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204: The immune system > Mucosal immunology > Flashcards

Mucosal immunology Flashcards

1
Q

MALT

A

Mucosa-associated lymphatic tissue

Divided into BALT and GALT

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2
Q

BALT

A

Bronchial associated lymphatic tissue

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3
Q

GALT

A

Gut associated lymphatic tissue

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4
Q

Why os the mucosal immune system very important?

A

The biggest immune compartment of the organism

Estimated surfaces area of 400m2, harbours 60% of all effector cells

In direct contact with the outside environment

Continuous antigen stimulation (food, endogenonus flora, pathogens)

Mucosal sites are the ports of entry for many infections and an important target site of vaccine induced protection

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5
Q

The main defence strategies of intestinal mucosa and oropharynx

A

Endogenous flora

Epithelium and mucus

Regionalised immune system and gut homing of B and T cells

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6
Q

Endogenous flora

A

10^14 bacteria

Hundreds of different species

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7
Q

Epithelium and mucus

A

Mechanical barriers (cells, tight junctions)

Specialised epithelial cells (goblet cells, absorptive epithelial cells, M cells, paneth cells)

Antimicrobial substances (defensins, lysozymes, lactoferrin, phospholipases)

Mucins (extgensively glycosylated proteins) form a viscous barrier

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8
Q

Regionalised immune system and gut homing of B and T cells

A

Wadeyer’s ring (linguinal and palatine tonsils, nasopharyngeal tonsils)

Peyer’s patches

Mesenteric lymph nodes

Intraepithelial immune cells

Lamina proporia immune cells, including sampling DCs

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9
Q

The main defence strategies of intestinal mucosa and oropharynx

A

Lymphoid complexes along the GI tract

Volume of the rings indicates the relative amount of lymphoid tissue

The largest amount of lymphoid tissue is found in the oropharynx and terminal ileum

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10
Q

Intestinal epithelial cells

A

Specialised epithelial cells have a number of functions improving defence but not inflammation

Goblet cells
Epithelial cells
M cells
Paneth cells

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11
Q

Goblet cells

A

Produce mucus

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12
Q

Epithelial cells

A

Express TLRs

TLR5 expressed on the basolateral surface and intracytoplasmic NLR for bacterial flagellins are activated only upon access of bacteria to the cytosol

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13
Q

M cells

A

Transport antigens to subepithelial lymphoid structures

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14
Q

Paneth cells

A

Produce human defensin precursor, HD6 precursor, trypsin

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15
Q

Is it a good thing that ligation of TLRs on the basolateral surface of gut epithelial cells does not promote inflammation?

A

If it did the entire gut would be inflamed

If it was inflamed it would not be able to absorb nutrients as well

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16
Q

Peyer’s patches and associated immune cells

A

PPs contain germinal centres for B and T cells

They are located in the distal ileum in areas of follicle associated epithelium

The foetal human small intestine contains on average 60 PPs before week 30 of gestation and their number steadily increases reaching a maximum of about 240 at puberty

Inductive site for immune response

17
Q

Architecture of Peyer’s patches

A

There are three main domains

  • the follicular area
  • the interfollicular area
  • follicle associated epithelium
18
Q

Follicular and interfollicular areas

A

Lymphoid follicles with a germinal center containing proliferating B lymphocytes, follicular dendritic cells and macrophages

The follicle is surrounded by the corona, or subepithelial dome, containing mixed cells including B cells and T cells, macrophages and dendritic cells

19
Q

The FAE

A

Differes from normal epithelium in regards to microvilli regularity and length, and the presence of infiltrating immune cells

20
Q

Naive lymphocytes

A

Immigrate into the PP via specialised high endothelial venules

Naive or activated lymphocytes leave the PP via efferent lymphatic vessels at the serosal side of the PPd

21
Q

M cells features

A

Small microvilli

Large cell membrane fenestrations
- features enhance antigen uptake from epithelium

Trans-cellular transport of antigen

Exocytosis at the basolateral membrane

Delivery to dendritic cells in dome region of underlying lymphatic structures

22
Q

Mesenteric lymph nodes

A

Located at the base of the mesentery and collect lymph, cells and antigens from the intestinal mucosa

Main site for oral tolerance induction

MLN drain lymph from intestinal mucosa

Many food antigens will bypass lymphatic tissue and reach the liver through the portal vein

23
Q

Immune cells in liver sinuses

A

Have an important function in protecting us from microbes/ microbial products in the portal vein

24
Q

Lamina proporia and intraepitheial lymphocyte comprtment

A

IEL are situated in the basolateral part of the epithelium

Irregular shape

Long extensions in close contact with neighbouring epithelial cells

Occur in variable numbers along the gut

Up to 12% eosinophils in IEL preparations

25
Q

IEL in the small intestine

A

Majority comproised of TCRalphabeta and CD8alphaalpha

Proportion increases in the distal region and may reach as much as 30% of the total IEL population in that area of the colon

26
Q

Intraepithelial cells subdivided into 3 main groups

A

TCRalphabeta and CD8alphabeta

TCRalphabeta and CD4alphabeta

TCRalphabeta and CD8alphaalpha

27
Q

MIC-A and MIC-B

A

Ligands for the NK cell activating receptor NKG2D

Also found on CD8alphaalpha T cells

28
Q

Thymus leukaemia antigen

A

An MHC-lb molecule that does not enable peptide binding

29
Q

Mucosal T cells

A

Differentiation influenced by epithelial cells and DCs

T regulatory cells produce IL-10 and are crucial in establishing and maintaining food tolerance and class switch, including TGF-B and others

Th1 cells produce IFN-y and are important in killing virally infected epithelial cells

Th2 cells may be induced by worm infection

30
Q

Dendritic cells

A

Sit in the lamina propria

Have long extensions reaching through the epithelium to sample contents of the intestinal tube

Such antigens are presented to the T cells

31
Q

Mucosal B cells and IgA

A

Secretory component binds to J chain and enable trans-endothelial transport of dimeric IgA

SIgA exerts cross reactive innate like and infection or vaccine induced protection against epithelial invasion

pigA and pigM exert non-inflammatory effects inside and below the epithelium

SIgA antibodies play no protective role following invasion of infectious agents

32
Q

IgA

A

Main antibody in secretions

Against food antigens provides immune exlusion

Activates the complement system only weakly

Secretions of IgA (coupled to J chain) depends on a trans-cellular transport mechanism

33
Q

B and T cell homing

A

Activated T cells and circulating memory cells exit the lymph node via efferent lymphatics and return to circulation through thoracic duct

Reach target tissues via blood stream

Different combinations of homing receptors guide effector cells to different tissues

At tissue sites, upregulation of respective ligand moecules will be related to the situation in these tissues

34
Q

T cells migrate through circulation

A

Intergrin and chemokine signals direct their emigration into tissues

Imprinted T cells have specific ket that allows access to restricted tissues under normal homeostatic conditions

204: The immune system (19 decks)

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