Mucosal Immunity Flashcards
What is the mucosa? (2)
Is the cellular lining of the body
Forms the barrier between the external and internal
What is the function of mucosal immunity? (2)
Mucosal immune system functions to maintain immune homeostasis at barrier sites whilst preserving physiological functions i.e. digestion within the intestine, respiration in the lungs
What are epithelia cells? (1)
Define the border between the environment and ourselves
What are the different types of epithelial barriers? (3)
Typified by the intestinal, respiratory and urogenital mucosa
Function of epithelial barriers (2)
Able to distinguish between outside world whilst also selectively transporting significant quantities of nutrients ions and water essential for life both locally and systemically
Immunity at the epithelium is supplemented by what and where is it found? (3)
Mucus
Produced by goblet cells interspersed between epithelium and antimicrobial peptides.
Role of epithelial cells (5)
Epithelium are the major route of infection
Epithelial cells direct numerous components of the innate and adaptive immune systems at various levels
At the same time, epithelial cells secrete, and respond to, variousmediators that profoundly affect the function of surrounding mucosal cell types.
Which components of the innate and adaptive immune response do epithelial cells direct? (4)
Barrier function
The processing and presentation of antigens
The expression of MHC and costimulatory molecules
The secretion of antimicrobial peptides.
What are Mucosa-Associated Lymphoid Tissue (MALT) (2)
MALT is an Umbrella term for organised lymphoid tissue at mucosal surfaces.
Feature of all MALT are the absence of classical lymphatic structures
How is MALT similar/different to lymphatic tissues at other sites? (2)
MALT is similar to draining lymphatic tissue at the other sites however it has direct contact with the overlaying epithelium.
Name the three different regions of MALT? (3)
Gut associated lymphoid tissue - GALT
Bronchus-associated lymphoid tissue (BALT)
Nasal-associated lymphoid tissue (NALT)
What elicits the B-cell-mediated immunoglobulin A (IgA) response? (1)
The presence of microbes in the gut
Describe the B-cell-mediated immunoglobulin A (IgA) response (3)
IgA is produced by B cells within the lamina propria of the small intestine
Transported across intestinal epithelial cells
Secreted into the gut lumen where it is called secretory IgA
Role of secretory IgA (3)
Microbe interactions in the gut through coating bacteria and modifying their ability to attach to the mucosal surface of the intestine and/or activate immune responses
What happens in the intestinal lamina propria (2)
Immune cells enter the bloodstream and undergo terminal differentiation in the intestinal lamina propria
What is the mucosal immune system divided into? (2)
Divided into distinct inductive sites and effector sites.
What are inductive sites? (2)
These are the organized MALT structures together with mucosa-draining lymph nodes.
What are effector sites? (2)
These are the mucosal epithelia and the underlying lamina propria, which contains stromal cells and associated connective tissue stroma.
What are Microfold cells (M cells) ? (3)
Called by specialised epithelial cells
Transportintactbacteria, abiotic particulates, and soluble antigens within vacuoles across their cell bodies
Transcytosis
What is the intestinal epithelial barrier (2)
Not a classical barrier but does inhibit bacteria from entering tissue
What are isolated lymphoid follicles? (5)
Develop after birth in response to antigen stimulation, by commensal bacteria
Mainly found in large intestine
Contain mainly B cells
Connect to draining lymph nodes, located in the mesentry a connective tissue tethered to intestinal wall
It is the largest collection of lymph nodes in the body
Why are Peyer’s patches and isolated lymphoid follicles called inductive sites? (1)
Because they are directly involved with antigen recognition
Mesenteric lymph nodes and Peyers Patches difference (2)
Mesenteric lymph nodes and Peyers Patches differentiate independently of the ILF and differences between them are imprinted early in life
What are host defence peptides (HDPs) (3)
HDPs are also known as anti-microbial peptides
Cationic so disrupt bacterial membranes
Also made by macrophages and neutrophils during inflammation
Function of HDPs (2)
Protect host cells from proteases, recruit can promote inflammation
What are the three subsets of innate lymphoid cells (ILC) (3)
ILC1, ILC2, and ILC3
Where are ILCs found? (3)
Lack antigen specific receptors (No
BCR/TCR), but derive from the common lymphoid progenitor
Although found in the blood in low numbers, ILC are enriched in tissue
Have a tendency for expansion at barrier surfaces, including the gut, skin, and lung.
Where are ILC1 predominantly found ? (1)
ILC1 are found in the epithelial compartment
Where are ILC2 predominantly found? (1)
ILC2 are found in the lungs
Where are ILC3 predominantly found? (1)
ILC3 are found in the gut
What is commensal bacteria? (2)
Breakdown essential carbohydrates, produce vitamins
Protection from pathogenic bacteria
What are the different intestinal microbiota functions? (5)
Detoxification
Biosynthetic
Immune maturation
Metabolic
Protective
What is detoxification? (2)
During detoxification, ingested xenobiotics are metabolized into inert by-products that can pass harmlessly in the faeces
What are the biosynthetic functions? (2)
Involve the synthesis of biomolecules that are absorbed and utilized by the host
What is Immune maturation? (3)
Requires an intestinal microbiota:
The microbiota facilitates the formation of Peyer’s patches and isolated lymphoid follicles and increases the recruitment of lymphocytes to the lamina propria
What are the metabolic functions? (2)
Involve the fermentation of indigestible dietary fiber into energy-rich metabolites, such as short-chain fatty acids, which can be utilized by the host
What are the protective functions? (3)
Performed by excluding potential pathogens, both by competing for limited nutrients and by physically excluding them from the epithelial barrier surface, thus protecting the underlying mucosa
Examples of how specific commensal populations aid in digestion (3)
Bacteria encode enzymes that metabolise foods such as cellulose
Produce essential cofactors such a Vitamin K1
Anaerobic bacteria produce butyrate that serves as an energy source for the TCA cycle in colonocytes
How are commensal bacteria are good for immunity in the gut? (6)
Capsular polysaccharide A fromB. fragilisinduces an immune response primarily consisting of interleukin (IL)-10 expressing regulatory T cells in the intestine. This leads to protection from experimental colitis in mice.
The presence of microbes in the gut also elicits B-cell-mediated immunoglobulin A (IgA) responses. Colonization withB. thetaiotaomicrongenerates secretory IgA responses in the gut that coat the microbe and diminish host responses to its presence in the GI tract.
Effects of antibiotics (2)
Effective at killing pathogenic but also commensal bacteria —> dysbiosis. Clostridium difficile
What is oral tolerance? (3)
If subjected to an antigen through oral root
Less likely to produce an immune response at a systemic level to that antigen
Antigen specific
What kind of antigens can induce oral tolerance? (1)
Microbial antigen
What kind of antigens cannot induce oral tolerance? (1)
Soluble antigen
How does activation of Toll-like receptor signalling in intestinal epithelial cells do? (2)
Induces responses that modify intestinal crypt dynamics and IEC functions to increase the integrity of the epithelial barrier
What factors are important in the pathophysiology of diseases related to gut bacteria? (2)
Interactions between a host and its microbes
Presence or absence of specific bacteria
What factors affect Interactions between a host and its microbes? (3)
Genetics and the Environment
Antibiotic administration
Diet
How does genetics and the environment affect pathophysiology of diseases? (2)
Genes in both the host and bacteria dictate niche colonization, microbial behaviour within those niches, and host responses to microbes
How does antibiotic administration affect pathophysiology of diseases? (2)
Can have direct effects to kill gut bacteria or indirect effects that can lead to transient or permanent changes in the bacterial community composition
How does diet affect pathophysiology of diseases? (2)
One of the strongest environmental influences on bacterial community composition and behaviour.
Different gut microbiomes are found in animals or humans consuming high-fat, high-sugar Western-style diets vs. those consuming plant-based diets
What is celiac disease? (4)
Disease of upper small intestine.
Immune response to gluten
Loss of villi in small intestine, increase of crypts size.
Loss of mature villi, severe inflammation of the intestinal wall.
Test for celiac disease? (2)
Serum IgA antibodies against transglutaminase.
How does celiac disease occur? (3)
Inappropriate priming of CD4+ T cells that produce IFN-gamma, to alpha-gliadin (a component of gluten) via a transglutaminase that Q to glutaminic acid, and this peptide binds HLA-DQ2
Difference between small and large intestines (8)
Small intestines:
- Digestion/adsorption of
nutrients
- Large surface area,
approx.
- 6 metres
- Villi projections to optimise nutrient adsorption
Large intestines:
- Adsorption of water
and salt
- 1.5 metres
- no villi
- Commensal bacteria
Peyer’s patches and isolated lymphoid follicles (3)
Peyer’s patches - Develop at birth, increased size after birth, respond to bacteria early in life
ILFs - come later in life
Paneth cells (3)
Located at bottom
of crypts
Secrete defensins
Also work by cell membrane
disruption
Increased exposure to commensals leads to what? (2)
Increased numbers of conventional
lymphocytes
Conventionally predominate in adults but ratio amounts always vary in individuals
Intra-epithelial T cells (2)
Intra-epithelial T cells are highly motile, reflecting their surveillance function
What are ILC1? (6)
Have an important role in gut epithelium
Respond to APCs making pro-inflammatory cytokines
Differentiate into TH1 or ILC1
Make cytokines, interferon gamma and TNF alpha
Activate immune system
Express and derive expression of T-bet
What is T-bet? (1)
The signature transcription factor of ILC1s and TH1 cells and is required for their generation
What are ILC2? (6)
Play a major role in defense against helminths and parasites
Respond to APCs making IL1-beta and IL-23
Produce cytokines, IL-17, IL-22, GM-CSF and lymphotoxin
These cytokines lead to
the recruitment of phagocytes, such as neutrophils, that clear the microbes, and also induce the production of antimicrobial proteins (AMPs) by epithelial cells and stromal cells
RORγt is the signature transcription factor
What is ROR gamma t (2)
The signature transcription factor
Required for the generation of ILC3s and TH17 cells, and its expression defines these cells
What are ILC3 (5)
To do with innate defence against worms
Respond to signals making IL-25 and IL-33
Producing IL-25, IL-33, or thymic stromal lymphopoietin (TSLP), which then promote the differentiation of ILC2s and TH2 cells, which produce IL-4, IL-5, and IL-13
These effector cytokines lead to vasodilation, the production of mucus and deposition of collagen, which are all involved
in the construction of a barrier against large parasites
Gata3 is the signature transcription factor
What is gata 3? (2)
Signature transcription factor
Required for the development of ILC2s and TH2 cells, and high expression of Gata3 defines these cells
Which ILC is involved in the immune-mediated inflammatory disease (IMIDs) asthma? (1)
ILC2
How is ILC2 involved in asthma? (4)
ILC2 contribute to disease by promoting recruitment, survival, and activation of eosinophils (IL-5/IL-13), augmenting mast cell degranulation and supporting immunoglobulin class
switching to proallergic IgE antibodies
IL-13 derived from ILC2 also promote production of the chemokine CCL17,
which recruits allergen-reactive TH2 T cells
Which ILC is involved in the immune-mediated inflammatory disease (IMIDs) psoriasis? (1)
ILC3
How is ILC3 involved in psoriasis? (2)
ILC3 act in conjunction with TH17 cells to promote neutrophil recruitment and hyper proliferation of skin epithelial cells
Which ILC is involved in the immune-mediated inflammatory disease (IMIDs) IBD ? (1)
ILC2
How is ILC3 involved in IBD? (3)
ILC1 may perform a similar
role to TH1 T cell
Activated by IL-12, they support
mononuclear phagocyte recruitment/activation, including
production of proinflammatory cytokines (e.g., TNF) and
tissue damaging enzymes, such as matrix
metalloproteinases (MMPs)
ILC3 may share pro-inflammatory activity with
TH17 cells, including production of IL17 and IL22, which in
turn promotes recruitment and activation of neutrophils
What kind of immunity can gluten stimulate? (2)
Stimulate both innate and adaptive
immunity
