immuno: mucosal

anatomical locations of mucosal sites

• Respiratory Tract (includes conjunctiva)

• GI tract

• Urogenital tract

• Mammary glands

components of mucosal immunity

• innate

• adaptive

innate mucosal

• Mucus: Lysozyme and secretory IgA

• Resident microflora: outcompete pathogens for space and nutrients

• Anatomic: Physiologic features

  • Nasal turbinates

  • pH

  • Intestinal motility

  • Muco-ciliary escalator

adaptive mucosal

• Scattered lymphoid cells (T & B lymphocytes)

• Organized lymphoid tissues

  • Peyer’s patches

  • Isolated lymphoid follicles

    • Other unique features

  • Microfold cells (M cells)

  • Enterocytes

  • Dendritic cells

gastrointestinal tract

unique features

• M cells

• Enterocyte

• Dendritic cells

• Lymphocyte trafficking or Homing

• Mucosal vaccination

• Secretion of IgA

M cells (microfold cells)

• specialized epithelial cells- have membrane ruffles

• located over MALT and peyer patches

• no mucus, enzymes, glycocalyx

• more direct contact with lumen microbes

M cells: transcytosis

• M cells take up antigen by endocytosis and phagocytosis

• then transported across M cells in vesicles and released @ basal surface

• antigen is bound by dendritic cells, which activate T cells

enterocyte

• absorb soluble nutrients

• can uptake soluble antigens and present them on MHCII mol.

  • Enterocytes are active cytokine producing cells (esp. chemokines)

• cannot activate naive T cells on their own

  • lack co-receptors

• down regulation of CD4 cells

DC function in lamina propria?

• travel to mesenteric LN as discussed in conventional dendritic cells

• tend to secrete IL-10 and TGFβ

anti-inflammatory in health or homeostasis:

• Presentation of antigen without co-receptors

  • Dendritic cells secreting cytokines that drive Treg or Th2 cells

    • IL-10 and TGFβ

    • IL-4

• Highly immuno-regulated (downregulated) environment

Lymphocyte tracking to mucosal tissues

• 3 step paradigm selectins, integrins, chemokines

  • Different integrins exist, and they direct cells to   specific places/tissues (like a zipcode, or a visa)

• During antigen presentation DC can direct the integrin expression on lymphocytes

  • integrin (α4β7) is specific for an adhesion molecule on endothelial cells that is found at mucosal sites (mucosal vascular addressin cell adhesion molecule-1, MadCAM-1)

IgA at mucosal sites: how do they get there? what do they do?

• poly-Ig receptors (expressed by enterocytes) mediate the transfer of IgA from the lamina propria into the lumen of the mucosa

• IgA then act on the lumen to neutralize toxins or pathogens before infection

  • if infection alr occured, IgA bound to toxin/pathogen may b transferred away from the lamina propria into the lumen

imprinting?

• The DCs can direct the integrin

• expression of integrins flavors on lymphocytes thingy!

• The site-specific trafficking is called “homing”

in lymphocyte homing, cell may home to

• different associated mucosal sites:

  • Common mucosal system

  • Lactogenic immunity