Central immune tissues and organs

The central immune organ, or primary lymphoid organ, is the place where immune cells occur, differentiate, develop, and mature. Central immune organs of humans or other mammals include bone marrow and thymus. Bird's superior cavity (French bursa) is equivalent to the bone marrow of mammals.

(A) bone marrow

Bone marrow is the place where various blood cells and immune cells occur and differentiate, and is an important central immune organ of the body.

Bone marrow structure and hematopoietic microenvironment

The bone marrow is located in the bone marrow cavity and is divided into red and yellow bone marrow. Red bone marrow has an active hematopoietic function and is composed of hematopoietic tissue and blood sinus. Hematopoietic tissue is mainly composed of stromal cells and hematopoietic cells. Stromal cells include reticulocytes, fibroblasts, vascular endothelial cells, macrophages, etc. -CSF, etc.) and the extracellular matrix together constitute the environment in which hematopoietic cells differentiate and develop, which is called the hematopoietic induction microenvironment.

Bone marrow function

(1) Bone marrow hematopoietic stem cells (HSCs) have the ability to differentiate into different blood cells, so they are called multiple hematopoietic stem cells. HSCs are in the bone marrow microenvironment. It first differentiates into myeloid stem cells and lymphoid stem cells, the former further differentiates and matures into granulocytes, monocytes, dendritic cells, red blood cells and platelets; the latter develops into various lymphoid cells Precursor cells of cells (T cells, B cells, NK cells)

Bone marrow pluripotent hematopoietic stem cells have the ability to self-renew and differentiate. Under the influence of the bone marrow microenvironment, they can undergo differentiation stages such as directional stem cells, progenitor cells, precursor cells, and finally differentiate and mature into various blood cells.

(2) The place where B cells differentiate and mature. Progenitor cells and precursor cells of various lymphocytes produced in the bone marrow enter the thymus with blood flow. It develops into mature T cells; the other part continues to differentiate into mature B cells or natural killer cells (NK cells) in the bone marrow. Mature B cells and NK cells migrate with the blood circulation and settle in peripheral immune organs.

(3) The place where the humoral immune response occurs The bone marrow is the main part where the humoral immune response occurs again. Memory B cells are activated after being stimulated by antigens in peripheral immune organs. They can then return to the bone marrow via lymph fluid and blood, differentiate into mature plasma cells in the bone marrow, produce a large number of antibodies (mainly IgG), and release them to the blood circulation. A re-immune response occurs in peripheral immune organs such as the spleen and lymph nodes. Its antibody production rate is fast, but the duration is short; and the re-immune response that occurs in the bone marrow slowly and persistently produces a large number of antibodies, becoming the main source of serum antibodies. Therefore, in this sense, bone marrow is both the central and peripheral immune organs.

Because bone marrow is a very important hematopoietic organ and immune organ of the human body, when the bone marrow is defective, it will not only seriously damage the body's hematopoietic function, but also cause severe cellular and humoral immune function defects. For example, high-dose radiation can inhibit or lose the body's hematopoietic and immune functions at the same time. At this time, only the normal bone marrow can be implanted to rebuild blood and immune functions. In addition, by using immune reconstruction, hematopoietic stem cells or lymphatic stem cells of normal immune function individuals are transplanted to immunodeficiency individuals, so that the latter's hematopoietic function and immune function can be fully or partially restored, which can be used to treat immunodeficiency diseases and leukemia.

(B) the thymus

The thymus is the place where T cells differentiate, develop, and mature. The thymus is differentiated from the endoderm of the pharyngeal sac in the third and fourth stages of the embryo. It is located in the upper part of the thoracic mediastinum and behind the sternum. The size and structure of human thymus vary significantly with age. The thymus appeared at the 9th week of the embryo. It matures at the 20th week of the embryo and has the structure of a normal thymus. It is the earliest immune organ. The neonatal thymus weighs about 15-20g, and then gradually increases, reaching 30-40g during puberty. After puberty, the thymus gradually shrinks and degenerates with age, showing a decrease in thymus cells, an increase in interstitial cells, and a large number of fat cells. Thymus atrophy in old age, mostly replaced by adipose tissue, functional decline, resulting in decreased cellular immunity, prone to infection and tumors.

Structure of thymus

The thymus is divided into left and right leaves, and the surface is covered with a layer of connective tissue capsule. The capsule extends into the thymus parenchyma and divides the parenchyma into several thymus leaflets. The outer layer of the thymus lobe is cortex, and the inner layer is medulla. The cortex-medulla junction contains a large number of blood vessels (Figure 10-2).

(1) Cortex The thymic cortex is divided into outer cortex and deep cortex. 85% to 90% of the cells in the cortex are immature T cells (ie, thymus cells), and there are thymus epithelial cell TEC, macrophage. Mф, and dendritic cells (DC) )Wait. Thymic epithelial cells in the thymus superficial cortex can surround thymic cells, called thymic nursing cells, and can produce certain hormones and cytokines that promote the differentiation and development of thymic cells. In the deep cortex, there are mainly small cortical thymocytes.

(2) The medullary medulla contains a large number of thymic epithelial cells and scattered mature mature thymocytes, monocytes-macrophages, and DCs. Hassall's corpuscle, also known as thymus, (Thymic corpuscle), an epithelial cell clustered by degeneration and gathered in a concentric circle, is an important feature of thymus structure. The function of Hershey bodies is unknown, and they disappear during thymic inflammation or tumors.

Thymic microenvironment

The thymic parenchyma is mainly composed of thymic cells and thymic stromal cells (TSC). The former are mostly immature T cells at different stages of differentiation. The latter are mainly thymic epithelial cells, including Mф, DC, and fibroblasts. TSC constitutes the thymic microenvironment that determines T cell differentiation, proliferation, and selective development.

Thymic epithelial cells are the most important component of the thymic microenvironment. These cells participate in the differentiation of thymic cells in two ways.

(1) Thymic stromal cells that secrete cytokines and thymosin-like molecules can produce multiple cytokines, such as SCF, IL-I, IL-2, IL-6, IL-7, TNF-α, and GM-CSF Factors, these cytokines regulate thymocyte development and intercellular interactions by binding to corresponding receptors on the surface of thymocytes. Thymic peptide molecules secreted by thymic epithelial cells include thymosin, thymulin, and thymopoietin (TP), etc., which have the functions of promoting the proliferation, differentiation and development of thymic cells.

(2) Cell-cell contact between thymic epithelial cells and thymic cells can be achieved through cell surface adhesion molecules and their ligands, cytokines and their receptors, co-receptors and their ligands, antigen peptide-MHC molecular complexes TCR interactions, etc., induce and promote the differentiation, development and maturation of thymocytes.

The extracellular matrix is also an important part of the thymic microenvironment, including a variety of collagens, reticular fibrin, and glycosaminoglycans. They promote the contact of epithelial cells with thymic cells and promote the migration and maturation of thymic cells within the thymus.

3. Thymus function

The thymus is the main organ for T cell differentiation, development, and maturation. The lymphoid progenitor cells migrated from the bone marrow, after interacting with unique thymic microenvironmental stromal cells (TSC), undergo complex differentiation and development processes, and eventually become functional CD4 ﹢ T cells and CD8 + T cells, outputting the thymus. , Located in peripheral lymphoid organs and tissues. If thymocytes develop abnormally and cannot produce functional T cells, there is no T cell immunity after birth.

The development of the thymus is closely related to thymic epithelial cells. For example, thymic nude mouse is a mutation of a certain transcription factor gene in the early embryo, which causes dysplasia of thymic epithelial cells. As a result, thymic hypoplasia or loss, and T cell deficiency . The loss of human thymic epithelial cells can cause DiGeorge syndrome. Children with congenital thymic hypoplasia and lack of T cell immunity are vulnerable to repeated infections and even death. In addition, if a gene of a bone marrow hematopoietic stem cell is mutated or deleted, lymphoid progenitor cells can migrate into the thymus and the thymic microenvironmental stromal cells are normal, but they cannot develop into functional T cells, which is seen in patients with severe combined immunity Defective mice and humans.

(3) Bursa

Bursa of fabricius, also known as supraluminal sac, is a unique lymphoid organ in birds. It is located on the dorsal side of the cloaca and has a short tube connected to it. The French bursa resembles a cherry, the chicken is a spherical oval sac, and the goose and duck cavity sacs are cylindrical sacs; they reach their maximum before sexual maturity, and then gradually shrink and degenerate until they completely disappear. The inner mucosa of the bursa of the bursa forms several longitudinal folds that protrude into the cavity of the capsule; there are a large number of lymph nodes in the lamina propria of the mucosa, which are densely arranged.

Bursa is a place where B cells are induced to differentiate and mature. Bone marrow-derived lymph stem cells are induced to differentiate into mature B cells in the bursal, and then migrate to peripheral lymph organs via lymph and blood circulation to participate in humoral immunity. The humoral immune response is inhibited if the bursa of the chicks in the late stage of embryos and the newly hatched shell is removed, showing that plasma cells are reduced or disappeared, and specific antibodies cannot be produced after antigen stimulation. The effect is small, and the chicks with the removed bursa can still reject the skin graft. Certain viral infections (such as infectious bursal disease virus) or certain chemicals (such as testosterone injections) can make the bursal atrophy. If the chickens are infected with the infectious bursal disease virus, the immune function is destroyed due to the damage to the bursal, which may lead to the failure of immunization.