THE MALT

Malt origin is buried in antiquity. There is a legend that early Egyptians manufactured malt by placing it in a basket, which was then lowered into the open wells of that time. It was first lowered into the water for steeping, after which it was raised above the water level for germination. But noooo

We are not going to talk about the history of the malt, the beverage and the grains! we are going to discuss the mucosal immune system (commonly described by the acronym MALT). The largest immune organ in the human body (O’Hara and Shanahan 2006).

MALT = Mucosa-Associated Lymphoid Tissues                             

The mucosal membranes are the primary contact between a host and its environment, large amounts of secondary lymphoid tissue are found here as a first line of defense. Secretory IgA (SIgA) has long been recognized as well as a first line of defense protecting against most pathogens that invade the body at a mucosal surface acting as a main effector of the mucosal immune system. SIgA generates a barrier that prevents Antigens from attaching to and penetrating the mucosal epithelium and forms immune complexes with Ags within epithelial cells of the gut lamina propria.

Once upon a time MALT was the unique terminology for the mucosal immune system. Medical doctor’s have been loving classifications and difficult words for centuries. We’ve been giving names to each place or immune compartment since then.

As MALT is situated along the surfaces of all mucosal tissues, the MALT lining the gut are known as Gut-associated lymphoid tissue or GALT.

Nasopharynx-associated lymphoid tissue (NALT)

Bronchus-associated lymphoid tissue (BALT)

Skin- associated lymphoid tissue (SALT)

Conjunctiva-associated lymphoid tissue (CALT), lacrimal duct-associated (LDALT), larynx-associated (LALT) and salivary duct-associated lymphoid tissue (DALT) have also been described.
Apart from these MALT sites, aggregations of lymphoid cells are present in the mucosae of many other tissues such as the genital tract (lamina propria). 

If you change the first letter of the acronym you will be fine. You don’t have to memorize everything like zombies.

So I think that The concept of compartmentalization of the mucosal immune system is clear.

You will find some terms as organized mucosa-associated lymphatic tissue O-MALT (tonsils) and diffuse mucosa-associated lymphatic tissue D-MALT. Don´t worry about it we don’t use those that much.

According to Croitoru and Bienenstock (1994) about a half of the lymphocytes of the immune system are in the Mucosa-associated lymphoid tissue (MALT). A big proportion 50% !!!!.

It is of capital importance to remember that Mucosa-associated lymphoid tissue is located in anatomically defined microcompartments throughout the organs of the body.

If we recall the general principles underlying the initiation of the adaptive (or acquired) immune response in the compartments comprising the peripheral lymph nodes and spleen. These compartments responds to antigens that have entered the tissues or spread into the blood. A second compartment of the adaptive immune system of equal size to this, and located near the surfaces where most pathogens invade, is the mucosal immune system (MALT).

Immune responses induced within one compartment are largely confined in expression to that particular compartment. The second is that lymphocytes are restricted to particular compartments by expression of homing receptors that are bound by ligands, known as addressins, that are specifically expressed within the tissues of the compartment.

It is well known that the mucosal surfaces of the body are particularly vulnerable to infection. They are thin and permeable barriers to the interior of the body because of their physiological activities in gas exchange (the lungs), food absorption (the gut), sensory activities (eyes, nose, mouth, and throat), and reproduction (uterus and vagina). The necessity for permeability of the surface lining these sites creates obvious vulnerability to infection.

The gut by example acts as a portal of entry to a vast array of foreign antigens in the form of food. This is very important to consider in pediatric population.

The immune system has evolved mechanisms to avoid a furious immune response to food antigens (not always) on the one hand. An Exception, allergic and food allergies (we will discuss this item in pathology).

On the other hand, to detect and kill pathogenic organisms gaining entry through the gut (pathogenic microorganisms and parasites) and to live happily ever after with commensal bacteria of gut. 

https://tenor.com/es/ver/excited-then-confused-gollum-hobbit-gif-13110271

Click here👆

The tonsils and adenoids form a ring, (A precious ring for the surgeons) known as Waldeyer's ring, at the back of the mouth at the entrance of the gut and airways. They represent large aggregates of mucosal lymphoid tissue, which often become extremely enlarged in childhood because of recurrent infections. Conclusion: Child’s needs their precious ring until proven otherwise. Watch and wait because large tonsils often shrink over time.

The importance of MALT from the rest of the peripheral lymphoid system is further underlined by the different lymphocyte repertoires in the compartments.

The T cells of the gut can be divided into two types. One type bears the conventional α:β T-cell receptors in conjunction with either CD4 or CD8 and participates in conventional T-cell responses to foreign antigens. The second type T cells with unusual surface phenotypes such as TCRγ:δ and CD8α:α TCRα:β.

GUT-ASSOCIATED LYMPHOID TISSUE (GALT)

•              This is comprised of:

A) Mucosa- lymphoid organs:

•              Tonsils (palatine, lingual, pharyngeal).

•              Peyer's patches in ileum.

•              Lymphoid aggregates in the appendix and large intestine.

•              Lymphoid tissue in the stomach (accumulates with age).

•              Small lymphoid aggregates in the esophagus.

B) Diffusely distributed immune cells

•              Lymphocytes and plasma cells.

•              M (microfold) cells.

•              Mucosal mast cells.

•              Antigen Presenting Cells (APC).

                                 Before we go further let´s take a look to basic histology.

What kind of cells you will found in MALT?

The simplest organization of cells in MALT is represented by

Diffuse cumules of :

Lymphocites (B and T).

Plasma cells

Histiocytes

Also you can find Dendritic Cells and M cells. 

Unlike lymph nodes, MALT aggregations are not penetrated by lymphatic vessels and are exposed to antigens directly from the mucosa they surround. 

MALT provides the immune system easy access to the organisms. Allows the immune system to sample microbial antigens for development of adaptive immune responses and provides a location for Plasma cell to synthesize IgA.

In the microphotograph we have a view of the stomach mucosa.  A round blue area is marked as GALT, a non encapsulated cumule of lymphocytes with some pale zones that means that is already activated. According to this concept should be a secondary folicle.

Primary folicles are completely blue. 

Human Lymph node with a Primary follicle 

Human Lymph node with Secondary Follicle. 

The  difference between MALT and lymphoid organs can be highlighted from these microphotographs.

MALT = diffuse , no capsule.
Organs = capsule present.

 

REFERENCES

Brandtzaeg P. Function of mucosa-associated lymphoid tissue in antibody formation. Immunological Investigations. 2010;39(4-5):303–355

Croitoru K, Bienenstock J, Ernst PB. Phenotypic and functional assessment of intraepithelial lymphocytes bearing a 'forbidden' alpha beta TCR. Int Immunol. 1994;6(10):1467-73.

Cesta, M. F. (2006). Normal Structure, Function, and Histology of Mucosa-Associated Lymphoid Tissue. Toxicologic Pathology. 2006; 34(5), 599–608. https://doi.org/10.1080/01926230600865531. 

Husband AJ. Novel vaccination strategies for the control of mucosal infection. Vaccine. 1993;11(2):107-12.

Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001.

 
Macpherson AJ, McCoy KD, Johansen FE, Brandtzaeg P . The immune geography of IgA induction and function. Mucosal Immunol.2008;1(1):11-22. doi: 10.1038/mi.2007.6.

McGhee JR, Fujihashi K (2012) Inside the Mucosal Immune System. PLOS Biology 10(9): e1001397. https://doi.org/10.1371/journal.pbio.1001397

O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006;7(7):688–693. doi:10.1038/sj.embor.7400731

Oral Alpan, Gregory Rudomen, Polly Matzinger. The Role of Dendritic Cells, B Cells, and M Cells in Gut-Oriented Immune Responses. The Journal of Immunology. 2001;166(8) 4843-4852; DOI: 10.4049/jimmunol.166.8.4843

Vaerman JP, Férin J. Local immunological response in the vagina, cervix and endometrium. Acta Endocrinologica. 1975;78(194):281–305