Term
| Where in the body is mucosal immunity most important? |
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Definition
| Gastrointestinal, respiratory, and genitourinary tracts |
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Term
| Is mucosal immunity less important than systemic? |
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Definition
| No, the lymphoid tissue along the mucous membrane is larger than that responsible for systemic immunity and, in many respects, functions independently |
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Term
| What is the major anatomical difference between mucosal and systemic immunity? |
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Definition
| Mucosal receives immunogen via epithelium rather than lymph or blood |
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Term
| What is the major Ig difference between mucosal and systemic immunity? |
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Definition
| sIgA and, to lesser extent, sIgM is more prevalent than IgG |
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Term
| What is the major T cell difference between mucosal and systemic immunity? |
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Definition
Mucosa-specific regulatory and effector characteristics.
Some mucosal T cells are not of thymic origin |
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Term
| What are some nonimmunologic (ie, physical) factors unique to mucosal immunity? |
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Definition
| Mucus, other secretions, cilial motion, etc |
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Term
| List four nonspecific factors operating with mucosal immunity |
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Definition
1. Normal flora
2. Mucosal motor activity (e.g., peristalsis and ciliary function)
3. Chemical (e.g., lysozyme, gastric acid, bile salts, lactoferrin, etc)
4. Mucous secretions |
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Term
| How can antibiotic therapy cause superinfection? |
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Definition
| Antibiotic therapy can alter the normal flora |
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Term
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Definition
| Surfaces that secrete thick mucus for protection against pathogens. Line respiratory tract and the gastrointestinal tract. |
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Term
| What does GALT stand for? |
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Definition
| Gut-associated lymphoid tissue |
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Term
| List the five lymphocyte locations within the GALT |
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Definition
1. Waldeyer's Ring
2. Peyer's patches
3. Isolated lymphoid follicles
4. Lamina propria
5. Intraepithelial lymphocytes |
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Term
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Definition
| Tonsils and adenoids form lymphoid tissue ring that guards the entrance to the airways and gut |
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Term
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Definition
| Secondary lymphoid follicles underneath the mucosal epithelium of the small intestine which contain lymphocytes (T and B) and follicular dendritic cells |
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Term
| Define Isolated Lymphoid Follicles |
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Definition
Located in the small and large intestine, these follicles contain mostly B cells overlaid by an epithelial M cell.
*Numerous isolated lymphoid follicles found in the appendix. |
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Term
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Definition
Area just beneath the basement membrane and contains numerous immune system cells.
Many B cells here are plasma cells secreting IgA. |
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Term
| Define Intraepithelial lymphocytes |
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Definition
Lymphocytes reside between lumenal epithelial cells beneath the tight junctions.
These are previously activated special CD8 T cells that contain cytotoxic granules like CTLs but have distinct receptors on their surface. |
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Term
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Definition
| Specialized flattened epithelial cells that pinocytose material from the overlying lumen and transport in an undegraded form to mucosal follicles. |
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Term
| Define Intraepithelial Dendritic Cells |
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Definition
| Dendritic cells that can capture antigens from the gut lumen by stretching long dendrites between the epithelial cells. |
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Term
| What do Intraepithelial Dendritic Cells do once they have captured antigen? |
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Definition
| They move into the T cell areas of the GALT or into draining lymph nodes to present the antigen to T cells. |
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Term
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Definition
| Transmembrane proteins form strands that band the epithelial plasma membranes together. This forms a tight seal that completely encircles the endothelial cells and provides a barrier against passive diffusion. |
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Term
| What are the names of the transmembrane proteins that form tight junctions? |
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Definition
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Term
| What is the difference between "afferent" and "efferent" lymphoid tissue? |
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Definition
| Lymphocytes activated in mucosal follicles (“afferent”) migrate to diffuse lymphoid tissue (“efferent” areas). |
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Term
| What receptor/protein binding allows lymphocytes to bind to mucosal epithelial cells? |
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Definition
| Integrin a4b7 binds to MAdCAM-1 on epithelial cells |
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Term
| What receptor/protein binding allows intraepithelial lymphocytes to bind to mucosal epithelial cells? |
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Definition
| integrin aEb7 binds to cadherins |
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Term
| What chemokine and receptor binding allows lymphocytes to migrate from the blood back into similar mucosal sites where they were activated? |
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Definition
| Chemokines CCL25 secreted by the gut epithelium bind to receptor CCR9 |
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Term
| What is the most abundant immunoglobulin when both serum and secreted antibodies are considered? |
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Definition
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Term
| List the steps by which IgA production is regulated by T cells |
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Definition
1.Mucosal tissue or lymph node T cells are activated by APCs
2. T cells interact with IgM-expressing B cells in lymphoid follicles at T cell/B cell zone interface.
3.The cytokine TGFβ and T cell interactions with B cells induce the B cells to switch from IgM production to IgA production. |
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Term
| After B cells start presenting IgA, what do they do? |
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Definition
B cells migrate via mesenteric lymph nodes to lamina propria.
In lamina propria the activated B cells again interact with T cells which induce the B cells to become plasma cells that secret large quantities of sIgA. |
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Term
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Definition
| Protein chain on sIgA which binds to the poly-Ig receptor on the epithelial cells and activates transport |
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Term
| Define secretory component. What is its function? |
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Definition
The part of the poly-Ig receptor which remains bound to the sIgA dimer when released by enzyme cleavage out into the mucus in the lumen.
Binds mucins via its carbohydrates and holds IgA to the mucosal surfaces. |
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Term
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Definition
| Transport of macromolecules from one side of a cell to the other via receptors. |
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Term
a) Is IgA inflammatory?
b) Does IgA promote the complement system?
c) Does IgA promote phagocytosis/lysis? |
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Definition
a) IgA is anti-inflammatory
b) IgA does not activate complement
c) IgA binding to Fc inhibits phagocytosis/lysis |
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Term
| What is the effector function of IgA? |
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Definition
The Fc/SC end is hydrophilic/mucophilic and assists in preventing microorganisms from binding to epithelial receptors.
Net effect is for sIgA to prevent colonization by parasites without inducing inflammation |
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Term
| If a person has selective IgA deficiency, what happens? |
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Definition
sIgM is usually present in small quantities but is often sufficient to replace sIgA
However, immune exclusion is ineffective, so they have high levels of immune complexes following ingestion of immunogenic macromolecules |
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Term
| Besides IgA, what other immunoglobulins can be synthesized in mucosal lymphoid tissue? |
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Definition
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Term
| Where is IgG significant in mucosal immunity? |
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Definition
| IgG is synthesized in large amounts in the distal respiratory tract and is an important defense in the pulmonary secretions. |
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Term
Why is therapy with human immunoglobulin usually ineffective?
What is the exception to this? |
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Definition
Human immunoglobulin is usually IgG, and IgG is highly synthesized or transported in mucosal immunity
The exception is in the distal respiratory tract, which is why this therapy is effective for pneumonia |
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Term
| How is IgE important in mucosal immunity? |
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Definition
| IgE can be synthesized in the mucosal tissue and is important in certain parasitic infections and allergic diseases. |
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Term
| How can transepithelial macromolecule absorption be harmful? |
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Definition
| Macromolecules are capable of transepithelial absorption into the circulation in an intact form which can lead to stimulation of an unnecessary or even harmful systemic immune response. |
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Term
| How does sIgA prevent macromolecule absorption? |
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Definition
| Immune exclusion which, along with hepatic clearance, restricts immune responses against mucosal immunogens to only the mucosal lymphoid system |
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Term
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Definition
It is the suppression of immune cell responses to antigens introduced via the oral route.
It is a type of acquired tolerance that is important for preventing food allergies and prevents immune cell reactions against the natural bacterial flora in the gut. |
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Term
| List some diseases that result when oral tolerance is ineffective |
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Definition
| Crohn's Disease, Ulcerative Colitis, gluten intolerance |
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Term
| List three mechanisms of oral tolerance |
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Definition
1. Induction of suppressor T cells
2. Activation of inhibitory class of macrophages
3. Activation of tolerance inducing dendritic cells |
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Term
| How do soluble protein immunogens affect tolerance/immunization |
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Definition
| Not understood, but administration of soluble protein immunogens with appropriate adjuvants appears to favor immunization over tolerance. |
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Term
| How does an infant get IgA protection? |
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Definition
secreting B cells migrate to the lactating breast in response to some gestational hormones.
Concentration of IgA in colostrum is as high as 50 mg/mL vs 2.5 mg/mL in the serum; it rapidly falls to serum levels in about 4 days postpartum |
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Term
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Definition
| A breast milk defense- substrates that are digested into small lipids that disrupt viral envelopes. |
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Term
| Define glycosylated proteins. Give two examples. |
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Definition
A breast milk defense- iDnhibit bacteria and virus binding to gut
lactadhedrin protects against rotavirus
mucin-1 protects against E. coli. |
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Term
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Definition
| A breast milk defense- receptor analogues that inhibit binding of bacterial pathogens and their toxins to receptors on gut epithelium |
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Term
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Definition
| A breast milk defense- cleaves peptidoglycans in cell walls of bacteria |
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Term
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Definition
| A breast milk defense- competes for ferric iron and inhibits bacterial growth |
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Term
| How do glycoproteins provide infant immunity in breast milk? |
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Definition
| Glycoproteins such as caseins promote the growth of Bifidobacterium bifidum and lactobacilli (good bacteria) in the newborn gut which in turn produce organic acids that inhibit growth of enteric pathogens |
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