IMMUNE SYSTEM Department of Histology and Embryology Li jinxin No.1020603

General description of the organs Hollow organs: wall of which is composed of 3-4 tunics.

Parenchymal organs: capsule Parenchyma Interstitium

In this chapter, the following are examined: General organisation of a lymphatic organ. Structure and function of the thymus, lymph nodes and spleen.

1. Introduction 1.1.1 Immune cells lymphocytes 1.1 Immune system contents 1.1.1 Immune cells lymphocytes cells of mononuclear phagocyte system antigen- presenting cells

diffuse lymphoid tissue 1.1.2 Lymphoid tissues diffuse lymphoid tissue lymphoid nodule 1.1.3 Lymphoid organs central lymphoid organs (thymus, bone marrow) peripheral lymphoid organs (lymph nodes, spleen and tonsils)

1.2 Functions a. immunologic defense: recognizing and removing antigens that invade into the body. b. Immunologic surveillance: removing body cells with changed surface antigens. c. Immunologic homeostasis: removing aging, dead and damaged cells.

2. Immune cells 2.1.1 T cells 2.1 Lymphocytes classified into 3 classes 2.1.1 T cells a. Stem cells migrate from the bone marrow through the blood and invade the thymus.

b. Naive T cells enter peripheral lymphoid organs, under stimulation of specific antigens, proliferate and transform into effector T cells and memory T cells.

c. Responsible for cellular immunity (directly kill target cells). T cells are divided into 3 subpopulations: helper T cell ( Th ), cytotoxic T cell ( Tc ), suppressor T cell ( Ts ) . c. Responsible for cellular immunity (directly kill target cells).

2.1.2 B cells a. Stem cells undergo a series of changes in the bone marrow to form B cell. b. Naive B cells enter peripheral lymphoid organs or lymphoid tissues, under stimulation of specific antigens, proliferate and transform into plasma cells ( effector B cell) and memory B cells. c. Responsible for humoral immunity.

2.1.3 NK cells a. Lack markers characteristic of T and B cells. b. Account for 10% – 15% of total lymphocytes in the peripheral blood. c. Attack virus-infected cells and cancer cells without previous stimulation.

2.2 Macrophages and mononuclear phagocyte system ( MPS ) A group of cells that are widely distributed collection of phagocytes. They are derived from monocytes.

MPS includes Monocytes in the blood and bone marrow. Macrophages in connective tissue, lymphoid tissue, peritoneal and pleural cavities and lungs (dust cells). Kupffer cells in the liver; Osteoclasts in the bone; Microglial cells of the nerve tissue; Langerhans cells in the skin.

2.3 Antigen presenting cells Have the major histo-compatibility complex molecules (MHC). Have the capacity to capture and process antigens, form a peptide- complex and then present the complex to T cells. Mainly include dendritic cells (DCs) and macrophages.

3. Lymphoid tissue reticular tissue + lymphocytes

3.1 Diffuse lymphoid tissue Diffuse collection of lymphocytes (T or B cells), no clear boundary. Lymphoid nodules appear after antigen stimulation.

Contains postcapillary, or high endothelial venule, as passages of lymphocytes to enter the blood.

3.2 Lymphoid nodules (Lymphoid follicles) Spherical collections of densely packed lymphocytes (mainly B cells).

After antigen stimulation, the primary nodule becomes larger with germinal center, called the secondary nodule. The Germinal center divides into dark zone and light zone, the latter is covered by a cap.

4. Thymus a central lymphoid organ General description Cortex Capsule Medulla

4.1 Capsule（被膜） connective tissue interlobular septa（小叶间隔） Thymic lobules（胸腺小叶）. Each lobule has a peripheral dark zone(cortex) and a central light zone(medulla).

4.2  Cortex（皮质） Thymic epithlial cells (胸腺上皮细胞）or epithelial reticular cells form a meshwork. Numerous, densely packed lymphocytes, termed thymocytes (胸腺细胞）.

Thymic epithelial cells These cells are large and branched, and desmosomes between adjacent cells.

Thymocytes These are densely packed and do not form nodules. They arise by division of stem cells which come from the bone marrow. Most degenerate and are removed by macrophages, only a small number will mature and leave the thymus.

4.3 Medulla（髓质） Rich in epithelial cells, fewer lymphocytes. Hassall’s or thymic corpuscles（胸腺小体） These composed of concentrically arranged（同心圆排列的） epithelial reticular cells that degenerate.

4.4 Blood-thymus barrier A continuous capillary endothelial layer. The basal lamina of the endothelial cells. A pericapillary space（血管周隙） containing macrophages. A continuous layer and the basal lamina of the epithelial reticular cells.

4.5  Functions Microenvironment for bone marrow- derived lymphocytes (stem cell) to proliferate into T cells. Secretion (by the epithelial reticular cells) of thymosin （胸腺素）and thymopoietin （胸腺生成素）.

5. Lymph nodes Cortex peripheral lymphoid organs, lying along the course of lymphatic vessels Capsule Cortex Medulla Capsule Medulla

5.1 Capsule Connective tissue several afferent lymphatic vessels . Trabeculae (小梁) extend from the capsule into the parenchyma. One or two efferent lymphatic vessels leave at the hilum(门部).

5.2 Cortex Beneath the capsule, three structural components Superfacial cortex (浅层皮质) Paracortical zone (副皮质区) Cortical lymphoid sinuses (皮质淋巴窦)

5.2.1 Superfacial cortex Contains lymphoid nodules and diffuse lymphoid tissue in between. It is mainly populated by B cells. When stimulated by antigen, a lymphoid nodule responds by forming a germinal center.

5.2.2 Paracortical zone Diffuse lymphoid tissue with T cells ( thymus dependent area ). Numerous postcapillary venules (毛细血管后微静脉).

5.2.3 Cortical lymphoid sinuses Include subcapsular sinus (被膜下窦) and peritrabecular sinuses (小梁周窦). Contain reticular cells and fibers, macrophages and lymphocytes.

5.3  Medulla – 2 components Medullary cords (髓索) are lymphoid tissue cords with many B cells and plasma cells. Medullary lymphoid sinuses (髓窦) are similar to the cortical sinuses.

5.4 Functions Serve as a filter for lymph-- lymph percolate slowly. Sites for immune responses – under stimulation of antigens, both B and T cells proliferate and produce antibodies and effector T cells causing humoral and cellular immunity.

lymph percolating

5.5 Recirculation of lymphocytes Definition: Lymphocytes circulate repeatedly from lymphoid tissue and organs through the lymphatic vessels and into the bloodstream. The most actively recirculating cells are memory cells of both T and B cells.

Course: Lymphocytes in the blood stream cross the wall of postcapillary venules into the lymphoid tissue. Lymphocytes in the lymphoid tissue enter lymphatic vessels, then into the bloodstream.

Recirculation of lymphocytes lymphoid tissue /organs postcapillary lymphatic venules vessels bloodstream

Significance: to increase the probability of meeting antigens, distribute information concerning antigens, and unite the different parts of the immune system.

6. Spleen A thick capsule of dense connective tissue, covered by mesothelium and containing smooth muscle cells. Trabeculae extend from capsule into the parenchyma. The parenchyma is made up of the white pulp(白髓) and red pulp (红髓).

capsule trabecula White pulp red pulp Spleen

6.1 White pulp Periarterial lymphatic sheath (动脉周围淋巴鞘) Lymphoid nodules

(1) Periarterial lymphatic sheath Diffuse lymphoid tissue sheath encircling a central artery. Mainly contains T cells (thymus-dependent area), some macrophages. (2) Lymphoid nodules Appended to the sheath and rich in B cells. Have germinal centers when stimulated by antigens.

(3) Marginal zone (边缘区) Lies between the white and red pulps, consisting of many marginal sinuses (边缘窦). The marginal zone harbours an abundance of blood antigens and thus plays a major role in the immunologic activity of the spleen. Lymphocytes in the white pulp enter the marginal sinuses to take part in recirculation.

Marginal sinuses White pulp Red pulp Marginal zone

6.2 Red pulp Splenic Cords(脾索) Splenic sinus (脾窦)

(1) Splenic cords a. Diffuse lymphoid tissue organized in cords, containing B cells, plasma cells. b. Most capillaries open and pour blood into the cords, so rich in erythrocytes.

(2) Splenic sinusoids a. Lined by elongated endothelial cells with wide spaces between them. b. Flexible blood cells pass from splenic cords to the lumen of the sinus.

6.3  Functions Blood filter – removal of aged erythrocytes and platelets in splenic cords. Immune responses – similar to lymph nodes. Production of lymphocytes. Blood storage.