Histology of Lymphoid Organs PDF

Histology of Lymphoid Organs Slides created by Audra Schaefer, PhD Modified by Casey Boothe, PhD ID767 10/10/22 Session Learning Objectives • Describe the key components (and their functions) of the immune system. • Describe the cellular organization and functions of the thymus. • Describe the str...

Histology of Lymphoid Organs Slides created by Audra Schaefer, PhD Modified by Casey Boothe, PhD ID767 10/10/22 Session Learning Objectives • Describe the key components (and their functions) of the immune system. • Describe the cellular organization and functions of the thymus. • Describe the structural architecture and cellular composition of lymph nodes, their function(s), and lymph and blood circulation within them. • Define the non-encapsulated collections of lymphoid tissue associated with the gastrointestinal tract (GALT): tonsils, Peyer's patches, and appendix. • Describe the structural architecture, cellular composition, and function of the spleen. Innate vs Adaptive Immunity • Innate – present from birth • Involves leukocytes, defensins, complement, lysozyme, interferons • Adaptive – develops slowly • Based on antigens being presented to lymphocytes that are in blood, lymph, epithelia and connective tissues • Produces memory cells that permit very rapid response upon re-exposure to same specific microbe Lymphoid Organs • Primary • Thymus, bone marrow • Secondary • Lymph nodes, spleen, mucosa -associated lymphoid tissue (MALT) Innate Immunity • Physical barriers – skin, mucous membranes of GI, respiratory and urogenital tracts – prevent infections or penetration of host body • Neutrophils and other leukocytes remove bacteria, fungi, parasites that do get through • Toll-like receptors (TLRs) on leukocytes allow recognition and binding of invaders • Natural killer cells (primitive lymphocytes)– destroy unhealthy host cells • Antimicrobial chemicals produced by leukocytes and cells of barriers: • Hydrochloric acid, defensins, lysozyme, complement, interferons Adaptive Immunity • Evolutionarily more recent development • B and T lymphocytes become activated against specific invaders • Presented with antigens by antigen presenting cells • Responses are aimed at specific invaders and involve memory lymphocytes Cytokines • Peptides and glycoproteins that coordinate cell activities in innate and adaptive immune responses • Roles: • • • • Chemotaxis - directed cell movements produced by chemokines Increased mitotic activity of certain leukocytes Stimulate/suppress lymphocyte activities in adaptive immunity Stimulate phagocytosis or directed cell killing by innate immune cells • IMPORTANT Clinically – site for pharmaceutical action Antigens & Antibodies • Antigen = molecule recognized by cells of adaptive immune system, typically eliciting response from these cells • Examples: bacteria, protozoa, tumor cells • Cellular Response = lymphocytes are in charge of eliminating the antigen • Humoral Response = antibodies are responsible for response • Antibodies (immunoglobulins) = glycoproteins that interact with antigen determinants/epitopes Which cell produces antibodies? Where do you find this cell in the body?* I do not care if you can memorize specific percentages. Have a general idea of which ones are more prevalent than others and know what their function(s) seems to be. Antigen Presentation • Major Histocompatibility complex (MHC) = protein complex on the surface of antigen-presenting cells • MHC Class I – present all nucleated cells • “self-antigens” – T cells ignore • MHC Class II – present on cell surface of cells of mononuclear phagocyte system • Bind fragments of proteins the cell has ingested • Antigen Presenting Cells (APCS) – all express MHC Class II molecules • Mononuclear phagocyte system • Dendritic cells (specialized immune cells) Immunosuppressive drugs (e.g. cyclosporin) inhibit cytotoxic T cell activation – prevents rejection of tissue grafts Lymphocytes • T lymphocytes – comprise ~75% circulating lymphocytes, recognize antigenic epitopes • Helper T cells (CD4) – assist with immune responses by producing cytokines to promote B cell differentiation, activate macrophages and CTLs • Cytotoxic T lymphocytes (CTLs; CD8+) – bind antigens on foreign cells or virusinfected cells • Cell-mediated immunity • Regulatory T cells (CD4+CD25+) – inhibit specific immune responses • Peripheral tolerance Lymphocytes • B lymphocytes – surface receptors for antigens are monomers of IgM or IGD • Receptor binds antigen and complex undergoes endocytosis • Degraded in endosomes, and peptides from antigens presented on MHC class II molecules • Helper T cell binds B cell and activates with cytokine – induces recombination of immunoglobulin genes and stimulates cell proliferation Where do we find lymphocytes? Lymphoid Nodule (a.k.a. follicle) • B cells attach to receptors of follicular dendritic cells in secondary lymphoid organs, become activated and aggregate as primary lymphoid nodule • Adjacent T cells help for larger secondary lymphoid nodule • Germinal center – large lymphoblasts undergoing immunoglobulin gene recombination, proliferation • Mantle – nonproliferating B cells get pushed aside and form this more darkly stained region Thymus • Bilobed structure of mediastinum develops from endoderm • Induces central tolerance – prevents autoimmunity • At birth – fully formed and actively producing T-cells • At puberty undergoes involution • Lobulated organ with cortex and medulla Thymic Cells • T lymphoblasts (thymocytes) • Thymic epithelial cells/Epithelial reticular cells • Cytoreticulum – processes with keratin tonofilaments are joined by desmosomes • Macrophages and lymphoblasts attach • These are APCs! Express MHC I and II, secrete cytokines • Blood-thymus barrier – joined by desmosomes and occluding junctions, line CT capsule and septa • This plus endothelial cells and pericytes prevent exposure of thymocytes to antigens • Corticomedullary barrier – also squamous and express MHC class II molecules In medulla epithelial reticular cells also form a cortiomedullary barrier, cytoreticulum and Hassall corpuscles. HC cells secrete several cytokines to control activity of local dendritic cells. MALT • 70% of body’s immune cells • Most are B cells, some CD4+ helper T cells • Mucous membranes of respiratory, GI and urogenital tracts contain • • • • Diffuse collections of lymphocytes IgA-secreting plasma cells APCs Lymphoid nodules Peyer’s Patches & M cells • Pharyngeal tonsil – covered by respiratory epithelium with thin underlying capsule, lacks crypts • Palatine – covered by stratified squamous epithelium, 10-20 tonsillar crypts, partial connective tissue capsule • Lingual – covered by stratified squamous epithelium, contains crypts, lacks capsule Lymph Nodes • Series of lymph filters that defend against spread of microorganism and tumor cells • Enclosed environment for antigen presentation and development of plasma cells secreting non-IgA antibodies • Reticular fiber stroma to support lymphocytes, plasma cells, dendritic cells, macrophages and other APCs • Lymph flow • Cortex – B cells in lymphoid nodules (which are organized around follicular dendritic cells) • Paracortex – rich in T cells and contains high endothelial venules • Endothelial cells express glycoproteins that mediate diapedesis of B and T cells from blood into paracortex • Medulla – contains medullary cords (T and B lymphocytes, plasma cells) and medullary sinuses • Sinuses have discontinuous endothelium, sometimes contain macrophages and neutrophils Subcapsular sinus – receives lymph from afferent lymphatics Cortical sinuses branch internally among lymphoid nodules, allowing lymph to percolate into surrounding lymphoid tissue Spleen • Largest single accumulation of lymphoid tissue in the body • Involved in blood filtration • Important for fighting bloodborne antigens • Destruction of old erythrocytes • Red pulp • White pulp White Pulp Periarteriolar lymphoid sheaths = PALS (mostly T cells, some plasma cells, macrophages, dendritic cells) surrounding a central arteriole. Surrounding the PALS is red pulp. Lymphoid nodule with a germinal center forms when B cells of PALS are activated, displacing central arteriole to the periphery. Red Pulp Blood flow in the spleen Structure and function of splenic sinusoids Stave cells are oriented length-wise in sinusoids. Blood cells in splenic cords move under pressure (or own motility) between stave cells to reenter vasculature. Cells that cannot move between stave cells are removed by macrophages. Study tip: Fill in this chart and use it to compare/contrast the lymphoid organs discussed. Add pictures to help with lab! Thymus MALT Lymph Nodes Spleen Cortex/medulla Distinctly present Absent Present Absent Lymphoid nodules Absent Present Present (in cortex only) Present (in white pulp only) Lymphatic vessels No afferents; few efferents in septa Unique features Afferents at capsule, emptying into subcapsular sinus; efferent at hilum