Introduction to Lymphoid Organs
- Lymphocytes, which are immature and generated in hematopoiesis gets mature and become committed to a particular antigenic specificity within the primary lymphoid organs.
- The cell becomes immune-competent only after the lymphocytes have matured in the primary lymphoid organs.
- T cells arise in the bone marrow and develop in the thymus.
- In many mammals including human and mice, B cells originate in bone marrow.
- Both thymus and bone marrow are responsible for promoting T- cell and B-cell development respectively.
- These two are considered to be primary lymphoid organs because initial lymphocyte differentiation in these organs is essential to the development of immune system.
- It is a lympho-epithelial structure derived from the epithelium of 3rd and 4th pharyngeal pouches at about 6th week of intrauterine life.
- Finally, by 8th week it grows into a compact epithelial structure.
- Maximum size is attained by the thymus at birth but gradually its size decreases by aging.
- It is a flat, bi-lobed organ situated above the heart and behind upper part of sternum.
- Each lobe is surrounded by a capsule and divided into lobules.
- Strands of connective tissue called trabeculae separate these lobules from each other.
- There are two compartments organized for each lobule: cortex being the outer compartment and medulla the inner one.
- Cortex is densely packed with immature T-cells called thymocytes whereas medulla is sparsely populated with thymocytes.
- The cortex and medulla of the thymus are crisscrossed by three-dimensional stromal cell network.
- These networks are composed of epithelial cells, dendritic cells, and macrophages, which make up the framework of the organ.
- All these structures contribute to the growth and maturation of thymocytes.
- Many of these stromal cells interact physically with the developing thymocytes.
- The function of thymus is to generate and select a repertoire of T cells that will protect the body from infection.
- Large number of different T-cell receptors is generated by gene arrangement as the thymocytes develop, which produces some T cells with receptors capable of recognizing antigen- MHC complexes.
- However, among those receptors generated by gene rearrangement process, most of them are incapable of recognizing antigen-MHC complexes.
- But, a small portion reacts with combinations of self antigen-MHC complexes.
- Using some mechanism, the thymus induces the death of those T cells that cannot recognize antigen-MHC complexes.
- Those T cells that react with self antigen-MHC strongly enough can pose a danger of causing auto-immune disease.
- More than 95% of all the thymocytes die by apoptosis in the thymus without ever reaching maturity.
- However, minority of cells around 2% of the cells leave the thymus as mature T cells and migrate to the secondary lymphoid organs during foetal and early postnatal life and possibly over a longer period.
- Thymus attains its maximum size at puberty and then atrophies.
- This results in the significant decrease in both cortical and medullary cells and an increase in the total fat content of the organ.
- The weight of thymus is 30 grams in human infants which get reduced to about 3 grams in elderly as it is dependent to age factor.
- This loss in mass of thymus is accompanied by a decline in T cell output.
- By age 35, the thymic generation of T cells has dropped to 20% and by age of 65, the output has fallen to only 2%of the new born rate.
- The life span of immunologically competent T cells is believed to be months or years, much longer than that of B cells (days or weeks).
- Bone marrow is a complex tissue where hematopoiesis and a fat depot occur.
- 50% or more of the marrow compartment will be filled by fat with the passage of the time.
- Bone marrow generates hematopoietic cells which move through the walls of blood vessels and enter the blood stream
- Blood carries them out of the marrow and distributes these various cell types to the rest of the body.
- In human and mice, B cell originates and develops in the bone marrow.
- Arising from lymphoid progenitor, B cells which are immature, proliferates and differentiates within the bone marrow which interact directly with the stromal cells within the bone marrow.
- Various cytokines are released by this interaction that is required for development.
- Bone marrow B cells are the source of 90% of the immunoglobulins IgG and IgA in plasma.
- During T cell maturation, thymic selection occurs which is similar to the selection process in bone marrow for B cells that possess self-reactive antibody receptors.
- Bone marrow might not be the site of B cell development for all species as in human and mice.
- In birds, bursa of Fabricius which is a lymphoid organ associated with the gut works as the primary site of B cell maturation.
- In mammals such as primates and rodents, there is not such organ which works as primary lymphoid organ.
- In cattle and sheep, fetal spleen plays a vital role as a primary lymphoid tissue hosting the maturation, proliferation and diversification of B cells early in gestation.
- Later in gestation, this function is assumed by tissues that are embedded in the wall of intestine called the ileal Peyer’s patch.
- These tissues contain a large number of B cells as well as T cells.
- The rabbit also uses gut associated tissues i.e. appendix as primary lymphoid tissue for important steps in the proliferation and diversification of B cells.
Primary lymphoid organs