Chapter 5 And 6 ( Secondary Lymphoid Tissue )

Question 1

Activated dendritic cells will begin to express what ? Which activated by what ?

Answer 1

A chemokine receptor called CCR7

Activated by chemokines that are produced by the endothelium

Question 2

FDA approved proteasome inhibitors ? In ttt of what ?

Answer 2

1- Bortezomib : in multiple myeloma and mantel cell lymphoma
2- Carfilzomib : in multiple myeloma

Question 3

Cross presentation ?

Answer 3

DCs activate both CD4 and CD8 T cells , so the CD4 t cells produce IL2 which is important for naive CD8 T cell activation into activated CTLs and memory cells

Question 4

First signal for T cell activation ?

Answer 4

Binding of MHC peptide complex by TCR and coreceptors CD4,CD8

Question 5

Second signal for activation of T cells ?

Answer 5

Binding of B7 to CD28

Question 6

Drugs acting on CTLA-4 ? Clinical use ?

Answer 6

Agonists as
Abatacept in rheumatoid arthritis
Belatacept in renal transplants

Antagonists as
Ipilimumab in melanoma

Question 7

Superantigens mechanism ? Examples ?

Answer 7

Cross link the variable Beta domain of TCR to an Alpha chain of class MHC ll outside the normal peptide binding groove —> activation of any clones of T cells expressing that particular Beta domain —> polyclonal activation of T cells —> overproduction of IFN-gamma —> overactivation of macrophages —> overproduction of proinflammatory cytokines —> systemic toxicity

Examples :
Staphylococcal enterotoxin
Toxin shock syndrome toxin-1 ( TSST-1)
Streptococcal pyrogenic exotoxins

Question 8

Th1 stimulant ? Effect ?

Answer 8

Intracellular infections
IL-12

Secrete IL-2 and INF-gamma which :
1- amplifies Th1 response 
2- inhibits Th2 response 
3- activates classic macrophages 
4- drive isotype switching to IgG

Question 9

Th2 stimulants ? Effects ?

Answer 9

Parasitic infections
IL-4

They secrete IL-4,5,10,13 and TGF-beta which :
1- IL-4 amplifies Th2 response
2- IL-4,10 inhibits Th1 response
3- IL-5 drives eosinophils differentiation
4- activate alternate macrophages
5- IL-4,13 drive isotype switching to IgE and alternative macrophage activation
6- IL-5 and TGF-beta drive isotype switching to IgAq

Question 10

Th17 stimulants ? Effects ?

Answer 10

Extracellular bacterial and fungal infections
IL-23,6 and TGF-beta

Secret IL-17,22 which :
1- IL-17 activates tissue cells and leukocytes to secrete inflammatory cytokines leading to recruitment of neutrophils
2- IL-22 stabilizes interactions between cells in the endothelium decreasing permeability
3- IL-17,22 act on epithelial cells to secrete antimicrobials and improve barrier function

Question 11

TI antigens ? Examples ?

Answer 11

They directly stimulate B cells to proliferate and differentiate into plasma cells

Macromolecules as :
Lipids
Polysaccharides
Lipopolysaccharides

Question 12

How the B lymphocytes undergo class switching ?

Answer 12

By changing the heavy chains constant domains to classes of antibodies with new and different effector function
It does this by rearranging the DNA encoding the constant regions that cause the intervening DNA to be looped out , excised and degraded