Lecture 14: Mucosal Immunology Flashcards
What is the primary antibody in mucosal immunity
IgA
What are some common intranasal vaccines
Influenza, bordetella/kennel cough
What are some common oral vaccines
Rabies, Sabin polio vaccine
What mucosal surface has the greatest concentration of immune cells
GI tract
What are some innate components of mucosal immunity
Tears, sneezing, mucus, cilia, coughing, normal flora, acidic pH of stomach neutrophils, eosinophils
What is the B cell response for mucosal immunity
IgA
What is the T cell response to mucosal immunity
Intraepithelial
What are the two primary functions of the mucosal immune system
Defensive and permissive
What is the defensive role of the mucosal immune system
Actions against pathogens that gain entry via mucosal surfaces via elimination or exclusion
What is the permissive function of the mucosal immune system
Actions to accommodate commensal organisms
What Ig primarily mediates exclusion
IgA
What Ig primarily mediates elimination
IgG and IgE
What is the major Ig in mucosal defense and prevents adherence of pathogens
IgA
What Ig responds to parasites that avoid IgA
IgE
What Ig responds to other organisms that avoid IgA
IgG
What makes IgA
Submucosal B cells
How many antigens can IgA bind
2-4
What are some mechanisms of action of IgA
Prevents adherence, inhibits bacterial cell division
What are the sites IgA can bind antigen
Cells-enterocytes, tissue fluids, lumen
How is secretory IgA formed
PIgR binds IgA in basolateral surface, internalized and the reexpressed on mucosal surface as secreted form, pIgR become secretory component and resistances protease degradation
How does antigenic stimulation occur at mucosal surface
Pathogen or vaccine
What controls IgM to IgA class switching
TNF-B
What controls terminal differentiation of IgA producing plasma cells
IL-6
What cytokines are involved in IgA production
IL-6, IL-5, IL-4, IL-10
What are the costimulatory molecules in IgA
APRIL/BAFF
What body fluid has the highest concentration of IgA levels
Colostrum
Where are alpha:beta T cells located
Lamina propria
Where are gamma:delta T cells located
Epithelial layer beneath or between enterocytes
Aka intraepithelial lymphocytes
What do gamma:delta T cells do
Present antigen, prevent oral tolerance, regulate B cells, and attack parasites
What do Th17 cells secrete
IL-17 and IL-22
what does IL-17 do
Neutrophil chemotaxis
what does IL-22 do
Promotes mucosal healing
What cells are involved in antigen processing in the intestinal wall
M+ cells, intraepithelial cells, and dendritic cells
Antigens that enter enterocytes is usually degraded in ___
Lysosome
Antigen that enters M cells is not degraded, what happens to it
May be presented to intraepithelial lymphocyte (gamma:delta T cell) within M cell or may pass along intercellular space to tissue fluid and then drain into lymph node
What are addressins
Molecules that regulate lymphocyte trafficking
What is an example of addressins
MadCAM-1 and ligand a4/B7
What are the inductive sites in GI tract mucosa
GALT, include M cells, dendritic cells, T cells, B cells
What are the effector sites in GI tract mucosa
IgA production sites like lymphoid nodules and isolated plasma cells
What is the process of antigen binding to Ig in intestine
Antigen binds mast cell with IgE
Mast cell degranulates
Vasoactive factors released
Increased vascular permeability
IgG exudes into tissue
Where are commensal bacteria located in GI
Behind glycocalyx barrier and don’t routinely contact enterocytes
What Ig is produced that prevents commensal from breaching mucosal barrier
IgA
What does IL-10 do in mucosal immunity
Inhibits inflammatory response to commensal by blocking TLR-MyD88 pathway
What does IL-2 do in mucosal immunity
Inhibits inflammatory response to commensal by blocking TLR independent pathways
Pathogens that breach glycocalyx may
Attach to enterocytes and produce toxins
What are some severe responses initiated relative to commensal pathogens
Pro inflammatory cells like IL-17-neutrophil chemotaxis
Commensal inhibit pathogens via ___
Competition
2% of food absorbed can cause immune recognition but what controls the response
Oral tolerance directed at TH1 cells does cellular suppression and anergy
What is the primary immunoglobulin in respiratory tract mucosa
IgA
What Ig is found in lower airway mucosa
IgG
Airway mucus contains what antimicrobials
Lysozymes, lactoferrin and surfactant
What does surfactant A and D do
Bind microbes and act as opsonins, enhance clearance of apoptosis cells and modulate actions of T cells and dendritic cells
What do B, C surfactant do
Decrease surface tension
What do PIMS do in large animals
Remove blood pathogens
What are some immunity functions in urogenital tract mucosa
Flushing from urine, low pH, IgA found in urine
What does urinary stasis lead to
Ascending infection
What covers the female reproductive tract epithelium
Antimicrobial mucous
What is present at lower female reproductive tract for mucosal immunity
Keratinocytes that express PRR’s, produce cytokines, abx peptides
What Ig is most prominent in the lower female reproductive tract
IgA
What is present in female upper reproductive tract for mucosal immunity
Macrophages, dendritic cells, innate lymphoid cells
What Ig is most prominent in mucus layer of upper reproductive tract of females
IgG
What is present in the urethral epithelium of male reproductive tract for mucosal immunity
Macrophages, dendritic cells
What is present in urethra, testes, and prepuce for mucosal immunity
T cells
What Ig predominates seminal fluid
IgG
What is present in non-lactating animals mammary gland for mucosal immunity
Keratin plug
What is present in lactating animals at mammary gland for mucosal immunity
Flushing activity of milk, lactenins-antimicrobial substances in milk
What are some functions of lactenins
Complement, lysozyme, lactoferrin, lactoperioxidase
What Ig predominates in milk in monogastrics
IgA
What Ig predominates in ruminant milk
IgG1
What important cells does colostrum contain
Macrophages and lymphocytes
What are the forms of contagious mastitis
Streptococcus and staphylococcus
What is environmental mastitis
Coliforms
How would cow appear if infected with gangrenous mastitis
Systemically ill
What would the California mastitis test look like if positive
DNA from cells form gel
What is the goal of oral/intranasal vaccination
Stimulate IgA production
Can you use dead organisms for oral/intranasal vaccines
Must use live organisms so they can invade mucosa and persist long enough to stimulate response
What are some examples of live oral/intranasal vaccines
Bovine rhinotrachetitis vaccine, feline rhinotracheitis vaccine, porcine transmissible gastroenteritis vaccine, equine strangles
