EXAM #1: IMMUNOLOGY OF THE GI TRACT Flashcards
What is the big difference between mucosal immunity and “normal” immunity?
Length of time
–>Mucosal immunity does NOT last very long
How long do mucosal antibody responses last?
Months to a year
vs. serum antibodies that persist for decades/life
What are effector cells?
Lymphocytes that are “primed” to preform function immediately on contact with antigen
What is tertiary lymphoid tissue?
Any place in the body that becomes infected by microorganisms
What kind of lympoid tissue is the gut considered?
Tertiary
What are the physical mechanisms that prevent infection of the GI tract?
1) Acidity of stomach
2) Peristoltic motility
3) Detergent action of bile
4) Mucus secretion
What is GALT?
Gut Associated Lymphoid Tissue
List the sites of GALT.
1) Peyer’s patches
2) Appendix
3) Lymphoid aggregates in appendix/ large intestine
4) Lymphoid cells in lamina propria
What is a Peyer’s Patch?
Aggregates of lymphoid tissue found in the ileum of the small intestine
What types of immunity are generated by Peyer’s Patches?
1) IgA antibodies
2) CTL
Describe the structure of a Peyer’s Patch.
- M-cells within the membrane of microfolds
- B-cell rich follicle
- T-cell area
- Germinal center
Where are APCs located in the Peyer’s Patch?
T-cell rich areas adjacent to the Germinal Center
What is the function of M-cells in Peyer’s Patches?
1) Uptake of antigen by endocyotsis and phagocytosis
2) Presentation of antigen to APCs
Note that M-cells are sites of infection*
List the microorganisms that utilize M-cells for introduction into the body?
1) Shigella–gets in via M-cells and then uses actin rockets to infect
2) Salmonella
3) Yersinia
4) Listeria
What are IELs?
Intraepithelial Lymphocytes i.e. between enterocytes in the epithelium
What type of lymphocytes are most IELs? What are the two subtypes of these cells?
T-cells
1) Alpha-Beta subtype*
2) Gamma-delta
*Classic T-cell
What is the function of CD8+ IEL cells?
Cell-mediated immunity against:
1) Viral antigens
2) Intracellular bacterial antigens
Where are CD4+ T-cells located in the gut wall?
Lamina Propria
vs. CD8+ T-cells in the epithelium
In addition to CD4+ T-cells, what other immune cells are in the lamina propria?
- B-lymphocytes
- Plasma cells
- Macrophages
- Dendritic cells
- Eosinophils
- Mast cells
Describe the basic immune response in the gut that results in IgA production.
1) M-cells uptake antigen
2) APCs bind antigen
3) APCs stimulate T-helper cells
4) T-helper cells stimulate antigen specific B-cells
Once B-cells have been stimulated, outline the path that the cell will take to find the Lamina Propria.
1) Pre-plasma cells leave Peyer Patch via efferent lymphatic capillaries
2) Migrates via mesenteric lymph channels
3) Enter bloodstream via the thoracic duct
4) Go “home” to the Lamina Propria
What is the role of addressins in B-cell stimulation?
These are the “homing” mechanisms that tell B-cells to go back to the Lamina Propria
How do IgA secreting Plasma Cells get from the Lamina Propria to the gut lumen?
1) IgA binds “poly-immunoglobulin receptors” on basolateral side of enterocyte
2) Endocytosis and transport to apical side
3) Release of IgA dimer + secretory component
What is “secretory component?”
Part of the poly Ig receptor that facilitates endocytosis of the IgA secreting plasma cell
What is the function of secretory component?
Prevents the breakdown of IgA in the gut lumen by proteolytic enzymes
What is the major immunoglobulin in secretions?
IgA
What are the two subclasses of IgA?
IgA1=
- cleaved by bacterial IgA protease
- can fix complement via alternate pathway
IgA2= not susceptible to IgA protease
What is the difference between the structure of IgA in the serum vs. mucousal sites?
Mucosal= IgA dimer
Serum= monomer
What is the role of IgA in immunity?
1) Opsonization of small pathogens for phagocytosis
2) Anti-parasite immunity by facilitating eosinophil degranulation
What is the role of gamma-delta T-cells?
1) Respond to NON-PEPTIDE antigen
2) Don’t recognize normal MHC
Quick immune response to pathogens that we are routinely exposed to without having to go through the entire process of normal T-cells*
What is the importance of mast cells in gut immunity?
1) Play a role in IgE-mediated immunity against parasites
2) Elicit food-induced allergic reactions
What is oral tolerance?
Prevention of an immune response to the food you eat
What is high dose tolerance?
Clonal deletion of antigen specific lymphocytes
What is low dose oral tolerance?
Clonal anergy and T-reg suppression of the immune response
What is the most common immunodeficiency?
Selective IgA deficiency
What is the clinical presentation of Selective IgA deficiency?
Most are Asymptomatic but have a higher risk for Autoimmune disease
Remember the A’s*
What compensates for the absence of IgA in Selective IgA Deficiency?
IgM
What class of antibody mediates Food Hypersensitivity?
IgE
In Gluten-Sensitive Enteropathy, what protein is the immune response directed against?
Gliadin
In what disease is there an increase in gamma-delta T-cells?
Gluten-Sensitive Enteropathy
What is the treatment for Gluten-Sensitive Enteropathy?
Lifelong gluten-free diet
What diseases are patients with Gluten-Sensitive Enteropathy at risk for?
1) GI Lymphoma
2) GI Carcinoma
What is the pathologic feature of Ulcerative Colitis?
Inflammation of the large bowel
What is the definitive treatment for Ulcerative Colitits?
Total Colectomy
What is the pathologic feature of Chron’s Disease?
Inflammatory AND granulomatous lesions of the terminal ileum and ascending colon
What drug can be used to treat Chron’s Disease?
Infliximab– anti-TNF-alpha monoclonal antibody
What disease is characterized by granulocyte inflammatory cells? Which is characterized by granulomatous lesions?
Granulocyte inflammatory cells= UC
Granulomatous lesions= CD
What is the most common cause of Pernicious Anemia?
Autoimmune antibodies against IF or gastric parietal cells
