in dendritic cells?

A

Toll-like receptors which lead to

  • activation of dendritic cell-increases efficiency by which antigens are taken-up, processed and presented by MHCII
  • an expression of CCR7 (receptor for CCL21-chemokine in secondary lymph tissue)- dendritic cells leave lymph and enters the tissue
  • maturation (no longer processes antigen, the job is to present antigen to naive T cells-MHC I and II expression increases)
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21
Q

What do T cells bind to get into the lymph node cortex (T cell area/T cell zone)?

A

High endothelial venules (HEV)

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22
Q

What are two modes of entry for T cells?

A
  1. ) blood or lymph via afferent lymph nodes

2. ) if the antigen is not encountered, T-cell leaves via the efferent lymphatics

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23
Q

How long does it take for a T cell to recirculate from the blood through a lymph node and back to the blood?

A

every 12 to 24 hours

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24
Q

What are quiescent, unactivated T cells?

A

small nondividing cells with condensed chromatin, little cytoplasm, and little RNA or protein synthesis

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25
What is homing?
process by which T cells leave the bloodstream and enter the T cell zone of the lymph node
26
What are CCL21 and CCL19 guide T-cell homing?
secreted by stromal cells and dendritic cells in the T cell area and bound to the surface of endothelial cells of HEVs
27
What are CC7 proteins?
proteins expressed on naive T cells that bind CCL21 and CCL19
28
What allows rolling interaction of T-cells?
binding of L-selectin to GlyCAM-1 nad CD34 allows rolling interaction
29
What protein on T cell binds to ICAM-1?
LFA-1
30
What are diapedeses?
lymphocytes leave blood and enter the lymph node
31
What does L-selectin on.T ell bind to?
CD34 and GLyCAM-1 on HEV
32
What strengthens the attachment between on T-cell and ICAM-1 and ICAM-2 on vascular endothelium attachment?
LFA-1
33
Describe the affinity between T cell and DC initially?
low affinity throi=ugh LFA-1 and ICAM-1 interactions
34
What is ICAM-3?
receptor on T cell that binds to LFA-1 on dendritic cell and also binds CD-SIGN on DC
35
Where does increased adhenesion occur?
between CD2 on T cells binds LFA-3 on dendritic cells allowing for "exploring" of MHC complexes (lecture 2, slide 14)
36
Describe wHAT HAPPENS WHEN AN ANTIGEN IS NOT ENCOUNTERED?
T CELLS PASS FROM THE CORTEX TO THE MEDULLA AND LEAVE THE LYMPH NODE (GUIDED BY A S1P GRADIENT SPHINGOSINE 1-PHOSPHATE (S1P) EXPRESSION ON STROMAL CELLS IS LOW IN THE T-CELL AREA AND INCREASES TOWARDS THE MEDULLA AND EFFERENT LYMPHATIC VESSELS ACTIVATED T CELLLS-EXPRESS CD69 WHICH SEQUESTERS S1P RECEPTOR IN THE CELL ONCE ACTIVATED , T CELLS MATURE THEN DECREASE CD69 EXPRESSIO-NOW CAN LEAVE LYMPH NODE
37
What happens to T cells when an antigen is encountered?
- If naive T cell receptor recognizes peptide: MHC complex, signal is sent for cell to be activated - LFA-1/ICAM interactions are strengthened by conformatial change - Conjugate or cognate pair (T-cell/dendritic cell coupling) - T cell proliferate-clonal expansion - dendritic cells maintain contact with all clones-"nursery" for propagation of T cells ***need costimulatory signal CD28-T cell B7- dendritic cell (only expressed on DC presenting antigen) Require simultaneous signaling from TCR, co-receptor, and costimulatory receptor for activation
38
WHAT COMPLEXES ARE FOUND BETWEEN T CELL AND DENDRITIC CELL SYNAPSE?
``` C-SMAC (CENTRAL SUPRAMOLECULAR ACTIVATION COMPLEX)-Iinner structure e.g. TCR CD2 CD4 CD8 CD28 PKC-theta P-SMAC- peripheral supramolecular activation complex-outer structure LFA-1 ICAM-1 talin ```
39
Describe the T-cell activation signaling cascade
TCR/MHC engagement induces phosphorylation of CD3 cytoplasmic tails and zeta chain ITAMs-immunoreceptor tyrosine-based activation motifs Lck-tyrosine kinase-binds to CD4 and CD8- phosphorylates CD3 I ITAMs-phosphorylates ZAP-70, which binds phosphorylated residues of the zeta chain ZAP70 initiates activation of various transcription factors-leads to changes in gene transcription that induces T cell proliferation, differentiation, and effector functions: - NFAT - NF-kB - AP-1
40
What does calcineurin do?
activates transcription factors like NFAT
41
What is PLC-gamma?
it is what ZAP-70 activates and cleaves PIP2 to DAG and IP3
42
What is IL2?
growth cytokine critical for T cell activation | - activated T cells express high affinity IL-2 receptor-they also express IL-2 (autocriensignaling)
43
What are drugs that suppress IL-2?
cyclospirin A, tacrolimus (FK506), and rapamycin
44
Are self antigen expressed in the thymus?
no
45
What is anergy and what can cause it?
absence of CD28 can cause this and it is when cells do not respond to external stimuli leading to no production of IL-2-irreversible
46
What is th4 master regulator for Th1 cells?
T-bet
47
What is the master egulator of Th17?
ROR-gammaT
48
What is the master regulator for Th2?
GATA3
49
What is the master regulator for Tfh cells?
Bcl6
50
What is the master regulator for T regulatory cells?
FoxP3
51
Do effector T cells attack pathogen?
no, assist other cells
52
Can local environment affect properties of cytokines?
Yes
53
WHat is cross presentation?
antigen gets brought into cell and without getting processed and is then presented to MHC class I receptor and presented out to T cell
54
How do MHC class 2 receptors process bacteria or viruses? (Broad Answer)
-Receptor mediated endocytosis -macropinocytosis (Lecture 2 slide 25)
55
How do MHC class 1 receptors process bacteria or viruses? (Broad Answer)
-processes viral infrection and dpresent to T cell -cross presentation -transfer of viral antigen from infected dendrtic cellto resident dendritic cell (Lecture 2 slide 25)
56
Does CD8 function homogenous or heterogenously?
homogenously; interacts with many target cell types-viral oer microbial infection
57
Why would some infectiosn require effector CD4 T cell help?
to produce IL-2
58
Where do Tfh cells reside?
stay in secondary lymph tissue and move to B cell area
59
What are the differences between naive and effector T cells?
naive - LFA-1 (alpha and beta subunit) - ICAM-1 (adhesion molecule) effector - VLA-4 - VCAM-1 - activated endothelium
60
What component of activated T cells prevents them form entering into the secondary lymph tissue?
effector T cell no longer express L-selectin
61
What is the main function of Th1 cells?
Help macrophages to suppress intracellular infections
62
What is the main function of Th2 cells?
helps basophils, mast cells, eosinophils, and B cell respond to parasite infections
63
What is the main function of Tfh cells?
help B cells become activated,switch isotype, and increase antibody affinity
64
What is the main function of Th17 cells?
enhance the neutrophil response to fungal and extracellular bacterial infections
65
What is the main function of Tregs cells?
suppress the activities of other effector T cell population
66
When are CD8 cytotoxins released to fight infection?
At the synapse only and contain cytotoxins packaged into granules
67
What do IFN-gamma cytokines do?
inhibit viral replication in infected cell and increases processing of viral antigens, presentation, and activates local macrophages
68
True/False: Cytoxic T cells can only target one infected cell
False; individual cytotoxic T-cells can target numerous infected cells
69
How do cells die by cytotoxic T-cells?
via apoptosis | -perforin, granulysin, and serglycin make a pore on target cell and deliver granzymes
70
What are granzymes?
initiate a cascade of proteolytic cleavages and activation of nucleases (degrade DNA, eventual loss of membrane integrity) eg. serine proteases
71
What is responsible for macrophage activation by IFN-gamma (CD8 also expresses) and CD40 ligand production?
Th1 cells
72
How are cytokines delivered to the pathogen?
via exocytosis to the synapse (specific activation)
73
What cells fuse more efficiently with lysosomes?
Phagosomes
74
What does increase in NO production and proteases lead to?
destruction of pathogen
75
What type of T cells activate B cells?
Tfh cells | - after activation, they move to the B cell area of the lymph node-interact with circulating naive B cells
76
What is an example of linked antigen?
B cell and Tfh cells are specific for epitopes of the same antigen (CD40)
77
How do Tregs suppress the Immune response?
- express high levels of CD25 (alpha chain IL2) - makes antinflammatory and immunosuppressive cytokines (IL-4, IL-10, and TGF-B) - interact with dendritic cells in secondary lymph tissue- prevent interaction with maive T-cells - direct contact with effector T-cells-cytokines