Immune System

IMMUNE SYSTEM

Professor Yunlian

Meng

Introduction The human body immune system has the ability to distinguish “self” from “non-self”, to neutralize or inactive foreign molecules, and to destroy microorganisms and abnormal cells in own body. On occasion, the immune system of individual reacts against its own normal body tissues or molecules, causing autoimmune disease.

Components of immune system The immune system comprises immune cells, lymphoid tissue and lymphoid organs. The immune cells include lymphocytes, plasma cells, mast cells, phagocytes and antigen presenting cells(APCs). The lymphoid tissue consists of reticular tissue and immune cells. The reticular tissue forms a network. The immune cells lie in the network. lymphoid tissue-1.ppt

There are two types of lymphoid tissue: diffused lymphoid tissue and lymphoid nodule. cortex of lymphoid node-1.ppt Lymphoid organs are mainly composed of lymphoid tissue and include thymus, bone marrow, lymph nodes, spleen, tonsils, etc. lymphoid organs.ppt

Antigens A substance that is recognized by cells of the immune system is called an antigen. Antigens may consist of soluble molecules or molecules belong to whole cells. The response of immune system elicited by the antigens is called immune response.

Antibodies The antibodies are also called immunoglobulins(Ig) which are a group of glycoproteins. The antibodies are produced by plasma cell, and can be divided into five typers: IgG, IgA, IgM, IgE and IgD. The main function of the antibodies is to neutralize the harmful effects of antigens on the body.

Basic types of immune response There are two types of immune response: humoral immune response and cellular immune response. Humoral immune response is related to the presence of antibodies that inactivate or destroy foreign substances. The antibodies are produced by plasma cells which derive from B lymphocytes, or B cells. immune reaction-1.ppt

The cellular immune response is mediated mainly by T lymphocytes, or T cells. In cellular immune response T cells react against and kill microorganisms, foreign cells (from transplants), tumor cells and virus-infected cells. immune reaction-1.ppt

Immune cells Lymphocyte Thymus dependent lymphocytes (T cells) come from thymus and have three subtypes: Cytotoxic T cell( Tc )

killing the tumor cells, virus

infective cells and foreign cells by secreting cytokine. Helper T cell( Th )

promoting activity of other

immune cells. Suppressor T cell( Ts ) other immune cells.

regulating the function of

Bone marrow dependent lymphocytes (B cells) come from bone marrow and can change into plasma cells which can secrete antibodies. Nature killer cells (NK cells) come also from bone marrow and can attack virus-infected cells and cancer cells without previous stimulation.

Antigen presenting cells(APCs) APCs are found in many tissues and constitute a heterogeneous cell population that includes macrophages , dendritic cells and B lymphocytes . Dendritic cells Langerhans cells in epidermis Interdigitating cells in spleen and lymph nodes Follicular dendritic cells in lymphoid nodules Microfold cells in small intestine

Function of APCs APCs have the capacity to capture the antigens, and to partially digest the protein of antigen into small peptides. The lymphocytes can only recognize the small peptides presented by APCs. In this way, APCs transport the antigens to lymphocytes and elicit the immune response.

Mononuclear phagocytic system (MPS) MPS has intense phagocytic activity, involving in immune response. The cells of MPS originate from monocyte series of bone marrow and distribute throughout the body Promonocyte monocyte different phagocytic cells Functions Phagocytosing abnormal cells, cell debris, bacteria, etc. As APCs Secreting enzymes and cytokines.

Cells of MPS Name Monocyte Macrophage Kupffer cell Alveolar macrophage Osteoclast Microglia Interdigitating cell Langerhans cell

Location Blood C.T., lymph node, spleen Liver Lung Bone CNS Lymphoid tissue Epidermis

Major Histocompatibility Complex (MHC) Why does the human body has the ability to distinguish “self” from “non-self” ? The immune system distinguishes self from non-self mainly by the presence on cell surfaces of MHC molecules. These molecules fall into 2 classes: MHCI is present in all cells, whereas MHC-II is found only in APCs. MHC molecules is unique to each individual.

This is the main reason tissue grafts and organ transplants are often rejected if they are not made between identical twins who possess identical MHC molecules.

Lymphoid tissue The lymphoid tissue consists of reticular tissue and immune cells. The reticular tissue forms a network. The immune cells lie in the network. Reticular cells stellate-shaped with processes to form network Reticular fiber Immune cells: lymphocytes, macrophage, plasma cell and mast cell,etc. lymphoid tissue-1.ppt

There are two types of lymphoid tissue: diffused lymphoid tissue and lymphoid nodule, or lymphoid follicle. cortex of lymphoid node-1.ppt Diffuse lymphoid tissue Irregular in shape, no clear boundary mainly consists of T cell postcapillary venules High endothelium Postcapillary venule.ppt Opening for lympycytes to enter lymphoid tissue from blood.

Lymphoid nodule spherical or ovoid; composed of B cells

have a clear boundary;

mainly

Well developed lymphoid nodule ( secondary lymphoid nodule) Cap small lymphocytes Germinal center middle sized lymphocytes large lymphoblasts

Lymphoid organs Central lymphoid organs: thymus and bone marrow 

develop earlier (fetal period )



place for stem cells to proliferate and differentiate

send lymphocytes to peripheral lymphoid organs two weeks before borne 

Peripheral lymphoid organs: lymph node, spleen and tonsils Develop

later

lymphocytes

come from central lymphoid organs

cell

proliferation need antigen stimulating( antigen dependent) place

for immune reactions

Lymph node lymph nodes lie along the course of the lymphatic vessels, especially in axilla, groin, neck, mesentery and prevertebral region. lymphoid organs.ppt The entire node is bean-shaped, the concavity constituting a hilum through which blood vessels enter and leave the node. Several afferent lymph vessels enter the node on its convex aspect. Usually, a single efferent lymph vessel leaves the node through its hilum. lymphoid node-M.ppt

Structure Capsule connective tissue with afferent lymph vessels and blood vessels. Trabeculae connective tissue, forming a framework. Parenchyma lymphoid tissue, can be divided into cortex: outer densely stained part medulla: inner paler stained part lymphoid node-M.ppt lymphoid nodecapsule.ppt

Cortex The cortex of lymph node consists of lymphoid nodules, paracortical region (thymus dependent zone) and cortical sinuses .

Lymphoid nodules with or without germinal center, B cell mainly, follicular dendritic cells Paracortical region (thymus dependent zone) diffuse lymphoid tissue, T cells mainly, marcophages, APCs. postcapillary venules, lymphocytes can pass this vessel through the endothelia or intercellular space cortex of lymphoid node-1.ppt

Postcapillary venule.ppt

Cortical sinuses lymphoid sinus subcapsular sinus and peritrabecular sinus lymphoid sinuses.ppt

Medulla The medulla includes medullary cords and medullary sinuses. Medullary cord The lymphoid tissue is arranged in the form of cords which contain B cells, T cells, plasma cells, macrophages and mast cells. Medullary sinuses similar to cortical sinuses, more irregular more macrophages lymphoid node-medulla.ppt

Lymph circulation in lymph node Afferent lymphoid vessels Subcapsular sinuses Peritrabecular sinuses Medullary sinus Efferent lymphoid vessels

Functions of lymph node ① Filter the lymph 99% of antigens and other debris are filtered by lymph node. ② Place to give rise to the immune response both T cells and B cells both cellular and humoral immune response ③ Involve in the recirculation of lymphocytes.

Recirculation of lymphocytes Pathway Lymphoid organs or tissues

Postcapillary venules

Efferent lymphoid vessel (Lymph circulation)

Blood circulation

Function ①An efficient surveillance. ②Promote the communication among immune system. ③Provide for more rapid and more persistent immune responses.

Spleen The spleen is the largest lymphoid organ of the body.

Structure Capsule The capsule of spleen is the visceral layer of peritoneum which is formed by connective tissue with smooth muscles and mesothelium. Trabeculae connective tissue with smooth muscles. Parenchyma lymphoid tissue white pulp, red pulp and marginal zone spleen.ppt

White pulp Periarterial lymphatic sheath T cells surround the central artery forming Periarterial lymphatic sheath. There are also some macrophages and interdigitating cells. thymus dependent area Lymphoid nodules (splenic corpuscle) B cells white pulp.ppt

Red pulp Splenic cord lymphoid cord, including T cell , B cell, plasma cell, macrophages, and blood cells. Place for filtering blood Splenic sinus specialized capillary; rod-like endothelium, incomplete basal lamina, large spaces between endothelium; large and irregular lumen. This permits blood cells to pass through the wall of splenic sinus freely. red pulp.ppt

Marginal zone It is between the white pulp and red pulp, about 100um width. There are T cells, B cells, macrophages and numerous APCs. Marginal sinusoids the branches of central artery, channels for lymphocytes entering lymphoid tissue from blood. This region seems to be specialized for bringing antigens (confined to circulating blood )into contact with lymphocytes in the spleen so that an appropriate immune response can be started against the antigens.

Blood supply of spleen splenic A

trabecular A central A

marginal sinuses

penicillar Arterioles Closed circulation splenic sinuses pulp venule blood circulation.ppt

Open circulation splenic cords trabecular vein splenic vein

Lymph vessels of the spleen Traditionally, it has been held that in the spleen lymph vessels are confined to the capsule and trabeculae. Recent studies have shown, however, that they are present in all parts of the spleen. Lymphocytes produced in the spleen reach the blood stream mainly through the lymph vessels.

Functions Filter blood The spleen acts as a filter for worn out red blood cells. Normal erythrocytes can change shape and pass easily through narrow passages. However, cells that are aged are unable to change shape and are trapped in the spleen where they are destroyed by macrophages. Where is the blood filtered in?

Place of immune response T cells Periarterial lymphatic sheath cellular immune response B cells Lymphoid nodules humoral immune response Produce blood cells In fetal life the spleen is a centre for production of all blood cells. After birth only lymphocytes are produced here.

Blood storage The spleen is often regarded as a store of blood which can be thrown into the circulation when required.

splenomegaly In

conditions

calling

for

increased

lymphocyte

production (leukaemia), or conditions in which there is increased phagocytosis by macrophages (as in any infection), and in conditions involving increased destruction of erythrocytes (e.g., malaria) there may be enlargement of spleen. The condition is called splenomegaly. When spleen becomes splenomegaly the function of spleen is facilitated, which may cause anemia.

Tonsils The tonsils constitute a lymphoid tissue that lies beneath, and contact with, the epithelium of the initial portion of the digestive tract. Depending on their location, tonsils in the mouth and pharynx are called palatine tonsil, pharyngeal tonsil and lingual tonsil. Tonsils are the place of immune response.

Palatine

tonsil

The palatine tonsils consist of diffuse lymphocytes and lymphoid nodules disposed under a stratified squamous epithelium which forms many crypts. The epithelium of crypts often contain dead epithelial cells and inflammatory cells. So it is called crypt infiltrated epithelium.

Thymus Central lymphoid organ Behind the upper portion of sternum

At birth the thymus weighs 10 ～ 15g. The weight increases to 30 ～ 40g at puberty. Subsequently, much of the organ is replaced by fat. However, the thymus is believed to produce T-lymphocytes throughout life.

Structure of thymus

thymus.ppt

Capsule: connective tissue Interlobular septum : connective tissue Parenchyma lobules cortex: dark-staining medulla: lighter-staining lymphoid tissue consists of epithelial reticular cell, thymocytes and macrophages. thymus-M.ppt

The thymus has a rich blood supply. It does not receive any lymph vessels, but gives off efferent vessels.

Cortex: Epithelial reticular cell in cortex have different shape: star-like with processes, forming a framework. flattened, secreting thymosin and thymopoietin The epithelial reticular cells in the cortex also act as thymic nurse cells. They promote Thymocytes proliferation and differentiation, and destroy Thymocytes that react against self antigens. thymus-M.ppt

T-CORTEX.ppt

Thymocytes Lymphocytes(T cell precursors) in thymus are called thymocytes. In the cortex they are densely packed, in various stages of differentiation and maturation. From superfacial cortex to deep cortex: Large low differentiated thymocytes. Middle sized thymocytes. Small maturation thymocytes .

thymus-M.ppt T-CORTEX.ppt

95% of thymocytes in cortex are destroyed by epithelial reticular cells and macrophages. Only 5% of thymocytes become T cell. Why? React against self antigens.

Medulla Many epithelial reticular cells A few mature thymocytes(T cells) Thymic corpuscles (Hassall corpuscles) They are acidophilic bodies that consist of concentric layers of epithelial reticular cells. They sometimes calcify. Their function is unknown, but they are characteristic structure of thymus. thymus-M.ppt T-medulla.ppt

Blood-thymus barrier There is a barrier between blood and thymic tissue. Large molecular substances in blood can not enter the cortex of thymus. Components Contineous capillary with contineous endothelial cell and complete basement membrane of endothelium peri-vessel space containing macrophages basal lamina of epithelial reticular cells Processes of epithelial reticular cells with desmosome T-B barrier.ppt

Function Provide

a

stable

environment

for

lymphocytes

development . It is difficulty that antigen and some medicine in blood pass into the parenchyma of thymus, especially in cortex. This is important for development of thymocytes.

Function of thymus Place for differentiation and mature of T cells. Secretion secreting thymosin and thymopoietin by epithelial reticular cells.

Questions 1. What is lymphoid tissue? How many types of lymphoid tissue are there? What differences are there between they? 2. Describe the differences between the lymph node and the spleen. 3. Describe the structure and function of blood-thymus barrier. 4. Describe the route and function of lymphocyte recirculation.