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Module 204, Theme 1: Immunology > Mucosal immunology > Flashcards

Mucosal immunology Flashcards

1
Q

MALT

A

Mucos-associated lymphatic tissue

Includes

  • BALT- bronchial
  • GALT- gut-associated
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2
Q

Importance of mucosal immune system

A

Largest immune compartment
- 60% of all effector cells

In direct contact with outside environment
- Ports of entry for many infections

Constantly stimulated by antigens

Target site for vaccine-induced protection

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3
Q

Main defence strategies of intestinal mucosa & oropharynx

A

Endogenous flora

Epithelium and mucus

Regionalised immune system

Gut homing of B and T cells

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4
Q

Endogenous flora of intestinal mucosa & oropharynx

A

10^14 bacteria of hundreds of species in the body
- Compete with pathogenic bacteria/ organisms

Commensal gut flora induces low affinity IgA responses.
- Food specific responses

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5
Q

Features of the epithelium and mucus that provides immunological defence

A

Tight junctions in epithelial cells

Specialised cells

  • Goblet
  • M cells
  • Paneth cells
  • Absorptive epithelial cells

Antimicrobial substances

Mucins
- viscous barrier

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6
Q

Regionalised immune system

A

Waldeyer’s tonsillar ring
- Lymphoid tissue in the pharynx

Peyer’s patch
- Small intestines

Mesenteric lymph nodes

Intrapethelial immune cells

Lamina propria immune cells

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7
Q

Lymphoid complexes in the GIT [5]

A

Waldeyer’s ring
- one of the largest

Gastric antrum tissue

Patches in the small bowel (payer’s)

Terminal ileum lyhoid tissue
- One of the largest

Large bowel patchers

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8
Q

Goblet cells

A

Provides a physics-chemical barrier by producing mucus

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9
Q

Innate immune receptors and epithelial cells

A

Express TLR depending on the region

  • 2, 4-7, 9.
  • Undergoes surface TLR ligation

TLR5
- Basolateral surface (in contact with invading bacteria)

NLR

  • Intracytoplasm
  • Recognises flagellants
  • In contact with bacteria in the cytosol
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10
Q

Surface TLR ligation

A

Mechanism of the intestinal epithelial cells.

Causes:

  • Tightening of epithelial junctions
  • Increase of proliferation and motility

NOT inflammation

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11
Q

M cells

A

Specialised epithelial cells

Transports antigens transcellulary to sub epithelial lymphoid structures.
- Exocytosis at basolater membrane
- Delivers dendritic cells to lymphatic structures
Structure
- Small microvilli
- Large cell membrane fenestrations

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12
Q

Paneth cells

A

Specialised epithelial cells

Produces antimicrobial peptides

  • Human defensive 5 precursor
  • HD6
  • Trypin (activates HD5, HD6)
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13
Q

Peyer’s patch

A

Lymphoid tissue in small intestines.
- Distal ileum, follicle associated epithelium (FAE)

Contains 3 domains

  • Follicular
  • Interfollicular
  • FAE

Site where immune responses are induced
- Has B and T cell germinal centres

Connected to circulation via endothelial venlues (where naive lymphocytes migrate in) and lymph vessels (where the lymphocytes exit out)

240 patches by puberty (60 in fetus)

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14
Q

Follicular and interfollcular areas of payer’s patch

A

Germinal centre containing;

  • B-lymphocytes
  • Follicular dendritic cels
  • Macrophages

Surrounded by corona/ sub epithelial cells, containing cells above.

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15
Q

FAE

A

Follicle associated epithelium

Different microvilli regularity and length compared to normal epithelium

Contains infiltrating immune cells

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16
Q

Mesenteric lymph nodes

A

Collects lymph, cells and antigens from intestinal mucosa.
- Main site for oral tolerance induction

Although many food antigens bypass intestines and enter liver.

17
Q

Mucosal IgA

A

Main antibody in secretions
- When coupled to J chain, depends on trans-cellular transport

Those secreted against food antigens= immune exclusion

Activates the complement system

18
Q

T-cell dependent IgA class switching in the gut

A

T-cell dependent:
- Dendritic cells in sub-epithelial zone take up bacterial antigens—> present to Cd4 after migrating to inter follicular zone

  • Activated helper cell stimulates IgM/IgD B cells–> class switch (via CD40L, TGF-B)
  • Ig A class switch stimulated by NO production from DCs
19
Q

T-cell independent IgA class switching in the gut

A

TLR ligand sections activate DCs.

DCs activate IgM/IgD B cell class switch to IgA via inducing TGF-Beta.

20
Q

Th17 cells in the gut

A

Produces IL-17, IL-22.

- Regulate the production of musicians and defensins

21
Q

Th2 T cells in the gut

A

Secrets IL-4, IL-13

  • Can be induced by worm infection
  • Increases fluid, mucus secretions
  • Increases bowel motility + smooth muscle contraction
22
Q

Th1 T cells in the gut

A

Produces IFN-g

- kills virally infected epithelial cells

23
Q

Treg cells in the gut

A

Establishes and maintains food tolerance
- Secretes IL-10

also stimulates class switch via TGF-b

24
Q

Dendritic cells in the gut

A

Located in the lamina propia.

Present antigen to T and B cells to stimulate class switching

Produces IL-16, retinal acid

25
Q

Coeliac disease

  • mechanism
  • Pathology
  • Genetics
A

DCs present gluten peptides (made from transgluatminase 2)

  • Activates CD4 T cells
  • Recognised by antibodies

B cells with Ab specific to the peptides are activated by CD4 Th1 cells
- Ab are secreted (Anti-tTG ab used in diagnostics)

CD8 cells are activated and attack epithelial cells (NK-like transformation)

Pathology= villous atrophy

Genetics

  • HLA DQ2
  • HLA DQ8
26
Q

Gut homing of B and T cells

A

DCs in GALT are induced by thymus stromal lymphopoietin (TSLP)
- Espresses retinaldehyde dehydrogenase (RALDH)–> converts Vit A to retinoic acid

Activated B and T cells in GALT are exposed to retinoic acids
- Induces the expression of receptors: CCR9, integrin alpha-4-B7

Effector B and T cells enter back into gut lamina propia via chemokine and adhesion molecules displayed on lamina propia and venular endothelial cells

  • CCL25–> CCR9
  • MadCAM–> alpha-4-B7
27
Q

Interepithelial lymphocytes

A

Mainly alpha/beta T cells

  • Treg
  • Th1
  • Th2
  • Th17

Required for anti-inflammatory responses to allow nutrient absorption

Module 204, Theme 1: Immunology (22 decks)

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