The lymphocytes and APCs for adaptive immunity are distributed throughout the body in the blood, lymph, and epithelial and connective tissues. Lymphocytes are formed initially in primary lymphoid organs (the thymus and bone marrow), but most lymphocyte activation and proliferation occur in secondary lymphoid organs (the lymph nodes, the spleen, and diffuse lymphoid tissue found in the mucosa of the digestive system, including the tonsils, Peyer patches, and appendix).
The immune cells located diffusely in the digestive, respiratory, or urogenital mucosae comprise what is collectively known as mucosa-associated lymphoid tissue (MALT). Proliferating B lymphocytes in the secondary structures of MALT are arranged in small spherical lymphoid nodules. The wide distribution of immune system cells and the constant traffic of lymphocytes through the blood, lymph, connective tissues, and secondary lymphoid structures provide the body with an elaborate and efficient system of surveillance and defense.
The lymphoid organs are classified into two types. They are primary (central) or secondary (peripheral).
Primary Lymphoid Organs
Primary lymphoid organs are major sites for lymphopoiesis. Here the lymphocytes develop, differentiate from lymphoid stem cells, proliferate and mature into functional cells. In mammals, T cells mature in thymus and B cells in fetal liver and bone marrow (bursa of Fabricius is the site for B cell development) in birds. It is in the primary lymphoid organs the lymphocytes acquire the antigen receptors to fight with the antigenic challenge subsequently during life.
Thymus (Sites for T Cell Development)
The thymus of mammals is composed of two lobes, each comprising multiple lobules being separated by connective tissue trabeculae. Lymphocytes (thymocytes) are placed more densely towards the periphery of each lobule than near its center, which gives rise to the outer cortex and inner medulla. The tightly packed outer cortex contains relatively more immature proliferating thymocytes. The medulla contains more mature cells. Mature thymocytes in the medulla express CD44, which is not detected in cortical thymocytes. There is a network of epithelial cells through out the lobules, which plays a role in differentiation processes from stem cells to mature T lymphocytes.
The epithelial component is made up of sheets and islands of squamous cells that make and secrete factors that attract T cell precursors from the blood and also promote subsequent maturation within the thymus. These factors include a chemokine called thymus expressed cytokine (TECK) and a number of small, incompletely characterized peptide hormones known as thymulin, thymopoietin, thymic humoral factors and thymosin. In addition interdigitating dendritic cells (IDCs) and macrophages, both derived from bone marrow, are found particularly in corticomedullary junction. Epithelial cells, IDCs and macrophages express major histocompatibility complex (MHC) molecules, which are crucial to T cell development and selection.
The mammalian thymus involutes with age. In man atrophy starts at puberty and continues through the rest of life. The involution begins with the cortex and the entire cortical areas disappear though medullary remnant persists. It is said that T cell generation in the thymus continues into adult life though at a lower rate.
Bone marrow is the primary source of pluripotent stem cells that give rise to all hemopoietic cells including lymphocytes. It is the major organ for B cell maturation and gives rise to the precursor cells of the thymic lymphocytes.
The bone marrow gives rise to all of the lymphoid cells that migrate to the thymus and mature into T cells, as well as to the major population of conventional B cells. B cells mature in the bone marrow and undergo selection for non-self before making their way to the peripheral lymphoid tissues: there they form primary and secondary follicles and may undergo further selection in germinal centers.
Secondary Lymphoid Organs
These organs provide the sites for the interaction of lymphocytes with the antigen, which then proliferate to become effector cells.
These are of following types:
- Lymph nodes
- Mucosal associated Lymphoid Tissue (MALT)
- Peyer’s patches of small intestine and appendix are also some of the secondary lymphoid organs.
The secondary (peripheral) lymphoid tissues consist of well-organized encapsulated organs—the spleen and the lymph nodes and non-encapsulated accumulations that are found throughout the body, specially with the mucosal surfaces and is called MALT. After acquiring immunological competence, in the primary lymphoid organs (thymus and bone marrow) the lymphocytes migrate along the blood and lymph stream, accumulated in their respective sites in lymph nodes and spleen. Following antigenic stimulus they cause the appropriate immune response. The spleen is responsive to blood born antigens and the lymph nodes protect the body from the antigens coming from the skin or internal surfaces via lymphatics.
In contrast, the mucosal system protects from antigens entering the body directly through mucosal epithelial surfaces—lining of the intestinal tract [gut-associated lymphoid tissue (GALT)], the respiratory tract [bronchus-associated lymphoid tissue (BALT)] and the genitourinary tract. The prime effector mechanism is secretory immunoglobulin A (sIgA) secreted directly on to the mucosal surfaces of the tract.
Function of secondary lymphoid organs
1.Secondary lymphoid tissues functions as filtration devices removing :-
- Dead cells
- Foreign matter
- Protein aggregates from the circulation.
2. Secondary lymphoid organs are rich in supply of blood vessels and lymphatic vessels these facilitates the movement of lymphocytes, monocytes and dendritic cells into and out of these organs.
3. Antibodies are formed in secondary lymphoid organs.
- Small round or oval shaped secondary lymphoid organs.
- Function as filter to purify lymph,the fluid and cellular content of the lymphatic circulatory system.
- provide site for lymphocytes,monocytes and dendritic cells for initiation of immune resposes
- Human lymph nodes are 2 to 10 µm in diameter, are round or kidney-shaped. Lymph node has an indentation called hilus through which blood vessels enter and leave. Lymph arrives at the lymph node via several afferent lymphatics and leaves the node through efferent lymphatic vessels at the hilus. Lymph node is surrounded by a fibrous capsule from which trabeculae penetrate into the node. The lymph node consists of a B cell area (cortex), a T cell area (paracortex) and a central medulla, which has cellular cords that has T cells, B cells, plasma cells and abundant macrophages.
Structure of lymph nodes
1. Cortex :-
- Outer most layer.
- Contains lymphocytes,macrophages follicular dendritic cells arranged in primary follicle.
2. Paracortex :-
- Contains T lymphocytes
- Thymus dependent area.
- The paracortex contains many APCs, which expresses high levels of MHC class II surface antigens. The accumulation of lymphocytes in the cortical area is known as primary follicle. Following antigenic stimulation, germinal center appears, which is known as secondary follicle. Lymph nodes act as a filter from the lymph, each group of nodes draining a specific part of the body. The macrophage phagocytose foreign materials including microorganisms. They help in proliferation and circulation of T and B cells. The lymph nodes enlarge following antigenic stimulation.
3. Medulla :-
- Inner most layer
- Contain blood vessels
How lymph nodes works
- Antigen reaches at regional node(lymph)
- It is trapped
- MHC molecules-Atigen(interdigitating dendritic cells)
- Resulting activation of T cells.
- Activation of B cells
- Initiation activation of B cells take place within Para cortex
- B cells differentiate into plasma cells
- Phagocytosis of antigen.
- Bean shaped organ.
- Present in left side of abdominal cavity.
- Specializes in filtering blood and trapping blood borne antigens.
- Blood borne antigens,lymphocytes through splenic artery.
- Spleen surrounded by capsule.
- Also contains large numbers of plasma cells secreting immunoglobulins into the circulation.
The spleen filters blood much as the lymph nodes filter lymph. It is enclosed in a thin and rather fragile connective tissue capsule, which penetrate into the parenchyma of the organ as trabeculae. The branches of the splenic artery (trabecular artery) travel along the trabeculae and on leaving them branch again, to form the central arterioles.
Each arteriole is encased in a cylindrical cuff of lymphoid tissue that mainly consists of mature T cells and are called periarteriolar lymphoid sheath (PALS). Primary and secondary lymphoid follicles protrude at intervals from the sheath. These are identical to the follicles found in other lymphoid tissues and are composed mainly of B cells surrounding the sheath and lymphatic follicles. Together the region is called marginal zone, composed mainly of B cells and macrophages.
The arterioles, sheaths, follicles, marginal zones and a small amount of associated connective tissue are together called white pulp. The lymphatic sheath immediately surrounding the central arteriole is thymus dependent area of the spleen. The perifollicular region, germinal center and mantle layer form the B cell-dependent areas. Blood flows from the arterioles into the red pulp, a spongy blood filled network of reticular cells and macrophage lined vascular sinusoids that makes of the bulk, of the spleen and then exits by way of the splenic veins.
During the course of each day, approximately half the blood volume passes through the spleen where lymphocytes, dendritic cells and macrophages survey for evidence of infectious agents. Then the spleen serves as a critical line of defense against bloodborne pathogens. Spleen, besides acting as a blood filter, also serves eliminating abnormal damaged and senescent red or white cells from the blood.
How spleen works :-
- Blood borne antigen and lymphocytes(splenic artery)
- Trapped by interdigiting dendritic cells
- Initial activation of B and T cells in PALS
- Combined with MHC molecules and T helper cells
- Activation of B cells
- Rapidly dividing B cells
- Plasma cells-antibody production
Mucosa-associated lymphoid tissue(MALT), Tonsils and Peyer’s Patches
- This is located within the lining of main tracts in the body like respiratory, digestive, urogenital tracts.
- MALT is populated by lymphocytes such as T cells and B cells, as well as plasma cells and macrophages, each of which is well situated to encounter antigens passing through the mucosal epithelium.
- The secondary lymphoid tissues that defends the mucosa surfaces are:-
- Tonsils in the nasopharynx.
- Peyer’s patches in the submucosal surfaces of the small intestine
Dense population of T and B lymphocytes, plasma cells macrophages can normally be found below the mucosal lining of alimentary system, genitourinary system and the respiratory system, to detect any foreign substances that contact these body surfaces. In most areas, the cells form diffuse disorganized mass with occasional isolated lymphoid follicle.
At other site, the cells are organized into discrete stable anatomic structures such as tonsils, Peyer’s patches. Tonsils are nodular aggregates of macrophages and lymphoid cells, without a capsule, lies beneath the stratified squamous epithelium of the nasopharynx and soft palate. Tonsils detect and respond to pathogens in the respiratory and alimentary tract. Similar to tonsils, some uncapsulated lymphoid nodules are present in the iliac submucosa of small intestine, called Peyer’s patches. They serve to detect the substances that diffuse across the epithelial surfaces. Together all of the organized and diffuse lymphoid tissues are known as MALT. Such lymphoid tissue in the gut and bronchial mucous membrane are known as GALT and BALT respectively. One important function of these tissues is to secrete antibodies across the mucosal surface, as a defense against external pathogens.