Lymphoid System and Defenses Against Diseases - Part 1 PDF

Lymphoid System and Defenses Against Diseases Marie A. Román Martínez, PhD Department of Biology Office hours: by appointment Email: [email protected] Copyright-This presentation is intended for educational purpose only. No part of this presentation may be reproduced or transmitted in any form wit...

Lymphoid System and Defenses Against Diseases Marie A. Román Martínez, PhD Department of Biology Office hours: by appointment Email: [email protected] Copyright-This presentation is intended for educational purpose only. No part of this presentation may be reproduced or transmitted in any form without written permission. Objectives 1. Describe the formation of lymph. 2. Describe the pathway of lymph in its return to the blood. 3. Describe how lymph is propelled through lymphatic vessels. 4. Describe the locations and functions of the red bone marrow, thymus, lymph nodes, and spleen. 5. Describe the locations and functions of the tonsils and mucosa associated lymphoid tissues. 6. Identify the components of nonspecific resistance. 7. Compare nonspecific resistance and specific resistance. 8. Explain the mechanism of cell-mediated immunity. 9. Explain the mechanism of antibody-mediated immunity. 10. Compare primary and secondary immune responses. 11. Explain the basis of vaccination. 12. Explain how rejection of a transplanted organ occurs. 13. Describe the common disorders of the lymphoid system. Function of the Lymphoid System A network of lymphatic vessels drains excess interstitial fluid and returns it to the blood. A one-way flow that moves slowly toward the subclavian veins. Lymphatic vessels in the small intestine aid in lipid absorption. Lymphocytes aid in the body’s defense against disease causing organisms or substances. Lymphatic Capillaries Closed-ended tubes within interstitial spaces of vascular tissues. Walls composed of overlapping endothelial cells. One way flow into lymphatic capillary. Once fluid enters the lymphatic capillaries, fluid is called lymph (fluid connective tissue). Excess fluid drainage by lymphatic capillaries is needed to prevent edema. Lymphatic Capillaries Lymphatic capillaries in small intestine called lacteals transport absorbed lipids and lipid-soluble vitamins away from digestive tract. Lymphatic Vessels and Trunks Lymphatic capillaries merge to form lymphatic vessels. Lymphatic vessels merge to form lymphatic trunks (larger vessels) that drain large body regions. Lymphatic vessels and trunks are similar to veins in structure (have the same three layers including valves). Image obtained from Figure 21.3 from Saladin Anatomy & Physiology 9 th edition Lymphatic Vessels and Trunks Lymph movement relies on mechanisms similar to those used in venous return. Skeletal muscle contraction Respiratory pressure changes Intestinal movements Peristaltic (rhythmic) contraction of some lymphatic vessels. Lymphatic Ducts Receive lymph from lymphatic trunks. Right lymphatic duct: Drains right of head and neck, right upper limb, and right thoracic region. Empty into the right subclavian vein. Thoracic duct: Begins at the abdominal cavity as a saclike enlargement called cisterna chyli. Drains lymph from the left thoracic region, left upper limb, left side of the head and neck, and all the areas below the diaphragm. Empty into the left subclavian vein. Lymphoid Organs Primary lymphoid organs: Red bone marrow and thymus. Lymphocytes originate in these organs. Secondary lymphoid organs: Lymph nodes and spleen. Sites of lymphocyte proliferation and immune responses. Red Bone Marrow Found in spongy bone of axial skeleton and the proximal epiphyses of femur and humerus. Site of origin of all formed elements in blood. Not all lymphocytes formed in the red bone marrow are immunocompetent (capable of recognizing and attacking foreign substances). To be immunocompetent, a lymphocyte must be able to elicit an immune response. B cells Move to secondary lymphoid organs after becoming immunocompetent in red bone marrow. Lymphocytes that will become T cells must move to thymus for maturation before moving to secondary lymphoid organs. Thymus Bilobed organ in the mediastinum above the heart. Large in infants and decreases in size with age. Plays a key role in the development of the lymphoid system before birth and during early childhood. Until the lymphoid system matures at about two years of age, an infant is more susceptible to disease than older children. Functions: Differentiation of T cells (T lymphocytes) into immunocompetent cells. Produces thymosins that promote T cell differentiation and division, making them immunocompetent. After maturation, T cells are distributed by the blood to secondary lymphoid organs and lymphoid tissues throughout the body. Image obtained from Chapter 17, Figure 17.8 from Saladin Anatomy & Physiology 9th edition. (a)The neonatal thymus is deeper red because of a richer blood flow. (b) In the thymus of an older adult, circulation is greatly reduced and most of the glandular tissue is replaced with fat and fibrous tissue. Lymph Nodes Usually occur in groups along larger lymphatic vessels. Widely distributed in the body. Large collections in inguinal, axillary, and cervical regions, plus thoracic and abdominopelvic cavities. None in CNS. Lymph node structure: Bean-shaped, 1.0 to 2.5 cm in length. Consists of lymphoid nodules. Collections of lymphocytes and macrophages within reticular tissue. Site of lymphocytes activation and proliferation. Image obtained from Figure 21.1 from Saladin Anatomy & Physiology 9 th edition Lymph Nodes Lymph flow through a lymph node. Lymph enters through afferent lymphatic vessels. Next it flows through lymphatic sinuses, which surrounds the lymphoid nodules. Then it enters efferent lymphatic vessel to exit lymph node at the hilum. Lymph nodes function to filter and cleanse lymph. Trapped substances in the reticular tissue of the lymph node are destroyed by lymphocytes and macrophages. Lymphocytes: remove cancerous cells and pathogens. Macrophages: remove cellular debris, dead/immobile bacteria, and viruses. Hilum Image obtained from Figure 21.10 from Saladin Anatomy & Physiology 9 th edition Lymphatic vascular network (3D) https://anatomy.mheducation.com/html/apr.html?animal=human&id=17028 Spleen Largest lymphoid organ: 5-7 cm wide and 13-16 cm long. Located in the left upper quadrant of the abdominopelvic cavity. Contains numerous centers for lymphocyte proliferation and a large venous sinuses. It's enveloped by a thin capsule of dense irregular connective tissue and is subdivided by reticular tissue into many compartments. The compartments contains two basic tissue types: White pulp: Consists of large number of lymphocytes. Concerned with immune functions. Red pulp: Used to store formed elements. Surrounds the white pulp and the venous tissues. Site where worn-out RBCs and pathogens are removed. Spleen Functions: In a fetus is the major blood-forming organ. In an adult: Cleanses and filters blood through actions of lymphocytes and macrophages. Store reserve supply of red blood cells and platelets which can be released in blood in times of need, such as after hemorrhage. Major site of RBC destruction and recycling. Major site of lymphocyte activation and proliferation. Splenectomy The spleen is not essential for life. But following a splenectomy, a person may be more susceptible to potential pathogens and the effects of hemorrhage. Tonsils Lymphoid tissue beneath to mucous membranes of pharynx and oral cavity. Contain both lymphocytes and macrophages. Intercept and destroy pathogens that enter through nose and mouth before they can reach blood. Three kinds of tonsils strategically located to carry out this function: Palatine tonsils are located at the junction of the oral cavity and the pharynx. Pharyngeal tonsil is located behind the nasal cavity in the upper portion of the pharynx. This tonsil is commonly called the adenoid. Lingual tonsils are located on the base of the tongue in the back of the oral cavity. Tonsillitis Tonsillectomy Image obtained from Figure 21.12 from Saladin Anatomy & Physiology 9th edition Mucosa Associated Lymphoid Tissue (MALT) Individual lymphoid nodules are located throughout body. These collections of numerous macrophages and lymphocytes trapped in reticular tissue provide additional barriers to pathogen invasion. MALT (mucosa associated lymphoid tissue) are large clusters of nodules located in respiratory, digestive, urinary, and reproductive tracts. Appendix →an extension of the large intestine located in the right lower quadrant of the abdominopelvic cavity. Part of the MALT that helps control bacterial growth in the large intestine. Nonspecific Resistance Protection against all pathogens and foreign substances. Not directed against a specific pathogen. Mechanical Barriers Inflammation Skin, mucous membranes, tears, saliva, vaginal secretions. Redness, pain, heat, and swelling. Chemical actions Fever Lysozyme, pH of the skin, gastric juice, interferon and complement. High blood temperature that accompanies infections. Phagocytosis Natural Killer Cells Neutrophils and monocytes. Lymphocytes that provide nonspecific defense. Nonspecific Resistance Mechanical Barriers Skin Closely packed epidermal cells of the skin make penetration by pathogens very difficult. Mucous membranes: Mucus is continuously produced by the mucous membranes lining the respiratory and digestive tracts. The mucus entraps pathogens and airborne particles and usually prevents their contact with the underlying membranes. Pathogens entrapped upon entering the nose and mouth tend to be destroyed by the tonsils. Tears Saliva Vaginal secretions Urine flow Fluid mechanical barriers that help to flush away pathogens before they can attack body tissues. Nonspecific Resistance Chemical actions Various body chemicals, including enzymes, provide nonspecific defense. Lysozyme→ destroys certain types of bacteria Present in tears, saliva, nasal secretion and perspiration. Acidic pH of skin→ inhibits bacterial growth. Pathogens the tonsils miss are swallowed at frequent intervals. Upon reaching the stomach, gastric juice→low pH and enzyme pepsin destroy pathogens. Interferon: Produced by viral-infected cells. Cause uninfected cells to make proteins that inhibit viral replication. In this way, the rapid growth of viruses may be inhibited. Nonspecific Resistance Chemical actions Complement Plasma proteins Complement proteins can bind to certain pathogens initiating a chain of events that leads to the destruction of the pathogen. Complement fixation involves binding of complements to a pathogen. Fixed complement punches holes in the pathogen’s plasma membrane, causing it to burst and the pathogen to be destroyed. Also enhance phagocytosis and inflammation. Nonspecific Resistance Phagocytosis The engulfing and destruction of pathogens, damaged or cancerous cells, and cellular debris. Carried out by neutrophils and monocytes. Monocytes entering the infected tissues are called macrophages. Infection occurs→neutrophils and monocytes are quickly attracted to the infected tissues. Tissue macrophage system Some macrophages remain in a fixed position. Example: in red bone marrow, spleen, liver, inner walls of blood and lymphatic vessels. Some macrophages wander among tissues, searching out and phagocytizing pathogens and cellular debris. Nonspecific Resistance Inflammation Pus, a whitish fluid, an accumulated mass of living and dead WBCs, tissue cells, and bacteria, may form at site of inflammation. Localized response to infection or injury. Promotes pathogen destruction and the healing process. Characterized by redness, pain, heat, and swelling. Chemicals, such as histamine and complement proteins, produced with injury or infection dilate arterioles and increase capillary permeability. ↑blood flow causes redness and heat. ↑ fluid movement out of capillaries causes swelling (edema). Pain results from irritation of nociceptors by pathogens, swelling, or chemicals from infected cells. Inflammatory chemicals attract WBCs. Fibrinogen and fibroblasts work to seal off the infected area and prevent pathogen spread. Phagocytes clean up dead pathogens and cells. New cells are produced by cell division to repair any damage. Nonspecific Resistance Fever High blood temperature that accompanies infections and is a necessary part of the immune response. It serves a useful purpose as long as the body-temperature does not get too high. Functions: Inhibit growth of certain pathogens. Increase rates of body processes, including those that fight infections. Natural Killer Cells Lymphocytes that provide nonspecific defense. Provide “immune surveillance” by traveling to the body looking for unhealthy cells. Kill viral-infected cells, bacteria, transplanted cells, and tumor cells. Inflammation (3D) https://anatomy.mheducation.com/html/apr.html?animal=human&id=17030 Immunity Immunity or specific resistance, is directed at specific antigens. An antigen is any substance that can cause an immune response. Immune responses involves production of specific cells and substances that attack a specific antigen. It has “memory”. Allows a quicker and stronger response to subsequent infections. Immune response involves two processes: 1. 2. Cell-mediated immunity Antibody-mediated immunity Specialization of Lymphocytes Lymphocytes are born in red bone marrow (around the time of birth). Lymphocytes must mature and become specialized within primary lymphoid organs before they can participate in immunity. Lymphocyte specialization: Lymphocytes become immunocompetent T cells in the thymus. Lymphocytes become immunocompetent B cells in red bone marrow. T and B cells flow through the blood to secondary lymphoid organs where they form large populations. 75% of circulating lymphocytes are T cells. 25% of circulating lymphocytes are B cells. Differentiation of T Cells and B Cells Recognizing Pathogens Cells of each persons has a unique set of surface recognition molecules that are antigens. Antigens are usually large molecules, such as proteins and glycoproteins. Lymphocytes “learn” how to distinguish “self” from “non-self” antigens during the specialization process. Allows them to recognize invading pathogen or abnormal self cells and launch an attack. Graft rejection→ lymphocytes recognize a transplanted organ as foreign. Autoimmune diseases→ lymphocytes in some cases fail to recognize certain body tissues as “self” and attack the body’s own tissues. Each B and T cells has specific receptors that bind with a specific antigen. Only those cells that can bind the antigen are involved in the immune response. Cell-Mediated Immunity T cells directly attack and destroy foreign cells or diseased body cells, intracellular pathogens and transplanted cells. T cells also develop a memory of their antigens. Cell-mediated immune response Begins when antigen-presenting cell (APC) often a macrophage, engulfs a foreign antigen. Expresses part of the antigen on its plasma membrane. A T cell that can bind to the antigen on the APC, is activated and begins repeated mitotic division. Forms a clone of identical T cells, which are capable of binding with the same antigen that activated the parent T cell. Cell-Mediated Immunity Cell-mediated immune response If activated T cell is a helper T cell (TH), it forms a clone with mostly active TH cells along with memory T cells (TM). Active TH cells bound to antigens secrete cytokines (chemicals) that: Attract neutrophils and macrophages and stimulate phagocytic activity. Stimulate mitotic division and immune responses of activated B and cytotoxic T cells. Cell-Mediated Immunity Cell-mediated immune response If activated T cell is cytotoxic T cell (TC), it forms a clone with mostly active TC cells along with some TM and regulatory T cells (TR). An active TC cell binds to any cell displaying the antigen. Releases a lethal dose of chemicals to kill the cell. TM cells remain after the pathogen is eliminated. Allow for a quicker and stronger attack if the pathogen is encountered again. Regulatory T cells monitor and direct actions of cytotoxic T cells by releasing cytokines that prevents cytotoxic T cells from being overactive. T Cell Activation and Cell-Mediated Immunity As more and more active T cells proliferate and the pathogen is eliminated, the immune response slows and stops. The long-lived TM cells remain to launch a quicker and stronger attack if the targeted antigen should reappear. Antibody-Mediated Immunity Involves both B and TH cells. Provides defense against extracellular pathogens. Involves the production of antibodies. Bind to foreign antigens tagging them for destruction. 1. Antigen recognition Begins when foreign antigens bind to B cell receptors. 2. B cell activation B cell engulfs antigen and displays it on its plasma membrane. TH cell binds to the displayed foreign antigen. The TH cell secretes cytokines that activate the B cell. Antibody-Mediated Immunity 3. Clone formation Clone of identical B cells that produce antibodies against the specific antigen. 4. Differentiation Most B cells in the clone become plasma cells. Some cell become memory B cells that allow for a stronger response with another encounter later on. 5. Action Plasma cells rapidly produce and release antibodies capable of binding with the targeted antigen. Antibody-Mediated Immunity Antibodies Proteins known as globulins, so another name for antibodies is immunoglobulins, which have a shorthand designation Ig. The structure of an antibody determines its classification, and each class plays a special role in antibody-mediated immunity. Antibodies do not destroy pathogens directly. Antibodies form antigen-antibody complexes that mark pathogens for destruction. For example: allows for complement fixation. Antibodies also neutralize bacterial toxins by binding the antigens. Which prevents the toxins from attaching to receptors of body cells. Antigen-antibody complexes are engulfed and destroyed by macrophages, eosinophils, and neutrophils.