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what is MALT&nbsp;mucosa-associated lymphoid tissue&nbsp;<br>- epithelial surfaces of gastrointestinal tract (GALT)&nbsp;<br>- lymphoid aggregates throughout the GIT&nbsp;
what is GALTgut associated lymphoid tissue
what is peyer's patch&nbsp;a group of well-organized lymphoid aggregates located in the lamina propria and submucosa of the ilium&nbsp;<br>- type of GALT
what are the mucosal immune system key concepts&nbsp;1. self vs non-self<br>2. harmless vs harmful<br>3. appropriate vs inappropriate immune response<br>4. innate vs adaptive immunity&nbsp;<br>5. pathology&nbsp;
what is the functions of the microbiome in the GIT&nbsp;1. protective function&nbsp;<br>2. structural function&nbsp;<br>3. metabolic function
what is the protective function of the microbiome in the GIT&nbsp;- pathogen displacement&nbsp;<br>- nutrient competition&nbsp;<br>- production of anti-micorbial factors (e.g. lactic acids)
what is the structural function of the microbiome in the GIT&nbsp;- barrier fortification&nbsp;<br>- induction of IgA<br>- apical tightening of tight junctions<br>- immune system development&nbsp;
what is the metabolic function of the microbiome in the GIT&nbsp;- control intestinal epithelial cell differentiation and proliferation&nbsp;<br>- metabolize dietary carcinogens&nbsp;<br>- synthesize vitamins&nbsp;<br>- ferment non-digestiable dietary residue and endogenous epithelial-derived mucous&nbsp;<br>- ion absorption&nbsp;<br>- salvage of energy&nbsp;
what amount of oxygen does the gut have&nbsp;it is hypoxic on the surface epithelial cells, where the microbiome is&nbsp;
what are the factors affecting our microbial conolisation&nbsp;- bacteria in amniotic fluid<br>- delivery procedure (e.g. natural vs c-section)<br>- breast-fed<br>- genetic background&nbsp;<br>- antibiotics (kill healthy micobiome)&nbsp;<br>- age (diversity decreases as we age)&nbsp;<br>- lifestyle&nbsp;
what diseases does the microbiome relate to&nbsp;- obestity&nbsp;<br>- IBD<br>- liver disease<br>- emerging infectious disease<br>- diabetes mellitus&nbsp;<br>- atherosclerosis<br>- metabolic syndrome&nbsp;
what are the mucosal immune system cell types&nbsp;- lymphocytes<br>- macrophages<br>- dendritic cells<br>- neutrophils&nbsp;<br>- epithelial cells<br>- gobelt cell&nbsp;<br>- crypt cells = peneth cells&nbsp;
how are B and T cells made&nbsp;1. lymphoid progenitor cells in bone marrow<br>2. develop in thymus = T cells, bone marrow = B cells&nbsp;<br>3. go to distal lymphoid aggregates&nbsp;
How do T Helper cells differenctiate&nbsp;"- IL-4 = TH2 = helps B cells (in gut)<br>- IL-12 = TH1 = helps macrophages&nbsp;<br>- TGF-beta1 &amp; IL-23 = TH17&nbsp;<br>- IGF-beta = T reg cell = regulate T cells&nbsp;<br><div>
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<div><img alt=""T helper cell differentiation IL-4 T lymphocytes: Undifferentiated T helper cell Helper T lymphocyte Each cell has IL-12 TGF-ß1 IL-23 IL-6 TGF-ß1 TH2 GATA.3 STAT-6 THI T-bet STAT •4 TH17 STAT-3 Foxp3 T reg IFN.7 IL-17 TGF-ß1 (Other factors?) Defence against parasitic worms Allergy, asthma Defence against intracellular pathogens Defence against extracellular bacteria Autoimmunity Cancer Immunosuppression Hel B cells Macrophages Regulate T cells Adapted from Tato et al. Nature 2006 TH2 responses predominate in the gut "" src=""paste-b97deea6a667de8ff7db8eaeb972c910fa9ba863.png""></div>
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what T-helper cell predominates in the gut&nbsp;T_H2 response&nbsp;
what do effector/cytotoxic T-cells do&nbsp;direct killing&nbsp;
what do dendritic cells do&nbsp;- interface b/t adaptive and innate immune system<br>- abiluty to reach though the tight junctions to the mucous and sample the material&nbsp;<br>- antigen presenting cells&nbsp;
what do neutrophils do&nbsp;- first responder to bacterial infection&nbsp;<br>- phagocytes<br>- first responder to infections&nbsp;<br>- can get neutrophilic damge with overreaction&nbsp;
what is the fucntion of epithelial cells&nbsp;barrier function
what is the functions of goblet cells&nbsp;protective secretions: mucins and lysozyme&nbsp;
what do macrophages do&nbsp;phagocytosis
what do paneth cells doprotective secretions: defensins and IgA&nbsp;
tolerance to microbiota (immune tolerance) is controlled by what cells&nbsp;M cells
tolerance to injested soluble antigens (oral tolerance) is controlled by what cells&nbsp;dentritic cells&nbsp;
what type of antigens are there in the GIT&nbsp;1. commensal (microbiome), driven by M-cells, in the intestine&nbsp;<br>2. oral antigen, driven by dentritic cell, intestine and systemic response&nbsp;
what are m cells (microfold cells)&nbsp;- unqiue to GALT<br>- epithelial cells with no microvilli&nbsp;
what is the structure of m cells&nbsp;- basolateral membrane is invaginated and contains T-cells, B-cells, and macropahges<br>- antigens are taken from the lumen and pased directly to antigen presenting cells by endocytosis&nbsp;<br>- some pathogens can enter directly through M-cells (salmonella, singella)&nbsp;
what does the mucosal immune system result in- oral tolerance from oral antigens&nbsp;<br>- immune tolerance from commenasal gut bacteria&nbsp;
what are the two receptors in the GIT immune response1) NLRS<br>2) TLR
"<span style=""color: rgb(0, 0, 0);"">what are NLRS (<span style=""background-color: rgb(255, 255, 255);"">nucleotide-binding oligomerization domain-like receptors)</span></span>"- cytoplasmic receptor&nbsp;<br>- recognizes PAMPs: DAP and MDP&nbsp;<br>- signal via NFkappaB or Caspase&nbsp;
what are NLR genes associated with&nbsp;inflammatory bowel disease (e.g. Chron's Disease - NOD2 polymorphisms)&nbsp;
what do TLR respond to&nbsp;LPS on bacterial cell wall&nbsp;<br>- TLR are located on the cell wall or the endosome membrane&nbsp;
what does the crosstalk b/t to produce&nbsp;active pro-inflammatory cytokine IL1beta&nbsp;
what is inflammatory bowel disease&nbsp;umbrella term comprising Chrohn's Disease and Ulcerative Colitis&nbsp;<br>- results from an inappropriate inflammatory response to intestinal microbes in a genetically susceptible host&nbsp;
what is the incidence of IBD8-14 per 100,000&nbsp;
what does Crohn's Disease affect&nbsp;any part of the GIT&nbsp;<br>- usually ileum and colon&nbsp;<br>- has skip lesions&nbsp;
what does ulcerative colitis affect&nbsp;only the colon
what are the symptoms of inflammatory bowel diseaserange of symptoms depending on serverity&nbsp;<br>- diarrhea&nbsp;<br>- weight loss<br>- intestinal bleeding&nbsp;<br>- fever<br>- abdominal pain&nbsp;
what is C.difficile colitis&nbsp;- usually hospital acquired<br>- can follow broad spectrum antibiotic use<br>- over-colonisation by C.diff<br>- internalised by colon cells<br>- toxin release and cell death&nbsp;