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

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

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
Q

What is homing?

A

process by which T cells leave the bloodstream and enter the T cell zone of the lymph node

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26
Q

What are CCL21 and CCL19 guide T-cell homing?

A

secreted by stromal cells and dendritic cells in the T cell area and bound to the surface of endothelial cells of HEVs

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27
Q

What are CC7 proteins?

A

proteins expressed on naive T cells that bind CCL21 and CCL19

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28
Q

What allows rolling interaction of T-cells?

A

binding of L-selectin to GlyCAM-1 nad CD34 allows rolling interaction

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29
Q

What protein on T cell binds to ICAM-1?

A

LFA-1

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30
Q

What are diapedeses?

A

lymphocytes leave blood and enter the lymph node

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31
Q

What does L-selectin on.T ell bind to?

A

CD34 and GLyCAM-1 on HEV

32
Q

What strengthens the attachment between on T-cell and ICAM-1 and ICAM-2 on vascular endothelium attachment?

A

LFA-1

33
Q

Describe the affinity between T cell and DC initially?

A

low affinity throi=ugh LFA-1 and ICAM-1 interactions

34
Q

What is ICAM-3?

A

receptor on T cell that binds to LFA-1 on dendritic cell and also binds CD-SIGN on DC

35
Q

Where does increased adhenesion occur?

A

between CD2 on T cells binds LFA-3 on dendritic cells allowing for “exploring” of MHC complexes (lecture 2, slide 14)

36
Q

Describe wHAT HAPPENS WHEN AN ANTIGEN IS NOT ENCOUNTERED?

A

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
Q

What happens to T cells when an antigen is encountered?

A
  • 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
Q

WHAT COMPLEXES ARE FOUND BETWEEN T CELL AND DENDRITIC CELL SYNAPSE?

A 
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
Q

Describe the T-cell activation signaling cascade

A

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
Q

What does calcineurin do?

A

activates transcription factors like NFAT

41
Q

What is PLC-gamma?

A

it is what ZAP-70 activates and cleaves PIP2 to DAG and IP3

42
Q

What is IL2?

A

growth cytokine critical for T cell activation

- activated T cells express high affinity IL-2 receptor-they also express IL-2 (autocriensignaling)

43
Q

What are drugs that suppress IL-2?

A

cyclospirin A, tacrolimus (FK506), and rapamycin

44
Q

Are self antigen expressed in the thymus?

A

no

45
Q

What is anergy and what can cause it?

A

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
Q

What is th4 master regulator for Th1 cells?

A

T-bet

47
Q

What is the master egulator of Th17?

A

ROR-gammaT

48
Q

What is the master regulator for Th2?

A

GATA3

49
Q

What is the master regulator for Tfh cells?

A

Bcl6

50
Q

What is the master regulator for T regulatory cells?

A

FoxP3

51
Q

Do effector T cells attack pathogen?

A

no, assist other cells

52
Q

Can local environment affect properties of cytokines?

A

Yes

53
Q

WHat is cross presentation?

A

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
Q

How do MHC class 2 receptors process bacteria or viruses? (Broad Answer)

A

-Receptor mediated endocytosis
-macropinocytosis
(Lecture 2 slide 25)

55
Q

How do MHC class 1 receptors process bacteria or viruses? (Broad Answer)

A

-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
Q

Does CD8 function homogenous or heterogenously?

A

homogenously; interacts with many target cell types-viral oer microbial infection

57
Q

Why would some infectiosn require effector CD4 T cell help?

A

to produce IL-2

58
Q

Where do Tfh cells reside?

A

stay in secondary lymph tissue and move to B cell area

59
Q

What are the differences between naive and effector T cells?

A

naive

  • LFA-1 (alpha and beta subunit)
  • ICAM-1 (adhesion molecule)

effector

  • VLA-4
  • VCAM-1
  • activated endothelium
60
Q

What component of activated T cells prevents them form entering into the secondary lymph tissue?

A

effector T cell no longer express L-selectin

61
Q

What is the main function of Th1 cells?

A

Help macrophages to suppress intracellular infections

62
Q

What is the main function of Th2 cells?

A

helps basophils, mast cells, eosinophils, and B cell respond to parasite infections

63
Q

What is the main function of Tfh cells?

A

help B cells become activated,switch isotype, and increase antibody affinity

64
Q

What is the main function of Th17 cells?

A

enhance the neutrophil response to fungal and extracellular bacterial infections

65
Q

What is the main function of Tregs cells?

A

suppress the activities of other effector T cell population

66
Q

When are CD8 cytotoxins released to fight infection?

A

At the synapse only and contain cytotoxins packaged into granules

67
Q

What do IFN-gamma cytokines do?

A

inhibit viral replication in infected cell and increases processing of viral antigens, presentation, and activates local macrophages

68
Q

True/False: Cytoxic T cells can only target one infected cell

A

False; individual cytotoxic T-cells can target numerous infected cells

69
Q

How do cells die by cytotoxic T-cells?

A

via apoptosis

-perforin, granulysin, and serglycin make a pore on target cell and deliver granzymes

70
Q

What are granzymes?

A

initiate a cascade of proteolytic cleavages and activation of nucleases (degrade DNA, eventual loss of membrane integrity)
eg. serine proteases

71
Q

What is responsible for macrophage activation by IFN-gamma (CD8 also expresses) and CD40 ligand production?

A

Th1 cells

72
Q

How are cytokines delivered to the pathogen?

A

via exocytosis to the synapse (specific activation)

73
Q

What cells fuse more efficiently with lysosomes?

A

Phagosomes

74
Q

What does increase in NO production and proteases lead to?

A

destruction of pathogen

75
Q

What type of T cells activate B cells?

A

Tfh cells

- after activation, they move to the B cell area of the lymph node-interact with circulating naive B cells

76
Q

What is an example of linked antigen?

A

B cell and Tfh cells are specific for epitopes of the same antigen (CD40)

77
Q

How do Tregs suppress the Immune response?

A
  • 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

Immunology (7 decks)

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