Lec 8: Mucosal Immunity

Question 1

Why do we need an effective mucosal immune system?

Answer 1

• animals interface with their external environments at multiple sites, including the mucosae of the airways, oral cavity, digestive tract and genitourinary tract and skin
• combined area of mucosal surfaces is greater than that of skin (also greater permeability)
• generally first point of entry for pathogens
• musocal surfaces also exposed to an enormous volume of irrelevant antigens that need to be ignored

Question 2

How did commensal bacteria evolve in the gut?

Answer 2

• extent of colonization by commensal bacteria increased during evolution particularly in vertebrates due to emergence of new organs that could be colonized (e.g. gut)
• with this increase in colonization, metazoans became dependent on an increasingly elaborate relationship with their gut flora
• the GI tract is the site whee divergent needs of nutrient absorption and host defense collide

Question 3

What are the 3 major benefits of gut microbes to the host?

Answer 3

1. metabolism of nutrients and organic substrates
2. development of intestinal epithelium, vasculature and lymphoid tissue
3. colonization resistance (i.e. formation of a barrier against pathogens)

Question 4

What does the gut mucosal immune system interact with?

Answer 4

• GI tract provides continuous contact with dietary antigens, commensal microflora and pathogens
• a striking property of the gut is its ability to induce oral tolerance
• the gut also plays host to a huge and diverse population of microbes

Question 5

What is immune ignorance?

Answer 5

• suggests that physical or physiological barriers maintain a segregation between tissues and immune cells and antibodies (i.e. passive mechanism where host is unaware of this antigen)

Question 6

What is immune privilege?

Answer 6

• indicates that certain sites in the body are able to tolerate the introduction of antigen without eliciting an inflammatory immune response
• unlike ignorance, these are active mechanisms where the host is aware of its presence
• evolutionary adaptation to protect vital structures from the damaging effects of an inflammatory immune response
• inflammation in the brain or eye can lead to loss of organ function, gut to inefficiency in nutrient absorption, while immune responses directed against a fetus can lead to the loss of progeny

Question 7

What does the epithelium overlying organized GALT contain?

Answer 7

• specialized M cells that constantly transport gut bacteria and antigens from the gut lumen into the lymphoid tissue
• DC in the LP reach through epithelial cells and also sample gut bacteria
• the epithelium is filled with CD8 T cells and the LP contains many CD4 T cells, macrophages, and IgA antibody producing plasma cells
• potentially tissue damaging T cell responses may be inhibited by immunosuppressive cytokines and regulatory T cells

Question 8

What is gut associated lymphoid tissue?

Answer 8

• mucosa associated lymphoid tissue

- includes Peyer’s patches, appendix, and solitary lymphoid nodules in the submucosa

Question 9

What are microfold cells (M cells)

Answer 9

• cells found in the follicle associated epithelium of the Peyer’s patch that have the unique ability to sample antigen from the lumen of the small intestine and deliver it via transcytosis to APCs and lymphocytes located in a unique pocket like structure on their basolateral side

Question 10

What is the lamina propria?

Answer 10

• a thin layer of loose connective tissue beneath the epithelium and together with the epithelium constitutes the mucosa
• contains capillaries and a central lacteal (lymph vessel) in the small intestine, as well as lymphoid tissue
• also contains glands with the ducts opening on to the mucosal epithelium that secrete mucous and serous secretions

Question 11

What are Peyer’s Patches?

Answer 11

• aggregations of lymphoid tissue that are usually found in the lowest portion of the small intestine in humans
• as such, they differentiate the ileum from the duodenum and jejunum in that the number of Peyer’s patches increase further down the intestine (i.e. terminal ileum contains most)
• located in the lamina propria of the mucosa and extending into the submucosa of the ileum

Question 12

What can deregulation of gut microflora balance lead to?

Answer 12

• commensal bacteria crucial in the pathogenesis of IBD such as Crohn’s and ulcerative colitis.

Question 13

Describe the role of sequestration of indigenous microflora by surface epithelia.

Answer 13

• commensals could be sequestered within the lumen while pathogenic bacteria equipped with virulence factors would be able to overcome barrier
• TLR5 expressed on model epithelia and polarized to basolateral surface

Question 14

Describe the non immune function of TLRs.

Answer 14

• TLR signalling thorugh MyD88 dependent pathway conferred protection from morbidity, mortality, colonic bleeding and intestinal epithelial damage caused by DSS administration
• commensal bacteria appeared responsible, either through direct TLR recognition or through indirect effects

Question 15

Why may it not be a good idea to target NFkB for inhibition of chronic inflammatory diseases?

Answer 15

• NFkB failure could break the intestinal barrier by compromising the survival of epithelial cells
• enhanced intestinal permeability may cause inflammatory bowel disease or death

Question 16

What are probiotics?

Answer 16

• live microorganisms which when administered in adequate amounts confer a health benefit on the host
• LAB are the most common type of microbes used
• LAB grow low food pH which may create fewer opportunities for spoilage organisms to grow
• also, probiotic cultures can assist naturally occurring gut flora to reestablish themselves
• strains of the genera lactobacillus and bifidobacterium are the most widely used probiotic bacteria

Question 17

What are probiotics?

Answer 17

• non digestible functional food ingredients that beneficially affect the host by selectively stimulating the growth and or activity pf one or a limited number of bacteria in the colon, and thus improve host health
• most are carbohydrates such as oligosaccharides
• is not limited to specific bacterial group
• often, however, it is assumed that a prebiotic should increase the number and or activity of bifidobacteria and lactic acid bacteria