Lecture 14: Mucosal Immunity Flashcards
what is the primary antibody at mucosal surfaces
IgA
common intranasal vaccines
influenza
bordetella
common oral vaccines
sabin polio (humans)
rabies
2 primary functions of mucosal immunity
- defensive: against pathogens that gain entry via mucosal surfaces
—> exclusion , elimination - Permissive: actions to accommodate commensal organisms
what immunoglobulin responds to parasites that avoid IgA
IgE
what immunoglobulin responds to organisms other than parasites that avoid IgA
IgG
what is the structure of IgA
Y shaped
monomer or dimer
binds 2 - 4 antigen molecules
secretory component
what cells make IgA
submucosal B cells
What does pIgR (polymetric immunoglobulin receptor) bind
binds IgA on the basolateral surface
what controls the production of IgA
TLR ligands and IL4, IL5, IL10
what controls IgM to IgA class switching
TGF-B
what interleukin controls terminal differentiation of IgA-producing plasma cells
IL6
what are the co-stimulatory molecules needed for class switching of IgM to IgA
BAFF / APRIL
what body fluids have high IgA levels
- colostrum
- tears
- nasal mucus
what are addressins
molecules that regulate lymphocyte trafficking
- MadCAM-1 and ligand a4/B7
- intestine and mamary gland
what subclass of T cells acts at the lamina propria
alpha-beta T cells
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
what interleukin is responsible for neutrophil chemotaxis
IL-17
(Th17 cells)
what interleukin is involved in mucosal healing (triggers regeneration of mucosal surfaces)
IL-22
(Th17 cells)
80% of activated B - cells are located where
the GI tract (GALT, MALT, Peyer’s patches)
what are the sites of IgA production (effector sites)
- diffuse lymphoid nodules
- isolated plasma cells
where are commensals (bacteria species) found
in GI lumen behind the glycocalyx barrier
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
