Mucosal Immunity Flashcards

Question

What is the lamina propria?

Answer 1

Tissue which underlies the epithelial layer.

Answer 2

Conventional cells: -Dendritic Cells -Macrophages -Neutrophils -Mast cells -Eosinophils -Basophils -T cells -B cells specific cells: -Epithelial cells -M cells -IntraEpithelial lymphocytes -gamma delta T cells

Answer 3

Majority are CD4+ i.e. Treg cells They outnumber the CD8+ cells by a factor of 2:1 Most of them express alpha4beta7 integrin which recognises the ligand MadCAM They produce cytokines dependent on their subset

Answer 4

Tregs act to regulate/supress other immune cells via IL-10 and TGFb Th1 act to activate macrophages via IFNy Th2 act to induce B cell class-switching to IgA via IL-5 Th17 act to maintain epithelial barrier function via IL-22 and activate neutrophils via IL-17

Answer 5

IELs (intraepithelial lymphocytes) These are all T cells, majority is CD8+ (a large number are CD8alpha-alpha) Gammadelta T cells may also be quite frequent in this population Unlike the T cells in the lamina propria, these cells express alphaEbeta7 integrin which recognises the ligand E-cadherin, which is particularly associated with enterocytes & epithelial cells Many of them are unresponsive to TCR stimulation & many are extrathymically derived ( not gone through regular T-cell production in the thymus)

Answer 6

Chemoattraction Rolling adhesion Tight adhesion Arrest of rolling lymphocyte Diapedesis

Answer 7

Chemokines recruit lymphocytes & induce expression of adhesion molecules on these lymphocytes & on surrounding endothelial cells In a naive lymphocyte, they'll induce the production of L-selectin on the surface of the lymphocyte L-selectin will then come into contact with a MadCAM-1 on the surface of endothelial cells, which will be triggered to be highly expressed in areas where we have an infection by chemokines

Answer 8

Lymphocyte binds loosely to endothelial cells & rolls along

Answer 9

Chemokine-mediated activation of alpha4beta7 integrin which binds to MadCAM-1

Answer 10

You then start to see the production of other cell surface molecules both in the endothelial cell & in the lymphocytes themselves LFA-1 binds ICAM-1 & ICAM-2 Further tighter binding

Answer 11

Junctions between endothelial cells become loose or the endothelial cell itself invaginates and allows the lymphocytes to penetrate through and into the surrounding tissues Thus the lymphocyte extravasates & gains access to the supplied tissue from which it can move to the point of infection

Answer 12

To produce IgA Under the influence of TGFBeta and IL-5, they switch production from IgM to IgA

Answer 13

-produced at mucosal sites -secreted across epithelial surfaces, found in all mucosal secretions (e.g. saliva) -It has different functions/activities to IgG -IgA is the most highly produced Ig

Answer 14

IEL protect & maintain the epithelial barrier layer, protecting against infection

Answer 15

IgG on top, IgA on bottom IgA = dimeric joined by J chain. 4 antigen binding sites instead of 2 slide 36

Answer 16

Normal immune function Tolerance can be local or systemic It requires a functional immune system Symbiosis - in the absence of commensals, a poor immune response develops and oral tolerance cannot be induced

Answer 17

State of immune non-responsiveness to antigen induced by feeding It is a feature of the common immune system Can also be induced by 'immunisation' at other mucosal sites - i.e. Intranasal

Answer 18

IgG and IgA both have : -Virus neutralisation -Enzyme and toxin neutralisation -Inhibition of adherence -Agglutination BUT IgG also has: -Complement activation -Opsonisation But IgA has: -Immune exclusion : preventing microbe getting into the body -Inta-cellular neutralisation -Virus excretion -Interactions with non-specific factors : lysozyme, lactoferrin, peroxidase

Answer 19

Activity of Tregs (TGFB + retinoic acid = centric cells drive the differentiation of Niave CD4 to iTreg) Induction of anergy

Answer 20

Antigen specific Often partial (eg. antibodies inhibited, but T cell responses may remain) Not complete (eg. may be a quantitative reduction in antibody levels) Wanes with time Easier to abrogate a response than reduce an established response Good immunogens are better at inducing tolerance Dose and route dependent.

Answer 21

immune responses to food: Leads to food intolerance, e.g. coeliac disease Immune responses to commensal bacteria: Leads to inflammatory bowel disease (IBD) E.g. Crohn's disease, ulcerative colitis

Answer 22

Provide/maintain an environment that: -Doesn’t respond to the commensal microbiota -Doesn’t respond to food/ingested antigens -Does respond to pathogenic microbes They regulate responses in conjunction with epithelial cells: -key in this process are the cytokine TGF-b and retinoic acid (a metabolite of vitamin A) These factors control immune responses by: -controlling mucosal homing -controlling dendritic cell activation/induction of Treg

Answer 23

Some epithelial cells in the gut and lung normally express class II MHC, but not costimulatory molecules Result is activation of TCR without the second (CD28) signal - leads to anergy of responsive T cells

Answer 24

Mucosal surfaces: large, exposed to external environment, major route of entry of infectious microorganisms. Mucosal (secretory) immune system is targeted by Lymphocyte homing and is the site of transport of sIgA. Mucosal immunity involves a wide variety of cells. Immunoregulation critical to avoid damaging inflammatory responses to commensal flora or food antigens (both high load). General unresponsiveness maintained by Treg. TGF and Retinoic acid may be major factors. Tolerance to an antigen can be induced by immunisation at a mucosal surface.

Mucosal Immunity Flashcards

(48 cards)