6 Myeloid System-I

Dr. M. N. Gupta

Objectives

  • Stem cell first differentiates into lymphoid and myeloid progenitors
  • B- and T- lymphocytes mature in the primary lymphoid organs
  • These circulate throughout the body and immune response is initiated in the secondary lymphoid organs

Concept Map

 

Description

 

In the beginning the fertilized egg has a multipotential stem cell. This first differentiates into lymphoid cells progenitor and myeloid cell progenitor.

 

Bone marrow and thymus are primary lymphoid organs. Spleen, lymph nodes and mucosa associated lymphoid tissues are secondary lymphoid organs.

 

The multipotential hematopoietic stem cell

 

 

The development of blood cells is called haematopoiesis. Most of the cells of the immune system originates from a common haematopoietic stem cell. Haematopoiesis begins in the early yolk sac. During embryogenesis, this process moves over to the fetal liver, fetal spleen and in the bone marrow of the neonate and adult. Hence, the common multipotential haematopoietic stem cells are found in the fetal liver, fetal spleen and in the bone marrow. Haemopoisis continues in the bone marrow throughout the life. These cells replicate and seed other organs.

Figure 2: Role of stromal cells in hemopoiesis. (a) Stromal cell bound cytokine (e.g. stem cell factor) and

  • (b) released cytokines (e.g. IL-7) determine the differentiation pathway of the stem cell (SC) attached through (c) specific adhesion molecules (e.g. CD44) on the SC attached to hyaluronic acid molecules on the stromal cell.

The differentiation of the stem cell is dependant upon its microenvironments , that is, the organ/tissue. This differentiation involves stromal cells and specific cytokines. Within the fetal liver, thymus and bone marrow, different stromal cells (including macrophages, endothelial cells, epithelial cells, fibroblasts and adipocytes) creates focii. At different focii, different cells can develop. Both cytokines and adhesion molecules play important roles. These interactions switch on gene expression necessary for the functioning of that particular differentiated cell.

 

Detailed outline of hematopoiesis

 

All the blood cells arise from this common stem cell. Hence pluripotent haematopoietic stem cell gives rise to two different types of stem cells:

 

Common lymphoid progenitor which gives rise to lymphocytes Common myeloid progenitor.

 

Lymphoid Tissues

 

Lymphoid organs contain lymphocytes in the framework of non lymphoid cells. The interaction of lymphocytes with the non-lymphoid cells is responsible for:

  • Lymphocyte development
  • Initiation of the adaptive immune response
  • Maintainence of the lymphocytes

Lymphoid organs are of two kinds:

  • Central or primary lymphoid organs
  • Peripheral or secondary lymphoid organs

Lymphocytes are generated in the primary lymphoid organs. Adaptive immune response is initiated in the secondary lymphoid organs. It is here that lymphocytes are sustained.

 

Primary Lymphoid Organs

There are two primary lymphoid organs: Bone Marrow and thymus

The bone marrow is an important haematopoietic tissue present in the long bones and axial skeleton. Venus sinuses are around a central artery and vein and enmeshed in developing cells. All blood cells are derived from the bone marroe stem cells. About 10% of the bone marrow cells are lymphocytes.

 

Fetal liver and Bone Marrow: Places where B-cells differentiate

 

B-lymphocyte precursors are present in the fetal liver by 8-9 week of pregnancy in humans (and 14 days in mouse). In further life, bone marrow takes over the production of B-lymphocytes.

 

Both B- and T- lymphocytes are formed in the bone marrow. B-lymphocytes develop in the bone marrow itself. T-cells migrate to the thymus and develop there.

Bursa of Fabricius

 

Bursa of fabricius is present in birds. Despite the early belief, the effort to find a similar organ in mammals failed.

 

Bursa of fabricius is the site where B-cells differentiate in birds. It atrophies with age.

 

At one time, it was believed that this organ is the site of B-cell development.

 

Contrary to what some books claim, B-cells were so named because of this belief. It is fortuitous the Bone (marrow) also has B as its first letter.

 

Bursa of fabricius is present at the common exit of intestinals and genitourinary tracts in birds. It has been shown that bursectomy of young chickens exhibits antibody synthesis.

Thymus

 

In mammals, it is a bilobed organ and located in the thorax.

 

Each lobe has lobules separated by connective tissue.

 

Each lobule has inner medulla containing mature T-cells and outer cortex which is more tightly packed with immature and proliferating T-cells.

 

Many epithelial cells present in the lobules play an important role in differentiation.

 

In mammals, atrophy of thymus begins with puberty and decline continues with age. Pregnancy and stress both promote thymus atrophy.

The secondary lymphoid organs

 

Immune system actually takes place in the secondary lymphoid organs:

  • Spleen
  • Lymph Nodes
  • Mucosa associated lymphoid tissues (MALT)
  • The mature B and T cells migrate to secondary lymphoid tissues

 

Circulation of cells

 

The cells (of the blood) and antibody circulate through tissues via the blood stream.

 

The lymphatic vessels return these cells and antibody from the tissues to the blood stream.

 

The circulation of lymphocytes between the tissue, the blood and the lymph glands then encounter with antigen or enable their participation where the immune response to the antigen has been already initiated.

The Spleen

 

The spleen is an encapsulated organ. Its interior, splenic pulp is spongy in appearance.

 

The white pulp islands are situated within the red pulp which is a network of RBCs, macrophages and B-cells (Plasma cells).

 

Spleen traps the microbes which enters it via the blood stream.

 

It also removes the dead RBCs and immune complexes.

 

Individuals with the spleen removed (splenectomized) are at a high risk to infections from encapsulated.

 

 

Lymph Nodes

 

Lymph nodes are small spherical encapsulated (2-10 nm size) structures located at various parts in the lymphatic system.

 

There are large groups of lymph nodes in axillae, groin and neck.

 

Lymph nodes trap antigens from the circulating lymph.

Mucosa associated lymphoid tissues (MALT)

Mucosa associated lymphoid tissues, commonly called MALT, is an uncapsulated lymphoid organ.

 

Greater than 50% of the lymphoid tissue in human body is part of MALT.

 

Mucosal surfaces associated with the respiratory, digestive and genitourinary tracts are the main sites of entry for microbes.

 

MALT tissues are of two kinds:

  • (a) Subepithelial lymphocytes forming follicles covered with specialized epithelial cells called microfold or M cells.
  • (b) diffused cell populations below the epithelial cells surface.

Some believe that MALT forms an interconnected system

 

NALT

 

NALT consists of lymphoid tissue at the back of the nose (pharyngeal, tonsil and other tissue) and that associated with Waldey’s ring (palatine and lingual tonsils) which is the lymphoid tissue of the neck and pharynx. NALT handles airborne microorganisms.

 

These tissues, unlike lymphatic nodes, do not  have lymphatics.

Tonsilar lymphoid tissue: Antigens trapped in the crypts are transported by M cells into the sub-epithelial areas where lymphocytes are stimulated via antigen presenting cells

 

BALT

 

It consists of aggregates of lymphocytes organized into follicles present in all lobes of the lung.

 

These are situated under the epithelium mostly along the bronchi M cells transport trapped antigens to underlying cells which include lymphocytes

GALT

 

Microbes trying to enter the body via the intestinal tract are prevented by GALT.

 

GALT has a mechanism to distinguish between harmless food and infecting microbes. This mechanism consists of microfolds (M cells) on the epithelia and associated antigen presenting cells(APCs).

 

A complex mechanism involving APC and T-cells decides whether the “sample antigen” results in tolerance or immune response.

 

In fact similar mechanism also exists in BALT, Nalt and lymphoid tissues associated with genitourinary tract.

Peyer’s patches are aggregates of lymphocytes which appear as pale patch on the gut wall.

 

Summary

  •  Differentiation of the multipotential cell gives rise to lymphocytes
  •  B-lymphocytes and T-lymphocytes mature in the bone marrow and thymus respectively
  •  Lymphocytes circulate in the tissues via the lymphatic circulation and reach there via the blood circulation
  •  The secondary lymphoid organs, spleen, lymph nodes and MALT help in trapping of the antigen and its processing