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MIC3046 Microbiota and Pathogens > Lecture A2 - The Mucosal Immune System > Flashcards

Lecture A2 - The Mucosal Immune System Flashcards

1
Q

What are the two integrated arms of the mucosal immune system?

A

Mucosal innate immune system.
Mucosal adaptive immune system.

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2
Q

What are the 3 main cells of the mucosal innate immune system?

A

Epithelial cells that line the mucosal surfaces.
Innate immune cells dispersed within the mucosa.
Innate lymphoid cells and their effector modules.

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3
Q

What are the 2 main sites of the mucosal adaptive immune system?

A

Inductive sites - antigen capture and presentation to naive B and T cells.
Effector sites - effector lymphocytes migrate to carry their functions.

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4
Q

Describe epithelial cells.

A

Highly polarised.
Distinct inner and outer surfaces.

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5
Q

What are the outer surfaces of epithelial cells made up of?

A

Apical membranes that face the air or a fluid filled organ cavities.
May have cilia or be highly folded forming microvilli.

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6
Q

What are the inner surfaces of epithelial cells made up of?

A

Basolateral membranes.
Lateral membranes mediate cell-cell interactions between epithelial cells and the basal membranes rest on an extracellular matrix called the basal lamina.

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7
Q

What are the 3 main fates of endocytosis?

A

Recycling
Degradation via a lysosome
Transcytosis

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8
Q

What is transcytosis?

A

A central aspect of transport of cells across the membrane.

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9
Q

When do neutrophils turn up?

A

Not resident cells, they only turn up on mucosal surfaces if there is something going on that requires their presence.

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10
Q

Where are systemic and mucosal immunocytes all derived from?

A

Pluripotent hematopoietic stem cells from the bone marrow.

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11
Q

What are the 3 mucosal associated lymphoid tissues?

A

NALT - nasopharynx respiratory and digestive tract.
BALT - respiratory tract.
GALT - gut, digestive tract (most complex).

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12
Q

What are some innate immunocytes?

A

NK cell
ILC
Immature and mature dendritic cells
Neutrophil
Eosinophil
Basophil
Mast cell
Macrophage

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13
Q

What are some adaptive immunocytes?

A

B cell
T cell
Plasma cell

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14
Q

What are the resident cells of the GALT?

A

Goblet cells
Dendritic cells

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15
Q

What are the anatomical features of the mucosal immune system?

A

Intimate interactions between mucosal epithelia and lymphoid tissues.
Discrete compartments of diffuse lymphoid tissue and more organised structures such as Peyer’s patches, isolated lymphoid follicles and tonsils.
Specialised antigen-uptake mechanisms.

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16
Q

What are the effector mechanisms of the mucosal immune system?

A

Activated/memory T cells predominate even in the absence of infection.
Multiple activated natural effector/regulatory T cells present.
Secretory IgA antibodies.
Presence of distinctive microbiota.

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17
Q

What is different about macrophages that reside on mucosal surfaces?

A

They are not pro-inflammatory.
In IBD there are more macrophages that are pro-inflammatory, leading to the disease.

18
Q

What do ILCs lack?

A

Specific antigen receptors.

19
Q

Where do ILCs populate?

A

Lymphoid tissues
Peripheral organs

20
Q

What can ILCs be stimulated by?

A

Cytokines
Microbes and nutrients

21
Q

What is the inducing cytokine of NK cells and ILC1 and what are the effector modules produced?

A

IL-12
NK cells effectors = IFN-gamma, perforin and granzyme
ILC1 effectors = IFN-gamma

22
Q

What are the inducing cytokines of ILC2 and what are the effector modules produced?

A

IL-25, IL-33, TSLP
Effectors = IL-5, IL-13

23
Q

What is the inducing cytokine of ILC3 and what are the effector modules produced?

A

IL-23
IL-22 and IL-17

24
Q

What are the functions of the ILCs?

A

ILC1 = immunity and defence against viruses and intracellular pathogens.
ILC2 = expulsion of extracellular parasites.
ILC3 = immunity to extracellular bacteria and fungi.

25
Q

What are mucosal inductive sites?

A

Where antigens are sampled and processed and then presented to naive B and T cells that then become activated.

26
Q

What are Peyer’s patches?

A

Lymph nodes that contain T cells, B cells, macrophages and dendritic cells.

27
Q

What are M cells and what can they do?

A

Distinct cells in the presence of a Peyer’s patch.
Can sample material from antigens and then present it to dendritic cells within the membrane. It then migrates and a specific homing programme make sure it goes back to where it came from.

28
Q

What is the problem for antigen sampling and immunoglobulin response in mucosa?

A

There is a physical barrier between the mucosal antigens and the immune effector cells/molecules.

29
Q

What is the solution to antigen sampling and immunoglobulin response in mucosa?

A

Antigens can be sampled by specialised cells.
IgA and IgM are transcytosed into the lumen of mucosa where they contribute to pathogen/toxins elimination.

30
Q

What is the aim of the cellular response in mucosa?

A

Directly kill infected cells.

31
Q

What is the role of the intraepithelial lymphocytes (IEL)?

A

Within the epithelium there are cells sitting beside the epithelial cells that have been primed against a specific antigen.
If a cell has been infected it can recognise it as being infected and will mediate the killing either directly because of the route 1 or because it triggers the specific adaptive immune response.
These cells are important against infection but also in maintaining the epithelium.

32
Q

What disease has an abnormal number of IEL cells?

A

Celiac disease.

33
Q

What are the 2 key antibodies specific to the gut?

A

IgM and IgA.

34
Q

Describe the polymeric immunoglobulin receptor?

A

Transports polymeric IgA and IgM.
From basolateral to apical membranes - unidirectional.
It is expressed by epithelial cells at mucosal surfaces.

35
Q

Describe the neonatal FcRn receptor.

A

Transports monomeric IgG.
From both basolateral to apical and apical to basolateral membranes - bidirectional.
It is expressed by numerous cells.

36
Q

What is some of the mucosal SIgA functions at mucosal surfaces?

A

Neutralising antigens in the lumen.
Potentially bind to a toxin, so the toxin won’t end up damaging the cells.
Bind to the microorganisms themselves so they will get trapped in the mucus.
Catch the antigen in the vesicles to be trafficked.
Remove the toxin through transcytosis.
Anti-inflammatory properties.

37
Q

What is fab or glycan dependent binding for?

A

Contributes at keeping the microbiota at bay.
Not specific so can bind to a broader range of organisms.
Can bind to microorganisms via the sugars - N or O glycans means these antibodies have both adaptive and innate function.

38
Q

Describe the expression of SIgA1 and SIgA2 across human mucosa.

A

IgA1 is predominant in all but one mucosa.
IgA2 is more highly proportioned in the colon.

39
Q

What is the structural difference between SIgA1 and SIgA2?

A

They possess different glycans.
SIgA1 - O-glycans and N-glycans
SIgA2 - just N-glycans
Longer hinge region in IgA so more effective at cross-linking because of the longer hinge region.

40
Q
A

MIC3046 Microbiota and Pathogens (20 decks)

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