Structure and Function of the Immune System Part 1 PDF

Structure and Function of the Immune System Spring 2024 Introduction The lymphoreticular system is a complex organization of cells of diverse morphology, distributed widely in different organs and tissues of the human body, and is responsible for immunity It consists of lymphoid...

Structure and Function of the Immune System Spring 2024 Introduction The lymphoreticular system is a complex organization of cells of diverse morphology, distributed widely in different organs and tissues of the human body, and is responsible for immunity It consists of lymphoid and reticuloendothelial components and is responsible for immune response of the host The lymphoid cells, which include lymphocytes and plasma cells, are responsible for conferring specific immunity On the other hand, the reticuloendothelial system, which consists of phagocytic cells and antigen presenting cells, is responsible for nonspecific immunity These cells kill microbial pathogens and other foreign agents, and remove them from blood and tissues Lymphoid Tissues and Organs The specific immune response to antigen is of two types: (a) humoral or antibody-mediated immunity, mediated by antibodies produced by plasma cells (b) Cell-mediated immunity, mediated by sensitized lymphocytes The immune system is organized into several special tissues, which are collectively termed lymphoid or immune tissues The tissues that have evolved to a high degree of specificity of function are termed lymphoid organs Lymphoid organs include the gut-associated lymphoid tissues—tonsils, Peyer’s patches, and appendix—as well as aggregates of lymphoid tissue in the submucosal spaces of the respiratory and genitourinary tracts The lymphoid organs, based on their function, are classified into central (primary) and peripheral (secondary) lymphoid organs  You have 2 minutes to search for the below questions: 1- What is the difference between primary and secondary lymphoid organs in terms of function 2- List the primary lymphoid organs 3- List the secondary Lymphoid organs Central (Primary) Lymphoid Organs Central or primary lymphoid organs are the major sites for lymphopoiesis These organs have the ability to produce progenitor cells of the lymphocytic lineage These are the organs in which precursor lymphocytes proliferate, develop, and differentiate from lymphoid stem cells to become immunologically competent cells The primary lymphoid organs include thymus and bone marrow In mammals, T cells mature in thymus and B cells in fetal liver and bone marrow After acquiring immunological competency, the lymphocytes migrate to secondary lymphoid organs to induce appropriate immune response on exposure to antigens Thymus Thymus is the first lymphoid organ to develop It reaches its maximal size at puberty and then atrophies, with a significant decrease in both cortical and medullary cells and an increase in the total fat content of the organ The thymus is a flat, bilobed organ situated above the heart Each lobe is surrounded by a capsule and is divided into lobules, which are separated from each other by strands of connective tissue called trabeculae Each lobule is organized into two compartments: cortex and medulla The stroma of the organ is composed of dendritic cells, epithelial cells, and macrophages  Thymus Cortex: It consists mainly of (a) cortical thymocytes, the immunologically immature T lymphocytes, and (b) a small number of macrophages and plasma cells In addition, the cortex contains two subpopulations of epithelial cells, the epithelial nurse cells and the cortical epithelial cells, which form a network within the cortex Medulla: It contains predominantly mature T lymphocytes and has a larger epithelial cell-to-lymphocyte ratio than the cortex Thymus is the site where a large diversity of T cells is produced and so they can recognize and act against a countless number of antigen– MHCs (major histocompatibility complexes) The thymus induces the death of those T cells that cannot recognize antigen–MHCs It also induces death of those T cells that react with self-antigen MHC and pose a danger of causing autoimmune disease More than 95% of all thymocytes die by apoptosis in the thymus without ever reaching maturity Functions of the thymus It has many functions: Production of thymic lymphocytes is the primary function of the thymus. It is a major organ for proliferation of lymphocytes in the body It is believed to play a key role in determining the differentiation of T lymphocytes. The lymphocytes during maturation acquire new surface antigens (Thy antigens) and are called as T lymphocytes or T cells (thymus dependent) The thymus confers immunological competence on these cells during their stay in the organ. Lymphocyte proliferation in thymus, unlike in the peripheral lymphoid organs, is not dependent on antigenic stimulus The T lymphocytes are primarily responsible for cell-mediated immunity (CMI). The absence of thymus in neonatally thymectomized mice is associated with gross deficiency of CMI, resulting in lymphopenia, deficient graft rejection, and runting disease  Bone marrow Some lymphoid cells develop and mature within the bone marrow and are referred to as B cells (B for bursa of Fabricius, or bone marrow) The function of bursa of Fabricius in birds is played by bone marrow in humans Bone marrow is the site for proliferation of stem cells and for the origin of pre-B cells and their maturation to become immunoglobulin-producing lymphocytes Immature B cells proliferate and differentiate within the bone marrow Stromal cells within the bone marrow interact directly with the B cells and secrete various cytokines that are required for the development of B cells Like thymic selection during T-cell maturation, a selection process within the bone marrow eliminates B cells with self-reactive antibody receptors Bone marrow B lymphocytes develop their B-cell receptors (BCRs) by DNA rearrangement They express auxiliary molecules, and begin to express IgM on their surfaces before leaving the bone marrow Subsequently, mature B lymphocytes also acquire C3 and Fc receptors on their surfaces B lymphocytes on their surfaces either bear IgM alone or in association with IgG or IgA depending upon the production of particular class of immunoglobulin The B lymphocytes are transformed into plasma cells and secrete antibodies B lymphocytes are primarily responsible for antibody- mediated immunity Which organ am I? First lymphoid organ to develop Site of differentiation of progenitor cells into B cells % of fat increases in this organ after puberty Stroma of the organ is composed of dendritic cells, epithelial cells, and macrophages Site of the selection process of B Lymphocytes Its cortex is made of immature T Lymphocytes whereas its medulla is made of mature T Lymphocytes Where lymphocytes acquire C3b and Fc receptors on their surface Responsible of the differentiation and maturation of T Lymphocytes Peripheral (Secondary) Lymphoid Organs Peripheral or secondary lymphoid organs consist of (a) lymph nodes, (b) spleen, and (c) nonencapsulated structures, such as mucosa-associated lymphoid tissues (MALT) These organs serve as the sites for interaction of mature lymphocytes with antigens Lymph nodes The lymph nodes are extremely numerous and disseminated all over the body They play a very important and dynamic role in the initial or inductive states of the immune response Lymph nodes measure 1–25 mm in diameter and are surrounded by a connective tissue capsule The lymph node has two main parts: cortex and medulla The reticulum or framework of the lymph node is composed of phagocytes and specialized types of dendritic cells  Peripheral (Secondary) Lymphoid Organs Lymph Node Cortex: The cortex and the deep cortex are densely populated by lymphocytes B and T lymphocytes are found in different areas in the cortex The primary lymphoid follicles predominately contain B lymphocytes They also contain macrophages, dendritic cells, and some T lymphocytes The larger, less dense follicles, termed secondary follicles, are found in the cortex of a lymph node draining an area in which an infection has taken place The secondary follicles contain clear germinal centers where B lymphocytes actively divide as a result of antigenic stimulation T lymphocytes are found predominantly in the deep cortex or paracortical area; for this reason, the paracortical area is designated as T-dependent Peripheral (Secondary) Lymphoid Organs Lymph Node Medulla: It is less densely populated and is composed mainly of medullary cords These cords are elongated branching bands of the lymphocytes, plasma cells, and macrophages As antigen is carried into a regional node by the lymph, it is trapped, processed, and presented together with class II MHC molecules by dendritic cells in the paracortex, resulting in the activation of TH cells The initial activation of B cells is also thought to take place within the T-cell-rich paracortex Once activated, TH and B cells form small foci consisting largely of proliferating B cells at the edges of the paracortex Some B cells within the foci differentiate into plasma cells secreting IgM and IgG Functions of the lymph nodes Lymph nodes serve the following functions: They act as filter for the lymph, the fluid, and cellular content of the lymphocytic circulatory system They also provide sites for mingling of lymphocytes, monocytes, and dendritic cells for initiation of immune responses Most antigen-activated B cells divide and differentiate into antibody-producing plasma cells in lymphoid follicles, but only a few B cells in the antigen-activated population find their way into germinal centers Those that do, undergo one or more rounds of cell division during which the genes that encode their antibodies mutate at an unusually high rate  Spleen The spleen is the largest lymphoid organ It is a large, ovoid secondary lymphoid organ situated high in the left abdominal cavity The spleen parenchyma is heterogeneous and is composed of the white and the red pulp It is surrounded by a capsule made up of connective tissue The spleen unlike the lymph nodes is not supplied by lymphatic vessels Instead, blood-borne antigens and lymphocytes are carried into the spleen through the splenic artery In the white pulp, T lymphocytes are found in the lymphatic sheath immediately surrounding the arteriole B lymphocytes are primarily found in perifollicular area and germinal center which lie more peripherally relative to the arterioles  Spleen The spleen plays a major role in: Mounting immune responses to antigens in the blood stream The circulating antigens are trapped by the macrophages present in the marginal zone These macrophages then process the antigen, migrate deeper into the white pulp, and initiate the immune response by interacting with T and B lymphocytes Filtering or clearing of (a) infectious organisms (b) aged or defectively formed elements (e.g., spherocytes, ovalocytes) (c) particulate matter from the peripheral blood In addition, the spleen traps blood-borne antigens and microbes The main filtering function is performed by the macrophages lining up the splenic cords Splenectomy The effect of splenectomy on the immune response depends on the age at which the spleen is removed In children, splenectomy often leads to an increased incidence of bacterial sepsis caused primarily by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae In adults, the adverse effects are less; although in some, it makes the host more susceptible to blood-borne bacterial infections Mucosa-associated lymphoid tissues Mucosa-associated lymphoid tissues (MALT) consist of the lymphoid tissues of the intestinal tract, genitourinary tract, tracheobronchial tree, and mammary glands All of the MALT contain both T and B lymphocytes, and the latter predominate Structurally, these tissues include clusters of lymphoid cells in the lamina propria of intestinal villi, tonsils, appendix, and Peyer’s patches Tonsils: These are present in the oropharynx and are predominantly populated by B lymphocytes These are the sites of intense antigenic stimulation, as shown by the presence of numerous secondary follicles with germinal centers in the tonsillar crypts Mucosa-associated lymphoid tissues Peyer’s patches: These are lymphoid structures that are found within the submucosal layer of the intestinal lining The follicles of the Peyer’s patches are extremely rich in B cells, which differentiate into IgA-producing plasma cells Specialized epithelial cells, known as M cells, are found in abundance in the dome epithelia of Peyer’s patches, particularly at the ileum These cells take up small particles, virus, bacteria, etc., and deliver them to submucosal macrophages, where the engulfed material is processed and presented to T and B lymphocytes MALTs play an important role in defense system of the human host This is demonstrated by large population of antibody-producing plasma cells in MALT, whose number far exceeds that of plasma cells in the spleen, lymph nodes, and bone marrow, when combined together In addition to spleen and lymph nodes, MALTs facilitate interaction among circulating leukocytes Characteristics Lymph nodes Spleen MALT General characteristics and Composition Cells present in the structure Main Function  Lymphatic Circulatory System Leukocytes and their products use two circulatory systems: cardiovascular system and the lymphatic circulatory system The cardiovascular system is responsible for circulation of blood throughout the body Peripheral blood is “filtered” by the spleen and liver Organisms and antigens that enter directly into the systemic circulation are trapped in these two organs, of which the spleen plays the most important role as a lymphoid organ The lymphatic circulatory system, on the other hand, is an extensive capillary network that collects lymph, a clear watery fluid containing leukocytes and cellular debris, from various organs and tissues Cleared lymph originating from below the diaphragm and the upper left half of the body drains via efferent lymphatics into the thoracic duct for subsequent drainage into the left subclavian vein Cleared lymph originating from the right side above the diaphragm drains into the right lymphatic duct, which subsequently drains into the origin of the right subclavian vein The same routes are followed by the lymphocytes stimulated and produced in the lymph nodes, or peripheral lymphoid tissues, which eventually reach the systemic circulation  Thank You T: +961 1 577055 Youssef Sursock Street – Rmeil, Beirut P.O. BOX: 16-5146 – Ashrafieh, Lebanon Email: [email protected] www.sgub.edu.lb