Mucosal Immunity Flashcards
What constitutes the GALT?
Waldeyer's Ring Peyer's Patches Isolated lymphoid follicles Lamina propria Intraepithelial lymphocytes
Waldeyer’s ring
tonsils and adenoids form lymphoid tissue ring that guards the entrance to the airways and gut
Peyer’s patches
secondary lymphoid follicles in the SMALL INTESTINE
lie underneath mucosal epithelium
contain T and B lymphocytes and follicular dendritic cells
Isolated lymphoid follicles
small and large intestine, contain mostly B cells
overlaid by epithelial M cell
many of these found in the appendix
Lamina propria
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
Intraepithelial lymphocytes
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
M cells
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.
Intraepithelial Dendritic cells
Dendritic cells that can extend processes across the epithelial layer to capture antigen from the lumen of the gut.
Nonspecific factors contributing to Mucosal immunity
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
Tight junctions: Claudin and Occludin
transmembrane proteins that form strands that band the epithelial plasma membranes together forming a tight seal providing a barrier against passive diffusion.
Mucosal Lymphoid Homing
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
During mucosal lymphoid homing how does the effector cell leave circulation?
integrin a4b7 and MAdCAM-1
During mucosal lymphoid homing how do intraepithelial lymphocytes bind to intestinal epithelium?
integrin aEb7 to bind to epithelial cadherins
What chemokine is secreted by gut epithelium and what is the receptor on mucosal lymphocytes?
Chemokine: CCL25
Receptor: CCR9
How do T cells regulate IgA synthesis
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
Transcytosis
transport of macromolecules from one side of a cell to the other side via receptors
How does IgA get transcytosed?
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)
IgA functions
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
Anti-inflammatory properties of IgA
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
Other mucosal immunoglobulins: IgM
IgM can be transported across epithelium and can be sufficient in replacing sIgA in deficient people
Other mucosal immunoglobulins: IgG
IgG in low amounts and not transported EXCEPT
in distal resp tract where it is transported in large amounts. Important defense in pulmonary secretions.
Other mucosal immunoglobulins: IgE
IgE can be synthesized in mucosal issue
IgE synthesized elsewhere can be found in mucosal issue bound to mast cells
What is oral tolerance?
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
Diseases caused by failure of oral tolerance
Crohn’s disease and Ulcerative Colitis
Passive transfer of immunity: Fetal Stage
IgG is passively acquired
FcRn binds to maternal IgG and transcytosis to fetal circulation
Neonate is born w/ significant protection
Passive transfer of immunity: Breast-milk fed neonate
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
Characteristics of infant gut at birth
little to no bacterial colonization
little to no mucus secretions
no IgA producing plasma cells
When is an infant most vulnerable to infection?
between 3-12 months because the passive immunity from mom is wearing off and their own immunity is just beginning to develop
Types of leukocytes in breast milk
macrophages(55-60%), neutrophils(30-40%), lymphocytes(5-10%)
Immunoglobulins and Cytokines in breast milk
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
How are maternal antigens transferred
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
Non immunoglobulin protective factors in breast milk: Lysozymes
cleaves peptidoglycans in cell walls
Non immunoglobulin protective factors in breast milk: Lactoferrin
competes for ferric iron and inhibits bacterial growth
Non immunoglobulin protective factors in breast milk: oligosaccharides
feed infant beneficial gut microbiota such as bifidobacteria and also inhibit binding of pathogenic bacteria to the gut
Non immunoglobulin protective factors in breast milk: antiviral lipids
substrates that are digested into small lipids that disrupt viral envelops
Non immunoglobulin protective factors in breast milk: glycosylated proteins
inhibit bacteria and virus binding to gut, lactahedrin protects against rotavirus, mucin-1 protects agains E. coli
