Mucosal Immunology 2

Question 1

What is the mesentery?

Answer 1

Mesentery: double fold of peritoneum that attaches the gut to the posterior abdominal wall. - since 2021 has been considered an organ in it’s own right

Question 2

Mesenteric lymph nodes are located at the … of the mesentery and collect lymph, cells and antigens from the intestinal …

Answer 2

Mesenteric lymph nodes are located at the base of the mesentery and collect lymph, cells and antigens from the intestinal mucosa.

Question 3

What is the main site for oral tolerance induction?

Answer 3

mesenteric lymph nodes

Question 4

What is oral tolerance?

Answer 4

avoidance of an immune response to foodstuffs (and other matter).

Question 5

Oral tolerance induction as a … option in allergy

Answer 5

Oral tolerance induction as a therapeutic option in allergy

Question 6

Oral tolerance induction as a therapeutic option in …

Answer 6

Oral tolerance induction as a therapeutic option in allergy

Question 7

Mesenteric Lymph Nodes (MLN): overview (2)

• Location of mesenteric lymph nodes in relation to small intestine
• What is the main function of the SI?

Answer 7

Main function - complete digestion of food and absorb nutrients.

Question 8

Mesenteric Lymph Nodes (MLN): overview (3)​

• Location of mesenteric lymph nodes in relation to large intestine
• What is the main role of the colon? (Large intestine?)

Answer 8

• absorbing water and electrolytes, producing and absorbing vitamins, and forming and propelling faeces toward the rectum for elimination

Question 9

Mesenteric Lymph Nodes (MLN): traffic (4)

• MLN drain lymph from intestinal …
• Naïve B-cells and T-cells arriving via … endothelial … will travel from Peyer’s patches (induction sites) via MLN to the thoracic duct and blood stream
• They will return to effector sites in the gut (‘homing’)

Answer 9

• MLN drain lymph from intestinal mucosa
• Naïve B-cells and T-cells arriving via high endothelial venules will travel from Peyer’s patches (induction sites) via MLN to the thoracic duct and blood stream
• They will return to effector sites in the gut (‘homing’)

Question 10

Mesenteric Lymph Nodes (MLN): traffic (4)

• MLN drain lymph from intestinal mucosa
• Naïve B-cells and T-cells arriving via high endothelial venules will travel from … patches (induction sites) via MLN to the thoracic duct and blood stream
• They will return to … sites in the gut (‘homing’)

Answer 10

• MLN drain lymph from intestinal mucosa
• Naïve B-cells and T-cells arriving via high endothelial venules will travel from Peyer’s patches (induction sites) via MLN to the thoracic duct and blood stream
• They will return to effector sites in the gut (‘homing’)

Question 11

Mesenteric Lymph Nodes (MLN): traffic (4)

• MLN drain lymph from intestinal mucosa
• Naïve B-cells and T-cells arriving via high endothelial venules will travel from Peyer’s patches (induction sites) via MLN to the thoracic duct and blood stream
• They will return to effector sites in the gut (‘…’)

Answer 11

• MLN drain lymph from intestinal mucosa
• Naïve B-cells and T-cells arriving via high endothelial venules will travel from Peyer’s patches (induction sites) via MLN to the thoracic duct and blood stream
• They will return to effector sites in the gut (‘homing’)

Question 12

Mesenteric Lymph Nodes (MLN): traffic (5)

• Food antigens (in particular …) will pass through lymph but also reach the … through capillaries and ultimately the portal vein.
• Immune cells in liver sinuses have an important function in maintaining food tolerance and in protecting us from microbes/microbial products in the portal vein (e.g. LPS)
• Whereas the main ‘program’ in the gut is tolerance induction, in some instances, protective immune responses are … (along with inflammation).

Answer 12

• Food antigens (in particular fats) will pass through lymph but also reach the liver through capillaries and ultimately the portal vein.
• Immune cells in liver sinuses have an important function in maintaining food tolerance and in protecting us from microbes/microbial products in the portal vein (e.g. LPS)
• Whereas the main ‘program’ in the gut is tolerance induction, in some instances, protective immune responses are raised (along with inflammation).

Question 13

Mesenteric Lymph Nodes (MLN): traffic (5)

• Food antigens (in particular fats) will pass through lymph but also reach the liver through capillaries and ultimately the … …
• Immune cells in liver sinuses have an important function in maintaining food tolerance and in protecting us from microbes/microbial products in the … … (e.g. LPS)
• Whereas the main ‘program’ in the gut is tolerance induction, in some instances, protective immune responses are raised (along with inflammation).

Answer 13

• Food antigens (in particular fats) will pass through lymph but also reach the liver through capillaries and ultimately the portal vein.
• Immune cells in liver sinuses have an important function in maintaining food tolerance and in protecting us from microbes/microbial products in the portal vein (e.g. LPS)
• Whereas the main ‘program’ in the gut is tolerance induction, in some instances, protective immune responses are raised (along with inflammation).

Question 14

Lamina propria and intraepithelial lymphocyte compartment (1)

• Intraepithelial lymphocytes (IEL) are situated in the … portion of the epithelium.
• Features of IEL include:
  
  • … shape
  • Long extensions in close contact with neighboring epithelial cells
  • Occurrence in variable numbers along the gut
  • Mixed with Eosinophils (up to 12% in intraepithelial cell preparations) ​

Answer 14

• Intraepithelial lymphocytes (IEL) are situated in the basolateral portion of the epithelium.
• Features of IEL include:
  
  • Irregular shape
  • Long extensions in close contact with neighboring epithelial cells
  • Occurrence in variable numbers along the gut
  • Mixed with Eosinophils (up to 12% in intraepithelial cell preparations) ​

Question 15

Lamina propria and intraepithelial lymphocyte compartment (1)

• Intraepithelial lymphocytes (IEL) are situated in the basolateral portion of the epithelium.
• Features of IEL include:
  
  • Irregular shape
  • Long … in close contact with neighboring epithelial cells
  • Occurrence in … numbers along the gut
  • Mixed with Eosinophils (up to 12% in intraepithelial cell preparations) ​

Answer 15

• Intraepithelial lymphocytes (IEL) are situated in the basolateral portion of the epithelium.
• Features of IEL include:
  
  • Irregular shape
  • Long extensions in close contact with neighboring epithelial cells
  • Occurrence in variable numbers along the gut
  • Mixed with Eosinophils (up to 12% in intraepithelial cell preparations) ​

Question 16

Lamina propria and intraepithelial lymphocyte compartment (1)

• Intraepithelial lymphocytes (IEL) are situated in the … portion of the epithelium.
• Features of IEL include:
  
  • Irregular shape
  • Long extensions in close contact with neighboring epithelial cells
  • Occurrence in variable numbers along the gut
  • Mixed with … (up to 12% in intraepithelial cell preparations) ​

Answer 16

• Intraepithelial lymphocytes (IEL) are situated in the basolateral portion of the epithelium.
• Features of IEL include:
  
  • Irregular shape
  • Long extensions in close contact with neighboring epithelial cells
  • Occurrence in variable numbers along the gut
  • Mixed with Eosinophils (up to 12% in intraepithelial cell preparations) ​

Question 17

Lamina propria and intraepithelial lymphocyte compartment (2)

• Intraepithelial Lymphocytes (IEL) can be subdivided into several groups
  
  • …-… … T-cells
    
    • TCRab+CD8ab+
    • TCRab+ CD8aa+
    • TCRab+CD4
  • Innate-like and innate lymphocytes including
    
    • mucosa-associated invariant T-cells cells (MAIT) ,
    • invariant
    • NK-T-cells,
    • g/d T-cells,
    • NK-cells

Answer 17

• Intraepithelial Lymphocytes (IEL) can be subdivided into several groups
  
  • Tissue-resident memory T-cells
    
    • TCRab+CD8ab+
    • TCRab+ CD8aa+
    • TCRab+CD4
  • Innate-like and innate lymphocytes including
    
    • mucosa-associated invariant T-cells cells (MAIT) ,
    • invariant
    • NK-T-cells,
    • g/d T-cells,
    • NK-cells

Question 18

Lamina propria and intraepithelial lymphocyte compartment (2)

• Intraepithelial Lymphocytes (IEL) can be subdivided into several groups
  
  • Tissue-resident memory T-cells
    
    • TCRab+CD8ab+
    • TCRab+ CD8aa+
    • TCRab+CD4
  • …-like and … lymphocytes including
    
    • mucosa-associated invariant T-cells cells (MAIT) ,
    • invariant
    • NK-T-cells,
    • g/d T-cells,
    • NK-cells

Answer 18

• Intraepithelial Lymphocytes (IEL) can be subdivided into several groups
  
  • Tissue-resident memory T-cells
    
    • TCRab+CD8ab+
    • TCRab+ CD8aa+
    • TCRab+CD4
  • Innate-like and innate lymphocytes including
    
    • mucosa-associated invariant T-cells cells (MAIT) ,
    • invariant
    • NK-T-cells,
    • g/d T-cells,
    • NK-cells

Question 19

Lamina propria and intraepithelial lymphocyte compartment (3)

• There are also NK cells in the gut, they carry NK-cell receptors
• Apart from NK-cells some T-cells carry NK-cell receptors such as NKG2D, for example TCRab+ CD8aa+ (NKG2D=natural killer group 2D receptor).
• NKG2D can bind to stress receptors expressed on damaged gut epithelial cells, MIC-A, or MIC-B (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.
• … expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)
• Intraepithelial … T-cells produce IFN-g and are important in killing infected epithelial cells (for example those infected with viruses).

Answer 19

• There are also NK cells in the gut, they carry NK-cell receptors
• Apart from NK-cells some T-cells carry NK-cell receptors such as NKG2D, for example TCRab+ CD8aa+ (NKG2D=natural killer group 2D receptor).
• NKG2D can bind to stress receptors expressed on damaged gut epithelial cells, MIC-A, or MIC-B (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.
• IEL expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)
• Intraepithelial CD8 T-cells produce IFN-g and are important in killing infected epithelial cells (for example those infected with viruses).

Question 20

Lamina propria and intraepithelial lymphocyte compartment (3)

• There are also NK cells in the …, they carry NK-cell receptors
• Apart from NK-cells some …-cells carry NK-cell receptors such as NKG2D, for example TCRab+ CD8aa+ (NKG2D=natural killer group 2D receptor).
• NKG2D can bind to stress receptors expressed on damaged gut epithelial cells, MIC-A, or MIC-B (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.
• IEL expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)
• Intraepithelial CD8 T-cells produce IFN-g and are important in … … epithelial cells (for example those infected with viruses).

Answer 20

• There are also NK cells in the gut, they carry NK-cell receptors
• Apart from NK-cells some T-cells carry NK-cell receptors such as NKG2D, for example TCRab+ CD8aa+ (NKG2D=natural killer group 2D receptor).
• NKG2D can bind to stress receptors expressed on damaged gut epithelial cells, MIC-A, or MIC-B (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.
• IEL expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)
• Intraepithelial CD8 T-cells produce IFN-g and are important in killing infected epithelial cells (for example those infected with viruses).

Question 21

… expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)

Answer 21

IEL expressing NKG2D can kill damaged/stressed epithelial cells by inducing apoptosis (= programmed cell death)

Question 22

Intraepithelial … …-cells produce IFN-g and are important in killing infected epithelial cells (for example those infected with viruses).

Answer 22

Intraepithelial CD8 T-cells produce IFN-g and are important in killing infected epithelial cells (for example those infected with viruses).

Question 23

NKG2D can bind to stress receptors expressed on damaged gut epithelial cells,… , or … (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.

Answer 23

NKG2D can bind to stress receptors expressed on damaged gut epithelial cells, MIC-A, or MIC-B (MHC class I polypeptide–related sequence A or B). Stress may be caused by toxins for example.

Question 24

T-helper-cell differentiation in the gut and the role of dendritic cells (DCs)

• T-helper cell differentiation is influenced by … cells and …s
• IL-17 producing T-helper cells are induced, for example, in response to bacteria in the gut lumen.
• The type often found in the gut produces IL-17 and IL-22. These cytokines interact with receptors on epithelial cells to regulate the production of mucins or defensins (antimicrobial peptides). They stabilize the intestinal epithelial barrier.
• Classic Th17 cells produce IL-17 and IFN-g and are … They may kill endothelial cells.

Answer 24

• T-helper cell differentiation is influenced by epithelial cells and DCs
• IL-17 producing T-helper cells are induced, for example, in response to bacteria in the gut lumen.
• The type often found in the gut produces IL-17 and IL-22. These cytokines interact with receptors on epithelial cells to regulate the production of mucins or defensins (antimicrobial peptides). They stabilize the intestinal epithelial barrier.
• Classic Th17 cells produce IL-17 and IFN-g and are cytotoxic. They may kill endothelial cells.

Question 25

T-helper-cell differentiation in the gut and the role of dendritic cells (DCs)

• T-helper cell differentiation is influenced by epithelial cells and DCs
• IL-… producing T-helper cells are induced, for example, in response to bacteria in the gut lumen.
• The type often found in the gut produces IL-… and IL-… These cytokines interact with receptors on epithelial cells to regulate the production of mucins or defensins (antimicrobial peptides). They stabilize the intestinal epithelial barrier.
• Classic Th17 cells produce IL-… and IFN-g and are cytotoxic. They may kill endothelial cells.

Answer 25

• T-helper cell differentiation is influenced by epithelial cells and DCs
• IL-17 producing T-helper cells are induced, for example, in response to bacteria in the gut lumen.
• The type often found in the gut produces IL-17 and IL-22. These cytokines interact with receptors on epithelial cells to regulate the production of mucins or defensins (antimicrobial peptides). They stabilize the intestinal epithelial barrier.
• Classic Th17 cells produce IL-17 and IFN-g and are cytotoxic. They may kill endothelial cells.

Question 27

T-helper-cell differentiation in the gut and the role of dendritic cells (DCs) (2)

• T … (…) cells are produced in response to harmless commensals in the presence of retinoic acid and TGF-b, a factor produced by dendritic cells for example.
• … produce IL-10 among other rcytokines and are crucial in establishing and maintaining tolerance to commensals and food.
• Dendritic cells (DCs) sit in the lamina propria. Some have extensions reaching through the epithelium to ‘sample’ contents of the intestinal tube.
• The various roles of CD4 T-cells in the gut and their regulation are incompletely understood. However, we know about their involvement in many diseases, for example, HIV infection, and having a basic understanding of these cells is important.

Answer 27

• T regulatory (Treg) cells are produced in response to harmless commensals in the presence of retinoic acid and TGF-b, a factor produced by dendritic cells for example.
• Tregs produce IL-10 among other rcytokines and are crucial in establishing and maintaining tolerance to commensals and food.
• Dendritic cells (DCs) sit in the lamina propria. Some have extensions reaching through the epithelium to ‘sample’ contents of the intestinal tube.
• The various roles of CD4 T-cells in the gut and their regulation are incompletely understood. However, we know about their involvement in many diseases, for example, HIV infection, and having a basic understanding of these cells is important.

Question 28

T regulatory (Treg) cells are produced in response to harmless … in the presence of retinoic acid and TGF-…, a factor produced by dendritic cells for example.

Answer 28

T regulatory (Treg) cells are produced in response to harmless commensals in the presence of retinoic acid and TGF-b, a factor produced by dendritic cells for example.

Question 29

Tregs produce IL-… among other cytokines and are crucial in establishing and maintaining tolerance to commensals and food.

Question 30

Tregs produce IL-10 among other cytokines and are crucial in establishing and maintaining … to commensals and …

Answer 30

Tregs produce IL-10 among other cytokines and are crucial in establishing and maintaining tolerance to commensals and food.

Question 31

Dendritic cells (DCs) sit in the … … - Some have extensions reaching through the epithelium to ‘sample’ contents of the intestinal tube.

Answer 31

Dendritic cells (DCs) sit in the lamina propria. Some have extensions reaching through the epithelium to ‘sample’ contents of the intestinal tube.

Question 32

The various roles of CD4 T-cells in the gut and their regulation are incompletely understood. However, we know about their involvement in many diseases, for example, … infection, and having a basic understanding of these cells is important.

Answer 32

The various roles of CD4 T-cells in the gut and their regulation are incompletely understood. However, we know about their involvement in many diseases, for example, HIV infection, and having a basic understanding of these cells is important.

Question 33

Lamina propria and intraepithelial lymphocyte compartment (7) - Induction of IL-17 producing and regulatory T-cells.

Answer 33

Question 34

Mucosal B cells & IgA (1)

• IgA is the main antibody in …
• IgA against food antigens provides immune …
• IgA activates the complement system only …
• Secretion of … IgA (coupled by a J chain) depends on a trans-cellular transport mechanism
• The poly-Ig receptor allows IgA binding to the basolateral surface of gut endothelial cells and a part of it remains attached to the IgA molecule throughout the transcellular transport.

Answer 34

• IgA is the main antibody in secretions
• IgA against food antigens provides immune exclusion
• IgA activates the complement system only weakly
• Secretion of dimeric IgA (coupled by a J chain) depends on a trans-cellular transport mechanism
• The poly-Ig receptor allows IgA binding to the basolateral surface of gut endothelial cells and a part of it remains attached to the IgA molecule throughout the transcellular transport.

Question 35

Mucosal B cells & IgA (2)

• IgA is the main antibody in secretions
• IgA against food antigens provides immune exclusion
• IgA activates the … system only weakly
• Secretion of dimeric IgA (coupled by a J chain) depends on a …-… transport mechanism
• The poly-Ig receptor allows IgA binding to the basolateral surface of gut endothelial cells and a part of it remains attached to the IgA molecule throughout the transcellular transport.

Answer 35

• IgA is the main antibody in secretions
• IgA against food antigens provides immune exclusion
• IgA activates the complement system only weakly
• Secretion of dimeric IgA (coupled by a J chain) depends on a trans-cellular transport mechanism
• The poly-Ig receptor allows IgA binding to the basolateral surface of gut endothelial cells and a part of it remains attached to the IgA molecule throughout the transcellular transport.

Question 36

Mucosal B cells & IgA (3)

• The …-Ig-receptor (pIgR) at the basal surface of epithelial cells can bind to the J-chain of IgA and to a lesser extent IgM
• It enables the …-… transport of dimeric IgA and also pentameric IgM (‘secretory component’).
• This mechanism helps … these Immunoglobulins in the mucus where they can exert their function of Immune exclusion. The role of secreted IgM is not entirely clear.

Answer 36

• The Poly-Ig-receptor (pIgR) at the basal surface of epithelial cells can bind to the J-chain of IgA and to a lesser extent IgM
• It enables the trans-endothelial transport of dimeric IgA and also pentameric IgM (‘secretory component’).
• This mechanism helps enriching these Immunoglobulins in the mucus where they can exert their function of Immune exclusion. The role of secreted IgM is not entirely clear.

Question 37

Mucosal B cells & IgA (3)

• The …-…-receptor (pIgR) at the basal surface of epithelial cells can bind to the J-chain of IgA and to a lesser extent IgM
• It enables the trans-… transport of dimeric IgA and also pentameric IgM (‘secretory component’).
• This mechanism helps enriching these … in the … where they can exert their function of Immune exclusion. The role of secreted IgM is not entirely clear.

Answer 37

• The Poly-Ig-receptor (pIgR) at the basal surface of epithelial cells can bind to the J-chain of IgA and to a lesser extent IgM
• It enables the trans-endothelial transport of dimeric IgA and also pentameric IgM (‘secretory component’).
• This mechanism helps enriching these Immunoglobulins in the mucus where they can exert their function of Immune exclusion. The role of secreted IgM is not entirely clear.

Question 38

Gut homing of B- and T-cells (1)

• Homing means that T-cells and B-cells are instructed to return to the … sites adjoining the induction sites where they were …, i.e. first confronted with their ‘cognate’ antigen.
• Homing happens in … tissues.
• Gut-homing … of effector lymphocytes are … in the …-associated … tissues where they have undergone differentiation from naive precursors (induction sites).
• They will home to the same organ, however, to an … site.

Answer 38

• Homing means that T-cells and B-cells are instructed to return to the effector sites adjoining the induction sites where they were primed, i.e. first confronted with their ‘cognate’ antigen.
• Homing happens in all tissues.
• Gut-homing properties of effector lymphocytes are imprinted in the gut-associated lymphoid tissues where they have undergone differentiation from naive precursors (induction sites).
• They will home to the same organ, however, to an effector site.

Question 39

… means that T-cells and B-cells are instructed to return to the effector sites adjoining the induction sites where they were primed, i.e. first confronted with their ‘cognate’ antigen.

Answer 39

Homing means that T-cells and B-cells are instructed to return to the effector sites adjoining the induction sites where they were primed, i.e. first confronted with their ‘cognate’ antigen.

Question 40

Gut homing of B- and T-cells (2): the basic principle in a nutshell

• T-cells primed in a specific … site will be able to re-enter the same tissue at an … site. … molecules on lymphocytes and receptor molecules on endothelial cells function as key & lock
• T-cells primed in a different specific … site will not be able to enter another tissue at an … site (there may be some overlap)

Answer 40

• T-cells primed in a specific induction site will be able to re-enter the same tissue at an effector site. Adhesion molecules on lymphocytes and receptor molecules on endothelial cells function as key & lock
• T-cells primed in a different specific induction site will not be able to enter another tissue at an effector site (there may be some overlap)

Question 41

Gut homing of B- and T-cells (2): the basic principle in a nutshell

• T-cells primed in a specific induction site will be able to re-enter the same tissue at an effector site. Adhesion molecules on lymphocytes and receptor molecules on endothelial cells function as … & …
• T-cells primed in a different specific induction site will not be able to enter another tissue at an effector site (there may be some overlap)

Answer 41

• T-cells primed in a specific induction site will be able to re-enter the same tissue at an effector site. Adhesion molecules on lymphocytes and receptor molecules on endothelial cells function as key & lock
• T-cells primed in a different specific induction site will not be able to enter another tissue at an effector site (there may be some overlap)

Question 42

Gut homing of B- and T-cells (4): nutrition and local factors

• … cells in gut-associated lymphoid tissues (including Peyer’s patches and mesenteric lymph nodes) are induced by local factors to express retinaldehyde dehydrogenase (RALDH). This enzyme converts dietary … … into retinoic acid.
• Retinoic acid induces upregulation of adhesion molecules on lymphocytes in mesenterial lymphnodes or PP.
• Lymphocytes leaving these lymph nodes will express CCR9 and a4/b7, the ligands for CCL

Answer 42

• Dendritic cells in gut-associated lymphoid tissues (including Peyer’s patches and mesenteric lymph nodes) are induced by local factors to express retinaldehyde dehydrogenase (RALDH). This enzyme converts dietary vitamin A into retinoic acid.
• Retinoic acid induces upregulation of adhesion molecules on lymphocytes in mesenterial lymphnodes or PP.
• Lymphocytes leaving these lymph nodes will express CCR9 and a4/b7, the ligands for CCL

Question 43

Gut homing of B- and T-cells (4): nutrition and local factors

• Dendritic cells in gut-associated lymphoid tissues (including Peyer’s patches and mesenteric lymph nodes) are induced by local factors to express retinaldehyde dehydrogenase (RALDH). This enzyme converts dietary vitamin A into … …
• This induces upregulation of adhesion molecules on lymphocytes in mesenterial lymphnodes or PP.
• Lymphocytes leaving these lymph nodes will express CCR9 and a4/b7, the ligands for CCL

Answer 43

• Dendritic cells in gut-associated lymphoid tissues (including Peyer’s patches and mesenteric lymph nodes) are induced by local factors to express retinaldehyde dehydrogenase (RALDH). This enzyme converts dietary vitamin A into retinoic acid.
• Retinoic acid induces upregulation of adhesion molecules on lymphocytes in mesenterial lymphnodes or PP.
• Lymphocytes leaving these lymph nodes will express CCR9 and a4/b7, the ligands for CCL

Question 44

Gut homing of B and T cells - overview

Answer 44

• (1) Lamina propria dendritic cells capture antigen (Ag) and Vitamin A from the gut lumen. They migrate to a mesenteric lymph node or a PP.
• (2) When naive B or T-cells are activated by antigen in gut associated lymphatic tissue, they are exposed to retinoic acid (RA) produced by the dendritic cells from Vitamin A .
• (3) This induces the expression of the chemokine receptor CCR9 and increased expression of integrin α4β7 on primed T-cells. The same mechanisms works for B-cells.
• (4) The effector lymphocytes then enter the circulation and travel via the lymphatic system, the thoracic duct, and the blood stream back ‘home’ to the gut (‘homing’).
• (5) The chemokine CCL25 (the ligand for CCR9) and the adhesion molecule MAdCAM (the ligand for α4β7) are displayed on lamina propria venular endothelial cells, allowing access to the homed cells (remember key & lock).
• (6) This was the journey of a naïve T-cell from entering an induction sites in the gut lymphatic tissue via a HEV to re-entering the gut at an effector site as an antigen-primed effector T-cell. It has now become a lamina propria T-cell.

Question 45

Gut homing of B and T cells - overview

Answer 45

• (1) Lamina propria dendritic cells capture antigen (Ag) and Vitamin A from the gut lumen. They migrate to a mesenteric lymph node or a PP.
• (2) When naive B or T-cells are activated by antigen in gut associated lymphatic tissue, they are exposed to retinoic acid (RA) produced by the dendritic cells from Vitamin A .
• (3) This induces the expression of the chemokine receptor CCR9 and increased expression of integrin α4β7 on primed T-cells. The same mechanisms works for B-cells.
• (4) The effector lymphocytes then enter the circulation and travel via the lymphatic system, the thoracic duct, and the blood stream back ‘home’ to the gut (‘homing’).
• (5) The chemokine CCL25 (the ligand for CCR9) and the adhesion molecule MAdCAM (the ligand for α4β7) are displayed on lamina propria venular endothelial cells, allowing access to the homed cells (remember key & lock).
• (6) This was the journey of a naïve T-cell from entering an induction sites in the gut lymphatic tissue via a HEV to re-entering the gut at an effector site as an antigen-primed effector T-cell. It has now become a lamina propria T-cell.

Question 46

Summary of Mucosal Immunology L2 P1

• Besides Peyer’s patches, lymph nodes at the base of the … play a major role as induction sites in the gut mucosa. They are called … lymph nodes or MLNs. They play a major role in inducing … to foods.
• Intraepithelial cells are very diverse, ranging from tissue resident memory T-cells via innate-like NK T-cells and g/d T-cells to innate NK cells. They are first to encounter invasive pathogens.
• Intraepithelial CD… T-cells include conventional CD8 T-cells and those with a CD8 alpha/alpha homodimer
• Intraepithelial CD… T-cells include Treg, Th1, Th2, and IL-17 producing T-cells.
• IL…-producing CD4 T-cells may also produce IL-… in addition, a type that stabilizes the intestinal barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is cytotoxic and can cause tissue damage.
• … T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.

Answer 46

• Besides Peyer’s patches, lymph nodes at the base of the mesentery play a major role as induction sites in the gut mucosa. They are called mesenterial lymph nodes or MLNs. They play a major role in inducing tolerance to foods.
• Intraepithelial cells are very diverse, ranging from tissue resident memory T-cells via innate-like NK T-cells and g/d T-cells to innate NK cells. They are first to encounter invasive pathogens.
• Intraepithelial CD8 T-cells include conventional CD8 T-cells and those with a CD8 alpha/alpha homodimer
• Intraepithelial CD4 T-cells include Treg, Th1, Th2, and IL-17 producing T-cells.
• IL17-producing CD4 T-cells may also produce IL-22 in addition, a type that stabilizes the intestinal barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is cytotoxic and can cause tissue damage.
• Regulatory T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.

Question 47

Summary of Mucosal Immunology L2 P1

• Besides Peyer’s patches, lymph nodes at the base of the mesentery play a major role as induction sites in the gut mucosa. They are called mesenterial lymph nodes or MLNs. They play a major role in inducing tolerance to foods.
• Intraepithelial cells are very diverse, ranging from tissue resident memory T-cells via innate-like NK T-cells and g/d T-cells to innate NK cells. They are first to encounter invasive pathogens.
• Intraepithelial CD8 T-cells include conventional CD8 T-cells and those with a CD8 alpha/alpha homodimer
• Intraepithelial CD4 T-cells include Treg, Th1, Th2, and IL-17 producing T-cells.
• IL17-producing CD4 T-cells may also produce IL-22 in addition, a type that stabilizes the intestinal barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is cytotoxic and can cause tissue damage.
• Regulatory T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.

Answer 47

• Besides Peyer’s patches, lymph nodes at the base of the mesentery play a major role as induction sites in the gut mucosa. They are called mesenterial lymph nodes or MLNs. They play a major role in inducing tolerance to foods.
• Intraepithelial cells are very diverse, ranging from tissue resident memory T-cells via innate-like NK T-cells and g/d T-cells to innate NK cells. They are first to encounter invasive pathogens.
• Intraepithelial CD8 T-cells include conventional CD8 T-cells and those with a CD8 alpha/alpha homodimer
• Intraepithelial CD4 T-cells include Treg, Th1, Th2, and IL-17 producing T-cells.
• IL17-producing CD4 T-cells may also produce IL-22 in addition, a type that stabilizes the intestinal barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is cytotoxic and can cause tissue damage.
• Regulatory T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.

Question 48

IL17-producing CD4 T-cells may also produce IL-… in addition, a type that stabilizes the … barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is … and can cause tissue damage.

Answer 48

IL17-producing CD4 T-cells may also produce IL-22 in addition, a type that stabilizes the intestinal barrier (tight junctions, mucus secretion). Alternatively, they may also produce IFN-g. This type is cytotoxic and can cause tissue damage.

Question 49

… T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.

Answer 49

Regulatory T-cell responses are important in regards to tolerance to food antigens, as absorption of nutrients and inflammation are incompatible.

Question 50

Summary of Mucosal Immunology L2 P2

• Mucosal B-cells are located in the … … where they secrete immunoglobulin. The main immunoglobulin in secretions, including in the gut mucosa is dimeric IgA. It consists of two Ig… molecules joined by a J chain.
• Secretion of Ig… happens via a … transport mechanism and requires an additional transport molecule, the secretory component (it originates from the poly-Ig receptor which is expressed at the basal surface of gut epithelial cells).
• Ig… does not efficiently activate complement but can neutralize toxins and prevent microbial invasion. Commensal gut flora induces low affinity Ig… esponses (aimed at immune exclusion).

Answer 50

• Mucosal B-cells are located in the lamina propria where they secrete immunoglobulin. The main immunoglobulin in secretions, including in the gut mucosa is dimeric IgA. It consists of two IgA molecules joined by a J chain.
• Secretion of IgA happens via a transcellular transport mechanism and requires an additional transport molecule, the secretory component (it originates from the poly-Ig receptor which is expressed at the basal surface of gut epithelial cells).
• IgA does not efficiently activate complement but can neutralize toxins and prevent microbial invasion. Commensal gut flora induces low affinity IgA responses (aimed at immune exclusion).

Question 51

Summary of Mucosal Immunology L2 P2

• Mucosal B-cells are located in the lamina propria where they secrete immunoglobulin. The main immunoglobulin in secretions, including in the gut mucosa is dimeric IgA. It consists of two IgA molecules joined by a …chain.
• Secretion of IgA happens via a transcellular transport mechanism and requires an additional transport molecule, the secretory component (it originates from the poly-Ig receptor which is expressed at the basal surface of gut epithelial cells).
• IgA does not efficiently activate … but can neutralize toxins and prevent microbial invasion. Commensal gut flora induces … affinity IgA responses (aimed at immune exclusion).

Answer 51

• Mucosal B-cells are located in the lamina propria where they secrete immunoglobulin. The main immunoglobulin in secretions, including in the gut mucosa is dimeric IgA. It consists of two IgA molecules joined by a J chain.
• Secretion of IgA happens via a transcellular transport mechanism and requires an additional transport molecule, the secretory component (it originates from the poly-Ig receptor which is expressed at the basal surface of gut epithelial cells).
• IgA does not efficiently activate complement but can neutralize toxins and prevent microbial invasion. Commensal gut flora induces low affinity IgA responses (aimed at immune exclusion).

Question 52

Summary of Mucosal Immunology L2 P3

• Antigen-primed B-cells and T-cells originate from naïve B- and T-cells whose … pattern is restricted to the blood stream and lymph nodes.
• These naïve B-cells and T-cells reach PPs and MLN via … endothelial … (HEVs).
• Following antigen contact (‘induction’) and tissue specific imprinting they travel through the lymphatic system and thoracic duct to reach the blood stream.
• They finally return to the gut via the blood stream and leave the blood stream via … (attachment) to the endothelium of small venules (not HEVs) and transmigration to reach the lamina propria and/or intraepithelial sites.

Answer 52

• Antigen-primed B-cells and T-cells originate from naïve B- and T-cells whose recirculation pattern is restricted to the blood stream and lymph nodes.
• These naïve B-cells and T-cells reach PPs and MLN via high endothelial venules (HEVs).
• Following antigen contact (‘induction’) and tissue specific imprinting they travel through the lymphatic system and thoracic duct to reach the blood stream.
• They finally return to the gut via the blood stream and leave the blood stream via adhesion (attachment) to the endothelium of small venules (not HEVs) and transmigration to reach the lamina propria and/or intraepithelial sites.

Question 53

Summary of Mucosal Immunology L2 P3

• Antigen-… B-cells and T-cells originate from naïve B- and T-cells whose recirculation pattern is restricted to the blood stream and lymph nodes.
• These naïve B-cells and T-cells reach PPs and MLN via high endothelial venules (HEVs).
• Following antigen … (‘induction’) and tissue specific imprinting they travel through the lymphatic system and thoracic duct to reach the blood stream.
• They finally return to the gut via the blood stream and leave the blood stream via adhesion (attachment) to the endothelium of small venules (not HEVs) and transmigration to reach the lamina propria and/or intraepithelial sites.

Answer 53

• Antigen-primed B-cells and T-cells originate from naïve B- and T-cells whose recirculation pattern is restricted to the blood stream and lymph nodes.
• These naïve B-cells and T-cells reach PPs and MLN via high endothelial venules (HEVs).
• Following antigen contact (‘induction’) and tissue specific imprinting they travel through the lymphatic system and thoracic duct to reach the blood stream.
• They finally return to the gut via the blood stream and leave the blood stream via adhesion (attachment) to the endothelium of small venules (not HEVs) and transmigration to reach the lamina propria and/or intraepithelial sites.

Question 54

Summary of Mucosal Immunology L2 P4

• This process is relatively …-specific because ‘imprinting’ will lead to the upregulation of adhesion molecules on the surface of antigen-primed B and T-cells that serve as a ‘key to a lock’.
• The ‘lock’ consists of certain ligands found on the venular endothelial surfaces of the gut. These molecules are upregulated during … and will grant access to those cells providing the right ligands (the ‘key’).
• This … behaviour of lymphocyte populations is referred to as ‘homing’.
• In the gut, Vitamin A plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Vitamin A deficiency decreases gut immunity probably by reducing homing.

Answer 54

• This process is relatively tissue-specific because ‘imprinting’ will lead to the upregulation of adhesion molecules on the surface of antigen-primed B and T-cells that serve as a ‘key to a lock’.
• The ‘lock’ consists of certain ligands found on the venular endothelial surfaces of the gut. These molecules are upregulated during inflammation and will grant access to those cells providing the right ligands (the ‘key’).
• This recirculation behaviour of lymphocyte populations is referred to as ‘homing’.
• In the gut, Vitamin A plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Vitamin A deficiency decreases gut immunity probably by reducing homing.

Question 55

Summary of Mucosal Immunology L2 P4

• This process is relatively tissue-specific because ‘imprinting’ will lead to the upregulation of adhesion molecules on the surface of antigen-primed B and T-cells that serve as a ‘key to a lock’.
• The ‘lock’ consists of certain ligands found on the venular endothelial surfaces of the gut. These molecules are upregulated during inflammation and will grant access to those cells providing the right ligands (the ‘key’).
• This recirculation behaviour of lymphocyte populations is referred to as ‘…’.
• In the gut, …. … plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Deficiency decreases gut immunity probably by reducing homing.

Answer 55

• This process is relatively tissue-specific because ‘imprinting’ will lead to the upregulation of adhesion molecules on the surface of antigen-primed B and T-cells that serve as a ‘key to a lock’.
• The ‘lock’ consists of certain ligands found on the venular endothelial surfaces of the gut. These molecules are upregulated during inflammation and will grant access to those cells providing the right ligands (the ‘key’).
• This recirculation behaviour of lymphocyte populations is referred to as ‘homing’.
• In the gut, Vitamin A plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Vitamin A deficiency decreases gut immunity probably by reducing homing.

Question 56

In the gut, … … plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Deficiency decreases gut immunity probably by reducing homing.

Answer 56

In the gut, Vitamin A plays an important role in ‘imprinting’ the ‘homing’ patterns onto naïve B and T-cells. Vitamin A deficiency decreases gut immunity probably by reducing homing.