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1 | Page: Immune Cells and Tissues Swailes Cells and Tissues of The Cells and Tissues of the Immune System N. Swailes, Ph.D. Department of Anatomy and Cell Biology Rm: B046A ML Tel: 5-7726 E-mail: [email protected] Required reading Mescher AL, Junqueira’s Basic Histology Text and Atlas, 12th Edition, Chapter 20: pp226-2480 Ross MH and Pawlina W, Histology: A text and Atlas, 6th Edition, Chapter 21: pp396-429 Learning objectives 1) Identify the major cells of the immune system and briefly outline their function 2) Describe the general structure of lymphoid tissue 3) Differentiate between primary and secondary immune organs 4) Identify the thymus and discuss the role of its cells in ‘educating’ immature T-cells 5) Identify a lymph node and outline how an immune response is triggered here 6) Identify the spleen and describe the role of red and white pulp in filtering the blood and reacting to blood borne antigens 7) Differentiate between MALT in the oral cavity (tonsils) 8) Know where to find and how to identify examples of BALT and GALT Major Take Home Points A. Lymphoid tissues are composed of different types of lymphocytes and supporting cells within a scaffold of Type III collagen/reticular fibers B. The major primary lymphoid organs are encapsulated organs where immature lymphocytes are born (bone marrow) and become immunocompetent (thymus) C. The major secondary lymphoid organs are encapsulated organs where immunocompetent lymphocytes differentiate into effector cells after exposure to antigen in the blood (spleen) or lymph (nodes) D. Mucosa Associated Lymphoid Tissues (MALT) are un-encapsulated areas of lymphoid tissue within the mucosa of organs that can be identified by their lining epithelium (tonsils, GALT: ileum and appendix, BALT) 1 | Page: Immune Cells and Tissues Swailes A1: Organization of the immune system 5a A. General organization 2 Organs of the immune system: 5b 1. Bone marrow (see MOHD1) - site of immune cell development 4 2. Thymus - located in superior mediastinum 5c - site of T-cell ‘education’ 3 3. Lymph nodes - filters lymph - a site where immune responses can be initiated 4. Spleen - filters the blood - largest lymphoid organ 1 - a site where immune responses can be initiated 5. MALT - Mucosa Associated Lymphoid Tissue located in the mucosa of a number of organs including - the tonsils - BALT (Bronchus Associated Lymphoid Tissue) - GALT (Gut Associated Lymphoid Tissue) - e.g.Peyer’s patch, appendix The organs of the immune system are composed of immune cells AND lymphoid tissue 2 | Page: Immune Cells and Tissues Swailes B. Immune cells There are two populations of immune cells: lymphocytes and supporting cells 1. Lymphocytes - are the main cellular constituent of lymphatic tissue - are classified as T-cells, B-cells and Natural Killer (NK) cells - all possess unique cell-surface markers called Cluster of Differentiation (CD) molecules a) T-cells - are born in the bone marrow but are educated in the thymus (hence the “T”) - all have CD2, CD3 and CD7 markers - all have a T-cell receptor (TCR) that recognizes antigens - are involved in cell mediated immune response (doesn’t involve antibodies) There are three types of T-cell: i. “Helper” CD4+ T-cells - are identifiable because they express a CD4 marker - help activity of other immune cells (e.g B-cell activiation)) ii. “Cytotoxic” CD8+ T-cells - are identifiable because they express a CD8 marker - recognize and destroy virus infected cells or tumor cells iii. “Gamma/Delta” γ/δ T-cells - have neither CD4 nor CD8 marker - colonize epithelia to form a first line of defense against mucosa breaching antigens BCR b) B-cells - are born and mature in the bone marrow - differentiate in lymphoid organs - have CD9, CD19, CD20 and CD24 markers - have a B-cell receptor (BCR) that recognizes antigens CD9, CD19 - are involved in the humoral immune response (involves antibodies) CD20, CD24 To activate a B-cell two signals are required: - B-cells must bind antigen at BCR - B-cells must bind an activated complementary T-helper cell Activated B-cells differentiate to form: i. Memory B-cells - respond rapidly when they next encounter the same antigen ii. Plasma cells - synthesize antibodies against the antigen 3 | Page: Immune Cells and Tissues Swailes CD16 CD56 CD94 c) Natural Killer/NK-cells Fc - are born and differentiate in the bone marrow - have CD16, CD56 and CD94 markers - have an Fc receptor that binds antibodies attached to tumor cells and virus infected cells - release perforin (a protein that punches holes in cell membranes) - release granzyme (enzyme that induces apoptosis) 2. Supporting cells a. Granulocytes i. Basophils - trigger allergic reactions and anaphylaxis - pro-inflammatory (release vasoactive agents; heparin) ii. Eosinophils - primarily anti-parasitic - migrate to areas of allergic reaction - degranulate to destroy antibody-antigen complex iii. Neutrophils - primarily antibacterial - phagocytose antibody-antigen complex - main component of pus b. Agranulocytes i. Monocytes - leave the circulation to form tissue macrophages (histiocytes) c. Antigen Presenting Cells (APCs) - phagocytose and breakdown antigen - display antigen fragments at the cell surface - interact with “Helper” T-cells and B-cells - Macrophages are APCs located throughout the body - Dendritic cells are APCs in the spleen and lymph nodes - Langerhans cells are APCs in the epidermis - Epithelioreticular cells are APCs in the thymus d. Other i. Reticular cells - fibroblast-like cells - synthesize the Type III collagen (reticular fibers) of lymphoid tissue. 4 | Page: Immune Cells and Tissues Swailes A2. Primary lymphoid organs Regions of the body where lymphocytes become immunocompetent (recognize self v non-self): 1. Bone Marrow (see MOHD1) - is the site of erythrocyte and leukocyte development from stem cells - was the subject of our histological investigations in MOHD1 - is the site of T-cell development, immature T-cells leave the marrow sinusoids and migrate to the thymus to mature - is the site of B-cell and NK-cell development and maturation, these cells are released into the blood stream for circulation 2. Thymus - develops in mediastinum from the third pharyngeal pouch - during development it is infiltrated by immature T-cells aka ‘thymocytes’ - forms a bilobed structure in the mediastinum that diminishes with age - is an encapsulated lymphoid organ a. General Structure - a connective tissue capsule gives off trabecula that surround thymic lobules - thymic lobules are organized into a medulla and cortex - the cortex is basophilic because it is packed with thymocytes and scattered epithelioreticular cells - the medulla is paler and contains Hassall’s corpuscles 5 | Page: Immune Cells and Tissues Swailes The cells of the thymic lobule play an important role in T-cell education (see below) 5. Negative selection 6. Single positive - in the medulla TCR receptors are - surviving T-cells lose a CD4 or exposed to huge array of self CD8 marker making them antigens on surface of Type V ‘cytotoxic’ or ‘helper’ epithelioreticular cells - those that bind are eliminated! 4. Corticomedullary junction - positive selected T-cells pass CORTEX CMJ MEDULLA through barrier created by failed! Type III and IV epithelio-reticular CD8 cells at the corticomedullary junction CD8 CD4 CD 4 3. Positive selection TCR - Type II epithelio - reticular cells express self MHC antigens. - if T-cells recognize CD8 these they pass CD4 - 80% fail and are killed! failed! failed! 2. CD4/CD8 T-cells - as they develop thymocytes express TCR and both CD4 and CD8 markers Hassall’s corpuscles (Type VI epithelioreticular cells) secrete cytokines that aid the education process 1. Thymocytes 7. Educated T-cells exit - immature T-cells in outer cortex - only about ~2% of thymocytes - naïve and do not express CD markers or TCRs re-enter the circulation as - Type I epithelioreticular cells form a blood-thymus functionally mature CD4+ or barrier ensuring T-cell exposure to antigen in the CD8+ T-cells thymus is a controlled event 6 | Page: Immune Cells and Tissues Swailes A3. Secondary lymphoid organs Regions of the body where immunocompetent lymphocytes differentiate into effector cells in an antigen dependent manner. 1. Lymph Nodes a. General Structure and function - bean shaped organs - located along the lymphatic vessels throughout body - encapsulated - filter the lymph - provide environment where antigen dependent differentiation of B-cells can take place i. Afferent lymphatics Lymph enters the node here ii. Capsule A dense irregular capsule iii. Subcapsular sinus Lymph drains into this space deep to the capsule iv. Trabeculae The capsule extends into the ix. Efferent lymphatics parenchyma to form trabeculae Lymph exits the node here v. Trabecular sinus The capsule extends into the parenchyma to form trabeculae vi. Cortex The outer cortex contains follicles. The paracortex contain HEVs vii. Medulla viii. Medullary sinuses The inner region of the lymphoid tissue. It is Lymph flows through these spaces as it organized into cords of lymphoid tissue proceeds through the medulla 7 | Page: Immune Cells and Tissues Swailes b. Flow of lymph The flow of lymph is important in ensuring the lymph node is a region where lymphocytes ( ) antigen ( ) and dendritic APCs ( ) can mix to promote B-cell differentiation i. Antigen-rich lymph enters at outer cortex paracortex afferent vessels and passes medulla into the subcapsular sinus vi. Lymph leaves via efferent lymphatics ii. Lymph percolate s through the lymphoid tissue in the medulla OR Travels direct ly through trabecular sinuses v. Lymph flows through the medullary sinuses iii. Macrophages & iv. Lymphocytes enter lymph nodes through high dendritic APCs trap and process endothelial venules (HEVs) in the paracortex antigen and present it to lymphocytes aiming to maximize B-cell, T-cell, antigen interaction c. Lymphoid nodules - The lymph node provides all the ingredients required to activate a B-cell! i. a constant flow of antigen filled lymph (filth!) ii. dendritic cells to sequester antigen and present it to lymphocytes iii. Helper T-cells ready to accept antigen and then bind their complementary B-cells iv.
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