MSI Mucosal Immunology Flashcards
Important inductive sites incude the Peyer’s patches and ____________ lymph nodes.
mesenteric
What are the two effector sites of the adaptive immune response?
Epithelium and the lamina propria
T-cells and B-cells leave PP’s via afferent lymphatics and return to the gut via the __________ and bloodstream. This cellular re-circulation pattern is referred to as _________.
thoracic duct, “homing”
This is a network of lymphoid cell aggregates and tissue that is distributed in submucosal layers of the gastrointestinal, genital, respiratory, and urinary tracts, as well as in the eyes, skin, thyroid, breasts, tonsils, and salivary glands.
Mucosa-associated lymphoid tissue(MALT)
The MALT is populated by which types of immune cells?
lymphocytes such asT cellsandB cells, as well asplasma cellsandmacrophages
What is the biggest immune compartment of the organism, harbouring 60% of all effector cells?
MALT
- _______ sites are the ports of entry for many infections and an important target site for vaccine-induced protection
Mucosal
Extensively glycosylated proteins that form a viscous barrier
mucins
Goblet cells, absorptive epithelial cells, M cells, and Paneth cells are specialised types of __________ cells
epithelial
The four main defence strategies of oropharynx and intestinal mucosa include:
- Endogenous flora
- Epithelium and Mucus
- Regionalised Immune System (incl _________ ______, PP’s, MLN’s)
- Gut homing of B and T cells
Waldyer’s ring
What are the two places where the largest amount of lymphoid tissue is found?
in the oropharynx (Waldeyer’s ring) and terminal ileum (Peyer’s patches)
Where are germinal centres for B- and T cells found?
Peyer’s patches
These are the sites where antigens sampled from mucosal surfaces stimulate cognate (ie related/connected) naive T and B lymphocytes
Inductor sites (for example, PP’s and MLN’s)
Effector sites are where the effector cells after extravasation, retention, and differentiation perform their action, for instance by contributing to the formation of __________
antibodies
What are two effector sites?
Lamina propria, intestinal epithelium
What type of cells actively transport luminal antigens to the underlying lymphoid follicles to initiate an immune response?
M cells
Induction sites (PP’s and MLN’s) contain __ cell follicles and ___ cells.
B, M
_______ cells are specialised secretory epithelial cells which are located in the Small intestinal crypts of Leiberkuhn. Their main function is to produce and export a variety of antimicrobial proteins. They provide the defence against the microbes in the small intestine.
Paneth
**These are the specialised cells which are found in the follicle-associated epithelium of the Peyer’s patches. These cells transport the Ag from the gut lumen to the sub-epithelial lymphoid structures, such as the Peyer’s patches. They play a role in the defence mechanism, as well.
M cells
Epithelial cells : Intestinal epithelial cells contain toll-like receptor (TLR) Intestinal epithelial cell ______ senses the composition and localization of the intestinal microbiota to prevent diseases associated with intestinal inflammation. (This TLR) tightens tight junctions upon contact with bacteria.
TLR5
** A group of well-organized lymphoid follicles located in the lamina propria and submucosa of the distal portion of the small intestine.
Peyer’s patches
** Almost 50% of Peyer’s patches are located in the
Distal ileum
** ________ ________ contain specialized cells called microfold cells (M cells) which sample antigen directly from the lumen and deliver it toantigen-presenting cells.
Peyer’s patches
M cells are located within the _______-associated epithelium of the Peyer’s patches
follicle
Within the inter-follicular area of the Peyer’s patches , the T cells activate the B cells, which then convert into plasma cells that produce Abs. So once this process is completed, B cell and T cells leave the Peyer’s patches, and either via the blood stream or thoracic duct, they come back to the lamina propria of the gut where they become ready to start the process again. This process of recirculation via the thoracic duct or bloodstream is known as
“homing”
Which immunoglobulin can neutralise toxins, food allergen, and prevent microbial invasion, which can contribute to the tolerance induction?
IgA
Naive B-cells enter the PP via specialized high __________ venules (HEV). If they recognize antigen coming in from the M-cells at the top of the PP, they get activated and may start proliferating
endothelial
When T and B cells activate each other within the intrafollicular area of the PP’s, the T-cells move on to become fully fletched mature cells and B-cells undergo Immunoglobulin ________-________ to turn into Plasma cells.
class-switch
Binding of antigens by IgA in the lumen prevents their uptake, and if antigens penetrate the epithelial barrier they can be bound to IgA and secreted back out into the lumen with the IgA. In this way, IgA’s contribute to mucosal homeostasis by limiting the uptake of antigens from the gut lumen.
As a ___________ antibody, IgA has been hypothesized to play a protective role in the context of food allergy.
neutralizing
- Food allergy in children has been reported to be associated with deficiency of which immunoglobulin?
IgA
Which important cytokine:
Regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool
Inhibits cytotoxic T lymphocyte, Th1-, and Th2-cell differentiation and T-cell tissue residence in response to immune challenges.
Controls the proliferation, survival, activation, and differentiation of B cells, as well as the development and functions of innate cells, including natural killer (NK) cells, macrophages, dendritic cells, and granulocytes.
Transforming Growth Factor beta (TGF Beta)
** Which cytokine plays a pivotal role in maintaining peripheral tolerance against antigens, such as food and commensal bacteria?
TGF-β
Which lymph nodes are the main site for oral tolerance induction?
(Oral tolerance: avoidance of an immune response to foodstuffs)
Mesenteric
Describe the route that T and B cells follow during the “homing” process
(Remember that MLN drain lymph from intestinal mucosa)
-Naïve B-cells and T-cells arriving via high endothelial venules will travel from Peyer’s patches (induction sites) via MLN, through the lymphatic circulation, to the thoracic duct and then through the blood stream, eventually returning to the effector sites of the gut (GI epithelium and lamina propria)
_________ means that T-cells and B-cells are instructed to return to the effector sites adjoining the induction sites where they were primed, i.e. first confronted with their ‘cognate’ antigen. This is a process that happens in all tissues.
Gut-homing properties of effector lymphocytes are imprinted in the gut-associated lymphoid tissues where they have undergone differentiation from naive precursors (induction sites).
They will home to the same organ, however, to an effector site
Homing
Gut homing of B and T cells is dependent on assistance from which Vitamin?
Vitamin A
Vitamin A and its active metabolite ___________ are essential for the development and function of many tissues including the immune system. The induction of mucosal homing receptors on T and B cells by mucosal dendritic cells (DC) depends on the presence of vitamin A.
retinoic acid
When naive B or T-cells are activated by antigen in gut associated lymphatic tissue, they are exposed to retinoic acid (RA) produced by the __________ cells from Vitamin A
dendritic
When naive B or T-cells are activated by antigen in gut associated lymphatic tissue, they are exposed to retinoic acid (RA) produced by the dendritic cells from Vitamin A . This induces the expression of the chemokine receptor _______ and increased expression of integrin α4β7 on primed T-cells. The same mechanisms works for B-cells
CCR9
How does a naive T cell become a lamina propria T-cell?
The naïve T-cell enters an induction sites in the gut lymphatic tissue via a HEV, travels through the circulation, and then re-entering the gut at an effector site as an antigen-primed effector T-cell.
