Mucosal Immunity Flashcards by Trenni Jefferson

What are the functions of the mucosal immune system?

Provides first immune defense barrier
Largest immune organ in the body
Greater concentration of Abs
Protects against harmful pathogens
Tolerizes the immune system to dietary and normal microbial flora

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What happens when the barrier is breached?

Phagocytic cells
Production of cytokines, chemokines and proteins
Recruit cells through the proinflammatory process
Activates acquired immune response

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What are the key players in mucosal immunity?

Lining epithelium
Commensal bacteria
Paneth cells
Microfold cells (M cells)
MALT
B cell secretion of IgA
T cells
Antigen presenting cells (dendritic)

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Which cells are most important in antigen sampling?

M cells

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Villus and mucus

Prevents adherence to epithelia cells

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IgA

Maintains homeostasis on commensal microbiota
Eliminates pathogens or antigens via IgA mediated excretory pathway
Immune exclusion

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Epithelial cells

Surfaces exposed to foreign particles, pollutants and microbes:
Type 2 pneumocytes (surfactatn proteins)
Paneth cells (antimicrobial molecules)
Goblet cells (mucins)
Intraepithelial lymphocytes (eradicate)

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Ciliated airway of epithelial cells

Mechanically removes invading pathogens

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Antimicrobial peptides (AMPs) of epithelial cells

Bind to pathogen surface and neutralize the pathogen:
Alpha and beta defensins
Cathelicidins

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Phagocytic ability of epithelial cells

Digestion of the bacterial components within the cell
Limits inflammatory signaling from extracellular bacterial killing
Helps maintain the homeostatic lung environment

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Commensals

Microbiomes that occupy mucosal surfaces
Begins immediately following birth
Alters immune cell development and homeostasis
Resistance to invasion

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Goblet cells

Produce mucin and mucous (proteoglycan gel)
Forms inner mucosal layer and outer mucous layer

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What is the goblet cell inner mucous layer composed of?

High concentration of bactericidal AMPs
Commensals specific secretory IgA
Makes it hard for bacterial colonization or penetration

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What are the 3 levels of protection that the intestinal microbiota promotes?

Saturation of colonization
Kill zone (mucin, AMP, IgA)
Microbiota enhances immune responses to invading pathogens

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What happens in conditions where microbiota is absent?

Reduced competition, barrier resistance and immune defense against pathogen invasion

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MALT: Mucosal Associated Lymphoid Tissue

Lymphoid elements associated with internal surfaces of the body:
GALT (GI, Peyer’s patches and salivary glands)
BALT and NALT (respiratory, tonsils, mammary glands, lacrimal gland, urogenital, inner ear)

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What are the functions of MALT?

Protection for most common pathogen entry points
Rapid elimination of initial foci of infection
Prevents dissemination of pathogens
Able to respond to vast number of pathogens
Distinguish pathogenic from non-path organisms and proteins

Microfold cells (M cells)

Specialized epithelial cells that cover lymphoid follicles dome in mucosal surface
Lack microvilli
Endocytic vesicles, limited # of lysosomes, antigen sampling and pathogen entry

MALT and B cell production of IgA

Main effector
First line of defense against host pathogens
Saliva, tears, colostrum and GI secretions
Homeostasis and lessens inflammatory response

Immune Exclusion

Limits the access of some microogs and antigens to mucosal barrier

SIgA

Recognizes multiple surface antigenic epitopes of pathogens within the lumen
Delays/ abolish potential to adhere to and/or penetrate the epithelium (neutralization)

Transcytosis

Polymeric IgA transport across epithelial cells

Intraepithelial lymphocytes

First immune cell line of defense in GI
Exclusively antigen experienced heterogenous T cells
Primary cytotoxic
Interferon gamma and tumor necrosis factor alpha

What is the function of intraepithelial lymphocytes?

Help to regulate dietary antigens

Chronic Enteropathy (Inflammatory Bowel Disease)

Condition of horses, dogs and cats Malabsorption and chronic protein-losing enteropathy Breakdown in mucosal immune tolerance to commensals Altered Treg mechanisms and regulatory cytokine imbalance

How long are GI diseases present?

GI diseases present for 3 weeks or longer

How is chronic enteropathy classified?

According to treatment response: Food-responsive enteropathy Antibiotic-responsive enteropathy Immunosuppressant -responsive enteropathy

Food allergies

Abnormal IgE mediated immune response to ingested food Clinical presentation: nonseasonal pruritis

What does overproduction of IgE lead to?

Sensitizes mast cell and basophils Facilitates degranulation cross-linking by food antigens

What does 20% of food-allergic pet have?

GI signs like flatulence, vomiting, diarrhea, loud intestinal sounds, defecating more than 4 or 5 times a day

How do you diagnose food allergies?

Strict elimination diet trial

"Ear and Rears"

Dogs scratching their face, ear, feet, groin or anal area or develop recurrent skin or ear infections

Asthma

An allergic reaction to inhaled allergens/ particles that stimulate the immune system Ex: grass, tree pollen, mold, dust

Asthma in genetically susceptible individuals

Exaggerated Th2-type responses involving IgE to harmless antigens

Antigen-induced airway eosinophilia

Neutrophilia in horses Complex antigen combinations that generate Th17 responses Smooth muscle atrophy and glandular hyperplasia (excess mucus)

Clinical presentation for asthma syndrome in horses and feline

Poor performance, wheezing, rapid breathing, chronic coughing/ hacking, open-mouther breathing

Histopathology for asthma syndrome in horses and feline

Epithelial linings of many bronchi are sloughed Moderate to numerous numbers of eosinophils, lymphocytes, plasma cells and macrophages infiltrate the airway

IgA deficiency

Most common primary human and dog immunodeficiency 1 in 300-500 people infected Common in Shar-Pei dogs and German shepherds

What signs do most people with IgA deficiency show?

They're asymptomatic!!!! Compensatory increase in IgM production Significant allergic and autoimmune diseases

Symptomatic patients with IgA deficiency

Recurrent ear infections, sinusitis, bronchitis, pneumonia Most susceptible to allergic increase (asthma, food allergy)

Immune exclusion for IgA deficiency

IgA binds to environmental antigens Promotes removal and prevent development of secondary T cell mediate inflammatory responses