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Intro to immunology > Mucosal Immunity > Flashcards

Mucosal Immunity Flashcards

1
Q

What is the mucosa? (2)

A

Is the cellular lining of the body

Forms the barrier between the external and internal

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2
Q

What is the function of mucosal immunity? (2)

A

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

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3
Q

What are epithelia cells? (1)

A

Define the border between the environment and ourselves

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4
Q

What are the different types of epithelial barriers? (3)

A

Typified by the intestinal, respiratory and urogenital mucosa

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5
Q

Function of epithelial barriers (2)

A

Able to distinguish between outside world whilst also selectively transporting significant quantities of nutrients ions and water essential for life both locally and systemically

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6
Q

Immunity at the epithelium is supplemented by what and where is it found? (3)

A

Mucus
Produced by goblet cells interspersed between epithelium and antimicrobial peptides.

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7
Q

Role of epithelial cells (5)

A

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.

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8
Q

Which components of the innate and adaptive immune response do epithelial cells direct? (4)

A

Barrier function
The processing and presentation of antigens
The expression of MHC and costimulatory molecules
The secretion of antimicrobial peptides.

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9
Q

What are Mucosa-Associated Lymphoid Tissue (MALT) (2)

A

MALT is an Umbrella term for organised lymphoid tissue at mucosal surfaces.

Feature of all MALT are the absence of classical lymphatic structures

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10
Q

How is MALT similar/different to lymphatic tissues at other sites? (2)

A

MALT is similar to draining lymphatic tissue at the other sites however it has direct contact with the overlaying epithelium.

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11
Q

Name the three different regions of MALT? (3)

A

Gut associated lymphoid tissue - GALT
Bronchus-associated lymphoid tissue (BALT)
Nasal-associated lymphoid tissue (NALT)

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12
Q

What elicits the B-cell-mediated immunoglobulin A (IgA) response? (1)

A

The presence of microbes in the gut

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13
Q

Describe the B-cell-mediated immunoglobulin A (IgA) response (3)

A

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

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14
Q

Role of secretory IgA (3)

A

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

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15
Q

What happens in the intestinal lamina propria (2)

A

Immune cells enter the bloodstream and undergo terminal differentiation in the intestinal lamina propria

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16
Q

What is the mucosal immune system divided into? (2)

A

Divided into distinct inductive sites and effector sites.

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17
Q

What are inductive sites? (2)

A

These are the organized MALT structures together with mucosa-draining lymph nodes.

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18
Q

What are effector sites? (2)

A

These are the mucosal epithelia and the underlying lamina propria, which contains stromal cells and associated connective tissue stroma.

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19
Q

What are Microfold cells (M cells) ? (3)

A

Called by specialised epithelial cells
Transportintactbacteria, abiotic particulates, and soluble antigens within vacuoles across their cell bodies
Transcytosis

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20
Q

What is the intestinal epithelial barrier (2)

A

Not a classical barrier but does inhibit bacteria from entering tissue

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21
Q

What are isolated lymphoid follicles? (5)

A

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

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22
Q

Why are Peyer’s patches and isolated lymphoid follicles called inductive sites? (1)

A

Because they are directly involved with antigen recognition

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23
Q

Mesenteric lymph nodes and Peyers Patches difference (2)

A

Mesenteric lymph nodes and Peyers Patches differentiate independently of the ILF and differences between them are imprinted early in life

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24
Q

What are host defence peptides (HDPs) (3)

A

HDPs are also known as anti-microbial peptides
Cationic so disrupt bacterial membranes
Also made by macrophages and neutrophils during inflammation

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25
Function of HDPs (2)
Protect host cells from proteases, recruit can promote inflammation
26
What are the three subsets of innate lymphoid cells (ILC) (3)
ILC1, ILC2, and ILC3
27
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.
28
Where are ILC1 predominantly found ? (1)
ILC1 are found in the epithelial compartment
29
Where are ILC2 predominantly found? (1)
ILC2 are found in the lungs
30
Where are ILC3 predominantly found? (1)
ILC3 are found in the gut
31
What is commensal bacteria? (2)
Breakdown essential carbohydrates, produce vitamins Protection from pathogenic bacteria
32
What are the different intestinal microbiota functions? (5)
Detoxification Biosynthetic Immune maturation Metabolic Protective
33
What is detoxification? (2)
During detoxification, ingested xenobiotics are metabolized into inert by-products that can pass harmlessly in the faeces
34
What are the biosynthetic functions? (2)
Involve the synthesis of biomolecules that are absorbed and utilized by the host
35
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
36
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
37
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
38
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
39
How are commensal bacteria are good for immunity in the gut? (6)
Capsular polysaccharide A from B. fragilis induces 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 with B. thetaiotaomicron generates secretory IgA responses in the gut that coat the microbe and diminish host responses to its presence in the GI tract.
40
Effects of antibiotics (2)
Effective at killing pathogenic but also commensal bacteria ---> dysbiosis. Clostridium difficile
41
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
42
What kind of antigens can induce oral tolerance? (1)
Microbial antigen
43
What kind of antigens cannot induce oral tolerance? (1)
Soluble antigen
44
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
45
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
46
What factors affect Interactions between a host and its microbes? (3)
Genetics and the Environment Antibiotic administration Diet
47
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
48
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
49
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
50
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.
51
Test for celiac disease? (2)
Serum IgA antibodies against transglutaminase.
52
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
53
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
54
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
55
Paneth cells (3)
Located at bottom of crypts Secrete defensins Also work by cell membrane disruption
56
Increased exposure to commensals leads to what? (2)
Increased numbers of conventional lymphocytes Conventionally predominate in adults but ratio amounts always vary in individuals
57
Intra-epithelial T cells (2)
Intra-epithelial T cells are highly motile, reflecting their surveillance function
58
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
59
What is T-bet? (1)
The signature transcription factor of ILC1s and TH1 cells and is required for their generation
60
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
61
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
62
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
63
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
64
Which ILC is involved in the immune-mediated inflammatory disease (IMIDs) asthma? (1)
ILC2
65
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
66
Which ILC is involved in the immune-mediated inflammatory disease (IMIDs) psoriasis? (1)
ILC3
67
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
68
Which ILC is involved in the immune-mediated inflammatory disease (IMIDs) IBD ? (1)
ILC2
69
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
70
What kind of immunity can gluten stimulate? (2)
Stimulate both innate and adaptive immunity

Intro to immunology (13 decks)

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