T- Cell Activation

Question 1

CD3

Answer 1

Signal transduction by TCR complex

Question 2

CD4

Answer 2

Signal transduction class II

Question 3

CD8

Answer 3

Signal transduction class I

Question 4

CD28

Answer 4

Signal transduction

matches with CD80 (B7-1)

Question 5

CTLA-4

Answer 5

Inhibition matches with CD80

Question 6

PD-1

Answer 6

Inhibition

Question 7

LFA-1

Answer 7

adhesion, signal transduction matches with ICAM-1

Question 8

migration of Naive T lymphocytes in lymphoid tissues

Answer 8

• Naïve T lymphocyte enters a lymph node and a dendritic cell presents an antigen
o L-selectin- initial weak adhesion of naïve T cells to high endothelial venule in lymph node
o LFA-1 and ICAM-1- stable arrest on HEV
• After activation from dendritic cells in the lymph node, development of effector T cells
o CD4 increases 100x to 1000x
o CD8 increases 100,000x
• B cells activate memory T-cells
• Effector T cells travel to the site of infection

Question 9

Ligand interaction on T-cells and Dendritic cells

Answer 9

• First Signal
o CD40L expression upregulated on T cells, CD40 expressed on APCs
o Expression of B7 (CD80) is upregulated on APC releasing IL-12, CD28 expressed on T cells
• Second Signal
o Maintains the specificity of the response to the epitope

Question 10

T-cell activation

Answer 10

1. Initiation of formation of the immunologic synapse
2. Activation of immunoreceptor tyrosine-based activation motifs (ITAMs)
3. Lck kinase phosphorylates and activates the tyrosine kinase ZAP-70 that is associated with the chain
4. ZAP-70 activations
   
   • PLCgamma1 to increase NFAT and NF-kB production
   • PI3-kinase to increase protein synthesis, NF-kB, and AP-1

Question 11

Activation of T cells transcription factors

Answer 11

c-Fos (min)

c-Myc (hr)

Question 12

Activation of T cells membrane effector molecules

Answer 12

CD40 ligand (hours)
Fas ligand (hours)

Question 13

Activation of T cells Cytokines

Answer 13

IL-2 (hours)
IFN-gamma (hours to days)
IL-4 (hours to days)

Question 14

Activation of T cells cytokine receptors

Answer 14

IL-2Ralpha (hours)

Question 15

IL-2

Answer 15

• T cell proliferation, regulatory T cell survival

- binding of IL-2 to high affinity IL-2R promotes T-cell proliferation and differentiation

Question 16

IFN-gamma

Answer 16

• Activation of macrophages
• activates B cells to stimulate class switching and complement binding
• Stimulates class II HLA and B7 (CD80) expression

Question 17

IL-4

Answer 17

B-cell switching IgE

Question 18

IL-5

Answer 18

Activation of eosinophils

Question 19

IL-17

Answer 19

Stimulation of acute inflammation

Question 20

IL-22

Answer 20

Maintenance of epithelial barrier function

Question 21

TGF-B

Answer 21

inhibition of T cell activation, differentiation of T cells

Question 22

Th1

Answer 22

• IFN-gamma, IL-12 activators
• macrophage activation
• defend against intracellular pathogens
• classically activated
• role in autoimmunity, chronic infammation (secrete IL-2, IFN-gamma)

Question 23

Th2

Answer 23

• IL-4 activators
• Eosinophil and mast cell activation
• transcription factors GATA-3
• Isotope class switching (IgE)
• alternative macrophage development
• defend against helminths
• role in allergies (secretes IL-4,5,13)
• anti-inflammatory and wound repair

Question 24

Th17

Answer 24

• IL-1,6 activatiors
• IL-17,22 secretion
• Neutrophil recruitment and activation
• defend against extracellular bacteria and fungi
• transcription factor RORgammat
• role in autoimmunity, inflammation

Question 25

How do CD4 cells help CD8 cells proliferate?

Answer 25

CD4 helper cells produce molecules that stimulates CTL differentiation by secreting IFN-gamma, and IL-2

Question 26

T regulatory cells

Answer 26

• CD4+ T cells
• influenced by IL-2 and TGF-beta
• Constitutively express CTLA-4, CD25
• Novel transcription factor FOXp3
• Secrete IL-10 and TGF-B
• binds more avidly than CD28

Question 27

What is the major difference between effector T cells and resting Naive T cells?

Answer 27

An effector T cell is able to respond to specific antigen eithout need for co-stimulation via B7 (CD80)- CD28 interaction

Question 28

CTL function

Answer 28

• ANTIGEN SPECIFIC MHC 1
• Two killing mechanisms
  
  1. Cytotoxins are delivered directly onto the surface of the infected target cell (granzymes and Perforin), perforin facilitates entry of granzymes into the cytosol, granzymes activates apoptosis
  2. FasL and Fas (CD95) induction of apoptotic pathways

Question 29

Mechanism of NK cell killing

Answer 29

• kill tumors and virus-infected cells
• kill by granzymes, perforin
• enhanced by IFN-alpha, IFN-Beta, and IL-12
• Inhibited by MHC class I
• CD16 and CD56 surface markers

Question 30

Memory T cells

Answer 30

• naive T cells will be activated to differentiate into effector cells and memory cells
• most become effector which are short lived
• Respond for rapidly than naive
• can respond in peripheral tissues
• require IL-7 and IL-15 for survival

Question 31

Mycobacteria evasion mechanisms

Answer 31

-inhibition of phagolysosome fusion

Question 32

Herpes simplex virus evasion mechanism

Answer 32

• inhibition of antigen presentation ( TAP transporter)

Question 33

CMV evasion mechanism

Answer 33

-inhibition of antigen presentation (proteasomal activity)

Question 34

EBV evasion mechanism

Answer 34

inhibition of antigen presentation (inhibition of proteasomal activity) or production of IL-10 (inhibition of macrophage activation)

Question 35

Pox virus mechanism

Answer 35

inhibition of effector cell activation