Lecture #11

Question 1

Properties of GALT (5)

Answer 1

1. Part of MALT
2. 100-400 m2 surface area
3. Tonsils, appendix, peyer patches
4. Highest amount of lymphocytes
5. 2/3 of Ig production in the body

Question 2

What are the 3 functions of GALT

Answer 2

1. Exclusion of infectious agents
2. Induce local or systemic immune response
3. Induction tolerance

Question 3

Cells of GALT present in the epithelial layer

Answer 3

CD8+ Tcell, gamma/delta Tcell, NKC, M cells, epithelial cells with tight junctions

Question 4

Cells of GALT present in the Lpropria

Answer 4

Mast cells, DC, CD4+ Tcells, macrophages, B cells

Question 5

What is the structure of a peyer patch?

Answer 5

M cell
SED - sub epithelial dome containing APCs
TDA - T dependent area with B cell follicles
And only efferent lymphatic darinage (ot afferent like other secondary lymphoid organs)

Question 6

What is the function of M cells?

Answer 6

Endocytosis/ phagocytosis of antigens from the lumen, vesicular transport of them throughout the cell and exocytosis in the BL side.

Question 7

What is the sequence of event once an antigen reached to the SED?

Answer 7

1. DC engolf the antigen and present it to naive T cell
2. Activation of the T cell and migration to the nearest mesenteric LN
3. Further activation and differentiation of T and B lymphocyes
4. Mature B and T cells migrate to other sites of the gut mucosa via blood circulation

Question 8

How do the lymphocytes know to go to the gut?

Answer 8

In the lymph node:
DC which were activated by antigens from the gut induce the expression of chemokine receptors on the lymphocytes for exmple CCR9 and alpha4beta7 which bind to CCL25 and MadCAM respectively on endothelial cells in the gut inducing homing.

Question 9

Humoral immune system in the mucosa i dominated by

Answer 9

IgA dimers induced by class switching of IgM pentameric to IgA dimeric (IL5 IL2 TGFbeta)

Question 10

IgM is pentameric where?

IgA is dimeric where?

Answer 10

Everyehre

Only in the mucosa

Question 11

What othe cell types can produce IgM in mucous membranes?

Answer 11

Salivary glands, Lacrimal glands, Nasal glands

Question 12

2 types of class switching of IgM to IgA in the gut

Answer 12

1. TD class switching - slower, higher affinity, normal condition
Th2 cells induce the class switching by releasing IL2, IL5, TGF beta
(Higer affinity due to activation of affinity maturation by CD40-CD40L binding)

2. TI class switching - faster, lower affinity, infection
DC induce the class switching by releasinf TGF beta, BAFF, APRIL, IL5

Question 13

The process of IgA dimer secretion through the mucosa

Answer 13

1. Dimeric IgA with J chain bind to polyIg receptor
2. Endocytosis
3. Release at the luminal surface with a part on the receptor (make it resistant to enzymatic degradation)

Question 14

IgA bound to an antigen in the gut can be ___________ or ____________

Answer 14

Secreted 
Endocytosed (neutralization of the antigen in the LP)

Question 15

What are the mechanisms for tolerance of commensial microbes in the gut?

Answer 15

1. Intracellular or basolaterl receptors (no PRRs on the villi) Ex: TLR9, TLR5(basolateral), NLR(NOD)
2. Tolerogenic DC (CD103+)
   Inducing naive Th cells to become Treg by TGF beta, IL10
   As oppose to conventional DC (CD11b+) that induce naive T cells to become Th17 and Th1 by IL12 and IL23 respectively in a IL6 rich environment

Question 16

The mucosal immune system as oppose to other systems constantly ___________ and ____________

Answer 16

Uptake antigens

Prodcue IgA

Question 17

How does P.gingivalis can cause chronic joint inflammation?

Answer 17

P.gingivalis present in periodontitis produces arginine deaminase - formation of citrullinated pr - Ab are produced against these pr (ACPA) - and memory cell remain - upon minor joint injury citrullinated pr will be froduced in the joints - APCA will form immune complexes with these proteins - deposition in the joint - further inflammation