molecules that regulate lymphocyte trafficking - MadCAM-1 and ligand a4/B7 - intestine and mamary gland

Lecture 14: Mucosal Immunity Flashcards by Riley Hrasky

what is the primary antibody at mucosal surfaces

IgA

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common intranasal vaccines

influenza
bordetella

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common oral vaccines

sabin polio (humans)
rabies

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2 primary functions of mucosal immunity

defensive: against pathogens that gain entry via mucosal surfaces
—> exclusion , elimination
Permissive: actions to accommodate commensal organisms

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what immunoglobulin responds to parasites that avoid IgA

IgE

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what immunoglobulin responds to organisms other than parasites that avoid IgA

IgG

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what is the structure of IgA

Y shaped
monomer or dimer
binds 2 - 4 antigen molecules
secretory component

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what cells make IgA

submucosal B cells

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What does pIgR (polymetric immunoglobulin receptor) bind

binds IgA on the basolateral surface

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what controls the production of IgA

TLR ligands and IL4, IL5, IL10

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what controls IgM to IgA class switching

TGF-B

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what interleukin controls terminal differentiation of IgA-producing plasma cells

IL6

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what are the co-stimulatory molecules needed for class switching of IgM to IgA

BAFF / APRIL

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what body fluids have high IgA levels

colostrum
tears
nasal mucus

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what are addressins

molecules that regulate lymphocyte trafficking

MadCAM-1 and ligand a4/B7
intestine and mamary gland

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what subclass of T cells acts at the lamina propria

alpha-beta T cells

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what subclass of T cells are specialized for epithelial defense

gamma delta T cells

prevent oral tolerance, regulate B-cells, attack parasites
ruminants have them in circulation, other mammals don’t really

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what interleukin is responsible for neutrophil chemotaxis

IL-17
(Th17 cells)

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what interleukin is involved in mucosal healing (triggers regeneration of mucosal surfaces)

IL-22
(Th17 cells)

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80% of activated B - cells are located where

the GI tract (GALT, MALT, Peyer’s patches)

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what are the sites of IgA production (effector sites)

diffuse lymphoid nodules
isolated plasma cells

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where are commensals (bacteria species) found

in GI lumen behind the glycocalyx barrier

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what are the important cytokines in the immune response to commensals?

IL-10, IL-2

what is the function of IL-10

inhibits inflammatory response to commensals by blocking TLR-MyD88 pathways

what is the function of IL-2

inhibits inflammatory response to commensals by blocking TLR independent pathway

if pathogens breach the glycocalyx, what damage can they cause

- attach to enterocytes and produce toxins

commensals inhibit pathogens by _______

competition

what are some common antimicrobials in airway mucus

- lysozyme - lactoferrin - surfactants (A,D and B,C) - cationic peptides (defensins, cathelicidins)

what do surfactants A and D do

- bind microbes and act as opsonins - enhance clearance apoptotic cells - modulate actions of T-cells and dendritic cells

what do surfactants B and C do

reduce surface tension

what is the goal of oral / intranasal vaccines

to stimulate IgA production *must use live organisms

contagious mastitis

- staphylococcus - streptococcus

environmental mastitis

coliforms ex: E.coli

gangrenous mastitis

cows become systemically ill - septic condition

how does the urinary tract naturally protect itself from infection?

- flushing from urine flow - low pH of urine - small amounts of IgA are in urine - urinary stasis leads to ascending infection

immunity of the lower female reproductive tract

antimicrobial mucus over the epithelium - keratinocytes express PRRs, produce cytokines, abx peptides - IgA is the most prominent antibody in mucus layer

immunity of the upper female RT

macrophages, dendritic cells, innate lymphoid cells - IgG most prominent in mucus layer

immunity of the male reproductive tract

- macrophages and dendritic cells in urethral epithelium - T cells in urethra, testes and prepuce - IgG predominates in seminal fluid (IgA also present) - antimicrobial peptides

how to test for mastitis

California mastitis test - looks for somatic cells, if present, DNA from the somatic cells forms gel

what are lactenins?

antimicrobial substances w/in milk - complement - lysozyme - lactoferrin - lactoperoxidase

what cells are involved in antigen presentation in the intestinal wall

- M cells, Dendritic cels, intraepithelial lymphocytes (IELs)

what usually happens to antigens that enter enterocytes

get degraded in lysosomes

what happens to antigens that enter M cells

They don't get degraded and are either - presented to IELs within the M cell or - pass into tissue fluid and then into draining lymph nodes

why do live organisms have to be used in mucosally administrated vaccines

since the organisms have to invade the mucosa and persist long enough to stimulate a response

what is one main disadvantage to administering live organism vaccines

potential to cause disease

what are the physical barriers of the innate mucosal immune system

mucus, cilia, defensin molecules, extreme pH actions like blinking, coughing, sneezing

what are the innate immune cells that act at mucosal surfaces

neutrophils eosinophils APCs macrophages, dendritic cels

Exclusion mechanisms are Ig_____ mediated, while elimination mechanisms are mediated by Ig_ or Ig____.

exclusion - IgA mediated elimination - IgE or IgG

IgA is present in mammals and birds but not in _____?

reptiles or amphibians

explain how mucosal stimulation at one mucosal site can protect other, distant mucosal sites, and contributes to what we call the common mucosal immune system

A small amount of IgA is released into the peripheral circulation. As this passes through the liver, some of the IgA is secreted in bile and enters the lumen of the small intestine.

T-cells specialized for epithelial defense

γδ T-cells - reside beneath and between enterocytes and therefore are also sometimes called intraepithelial lymphocytes (IELs).

γδ T-cells effector functions

antigen presentation, prevention of oral tolerance, regulation of B-cells, and defense against parasites.

cell types involved in antigen processing in the intestinal wall

M-cells, dendritic cells, and IELs

what 2 cytokines are involved in the response to commensals? * These inhibit inappropriate innate immune responses to innocuous commensals

IL-10 - which inhibits an inflammatory response to commensals by blocking the TLR-MyD88 pathway IL-2 - which inhibits an inflammatory response to commensals by blocking TLR independent pathways

term for the lymphoid tissue present in the bronchi and nasal passages

BALT (bronchus associated lymphoid tissue).

The mammary epithelium is protected by the physical barrier of a _______ in non-lactating animals.

keratin plug