BMOL30090 L2 epithelial barriers & immune reservoirs

L2-6 learning objectives

First line of defence?

prevention (forming a barrier against entrance of pathogens)

body is in constant threat of infection by microbes in our env.

surfaces of contact: eyes, GI tract, lungs

gut epithelial cells

• monolayer

• absorbs O2 and monosaccharides

lung epithelial cells

• pseudostratified (large airways)

• absorption (O2)

• gas exchange (release CO2)

skin epithelial cells

• multi-stratified

• low absorption (well-sealed)

Q: what type of epithelium is this?

lung

Q: what type of epithelium is this?

skin

Q: what type of epithelium is this?

gut

epithelial barriers: multiple layers of defense

some are:

• physical (e.g. goblet cells)

• biochemical (e.g. paneth cells)

• help the IS (e.g. microfold cells)

goblet cells

• example of physical function

  intestine and lung

• produce mucins (many mucins for mucus, mucus covers external surface of epithelium and traps microbes)

mucins

• proteins packed into goblet cell granules

• mucin can be memb-bound or gel forming

  • Muc2: most abundant gel-forming mucin in intestines

  • Muc5A & 5B: most abundant mucin in airway

mucin —> mucus

• goblet cells secrete granules, releasing mucin monomers, which oligomerise to form the mucus

• mucins expand to form mucus - process requires Ca2+ and increased pH

• creates an extra layer of protection, reducing direct contact between microbes and epithelium

mucus in the skin?

NO mucus in the skin, instead there is a cornified envelope

infectious agents and mucus

• infectious agents often use specialised mechanisms (e.g. flagella) to ‘swim’ through mucus and reach epithelium

Q: mucus is found in and produced by _____

goblet cells in the airway and intestine

paneth cells

• biochemical functions

• NOT epithelian stem cells (SCs), but help them by providing signals:

  • bactericidal mediators (e.g. lysozyme and defensins) to kill certain bac. types

  • SC-stimulating factors to promote proliferation and differentiation

• located in intestinal crypts surrounding SCs

stem cell progenitors

migrate and differentiate into diff types of epithelium

self renewal and repair:

• homeostasis - replace old cells

• disease - heal wounded tissue, replace cell loss

microfold (M) cells

• immune supportive functions

• aid in exposing local IS to antigens & surveyal of potential harmful agents that could cause IR

• in intestine and airway, in prox. to MALT

• M cells do not present antigens, but capture & establish a controlled flux for recogn. by APCs

mucosal-associated lymphoid tissues (MALT)

• multifolicular structures that can be found in diff. tissues

• cells present in MALT typically:

  • antigen-presenting mononuclear phagocytes (DCs and Macs)

  • B and T lymphocytes

MALT and M cells process

1. M cells allow controlled pass of microbial components from exterior into MALT

2. APCs capture these & present them on surface

3. lymphocytes recognise these to learn about potential threats

Q: which of these is an example of a physical epithelial barrier?

goblet cells

Q: which of these is an example of an immune supportive epithelial barrier?

M cells

Q: which of these is an example of a biochemical epithelial barrier?

paneth cells

MALT location and structure

• mucosa beneath epithelium is rich in scattered immune cells

• structures rich in lymphocytes and APCs called MALT

• MALT located in intestinal tract (Peyer’s patch), pharynx (tonsils), Bronchial-Assoc. Lymphoid Tissue (BALT)

epithelial localisation near MALT function

• makes M cells antigen ‘shuttles’

  • M cells provide controlled flow of antigens to Malt to be recognised

summaries of epithelial cells with protective roles

barrier defects: cause or consequence of disease

certain infections, e.g.:

• S. aureus exploits damaged skin barrier

• S. typhi ‘swims’ through mucus, bypassing epithelium

chronic inflam diseases:

• IBS: loss of epithelium

• Psoriasis: excess./unorg. keratinocyte growth

• asthma & eosinophilic esophagitis: hypertropic/unorg. epithelium