PowerPoint Lecture Outlines to accompany Hole’s Human Anatomy and Physiology Eleventh Edition Shier w Butler w Lewis Chapter 16 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Chapter 16 Lymphatic System and Immunity network of vessels that assist in circulating fluids closely associated with the cardiovascular system transports excess fluid away from interstitial spaces transports fluid to the bloodstream transports fats to bloodstream help defend the body against diseases

Lymphatic Pathways

Lymphatic Capillaries microscopic closed-ended tubes in interstitial spaces of most tissues

Lymphatic Vessels walls are similar but thinner than those of veins composed of three layers endothelial lining (inner) smooth muscle (middle) connective tissue (outer) larger vessels lead to lymph nodes and then to larger lymphatic trunks

Collecting Ducts Right lymphatic duct Thoracic duct drains lymph from the upper right side of the body Thoracic duct drains lymph from the rest of the body

Lymph Trunks & Ducts Vessels unite to form trunks & thoracic ducts Right side head, arm & chest empty into right lymphatic duct and rest of body empties into thoracic duct Lymph is dumped directly into left & right subclavian veins

Summary of Lymphatic Pathway Lymphatic vessel to afferent lymphatic to lymph node to efferent lymphatic

Tissue Fluid and Lymph Lymph tissue fluid that has entered a lymphatic capillary Lymph formation dependent on tissue fluid formation

Tissue Fluid Formation originates from plasma contains water and dissolved substances contains smaller proteins which create colloid osmotic pressure

Lymph Formation increasing hydrostatic pressure within interstitial spaces forces tissue fluid into lymphatic capillaries resultant fluid is lymph this process prevents accumulation of excess tissue fluid or edema

Lymph Function absorption of dietary fats delivers fats to bloodstream collection of excess interstitial fluids delivers excess fluids to bloodstream delivers foreign particles to lymph nodes

Lymphatic Capillaries Found throughout the body except in avascular tissue (cartilage, epidermis & cornea) Structure is designed to let tissue fluid in but not out anchoring filaments keep tube from collapsing under outside pressure overlapping endothelial cells open when tissue pressure is high (one-way valve)

Lymph Movement action of skeletal muscles respiratory movements smooth muscle in larger lymphatic vessels valves in lymphatic vessels

Major Organs of Lymphatic System

Lymph Nodes - Overview Lymph nodes are encapsulated oval structures located along lymphatic vessels T cells, macrophages, follicular dendritic cells, and B cells. Lymph enters nodes through afferent lymphatic vessels, is filtered to remove damaged cells and microorganisms, and exits through efferent lymphatic vessels. Foreign substances filtered by the lymph nodes are trapped by nodal reticular fibers. Macrophages then destroy some foreign substances by phagocytosis and lymphocytes bring about the destruction of others by immune responses. Lymph nodes are the site of proliferation of plasma cells and T cells. Location of the lymph nodes and the direction of lymph flow is important in the diagnosis and prognosis of the spread of cancer by metastasis

Lymph Nodes

Locations of Lymph Nodes cervical region axillary region supratrochlear region inguinal region pelvic cavity abdominal cavity thoracic cavity

Functions of Lymph Nodes filter potentially harmful particles from lymph immune surveillance by macrophages and lymphocytes areas of lymphocyte production

Lymphatic Nodules Concentrations of lymphatic tissue not surrounded by a capsule scattered throughout connective tissue of mucous membranes mucosa-associated lymphoid tissue (MALT) Peyer’s patches in the ileum of the small intestine Appendix Tonsils form ring at top of throat adenoids (pharyngeal tonsil) palatine tonsils (on each side wall) lingual tonsil in the back of the tongue

Thymus small in an adult site of T lymphocyte production secretes thymosins

Thymus Gland Large organ in infants (70 g) but atrophied as adult (3 g) 2 lobed organ located in mediastinum Capsule & trabeculae divide it into lobules Each lobule has cortex & medulla Cortex tightly packed lymphocytes & macrophages Medulla reticular epithelial cells produces thymic hormones Hassall’s corpuscles

Spleen largest lymphatic organ located in upper left abdominal quadrant sinuses filled with blood contains two tissue types white pulp lymphocytes red pulp red blood cells macrophages platelets

Spleen The red pulp consists of venous sinuses filled with blood and splenic cords consisting of RBCs, macrophages, lymphocytes, plasma cells, and granulocytes. Macrophages remove worn-out or defective RBCs, WBCs, and platelets. The spleen stores blood platelets in the red pulp. The red pulp is involved in the production of blood cells during the second trimester of pregnancy.

Body Defenses Against Infection pathogen disease causing agent bacteria, viruses, complex microorganisms, spores of multicellular organisms innate defenses general defenses protects against many pathogens adaptive defenses immunity more specific memory carried out by lymphocytes

Innate (Nonspecific) Defenses

Inflammation Response KNOW in order!!!

Adaptive (Specific) Defenses or Immunity Two key features Specificity Memory

Adaptive (Specific) Defenses or Immunity resistance to particular pathogens or to their toxins or metabolic by-products based on the ability to distinguish “self” from “non-self” antigens elicit immune responses

Antigens proteins polysaccharides glycoproteins glycolipids most effective are large and complex haptens are small molecules that are not antigenic by themselves

Lymphocyte Origins Insert figure 16.16

Lymphocyte Functions T cells secrete lymphokines (cytokines) help activate T cells cause T cell proliferation activate cytotoxic T cells stimulate leukocyte production stimulate B cells to mature activate macrophages secrete toxins that kill cells secrete growth-inhibiting factors secrete interferon cellular immune response

T Cells and the Cellular Immune Response requires antigen-presenting cell requires MHC antigens types of T cells helper T cell (T4) cytotoxic T cell (T8) memory T cell

Lymphocyte Functions B cells differentiate into plasma cells produce antibodies humoral immune response

Comparison of T and B Cells Know!!!

Maturation of T and B Cells T cells mature in thymus cell-mediated response killer cells attack antigens helper cells costimulate T and B cells effective against fungi, viruses, parasites, cancer, and tissue transplants B cells in bone marrow antibody-mediated response plasma cells form antibodies effective against bacteria

Types of Immune Response Cell-mediated immunity (CMI) refers to destruction of antigens by T cells. particularly effective against intracellular pathogens, such as fungi, parasites, and viruses; some cancer cells; and foreign tissue transplants. CMI always involves cells attacking cells. Antibody-mediated (humoral) immunity (AMI) refers to destruction of antigens by antibodies. works mainly against antigens dissolved in body fluids and extracellular pathogens, primarily bacteria, that multiply in body fluids but rarely enter body cells. Often a pathogen provokes both types of immune response.

Antigens Molecules or bits of foreign material (see slide 30 above) entire microbes, parts of microbes, bacterial toxins, pollen, transplanted organs, incompatible blood cells Required characteristics to be considered an antigen immunogenicity = ability to provoke immune response reactivity = ability to react to cells or antibodies it caused to be formed Get past the bodies nonspecific defenses enter the bloodstream to be deposited in spleen penetrate the skin & end up in lymph nodes penetrate mucous membrane & lodge in associated lymphoid tissue

Major Histocompatibility Complex Antigens Almost all cells have unique surface markers (1000s molecules) integral membrane proteins called HLA antigens MHC-I molecules are built into cell membrane of all cells except red blood cells Function if cell is infected with virus, MHC-I contain bits of virus marking cell so T cells recognize the problem Some cells also display MHC class II antigens. MHC-II markers seen only on membrane of antigen presenting cells (macrophages, B cells, thymus cells) if antigen presenting cells (macrophages or B cells) ingest foreign proteins, they will display as part of their MHC-II

Pathways of Antigen Processing B and T cells must recognize a foreign antigen before beginning their immune response B cells can bind to antigen in extracellular fluid T cells can only recognize fragments of antigens that have been processed and presented to them as part of a MHC molecule Helper T cells “see” antigens if part of MHC-II molecules on surface of antigen presenting cell Cytotoxic T cells “see” antigens if part of MHC-I molecules on surface of body cells

Processing of Exogenous Antigens Cells called antigen-presenting cells (APCs) process exogenous antigens (antigens formed outside the body) and present them together with MHC class II molecules to T cells. APCs include macrophages, B cells, and dendritic cells. The presentation of exogenous antigens together with MHC II molecules on antigen presenting cells alerts T cells that “intruders are present”.

Processing of Exogenous Antigens Foreign antigen in body fluid is phagocytized by APC macrophage, B cell, dendritic cell (Langerhans cell in skin) Antigen is digested and fragments are bound to MHC-II molecules stuck into antigen presenting cell membrane APC migrates to lymphatic tissue to find T cells

Processing of Endogenous Antigens Endogenous antigens are synthesized within the body and include viral proteins or proteins produced by cancer cells Most of the cells of the body can process endogenous antigens Fragments of endogenous antigen are associated with MHC I molecules inside the cell. The antigen MHC I complex moves to the cell’s surface where it alerts T cells.

T Cell and B Cell Activation

B Cell Activation, Stimulation and Proliferation

B Cell Proliferation and Differentiation

Activation, Proliferation, and Differentiation of T Cells T cell receptors recognize antigen fragments associated with MHC molecules on the surface of a body cell. Proliferation of T cells requires costimulation, by cytokines such as interleukin-1 (IL-1) and interleukin-2 (IL-2), or by pairs of plasma membrane molecules, one on the surface of the T cell and a second on the surface of an APC.

Activation, Proliferation & Differentiation of Cytotoxic T Cells Receptor on CD8 cell binds to foreign antigen fragment part of MHC-I Costimulation from helper T cell prevents accidental immune response Proliferates & differentiates into population (clone) of Tc cells and memory Tc cells Occurs in secondary lymphatic organs such as lymph node

Activation, Proliferation & Differentiation of Helper T Cells Receptor on CD4 cell binds to foreign antigen fragment associated with MHC-II Costimulation with interleukin Proliferates & differentiates into population (clone) of TH cells and long-lived memory TH cells

Overview of Mature T Cells Helper T (TH) cells, or T4 cells, display CD4 protein, recognize antigen fragments associated with MHC-II molecules, and secrete several cytokines, most important, interleukin-2, which acts as a costimulator for other helper T cells, cytotoxic T cells, and B cells Cytotoxic T (TC) cells, or T8 cells, develop from T cells that display CD8 protein and recognize antigen fragments associated with MHC-I molecules. Memory T cells are programmed to recognize the original invading antigen, allowing initiation of a much swifter reaction should the pathogen invade the body at a later date.

Steps in Antibody Production

Antibody Structure Antibodies consist of heavy and light chains and variable and constant portions Based on chemistry and structure, antibodies are grouped into five principal classes each with specific biological roles (IgG, IgA, IgM, IgD, and IgE).

Antibody Molecules

Types of Immunoglobulins

Antibody Actions

Antibody Actions Neutralization of antigen by blocking effects of toxins or preventing its attachment to body cells Immobilize bacteria by attacking cilia/flagella Agglutinate & precipitate antigens by cross-linking them causing clumping & precipitation Complement activation Enhancing phagocytosis through precipitation, complement activation or opsonization (coating with special substance)

Immune Responses

Classifications of Immunity

Allergic Reactions Immune attacks against nonharmful substances that can damage tissues

Allergic Reactions Type I immediate-reaction allergy occurs minutes after contact with allergen hives hay fever asthma eczema gastric disturbances anaphylactic shock

Allergic Reactions Type II antibody-dependent cytotoxic reaction takes 1-3 hours to develop transfusion reaction Type III immune-complex reaction takes 1-3 hours to develop antibody complexes cannot be cleared from body damage of body tissues

Allergic Reactions Type IV delayed-reaction allergy results from repeated exposure to allergen eruptions and inflammation of the skin takes about 48 hours to occur

Transplantation and Tissue Rejection Tissue rejection reaction resembles cellular immune response against antigens important to match MHC antigens immunosuppressive drugs used to prevent rejection Transplanted tissues and organs cornea kidney liver pancreas heart bone marrow skin

Rejection mechanisms Rejection is an adaptive immune response and is mediated through both T cell mediated and humoral immune (antibodies) mechanisms. The number of mismatched alleles determines the speed and magnitude of the rejection response. Different grafts usually have a proclivity to a certain mechanism of rejection.

Transplant Rejection Organ/tissue Mechanism Blood Antibodies, (iso-hemagglutinins) IgM Kidney Antibodies, CMI Heart Antibodies, CMI Skin, CMI Bone marrow, CMI Cornea Usually accepted unless vascularized, CMI

Autoimmunity inability to distinguish “self” from “non-self”