Mucosal Immunology - Lee 4/13/16 Flashcards
mucosal associated lymphoid tissues
NALT - nasopharyngeal
BALT - bronchial
GALT - gastroint
antigen sampling in aerodigestive tract
M cells in follicle-assoc epithelium → overlays organized lymphoid tissue in GALT, NALT → production of mucosal IgA (acquired)
M cells in epithelium → overlays diffuse lymphoid tissue → production of systemic IgG (acquired) [and maybe mucosal IgA?]
DCs in epithelium →overlays diffuse lymphoid tissue → production of systemic IgG [maybe mucosal IgA]
common signaling features
*Wnt signaling : tells all intestinal stem cells (from basal crypts) where to go
*Notch signaling : determines cell lineage specification (what they produce, etc)
mucosal barrier components
mucus
paracellular pathway
antimicrobial peptides
mucus
highly hydrated, viscous secretion with complex macromolecular profile
- viscosity due to olymeric mucin glycoproteins
- mucin : permeable to macromolecules (like antimicrobial peptides, Ig) but also serves as a barrier to undesirable mols
intercellular jx
1. tight junctions : transmembrane proteins located at lateral surface of epi cells made of claudin and occludins
2. adherent junctions : made of cadherins
3. desmosomes
antimicrobial peptides
1. cathelicidins
- chemotactic for neutrophils, monocytes, mast cells, T cells
- induces mast cell degranulation
- alters macrophage transcriptional responses
2. defensins
- microbicidal against bacteria, fungi, spirochetes, protozoa, viruses
- present in various cell types
cellular constituents
in layers:
epithelial cells
intraepithelial cells
lamina propria lymphocytes
- mucosal B cells, dendritic cells, intestinal macrophages, mucosal basophils/eosinophils/mast cells, M cells
secretory cells in mucosal epithelium
1. goblet cells : mucus producing cells, abundant in GI epi
2. specialized cells producing antimicrobial peptides, found throughout GI tract
*nonspecialized cells show high plasticity → secretory phenotype of lineage can be modified in response to infection or inflammation
intraepithelial lymphocytes
wedged between epithelial cells (on basal ends)
balance protective immunity & barrier fx
can be natural (innate) or induced (acquired via exposure to pathogens)
- at start, natural > inducible → over time, natural (stays constant) < inducible
features:
- small mononuclear cells
- mostly CD4-/CD8+ or CD4-/CD8-
- express NK cell receptors
- express integrins : interact with epi cells’ Ecadherins
IELs send signals to thymus where T cells are maturing → inform selection → selected T cells home to lymph nodes or to where theyre going to fx
T cells in lamina propria
- predominantly CD4 cells
- receive signals from epi cells, IELs, stromal cells, integrin receptors
- interact with microbiota : diff biota induce diff cytokine responses in mucosal T cells
mucosal B cells
evidence for mucosal B cells: all mucosal secretions (tears, nasal secretion, saliva, int juice, breastmilk) contain antibodies!
- abs are produced by mucosal B cells = plasmablasts in lamina propria
- IgA, IgM are dominant mucosal Igs
epithelial transcytosis of secretory Ig
how do antibodies get from lamina propria to the lumen?
can’t make it past tight jx…need to find another way through
transcytosis is mediated by polymeric immunoglobulin receptors (pIgR) found on basolateral surface of epithelial cells
- pIgA and pIgM bind to pIgRs → receptor-mediated endocytosis of pIg-pIgR complex into epi cell → transcytosis to apical surface of epi cell → cleavage of complex, release of secretory Ig at apical face
- expression of pIgR is affected by microbial factors, cytokines, hormones
- sIgA and sIgM anchor to mucin, provide immunological barrier to infection
dendritic cells
immature DCs capture, process, and present antigens via MHC
- pick up self-antigens (apoptotic bodies), soluble exogenous antigen (ex. food proteins), commensal bacterial from skin/mucosa
once stimulated, DCs mature
- elongate dendrite
- increase antigen presentation
- enhance co-stim molecules
mature DCs migrate from nonlymphoid tissue to T cell zone of draining lymph nodes → select/activate naïve T cells
- induce peripheral tolerance via clonal deletion or anergy; potential pathways include…
- antigen-specific T cell deletion
- induction of Treg differentiation
- production of IgA that prevents antigen/microbial uptake
how do intestinal dendritic cells effect a response to an antigen?
also: role in T cell response
- drive Treg cells involved in tolerance to oral antigen and commensal bacteria
- provide differentiation signals for IgA-producing B cells
- once stimulated, migrate to lymph nodes and thymus → cause maturation of T cells and imprint lymphocytes with homing signals back to int tissues
role in T cell response
intestinal DCs pick up an antigen, mature, and travel to thymus or lymph nodes → stimulate naive T cell maturation → mature T cells then home to the site of antigen-pickup to go aid in the immune response
fx of intestinal dentrici cells
macrophage
derived from stem cells in bone marrow → continuously populate healthy int mucosa
- foot soldiers that serve as first-line of immune resp: kill invaders and activate other aspects of response
specialize in scavenging dead/dying cells, repairing damaged tissues, killing intracellular microbes
- has endocytic properties; has lysozymes and cathepsins that degrade antigens
do not present antigens
- no dendrite, yes HLA-DR expression, but no expression of costim molecules
