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Principles of Anatomy and Physiology Thirteenth Edition Gerard J. Tortora • Bryan H. Derrickson Chapter 22 The Lymphatic System and Immunity Copyright © 2012 by John Wiley & Sons, Inc. Palatine tonsil Submandibular node Cervical node Right internal jugular vein Left internal jugular vein Right lymphatic duct Thoracic duct Right subclavian vein Axillary node Lymphatic vessel Left subclavian vein Spleen Aggregated lymphatic follicle (Peyer’s patch) Thoracic duct Cisterna chyli Small intestine Intestinal node Iliac node Large intestine Inguinal node Appendix Red bone marrow Lymphatic vessel (a) Anterior view of principal components of lymphatic system (b) Areas drained by right lymphatic and thoracic ducts Area drained by right lymphatic duct Area drained by thoracic duct Blood capillary Venule Tissue cell Arteriole Blood Blood Lymph Interstitial fluid Lymphatic capillary (a) Relationship of lymphatic capillaries to tissue cells and blood capillaries Lymph Endothelium of lymphatic capillary Tissue cell Interstitial fluid Anchoring filament Opening (b) Details of a lymphatic capillary Right internal jugular vein Left internal jugular vein RIGHT JUGULAR TRUNK LEFT JUGULAR TRUNK RIGHT SUBCLAVIAN TRUNK THORACIC (LEFT LYMPHATIC) DUCT Right subclavian vein LEFT SUBCLAVIAN TRUNK RIGHT LYMPHATIC DUCT Left subclavian vein First rib Left brachiocephalic vein Right brachiocephalic vein Accessory hemiazygos vein RIGHT BRONCHOMEDIASTINAL TRUNK LEFT BRONCHOMEDIASTINAL TRUNK Superior vena cava Rib Intercostal muscle THORACIC (LEFT LYMPHATIC) DUCT Azygos vein Hemiazygos vein CISTERNA CHYLI RIGHT LUMBAR TRUNK LEFT LUMBAR TRUNK Inferior vena cava INTESTINAL TRUNK (a) Overall anterior view Right jugular trunk Left jugular trunk Left subclavian trunk Right subclavian trunk Thoracic (left lymphatic) duct Right lymphatic duct Left bronchomediastinal trunk Right bronchomediastinal trunk (b) Detailed anterior view SYSTEMIC CIRCULATION PULMONARY CIRCULATION Lymph node Lymphatic capillaries Lymphatic duct Subclavian vein Lymphatic vessel Pulmonary blood capillaries Veins Valve Heart Arteries Lymph node Systemic blood capillaries Lymphatic capillaries Thyroid gland Trachea Right common carotid artery Brachiocephalic veins Superior vena cava Right lung Thymus Left lung Fibrous pericardium Diaphragm (a) Thymus of adolescent Capsule Lobule: Cortex Thymic (Hassall’s) corpuscle Medulla Trabecula LM (b) Thymic lobules 30x T cell Thymic (Hassall’s) corpuscle Epithelial cell LM (c) Details of the thymic medulla 385x Cells of inner cortex T cells Cells around germinal center of outer cortex Cells in germinal center of outer cortex Macrophages Follicular dendritic cells Dendritic cells B cells B cells Subcapsular sinus Reticular fiber Cells of medulla Trabecula Trabecular sinus B cells Outer cortex: Germinal center in secondary lymphatic nodule Cells around germinal center Inner cortex Medulla Medullary sinus Plasma cells Macrophages Valve Reticular fiber Afferent lymphatic vessel Efferent lymphatic vessels Valve Hilum Route of lymph flow through a lymph node: Afferent lymphatic vessel Subcapsular sinus Afferent lymphatic vessels Capsule (a) Partially sectioned lymph node Trabecular sinus Medullary sinus Efferent lymphatic vessel Capsule Subcapsular sinus Outer cortex Trabecular sinus Germinal center in secondary lymphatic nodule Trabecula Inner cortex Medullary sinus Medulla LM (b) Portion of a lymph node 40x Efferent lymphatic vessels Nerve Skeletal muscle Lymph node Afferent lymphatic vessels (c) Anterior view of inguinal lymph node SUPERIOR Splenic vein Splenic artery Colic impression Gastric impression Hilum Renal impression POSTERIOR ANTERIOR (a) Visceral surface Splenic artery Splenic vein White pulp Red pulp: Venous sinus Splenic cord Central artery Trabecula Capsule (b) Internal structure Capsule Red pulp Trabecula Central artery White pulp LM (c) Portion of the spleen 25x Jugular lymph sac Thoracic duct Internal jugular vein Subclavian vein Cisterna chyli Inferior vena cava Retroperitoneal lymph sac Posterior lymph sac 1 CHEMOTAXIS Microbe Phagocyte 2 ADHERENCE 3 INGESTION Pseudopod Phagosome Lysosome 4 DIGESTION Digested microbe in phagolysosome Plasma membrane 5 KILLING Digestive enzymes (a) Phases of phagocytosis Residual body (indigestible material) Phagocyte Microbe SEM 1800x (b) Phagocyte (white blood cell) engulfing microbe Tissue injury Microbe Chemotaxis Phagocytes Emigration Vasodilation and increased permeability Phagocytes migrate from blood to site of tissue injury Primary lymphatic organs Thymus Secondary lymphatic organs and tissues PreT cells Mature T cells Red bone marrow Mature B cells Antigen Helper receptors T cell B cell B cell CD4 protein Activation of helper T cell Formation of helper T cell clone: Memory helper Help T cells Help Active helper T cells Activation of Activation of B cell cytotoxic T cell Formation of B cell Formation of cytotoxic T cell clone: clone: Antibodies Memory Active cytotoxic cytotoxic Memory Plasma T cells B cells T cells cells Cytotoxic T cell CD8 protein Active cytotoxic T cells leave lymphatic tissue to attack invading antigens CELL-MEDIATED IMMUNITY Directed against intracellular pathogens, some cancer cells, and tissue transplants Antibodies bind to and inactivate antigens in body fluids ANTIBODY-MEDIATED IMMUNITY Directed against extracellular pathogens Epitopes Antigen Key: Exogenous antigen 1 Phagocytosis or endocytosis of antigen 5 Vesicles containing antigen peptide fragments and MHC-II molecules fuse 6 Antigen peptide fragments bind to MHC-II molecules Phagosome or endosome 2 Antigen-presenting cell (APC) Digestion of antigen into peptide fragments 7 4 Packaging of MHC-II molecules into a vesicle Vesicle undergoes exocytosis and antigen– MHC-II complexes are inserted into plasma membrane Endoplasmic reticulum 3 Synthesis of MHC-II molecules APCs present exogenous antigens in association with MHC-II molecules Antigen peptide fragments MHC-II self-antigen Key: Antigen peptide fragments 5 Endogenous antigen 1 Vesicle undergoes exocytosis and antigen–MHC-I complexes are inserted into plasma membrane MHC-I self-antigen Digestion of antigen into peptide fragments 4 Packaging of antigen–MHC-I molecules into a vesicle Antigen peptide fragments bind to MHC-I molecules 3 Endoplasmic reticulum 2 Synthesis of MHC-I molecules Infected body cell Infected body cells present endogenous antigens in association with MHC-I molecules Antigen-presenting cell (APC) Costimulation Antigen recognition Inactive helper T cell MHC-II Activated helper T cell Antigen TCR CD4 protein Inactive helper T cell Clonal selection (proliferation and differentiation) Formation of helper T cell clone: Active helper T cells (secrete IL-2 and other cytokines) Memory helper T cells (long-lived) Infected body cell Helper T cell Antigen recognition CD8 protein MHC-II Antigen Inactive cytotoxic T cell Costimulation by IL-2 TCR Inactive helper T cell Activated cytotoxic T cell Clonal selection (proliferation and differentiation) Formation of cytotoxic T cell clone: Active cytotoxic T cells (attack infected body cells) Memory cytotoxic T cells (long-lived) Activated cytotoxic T cell Activated cytotoxic T cell Granzymes Recognition and attachment Recognition and attachment Granulysin Perforin Microbe Infected body cell Infected body cell Infected body cell undergoing cytolysis Infected body cell undergoing apoptosis Microbe Phagocyte (b) Cytotoxic T cell destruction of infected cell by release of perforins that cause cytolysis; microbes are destroyed by granulysin Key: CD8 protein Antigen-MHC-I complex TCR (a) Cytotoxic T cell destruction of infected cell by release of granzymes that cause apoptosis; released microbes are destroyed by phagocyte Channel B-cell receptor Inactive B cell Activate d B cell B cell recognizing unprocessed antigen Clonal selection (proliferation and differentiation) Activated B cell Helper T cell Costimulation by several interleukins B cell displaying processed antigen is recognized by helper T cell, which releases costimulators Formation of B cell clone: Antibodies Plasma cells (secrete antibodies) Memory B cells (long-lived) Light chains Carbohydrate chain Antigen binding site Heavy chains (a) Model of IgG molecule Antigen binding site Antigen binding sites VH VH VL CH VL CH CL CL Light (L) chain Hinge region CH CH CH CH Stem region Carbohydrate chain Heavy (H) chain (b) Diagram of IgG heavy and light chains IgG IgA IgM IgD IgE C3 1 2 C3b C3a Histamine C5 3 C5b C5a Microbe C6 PHAGOCYTOSIS: Enhancement of phagocytosis by coating with C3b C7 C8 Mast cell INFLAMMATION: Increase of blood vessel permeability and chemotactic attraction of phagocytes C9 4 C6 Microbial plasma membrane C5b C7 C8 Channel Membrane attack complex forms channel C9 CYTOLYSIS: Bursting of microbe due to inflow of extracellular fluid through channel formed by membrane attack complex C5–C9 Antibody titer (arbitrary units) 1000 Primary response Secondary response 100 IgG 10 IgM 1 0.1 0 14 28 42 56 Days First exposure Second exposure Deletion (death) of T cell Does immature T cell recognize self-MHC proteins? Is TCR capable of binding to and recognizing selfpeptides? No Death of cells that cannot recognize self-MHC molecules Positive selection Negative selection Anergy (inactivation) of T cell Survival of T cells that can recognize self-MHC proteins but not self-peptides (a) Positive and negative selection of T cells in the thymus Activation of T cell, which proliferates and differentiates Mature T cell in lymphatic tissue Antigen recognition without costimulation Anergy (inactivation) of T cell Death of T cell (b) Selection of T cells after they emerge from the thymus Does immature B cell in bone marrow recognize self- MHC molecule or other selfantigens? No Negative selection Mature B cell recognizes antigen (first signal) Costimulation (second signal) Yes Deletion (death) of B cell in bone marrow (c) Selection of B cells Activation of B cell, which proliferates and differentiates into clone of plasma cells Anergy (inactivation) of B cell in secondary lymphatic tissues and blood Key: Cell survival or activation Cell death or anergy (inactivation) Glycoproteins Envelope Lipid bilayer Protein coat (capsid) Reverse transcriptase RNA (single stranded) 100–140 nm Human immunodeficiency virus (HIV)
