Mucosal Immunity

Question 1

What constitutes the GALT?

Answer 1

Waldeyer's Ring 
Peyer's Patches
Isolated lymphoid follicles
Lamina propria
Intraepithelial lymphocytes

Question 2

Waldeyer’s ring

Answer 2

tonsils and adenoids form lymphoid tissue ring that guards the entrance to the airways and gut

Question 3

Peyer’s patches

Answer 3

secondary lymphoid follicles in the SMALL INTESTINE
lie underneath mucosal epithelium
contain T and B lymphocytes and follicular dendritic cells

Question 4

Isolated lymphoid follicles

Answer 4

small and large intestine, contain mostly B cells
overlaid by epithelial M cell
many of these found in the appendix

Question 5

Lamina propria

Answer 5

just beneath basement membrane
lots of effector leukocytes- macs, dendritic cells, T cells, B cells, (CD8 T cells, mast cells, CD4 T cells)
MANY IgA secreting B cells

Question 6

Intraepithelial lymphocytes

Answer 6

reside between lumenal epithelial cells beneath tight junctions
they are previously activated CD8 T cells that contain cytotoxic granules like CTLs but have distinct receptors

Question 7

M cells

Answer 7

AKA: microfold cells
specialized flattened epithelial cells that pinocytose material from the overlying lumen and transport in an undegraded form to mucosal follicles.
Antigen is then bound by dendritic cells which activate T cells.

Question 8

Intraepithelial Dendritic cells

Answer 8

Dendritic cells that can extend processes across the epithelial layer to capture antigen from the lumen of the gut.

Question 9

Nonspecific factors contributing to Mucosal immunity

Answer 9

Mechanical: epithelial cells joined by tight junctions, longitudinal flow of air or fluid, movement of mucus by cilia
Chemical: fatty acids (protective skin barrier), low pH, salivary enzymes (lysozyme), gastric acid, bile salts, antibacterial peptides (defensins)
Microbiological: normal flora in the nose, mouth and gut

Question 10

Tight junctions: Claudin and Occludin

Answer 10

transmembrane proteins that form strands that band the epithelial plasma membranes together forming a tight seal providing a barrier against passive diffusion.

Question 11

Mucosal Lymphoid Homing

Answer 11

Naive lymphocytes activated in mucosal follicles (afferent) give rise to effector cells that travel in the lymph and blood to gain access to the lamina propria of the mucosal tissue

Question 12

During mucosal lymphoid homing how does the effector cell leave circulation?

Answer 12

integrin a4b7 and MAdCAM-1

Question 13

During mucosal lymphoid homing how do intraepithelial lymphocytes bind to intestinal epithelium?

Answer 13

integrin aEb7 to bind to epithelial cadherins

Question 14

What chemokine is secreted by gut epithelium and what is the receptor on mucosal lymphocytes?

Answer 14

Chemokine: CCL25
Receptor: CCR9

Question 15

How do T cells regulate IgA synthesis

Answer 15

T cell activation by dendritic cells carrying antigen
T cells interact with IgM-expressing B cells in lymphoid follicles at T cell/B cell zone interface
The cytokine TGFb and T cell interactions with B cells induce class switching to IgA production
B cells migrate via mesenteric lymph nodes to lamina propria
In lamina propria the activated B cells again interact with T cells expressing CD40L and with cytokines IL-5 and IL-6. These interactions drive IgA plasma cell differentiation

Question 16

Transcytosis

Answer 16

transport of macromolecules from one side of a cell to the other side via receptors

Question 17

How does IgA get transcytosed?

Answer 17

IgA binds to receptor on basolateral side of epithelial cell
receptor mediated endocytosis of IgA
transport of IgA to apical face of epithelial cell
receptor is cleaved, IgA is bound to mucus through the secretory piece (secretory component)

Question 18

IgA functions

Answer 18

during secretion IgA can: export toxins and pathogens or bind and neutralize antigens
sIgA can bind pathogens/antigens and carry them in through an M cell to deliver to lymphoid tissue

Question 19

Anti-inflammatory properties of IgA

Answer 19

doesn’t activate complement
binding to neutrophils and macs via Fc receptors tends to inhibit phagocytic/lytic functions
the FC/SC end is hydrophilic/mucophilic which assists in preventing microorgs from binding to epithelial receptors
sIgA prevents colonization of parasites w/o inducing inflammation

Question 20

Other mucosal immunoglobulins: IgM

Answer 20

IgM can be transported across epithelium and can be sufficient in replacing sIgA in deficient people

Question 21

Other mucosal immunoglobulins: IgG

Answer 21

IgG in low amounts and not transported EXCEPT

in distal resp tract where it is transported in large amounts. Important defense in pulmonary secretions.

Question 22

Other mucosal immunoglobulins: IgE

Answer 22

IgE can be synthesized in mucosal issue

IgE synthesized elsewhere can be found in mucosal issue bound to mast cells

Question 23

What is oral tolerance?

Answer 23

suppression of immune cell responses to antigens introduced via the oral route.
Acquired tolerance
Important from preventing food allergies and prevents immune cell reactions against natural bacterial flora n the gut

Question 24

Diseases caused by failure of oral tolerance

Answer 24

Crohn’s disease and Ulcerative Colitis

Question 25

Passive transfer of immunity: Fetal Stage

Answer 25

IgG is passively acquired
FcRn binds to maternal IgG and transcytosis to fetal circulation
Neonate is born w/ significant protection

Question 26

Passive transfer of immunity: Breast-milk fed neonate

Answer 26

sIgA secreting B cells migrate to breast in response to hormones; sIgA is transported to milk via SC transport process
Infant gut has not developed germinal centers and produces little to no sIga for its mucosal surfaces

Question 27

Characteristics of infant gut at birth

Answer 27

little to no bacterial colonization
little to no mucus secretions
no IgA producing plasma cells

Question 28

When is an infant most vulnerable to infection?

Answer 28

between 3-12 months because the passive immunity from mom is wearing off and their own immunity is just beginning to develop

Question 29

Types of leukocytes in breast milk

Answer 29

macrophages(55-60%), neutrophils(30-40%), lymphocytes(5-10%)

Question 30

Immunoglobulins and Cytokines in breast milk

Answer 30

sIgA- provides protection via immune exclusion (keeps pathogens from colonizing without inducing inflammation)
sIgM- crosses via J-chain
TGFb and IL-10 thought to be important for infant development of tolerance to ingested antigens

Question 31

How are maternal antigens transferred

Answer 31

processed in mom and passed via breast milk-may have been airborne and processed through resp mucosal system or via gut mucosal system
antigens passed from mom’s skin to baby and/or general handling of baby

Question 32

Non immunoglobulin protective factors in breast milk: Lysozymes

Answer 32

cleaves peptidoglycans in cell walls

Question 33

Non immunoglobulin protective factors in breast milk: Lactoferrin

Answer 33

competes for ferric iron and inhibits bacterial growth

Question 34

Non immunoglobulin protective factors in breast milk: oligosaccharides

Answer 34

feed infant beneficial gut microbiota such as bifidobacteria and also inhibit binding of pathogenic bacteria to the gut

Question 35

Non immunoglobulin protective factors in breast milk: antiviral lipids

Answer 35

substrates that are digested into small lipids that disrupt viral envelops

Question 36

Non immunoglobulin protective factors in breast milk: glycosylated proteins

Answer 36

inhibit bacteria and virus binding to gut, lactahedrin protects against rotavirus, mucin-1 protects agains E. coli