L2. Epithelial barriers and immune reservoirs.

and antibody classes for extra.

Physical barriers. 3 main surfaces of contact between us and environment..

• Skin

• Lungs, respiratory tract.

• GI tract

Epithelial cells with active protective roles

• Goblet cells and mucus

• Paneth cell functions

• M cells and antigen sampling

Local immunity and immune reservoirs

• Mucosal associated lymphoid tissues (MALT)

• Lymph nodes.

Intestinal barrier

A single layer of cells, thus more permissive to absorption.

Respiratory epithelium

Pseudostratified ciliated columnar epithelium.

Skin

Multi-stratified, poorly absorptive, tightly closed.

Goblet cells

• Goblet cells are abundant in the epithelium of the intestine and the lung.

• Specialised in the production of mucins.

• Mucins form a film known as mucus.

• Mucus covers external surfaces of the epithelium. Forms a film that traps and helps the clearing of microbes.

In the skin instead of mucus, there’s a cornfield envelope; a tough, insoluble, and rigid protein and lipid shell.

Mucins

• Proteins packed into goblet cell granules.

• Goblet cells secrete these granules to release mucin monomers, which oligomerise to form the mucus.

• Muffins expand to form mucus, in a process that requires low calcium and increased pH.

• Mucins can be divided in: Membrane bound or Gel forming.

• Mucus composition is different depending on the tissue.

• Muc2 is the most abundant gel forming mucin in the intestines, while Muc5A and 5B are the most abundant in the airway.

• Mucins create an extra layer of protection, reducing direct contact between microbes and epithelium.

How often does the intestinal epithelium self renew?

Every 48 hours.

• Epithelial stem cell loss may have catastrophic consequences, stem cells are protected by Paneth cells.

Paneth cells are located in the intestinal crypts, what two types of signals do they have?

• Bacterial mediators like lysozyme and defensins: proteins that may kill certain types of bacteria.

• Stem cell-stimulating factors to promote proliferation and differentiation.

Stem cells roles

• Allow epithelial barriers to have the capacity for self-renewal and repair, based on cell division and differentiation. As stem cell progenitors can migrate and differentiate into different types of epithelium.

• This renewal can happen: in homeostasis, to replace old cells. In disease, to heal wounded tissue and replace cellular loss.

Microfold (M) cells.

M cells aid in exposing the local immune system to antigens. Found in the intestines and airways and in the proximity of MALT tissue.

They aid in the surveying for potential harmful agents that could activate the immune response.

M cells don’t present antigens but can capture and establish a controlled flux for recognition by APCs.

M cells are like antigen ‘shuttles’. M cells provide a controlled flow of antigens to MALT for their recognition.

Cells usually present in Mucosal Associated Lymphoid Tissue (MALT)

• Antigen presenting mononuclear phagocytes (DCs and Macrophages)

• B and T lymphocytes.

M cells allow

the controlled pass of microbial components from the exterior into MALT.

APCs capture these and present them in their surface.

Lymphocytes recognise these to learn about potential threats.

Where are MALTs located.

In the intestinal tract (Peyers patches), the pharynx (tonsils), or the bronchial-associated lymphoid tissue (BALT) as well as others.

M cells provide a controlled flow of antigens to MALT for their recognition

The barrier can be compromised in certain infections

• S.Aureus exploits skin barrier defects to infect.

• S.Typhi has developed mechanisms to ‘swim’. through mucus, invade epithelial cells and replicate.

Barrier defects are associated to many chronic inflammatory diseases

• A loss of epithelial barrier may contribute to inflammatory bowel disease, including Crohns disease and ulcerative colitis

• Excessive/ unorganised keratinocyte growth is found in Psoriasis.

• A hypertrophic and disorganised epithelium is a feature of allergic diseases such as asthma and eosinophilic esophagitis.

IgG

Mediates secondary immune responses, neutralises toxins/ bacteria and activates complement

It is the only antibody that crosses the placenta to protect newborns.

Makes up 70-75% of serum antibodies.

IgM

The first antibody produced during a primary pathogen invasion and acts as a B-cell receptor on naive B cells.

It’s highly effective at activating the complement system.

IgA

Provides mucosal immunity by preventing bacteria and viruses from attaching to epithelial surfaces.

IgD

Acts mainly as a receptor to assist with B-cell activation and maturation. Present in very low levels in blood serum.

IgE

Involved in allergic and inflammatory reactions (such as histamine release) and defence against parasitic worm infections.

It’s the least abundant antibody class in serum.