HI18 - Mucosal Immunology

Biomedical Sciences IV

What are the primary entry points for infectious agents?

Mucosal surfaces, especially the mouth and nose.

What are the major mucosal tracts?

GI tract, respiratory tract, urogenital tract, and middle ear.

Which exocrine glands are part of the mucosal immune system?

Salivary glands, lacrimal glands, pancreas, and mammary glands during lactation.

Why are mucosal surfaces especially vulnerable?

Because they are thin, permeable, constantly exposed to the environment, and have a huge surface area.

How large is the mucosal surface area?

About 400 m² — roughly 200× larger than skin.

What are the three major layers of the GI mucosa?

• Epithelium

• Lamina propria

• Mucosal lymphoid tissues (e.g., Peyer’s patches)

How often do intestinal epithelial cells turn over?

Every 2 days.

What are M cells and what do they do?

Microfold cells — Specialized epithelial cells that transcytose antigens from the lumen to immune cells.

What is a major benefit of M-cell transport?

Rapid sampling of gut contents by the immune system.

What is a major drawback of M-cell transport?

Important entry route for pathogens such as Shigella, Salmonella, polio, and prions.

What is GALT?

Gut-associated lymphoid tissue, including Peyer’s patches, isolated lymphoid follicles, and lamina propria lymphocytes.

What proportion of immune cells reside in mucosal tissues?

Approximately 75% of all lymphocytes / plasma cells.

What is Waldeyer’s Ring?

A ring of lymphoid tissue including the palatine tonsils, lingual tonsils, and adenoids.

Does tonsillectomy significantly impair immunity?

No — minimal long-term effect on systemic or mucosal immunity.

How does systemic immunity respond to pathogens?

It is reactive, heavily dependent on inflammation.

Why is systemic-style inflammation dangerous at mucosal surfaces?

It can cause tissue destruction, barrier breakdown, and increased infection risk.

How does mucosal immunity differ from systemic immunity?

It is proactive, constantly active, and designed to be non-inflammatory.

Why is inflammation minimized in mucosal tissues?

To protect delicate epithelial structures and prevent unnecessary damage.

Which antibody is dominant at mucosal surfaces?

Dimeric secretory IgA (sIgA).

Which antibody is dominant in serum?

IgG.

Why is IgA protection short-lived?

sIgA is constantly flushed out with mucus and secretions.

What is the typical duration of mucosal IgA protection?

Around 4–6 months (compared to 6 months IgG)

Can systemic IgG protect mucosal surfaces?

Not effectively — it is largely excluded from mucosal lumens.

What are the two major antigen-sampling routes in the gut?

• M cells → DCs in Peyer’s patches

• Direct capture by CD103+ dendritic cells in lamina propria

Which antigen route is more likely to generate inflammation?

M-cell transport, because it delivers particulate antigens with microbial components (MAMPs).

Which route promotes tolerance?

Direct capture by CD103+ dendritic cells of soluble or digested antigens (does not present MAMPs → doesn’t activate PRR’s)

What are characteristics of CD103+ dendritic cells?

They produce TGF-β, migrate to lymph nodes, and induce T regulatory (Treg) cells.

What do lamina propria macrophages specialize in?

Phagocytosis without inflammation.

Why are intestinal macrophages non-inflammatory?

They don’t produce inflammatory cytokines, lack B7, and can’t activate naïve T cells.

What is oral tolerance?

Systemic and local unresponsiveness to food antigens.

What conditions result from loss of oral tolerance?

Food allergies and celiac disease.

Why is oral tolerance systemic rather than only local?

Food antigens enter the bloodstream and are processed by liver APCs (e.g., Kupffer cells). Your whole body needs to tolerate food!

What are Kupffer cells?

Liver-resident macrophages promoting tolerogenic antigen presentation.

What is intestinal tolerance?

Local tolerance to commensal microbiota.

Is intestinal tolerance systemic?

No — it is limited to the gut.

What disease results from failure of intestinal tolerance?

Inflammatory bowel disease (IBD):

• Crohn’s disease

• Ulcerative colitis

What are T regulatory cells (Tregs)?

CD4+ T cells that suppress immune responses and maintain tolerance.

What are tTregs?

Thymus-derived Tregs selected for self-antigen recognition.

What are pTregs?

Peripherally induced Tregs formed from naïve CD4+ T cells encountering antigen with TGF-β but no IL-6.

What cytokines do Tregs produce?

IL-10 and TGF-β.

What is required to generate pTregs?

TGF-β, absence of IL-6, and steady-state (self) antigen presentation.

What form of IgA is found in mucosal secretions?

Dimeric IgA bound to secretory component (SC).

What receptor transports IgA across epithelium?

Poly-Ig receptor (pIgR).

What is the function of secretory component?

Protects IgA from proteolysis in the lumen.

What are the major functions of IgA in the lamina propria?

Bind and neutralize antigens before they access tissues.

What are major functions of IgA in the lumen?

Neutralize pathogens, block attachment, and avoid inflammation.

Why is IgA considered non-inflammatory?

It does not fix complement via the classical pathway and is a poor opsonin.

Can IgM contribute to mucosal immunity?

Yes — pentameric IgM also uses pIgR and is effective early.

Can IgG contribute to mucosal immunity?

Yes — transported by FcRn into some mucosal sites.

What produces mucus?

Goblet cells.

What is the function of mucus?

Physical barrier, traps microbes, contains defensins, sIgA, and prevents dehydration.

What produces defensins?

Paneth cells in the crypts of the intestine.

What is the function of defensins?

Create pores in microbial membranes → rapid killing.

Why is microbiota beneficial?

• Aid digestion

• Produce vitamins

• Outcompete pathogens

• Stimulate immune development

• Strengthen epithelial barriers

What happens if tolerance to microbiota fails?

Chronic inflammation → IBD.

What are MAMPs?

Microbe-associated patterns recognized by PRRs like TLRs.

Why are apical TLRs unresponsive to many commensals?

To avoid unnecessary inflammation.

Why are basolateral TLRs important?

Detect when microbes breach the epithelium, triggering strong responses.

What are inductive sites in mucosal immunity?

Where immune responses start: Peyer’s patches, individual lymphoid follicles (ILFs), GALT, MLNs.

What are effector sites?

Lamina propria and epithelial layer.

Where do lymphocytes activated in the gut preferentially home?

Back to mucosal tissues, including other mucosal sites (common mucosal immune system).

What are intraepithelial lymphocytes (IELs)?

Mostly CD8+ T cells embedded within the epithelium.

What is special about IELs?

They are antigen-experienced, respond rapidly, and promote epithelial repair.

What are γδ T cells?

Unconventional T cells recognizing stress signals rather than peptides.

What is a major function of γδ T cells?

Kill damaged or stressed epithelial cells and promote repair.