Lecture 25 (Mucosal Immunity) Flashcards
what are the 6 categories of mucosal innate defense mechanisms?
- physical barrier
- clearance mechanisms
- physiologic adaptations
- chemical defenses
- enzymatic proteins
- antimicrobial peptides
physiologic adaptations of mucosal innate defense mechanisms can further be broken down into these 3 categories:
- chemical defenses
- enzymatic defenses
- antimicrobial peptides
mucus, normal epithelium, flora, and keratin plug (mammary gland)
a) physical barrier
b) clearance mechanisms
c) physiologic adaptations
a) physical barrier
peristalsis and phagocytosis
a) physical barrier
b) clearance mechanisms
c) physiologic adaptations
b) clearance mechanisms
temperature, pH, and secretions
a) physical barrier
b) clearance mechanisms
c) physiologic adaptations
c) physiologic adaptations
what is the 5 step predictable pathway for mucosal antigen response?
- antigen crosses intestinal barrier assisted by Microfold/M cells
- APCs process and present the antigen (found at basal surface of intestinal cells)
- T cell & B cell activation occurs in the regional lymph tissue
- cells leave the inductive tissue (which includes regional lymph tissue) via lymphatics
- cells travel to other lymphoid tissue homing in on the mucosa with adhesion molecules; do their jobs
t/f: bile is able to inactivate some viruses and bacteria
true
what are the 3 components of the inductive sites?
- Microfold (M) Cells
- Follicle
- Parafollicular Region
where are most effector sites found?
a) Ileal Peyer’s Patches
b) Peyer’s Patches collectively
c) Diffuse Lymphoid Nodules
c) Diffuse Lymphoid Nodules
what is the predominant antibody needed in mammary glands?
IgG
these cells are responsible for transcytosis of antigens across gut epithelium and release APCs at basal surface
M (microfold) cells
sites where antigens are processed and immune responses are initiated
inductive sites
sites where antibodies and cell mediated responses are generated
effector sites
B cells that originate in inductive tissue travel to lymphoid follicles for expansion then migrate to ________ ________
lamina propria
when B cells reach lamina propria they secrete IgA, IgM, IgG, and IgE…which one dominates in the antibody response?
IgA (80% of plasma cells in the body)
what are the 3 mechanisms IgA can utilize in immunity?
1) bind pathogen in lumen and exclude it from absorption
2) bind pathogen already in cell and neutralize it (exclusion or elimination)
3) bind pathogen that made it to the lamina propria and drag it out with it (as secreted) - elimination
Poly-Ig receptor is inverse to this receptor? Why?
fetal Fc receptor
*Poly-Ig receptor is on the interior and transfers out (fetal Fc receptor is the opposite)
IgA binds to this receptor before traveling through enterocyte to the lumen to avoid being degraded by acid
Poly-Ig receptor
-advantages: immediate protection & good against poor antigens
-disadvantages: allergic reactions & transfer of disease
a) Active Immunity - Infectious Vaccines
b) Active Immunity - Non-Infectious Vaccines
c) Passive Immunity - Therapeutics (toxids, MCA)
d) Passive Immunity - Maternal/Colostral
d) Passive Immunity - Maternal/Colostral
-advantages: safe in immunocompromised & pregnant patients, stable, not going to spread
-disadvantages: weaker, require adjuvants (can cause allergies), require repeat shots
a) Active Immunity - Infectious Vaccines
b) Active Immunity - Non-Infectious Vaccines
c) Passive Immunity - Therapeutics (toxids, MCA)
d) Passive Immunity - Maternal/Colostral
b) Active Immunity - Non-Infectious Vaccines
-advantages: stronger response, single shot often, memory cells, less chance of allergies, no adjuvants, may be given in a natural route
-disadvantages: reversion to virulence possible, less stable, and risk to immunocompromised animals or fetuses
a) Active Immunity - Infectious Vaccines
b) Active Immunity - Non-Infectious Vaccines
c) Passive Immunity - Therapeutics (toxids, MCA)
d) Passive Immunity - Maternal/Colostral
a) Active Immunity - Infectious Vaccines
key features: mass of antigen is critical to successful immunization, causes a TH2 CD4+ response
a) Active Immunity - Infectious Vaccines
b) Active Immunity - Non-Infectious Vaccines
c) Passive Immunity - Therapeutics (toxids, MCA)
d) Passive Immunity - Maternal/Colostral
b) Active Immunity - Non-Infectious Vaccines
key features: Promotes the host’s natural immunologic mechanisms for lasting immunity; causes a TH1 & TH2 response
a) Active Immunity - Infectious Vaccines
b) Active Immunity - Non-Infectious Vaccines
c) Passive Immunity - Therapeutics (toxids, MCA)
d) Passive Immunity - Maternal/Colostral
a) Active Immunity - Infectious Vaccines
is secretory IgA hydrophilic or hydrophobic?
hydrophobic (gets entrapped in mucus)
when IgA binds pathogen in the lumen it is called __________
exclusion
IgA can export toxins and pathogens from the _____ _____ while being secreted
lamina propria
IgA is able to bind and _________ antigens internalized in endosomes
neutralize
secreted IgA on the gut surface can bind and _________ pathogens and toxins
neutralize
these two antibodies serve as a second line of humoral defense for pathogens that avoid IgA exclusion
IgE and IgG
in the cell-mediated mucosal defense, what is the type of T cell that makes up the majority at mucosal surfaces?
CD8+ cytotoxic
what are intra-epithelial lymphocytes? (IELs)
lymphocytes found within the epithelium layer
up to 90% of IELs are γδ T cells in which of the following?
a. cats
b. pigs
c. ruminants
d. birds
c. ruminants
IEL γδ CD8-/CD4- T cells in GIT are unique how?
they can recognize directly to antigen without presentation
this is expressed on the basolateral surface of stressed cells that γδ T cells bind to and apoptose the infected cell
MICs (MHC 1B)
γδ T cells bind to MIC via what receptor?
NKG2D
t/f: γδ T cells can bind to an infected cell with MIC molecules without APCs
true
list the following in the order a pathogen would have to pass from first to last
-humoral immunity (IgA, IgG, IgE)
-physical barriers
-cell-mediated immunity
-γδ T cells
- physical barriers
- humoral immunity (IgA, IgG, IgE)
- cell-mediated immunity
- γδ T cells
what are two ideal locations to give a vaccine to prevent infections of mucosal surfaces?
orally and nasally
it is ideal for a mucosal vaccination to stimulate a response of which antibody?
IgA
systemic vaccination leads to a response of this antibody
IgG
why is mucosal protection important?
-small animal practice (kennel cough, corona virus/FIP, influenza virus, FeLV/FIV)
-farm animal practice (BVD, BRD, mastitis)
-equine practice (strangles, herpes, salmonella)
why is it important for antimicrobial peptides to be hydrophobic?
so that it can be translocated through the membrane and get trapped in the mucus (stays local) → if hydrophilic they would get destroyed more quickly