Cutaneous and Mucosal Immune System (MIS)

Question 1

The MIS is composed of what kind of tissues?

Answer 1

The MIS is composed of: mucosal-associated lymphoid tissues (MALT); a collection of dispersed aggregates of non-encapsulated lymphoid tissues found especially in the epithelia, lamina propria, and submucosal areas of GI and respiratory tracts.

Question 2

Name some gut-associated lymphoid tissues (GALT).

Answer 2

Peyer’s patches, cecal tonsils (avian), tonsils, and appendix (colon).

Question 3

What do tonsils respond to?

Answer 3

Tonsils respond to antigens entering through the nasal and oral epithelial routes.

Question 4

Name some bronchus-associated lymphatic tissues (BALT).

Answer 4

Genitourinary tract (ureter, bladder), mammary gland, conjunctiva, and salivary glands.

Question 5

What does the presence of antibody in local secretions correlate with?

Answer 5

The presence of antibody (sIgA generated by MALT) in local secretions correlates better with protection against pathogenic microbes than serum antibody.

Question 6

Where are the 3 main regions where GALT is found?

Answer 6

1) Intraepithelial lymphocytes (IELs) found within the epithelium.
2) Lamina propria.
3) Peyer’s patches in the submucosa.

Question 7

Where are IELs? What kind of cells are they? What do they express?

Answer 7

IELs are found within the epithelium of the intestinal tract; the majority of which are CD8+ T cells that express ysTCRS, with a limited diversity of antigen receptors.

Question 8

What lymphoid cells does the lamina propria of the intestine contain?

Answer 8

Activated B cells, plasma cells, activated CD4+ T cells, follicular dendritic cells (FDCs), and macrophages in loose clusters.

Question 9

What kind of lymphoid cells are found in Peyer’s patches?

Answer 9

Peyer’s patches possess all the components required to mount an immune response; namely T cells, B cells, FDCs, and macrophages.

Question 10

T or F?

There are no afferent lymphatics that carry antigens to Peyer’s patches.

Answer 10

TRUE.

Question 11

What carries out antigen transport from the luminal surface to Peyer’s patches?

Answer 11

Antigen transport from the luminal surface to Peyer’s patches is carried out by specialized epithelial cells overlying Peyer’s patches called M (microfold) cells.

Question 12

Describe the appearance and location of M cells. What do they contain?

Answer 12

M cells are flattened epithelial cells scattered among the enterocytes. They lack microvilli but possess deep invaginations of the basolateral plasma membrane which forms pockets containing T and B lymphocytes, FDCs, and macrophages.

Question 13

T or F?

M cells function as antigen presenting cells.

Answer 13

FALSE.

M cells do NOT function as antigen presenting cells.

Question 14

T or F?

M cells are also found in secondary lymphoid-associated cell accumulations which are called “inductive sites”.

Answer 14

TRUE.

Question 15

What are inductive sites?

Answer 15

Small regions of a mucous membrane that lie over organized lymphoid follicles.

Question 16

Antigens transported across the mucous membrane by M cells at an inductive site activate ____ cells in the underlying lymphoid follicles.

Answer 16

B cells.

Question 17

What do activated B cells at inductive sites differentiate into?

Answer 17

Mainly IgA-producing plasma cells, but B cells expressing IgM, IgG, or IgE BCRs are also present.

Question 18

T or F?

The IgA produced at inductive sites are transported across the epithelial cells and released as secretory IgA into the lumen where they can interact with antigens present in the lumen.

Answer 18

TRUE.

Question 19

What types of cells in the mucosal epithelia take up antigens, process them, and transport them to regional lymph nodes where they present them to CD4+ T cells?

Answer 19

Interdigitating dendritic cells.

Question 20

Many of the activated B cells and plasma cells migrate via __1__ lymphatics to _____2 _____ and the ____3____ and into the bloodstream.

Answer 20

1) efferent.
2) regional lymph nodes.
3) thoracic duct.

Question 21

What makes specific recirculation possible within the MIS?

Answer 21

Specific recirculation within the MIS is made possible because the lymphoid cells express “homing molecules” that bind to vascular addressins expressed on mucosal high endothelial venules, which in contrast, are absent from lymph node HEVs.

Question 22

Why is the movement of IgA-producing cells to the mammary gland during lymphocyte recirculation important?

Answer 22

This is very important in domestic animals because it provides a route by which cells stimulated by intestinal pathogens can secrete their IgA into colostrum and milk, thus protecting the intestines of newborn animals.

Question 23

What is the predominant Ig synthesized in the MIS? Where is it found in significant amounts?

Answer 23

IgA; in intestinal fluid, nasal and tracheal secretions, milk, colostrum, urine, tears, saliva, etc.

Question 24

Since the MIS contains up to 1% of all the B cells in the body, Ig_2_ accounts for 60-70% of the daily output of antibodies.

Answer 24

1) 75%

2) IgA.

Question 25

T or F?

IgA isotype switch is mediated by transforming growth factor-B (TGF-B).

Answer 25

TRUE.

Question 26

What are the predominant helper cells in the MIS?

Answer 26

TH2 cells.

Question 27

IgA is produced by plasma cells in the lamina propria in the form of a ___ that is held together by a __ chain.

Answer 27

IgA is produced by plasma cells in the lamina propria in the form of a dimer that is held together by a J chain.

Question 28

What is poly-Ig receptor/pIgR?

Answer 28

It is the “mucosal transport receptor”, which is a glycoprotein synthesized by mucosal epithelial cells and expressed on their basal and lateral surfaces. It is a member of the Ig superfamily.

Question 29

Once the dimeric IgA binds to the pIgR, what happens?

Answer 29

After binding, the complex is endocytosed into the epithelial cell and is actively transported in vesicles to the luminal surface.

The extracellular domain of the PIgR, which carries the IgA molecule, is then cleaved by proteolytic enzymes so that the IgA, with the receptor peptide still attached (secretory IgA) is released into the intestinal lumen.

Question 30

The IgA-associated receptor peptide is also called what? What is its function?

Answer 30

The IgA- associated receptor peptide is called the SECRETORY COMPONENT; it protects the dimeric IgA from proteolytic enzymes in the lumen.

Question 31

What is the most important mode of action of the sIgA?

Answer 31

The most important mode of action of sIgA is the prevention of the adherence of microorganisms and toxins to epithelial surfaces.

Question 32

Where is the dimeric IgA formed?

Answer 32

In the lamina propria.

Question 33

1) In ruminants, what is the most predominant Ig in colustrum, milk, intestinal contents and nasal washings? 2) What about on other body surfaces?

Answer 33

1) IgG1.

2) IgA.

Question 34

T or F?

IgG is as resistant to proteolysis as sIgA, hence, its role in defending the intestinal mucosa is equally significant.

Answer 34

FALSE.

IgG is NOT as resistant to proteolysis as sIgA, hence, its role in defending the intestinal mucosa is LESS significant.

(It is, however, more significant in the respiratory tract)

Question 35

What is IgE mainly synthesized by?

Answer 35

IgE is mainly synthesized by plasma cells in the lamina propria of the respiratory and intestinal tracts.

Question 36

Where is IgE found?

Answer 36

In the secretions of the nose, eyes, bronchi, and gut.

Question 37

What is the production of IgE associated with?

Answer 37

The production of IgE is associated with immunity to helminths and type-1 hypersensitivity.

Question 38

IgM also binds to __1__ and is carried through the epithelial cell to the lumen. However, __2__ is susceptible to proteolytic degradation and it is a minor component in secretions.

Answer 38

1) pIgR.

2) SIgM.

Question 39

List the 5 things that contribute to immunity in the GI tract.

Answer 39

1) Low pH of the stomach; peristaltic movement; proteolytic enzymes, bile acids, and pancreatic secretions.
2) Normal flora.
3) SIgA (prevents microbial adherence).
4) IgG (diffusion from the blood into an area of an inflammatory response).
5) IgE (immunity to helminth parasites).

Question 40

What clears most of the inhaled suspended particles in the respiratory tract?

Answer 40

Turbulence that directs the particles onto the mucous-covered walls, where they adhere.

Question 41

What serves to remove particles as small as 5um in size before they reach the alveoli?

Answer 41

The “turbulence filter”.

Question 42

Name the 6 things that contribute to immunity in the respiratory tract.

Answer 42

1) Mucociliary escalator: microorganisms in the LOWER respiratory tract are trapped in mucus produced by goblet cells, then propelled upward by the synchronized beating of cilia. (mucus also contains sIgA and lysozyme).
2) Alveolar macrophages
3) Pulmonary intravascular macrophages: adherent to the capillary endothelium of the lungs. These are found in ruminants cats and pigs - they clear microbes in the blood.
4) IgA (synthesized in lymphoid nodules in the walls of the bronchi and lymphocytes distributed diffusely throughout the lung and walls of the airways).
5) IgG (of major importance during acute inflammation when transudation of serum protein occurs).
6) IgE (mediates type-1 hypersensitivity reactions in the respiratory tract).

Question 43

Between milking, what happens to the teat canal?

Answer 43

Between milking, the teat canal will dry out, forming a seal to the teat entrance.

Question 44

What lines the teat canal that can bind ~1x10^6 bacteria?

Answer 44

Keratin.

Question 45

T or F?

Between milking, the keratin layer of the teat canal will shed periodically, which aids to remove bacteria from the area.

Answer 45

TRUE.

Question 46

What substance does the keratin layer of the teat canal contain that acts as a bactericidal?

Answer 46

Dissolved fatty acids.

Question 47

T or F?

It is normal for the teat canal to be dilated for ~6 hours after milking, which makes the udder very susceptible to infection.

Answer 47

FALSE…

It is normal for the teat canal to be dilated for ~TWO hours after milking, which makes the udder very susceptible to infection.

Question 48

How can we help prevent bacterial infection during the normal teat canal dilation period following milking?

Answer 48

Cows should be fed immediately after milking so that they remain standing for as long as possible and therefore avoid udder contact with the ground (the source of the pathogens).

Question 49

Does normal milk flow (aka the flushing of milk) aid in the immunity of the mammary gland?

Answer 49

Yes, of course.

Question 50

Why do we care about the citrate-lactoferrin ratio of the mammary gland?

Answer 50

Lactoferrin permanently binds iron, which is an essential growth factor for bacteria, but when citrate binds iron, the bacteria are able to utilize it.

Thus, The binding of iron to citrate competes with chelation of iron by lactoferrin.

A high molar ratio of citrate to lactoferrin enhances bacterial growth!

Question 51

What are somatic cells in milk? What’s their normal concentration in milk? What does a low somatic cell count mean clinically?

Answer 51

Normally, in the dairy cow, there are 0.5-2.0 x 10^5 somatic cells/ml of milk.

Somatic cells are mostly macrophages, epithelial cells, and some lymphocytes.

A low somatic cell count predisposes the udder to infection by opportunistic pathogens.

Question 52

What does acute mastitis do to the somatic cell count of dairy cow milk?

Answer 52

Acute mastitis will cause a neutrophil influx into the mammary gland cistern, which increases the somatic cell count in milk.

Question 53

Is IgA found in the mammary gland? If so, how did they get there?

Answer 53

Yes; IgA is locally synthesized in the mammary gland, but most of them originated form precursor cells in the intestinal tract.

Question 54

How does IgG get into the mammary gland?

Answer 54

It is selectively transferred by an active transport mechanism from the serum.

Question 55

What are the 5 things that contribute to the immunity in the urogenital tract?

Answer 55

1) Flushing action of urine.
2) pH of urine (carnivores have more acidic urine than herbivores).
3) In females, the squamous epithelial cells of the vagina store glycogen that is later used by lactobacillus acidophilus, that in turn, generate large quantities large quantities of lactic acid, which protects the vagina (pH 3.5-4.5) against invasion. (THIS ONLY OCCURS IN SEXUALLY MATURE ANIMALS - this means vaginal infections are more common in prepubescent animals)
4) IgA (predominant Ig in cervicovaginal mucus; low amounts in urine).
5) IgG (predominant Ig in the uterus).

Question 56

What are the components of the cutaneous immune system?

Answer 56

1) Anatomic barrier to the external enviornment.
2) Secretion of sebum.
3) Resident flora.
4) Epithelial desquamation.

Question 57

What cells play a role in local inflammatory reactions in the cutaneous immune system? What cytokines do they possess?

Answer 57

Keratinocytes; IL-1,6,8.

Question 58

What antigen-presenting cells are found in the cutaneous immune system.

Answer 58

Langerhans cells.