22. Mucosal Immunity Flashcards
What part of the nasopharyngeal tract is sterile? What Ig is dominant?
Lower
IgG
What part of the nasopharyngeal tract is colonized? What Ig is dominant?
Upper (aerobic bacteria)
IgA
What structures are included in waldeyer’s ring?
Palatine tonsils
Tubal tonsils
Adenoid
Lingual tonsil
All of the MALT tissues are _____, excluding the mesenteric tissues
Unencapsulated
What epithelium is present in the oral cavity
Partially keritonized stratified squamous
What epithelium is present in the esophagus
Non-keritonized stratified squamous
What epithelium is present in the stomach
Simple columnar with goblet cells
What epithelium is present in the small intestine
Simple columnar with goblet cells, crypts, and villi
What epithelium is present in the colon
Simple columnar with crypts
What epithelium is present in the anus
Non-keritonized stratified
Where in the esophagus do immune cells accumulate with physiologic inflammation?
In the lamina propria (right under the epithelium)
Once antigens enter lacteals in the villi, where do they drain?
Lamina propria follicles (span the lamina propria and may extend into the submucosa)
Where can antigens drain from the lamina propria folicles?
Mesenteric lymph nodes (outside the mucosa), not a part of MALT
What pathology is hypertrophy of ileal Peyer’s patches associated with?
Idiopathic intussusception
What lies over Peyer’s patches in the ileum?
Follicle-associated epithelium
What is the distinctive cell type in follicle-associated epithelium?
M cells
Once antigens enter Peyer’s patches, what receptor recognizes free antigen? Antigen presented by APCS?
BCR
TCR
Organization of a Peyers patch is similar to that of:
Lymph node, except it is not encapsulated
What are the main proteins involved in tight junctions between epithelial cells?
Claudins
Occludins
What protein is involved in adherens junctions between epithelial cells?
E-cadherin
What are three kinds of APCs?
- DC
- Activated macrophages
- Follicular DCs (germinal centers)
A DC presents an antigen to a T cell.
- What happens in the presence of TGF-beta and IL-6?
- What happens in the presence of TGF-beta and RA?
Immune response
Tolerance response–naive T cell becomes a Treg cell
What pattern recognition receptor is cytoplasmic (in intestinal epithelial cells)? Which one is expressed on the basolateral surface of the cell, facing the extracellular env?
NLR
TLR
What are genes activated downstream of pattern recognition receptors?
Cytokines: TNF, IL-1, IL-12 Chemokines E-selectin Costimulatory molecules Antiviral cytokines: IFNalpha/beta
What are the two gut homing molecules that IgA secreting B cells and effector T cells express?
alpha4beta7 integrin
CCR9
What do alpha4beta7 integrin and CCR9 bind?
alpha4beta7: MADCAM (on gut endothelial cells)
CCR9: CCL25
What do DCs in Peyers patches or mesenteric lymph nodes produce to induce the expression of CCR9 and alpha4beta7?
Retinoic acid
**intestinal epithelial cells also express retinal dehydrogenase, leading to elevated retenoic acid in gut tissues
What cytokine is produced by Th1?
IFN-y
What cytokines are produced by Th2?
IL-4
IL-5
IL-13
What cytokine is produced by Th17?
IL-17
What induces differentiation of:
Th1
Th2
Th17
IL-12, IFN-y
IL-4
IL-6, IL-23
The following are for host defense against:
- Th1
- Th2
- Th17
Intracellular microbes
Helminthic parasites
Extracellular bacteria and fungi
What are the three key things that are going on in the germinal center of follicles?
Antibody secretion
Class switching
Affinity maturation
What is complement?
System of serum and cell surface proteins that interact with one another and other molecules of the immune response to generate effectors of innate and adaptive immune systems
What is the first step of all three complement pathways? Next steps?
Binding of complement to the microbial cell surface or a surface antibody
Formation of C3 convertase
Cleavage of C3
Binding of C3 to the cell surface
What complement pathway is particularly important in the gut?
Lectin pathway: gut has more bacteria than cells in the body and mannose is on the bacterial surface
Mannose binding lectin binds mannose to start cascade
T dependent class switching to IgA
- DCs in peyers patches present antigen to naive T cells to make Th1 cells
- CD40L on Th1 and TBFbeta from DC activate naive B cell to make IgA
T-independent class switching to IgA
- TLRs expressed on DCs stimulate the release of TGFbeta, RA (and APRIL, BAFF, IL-6) from the DC
- B cell stimulated to produce IgA
IgA as a dimeric protein held together by:
The J chain
How does IgA get transported from the lamina propria across the mucosal epithelial cell to the lumen?
J chain of IgA bound by poly-Ig receptor
Poly-Ig receptor bound to IgA is endocytosed
Proteolytic cleavage allows freeing of IgA into the lumen
What is the difference between an immunogen and an antigen
Immunogen: antigen that induces an immune response
Antigen: any molecule that is bound by an antibody or T cells
Effect of size on immunogenicity
Large: increased
Small: decreased
Effect of dose on immunogenicity
Intermediate: increased
High or low: decreased
Effect of route on immunogenicity
SubQ>intraperitoneal>IV or IG
Effect of composition on immunogenicity
Complex: increased
Simple: decreased
What is hypersensitivity?
Excessive or aberrant immune responses following challenge with antigen
What are two things that hypersensitivity is caused by?
- Dysregulated or uncontrolled response to foreign antigens resulting in tissue damage and injury
- Failure or self-tolerance followed by immune responses directed against “self” antigens
What are the 4 types of hypersensitivity?
I: IgE (immidiate)
II: IgG/IgM (antibody mediated)
III: Immune complex mediated
IV: T cell mediated
Mechanism of tissue injury in type I hypersensitivity?
Mast cells and eosinophils and their mediators
Inflammation
Mechanism of tissue injury in type II hypersensitivity?
Opsonization/phagocytosis
Complement and Fc recruitment of leukocytes
Mechanism of tissue injury in type III hypersensitivity?
Complement and Fc recruitment of leukocytes
Mechanism of tissue injury in type IV hypersensitivity?
CD4: macrophage activation, infl
CD8: target cell killing, inflammation
What is the name for the specific unresponsiveness of the normal immune system to an individuals own self antigens
Tolerance
How does tolereance in the T and B cell compartments differ?
T cell tolerance is long-lived
B cell tolerance is short-lived, less complete
***STOPPED BEFORE THE LAST FEW
SLIDES
