Cutaneous and Mucosal associated Lymphoid Tissue

Question 1

Mucosal-associated Lymphoid Tissues

Answer 1

• digestive, respiratory, urogenital systems are lined by mucous membranes that are defended from pathogens by MALT
• includes loose clusters of lymphoid cells in the lamina propria of the intestine
• includes Peyer’s patches found in submucosal layer of the intestine, tonsils and appendix
• Peyer’s patches and tonsils contain B lymphocytes organized into primary follicles and germinal centres, T cells are found around germinal centers
• contains large pop. of IgA-secreting plasma cells and intraepithelial lymphocytes (mainly T cells) that mediate cell immunity

Question 2

Mucous Membranes

Answer 2

• mechanical barriers to many pathogens-tight junctions that exist b/w epithelial cells which makes penetration by pathogens difficult
• colonized by normal microbial flora that compete w/ potential pathogens for attachment sites and nutrients

Question 3

Mucous Membranes-Mucous

Answer 3

• viscous fluid
• secreted by mucosal epithelial cells
• traps and washes away pathogens
• secretions contain antibacterial and antiviral substances (e.g. lysozyme)

Question 4

Mucous Membranes-Epithelial cells

Answer 4

-important sources of cytokines (e.g. IL1) that induce a local inflammatory response

Question 5

Antigen Processing and Presentation-M cells

Answer 5

• specialized epithelial cells that are flattened
• transport antigen from lumen of the respiratory, digestive, urogenital tracts to underlying MALT
• contain a pocket filled w/ B cells, T cells, macrophages
• found at inductive sites that overlie organized lymphoid follicles in the lamina propria
• antigens endocytosed by M cells are transported within vesicles from the luminal membrane to the pocket membrane
• the vesicles fuse and deliver their contents to APC
• B cells within lymphoid follicles and Peyer’s patches are activated by antigen transported by M cells
• differentiate into IgA synthesizing plasma cells
• IgA is transported across the epithelial cells and released into the lumen as secretory IgA

Question 6

Secretory IgA

Answer 6

• defense of mucosal surfaces against bacteria and viruses
• cross links large antigen which are then easily trapped in mucus and eliminated by the action of cilia in respiratory tract or peristalsis in the gut, due to polymeric structure
• binds to bacteria and viruses, preventing receptor mediated attachment to mucosal epithelial cells

Question 7

Secretory IgA structure

Answer 7

• dimer/tetramer of IgA
• J chain polypeptide that promotes polymerization
• 70 kDa polypeptide secretory component that masks cleavage sites in the hinge region–>protects secretory IgA in mucosal secretions from enzymatic digestion

Question 8

Formation of Secretory IgA

Answer 8

• IgA secreting plasma cells traffick to sub epithelial tissues
• the secreted IgA binds via J-chain to poly-Ig receptor expressed on basolateral surface of mucosal epithelial cells
• receptor IgA complex transported in a vesicle across the epithelium to the lumen
• enzymes cleave the poly-Ig receptor which becomes the secretory component bound to polymeric IgA
• pentameric IgM transported into mucosal secretions by same mechanism

Question 9

Intraepithelial Lymphocytes (IELs)-T cells

Answer 9

• T cells that express TCRs w/ limited diversity, encoded by only a few TCR genes
• some have TCRs that interact w/ microbial phospholipids (bacteria, parasites), activated w/o MHC presentation
• some recognize stress induced MHC-like molecules

Question 10

Intraepithelial Lymphocytes (IELs)-NKT cells

Answer 10

-have TCRs that react w/ bacteria derived glycoprotein antigens presented like CD1 molecules on APC 
CD1 molecules=non classical class I MHC like molecules that assoc. w/ beta2-microglobulin

Question 11

IELs-Role in Adaptive Immune Response

Answer 11

• cytokines secreted by IELs in response to microbial stimulation shape the subsequent adaptive immune response so it is the correct type to eliminate the pathogen
• mucosal mast cells shape the adaptive immune response by secreting cytokines after pattern recognition receptors are triggered (e.g. TLRs) that recognize LPS (TLR4) or peptidoglycan (TLR2)
• IELs are cytotoxic, kill tumour cells

Question 12

Lymphocyte Trafficking to MALT

Answer 12

• lymphocytes initially activated in MALT and then recirculate in the blood home back to mucosal tissues
• meditaed by vascular addressins (MadCam-1-mucosal addressing cell adhesion molecule-1, found in peyer’s patches)
• different adhesion molecules specify homing

Question 13

Cutaneous-assoc. Lymphoid Tissues-Epidermis and Dermis

Answer 13

• skin consists of the epidermis-several outer layers of tightly packed epithelial cells, keratinocytes
• dermis-thicker inner layer of connective tissue, contains blood vessels, hair follicles, sebaceous glands, sweat glands
• epidermis is mechanical barrier to pathogenic infection
• sebum secreted by sebaceous glands creates an acidic enviro., inhibits growth of microorganisms
• sweat contains substances that have antibacterial activity (lysozyme)

Question 14

Cutaneous-assoc. Lymphoid Tissues-Keratinocytes and skin mast cells

Answer 14

• secrete cytokines that induce local inflammatory response

- keratinocytes can be induced to express classII MHC and may fxn as APC

Question 15

Cutaneous-assoc. Lymphoid Tissues-Langerhans Cells

Answer 15

• within epidermis
• immature dendritic cell that internalizes antigen (phagocytosis/endocytosis)
• transports the antigen by lymphatic vessels from the epidermis to regional lymph nodes
• in regional lymph nodes, differentiates into mature dendritic cell

Question 16

Cutaneous-assoc. Lymphoid Tissues-Intraepidermal Lymphocytes

Answer 16

• contained in the epidermis
• most are T cells
• well situated to encounter antigens from pathogens that enter through the skin
• dermis contains CD4+ and CD8+ T cells (previously activated or memory T cells that migrate to site of initial contact w/ antigen), macs