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24 Cards in this Set
- Front
- Back
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What is MALT?
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mucosa assosiated lymphoid tissue, a highly specialized immune system that protects the mucosal surfaces. Largest mammalian lymphoid organ system.
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Why does knowing which compartment an immune response begins important?
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Where the initial immune response starts is where the effector cells will come back to.
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What makes the job of the MALT difficult?
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It needs to distinguish not only between self and non-self, but harmulf non-self and nonharmful non-self.
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What cells are the central component of an effective mucosal immune response?
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B-cells. The main mediator is secretory IgA and to a lesser extent secretory IgM.
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Why is IgA so important to the mucosal immune response?
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It is resistant against common intestinal proteases and it does not interact with complement. It inhibits adherence, neutralizes viruses, and neutralizes enyzmes and toxins
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What is the critical class swith factor that will cause the B-cell to secrete IgA?
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TGF-Beta. However it also needs Th2 cytokines like IL-4, IL-5, IL-6, and IL-10. Once this occurs you are a fully competent IgA producing B-cell
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What is the J-chain
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Binds to the tail pieces of IgM and IgA. It stabilizes polymers of IgA amd IgM allowing it to bind the Ig receptor or secretory complement.
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How do you get the IgA into the lumen?
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J-chain binds receptor on the basal surface of epithelium, transcytosis to lumen, receptor is cleaved with polymeric IgA and J chain.
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What are the two sites of the mucosal response?
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inductive sites (peyer's patches) with lots of alpha-beta T-cells with a lot of CD4 Th1 and Th2 cells. The effector site with lamina propria lymphocytes mostly CD4 Th2 and intra epithelial lymphocytes CD8+
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How are IEL localized to the intra columnar villi spaces?
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They express specific integrin that localize them to the inter epitheim of the mucosal immune system
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What kind of cytokine profile is released from IELs?
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IFN-gamma and TNF-alpha.
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What is the role of the IELs?
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possibly destroy epithelial cells that have underone transformation, regulatory role in oral tolerance
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What do M-cells do?
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Sample the environment of the lumen. Have receptors for secretory IgA. Binds IgA in the lumen and sample the environment. M-cells are in close apposition to other immune cells. This can be a good entry point for pathogens.
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How do DCs play a role in the mucosal immune system?
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In lamina propria have dendrites that go between cells to lumen and capture pathogens.
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What receptor is important for the formation of functional dendrites
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CX3CR1
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Describe the path from pathogen recognition in MALT to the activation of T-cells that enter the blood.
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at the inductive lymphoepithelium pathogens are sampled and brought in via DCs or Mcells. They are directly provided to APCs, B-cells or DCs. T-cell APC interaction activates T-cell. Activated T-cells interact with B-cells. B-cell switch to IgA. activated T-cells leave and enter the circulatory system.
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What happens to the T-cells that enter the blood stream?
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They may undergo additional differentiation, but they ultimately return to the site of initial immune response.
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IgA deficiency
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most common primary immunodeficiency, less than 50ug/ml. Important for receiving blood products containing IgA b/c you can get IgE response against IgA. Higer incidence of infections of URT/LRT and GI. increased autoimmunity
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IBD
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chronic relapsing and remitting inflammation condition. Crohn's and Ulcerative colitis. Patients have increased numbers of activated mucosal T-cells secreting INF-gamma. IL12, IL-18, and produced drive toward Th1-TNF-alpha and IL-1. Increased IgG and complement fixing.
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Crohn's disease
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affects the small intestine and the colon. Thought to be associated with NOD2 (like TLR receptor) defects causing an increase in T-cell recruitment and increased inflammatory response.
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Ulcerative Colitis
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which predominately affects the colon in a superficial manner.
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Celiac Disease
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T cell mediated immune disease of the small intestine triggered b gluten. major feature include villous atrophy with a lymphocytic infiltrate, increased epithelial proliferation with crypt hyperplasia and malabsorption. CD4 mediated disease associated with HLA DQ2 and DQ8. Intraepithelial CD8 cells make it different that IBD
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Oral Tolerance
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give an antigen orally and come back systemically the immune system will ignore it.
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The goal of oral vaccines
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elicit a long lasting mucosal antibody response to an antigen, the problem is that the mucosal immune system is good at down regulating immune responses (possible use in autoimmune disease)
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