THE LYMPHATIC SYSTEM AND IMMUNITY

Transcription

1 Anatomy and Physiology Lecture Biology 2402 CHAPTER 22 THE LYMPHATIC SYSTEM AND IMMUNITY

2 THE LYMPHATIC SYSTEM AND IMMUNITY Pathogens are disease-producing organisms. Survival and good health depends on fending off attacks of pathogen. Resistance is the ability to ward off diseases through our defenses. Susceptibility is vulnerability or lack of resistance. Resistance grouped in two broad areas: (1) Nonspecific resistance - Includes defense mechanism that provide general protection against invasion by a wide range pathogens, such as the many different kinds of bacteria and viruses. These include: (a) Mechanical barriers provided by the skin and mucus membranes; (b) Antimicrobial chemicals; (c) Phagocytosis; (d) Inflammation; and (e) Fever (Example: The acidity of the stomach contents kills many bacteria ingested in food). (2) Immunity - Involves activation of specific lymphocytes that combat a particular pathogen or other foreign substance. Specific resistance. The body system that carries out immune response is the lymphatic system.

3 3 Lymphatic System - Consist of: 1) Liquid called lymph 2) Lymphatic vessels (lymphatics) - that transport lymph 3) Structures and organs that contain lymphatic (lymphoid) tissue 4) Bone marrow which houses stem cells that develop into lymphocytes. Interstitial (tissue) fluid and Lymph are basically the same. The major difference between the two is location. Fliud from interstitial tissue becomes lymph after it passes from interstitial space to lymphatic vessels. Lymphatic tissue is a specialized form of reticular connective tissue (blood) that contains large number of lymphocytes. FUNCTIONS OF THE LYMPHATIC SYSTEM 1. Fluid Balance - Lymphatic vessels drain tissue spaces of excess interstitial fluid. 2. Fat absorption - Lymphatic system absorbs fats and other substances from the digestive tract. Fats enter the lacteals (special lymphatic vessels located in the small intestine) and pass through the lymphatic vessels to the venous circulation. 3. Defense Microorganisms and other foreign substances are filtered from lymph by lymph nodes and from blood by the spleen. Lymphocytes (A type of white blood cell found in lymph nodes), aided by macrophages (phagocytic cell derived from a monocyte), recognize foreign cells and substances, microbes, and cancer cells.

4 4 Respond to foreign cells in two basic ways: 1. Some lymphocytes (T cells) destroy the intruders directly (by causing them to rupture) or indirectly by releasing cytotoxic (cell-killing) substances. 2. Other lymphocytes (B cells) differentiate into plasma cells that secrete antibodies. These are proteins that combine with and cause destruction of specific foreign substances. LYMPHATIC VESSELS AND LYMPH CIRCULATION Lymphatic Vessels begin as closed-ended vessel called lymphatic capillaries in spaces between cells. Lymphatic Capillaries unit to form large tubes called lymphatic vessels; just as blood capillaries unit to form venules and veins. Lymphatic vessels resemble veins in structure but have thinner walls and more valves. At intervals, have structures called lymph nodes. In the skin, lymphatic vessels lie in subcutaneous tissue and generally follow veins. Lymphatic vessels of the Viscera (the organs inside the ventral (anterior) body cavity) generally follow arteries, forming plexuses around them. Lymph capillaries Are microscopic vessels in spaces between cells from which lymphatic

5 5 vessels originate. Capillaries containing lymph are found throughout the body, except in: (1) Avascular tissue (bloodless) (2) Central Nervous system (3) Splenic pulp and (4) Bone marrow Lymphatic capillaries have a slightly larger diameter than blood capillaries. Permits interstitial fluid to flow into them but not out. Anchoring filaments attach lymphatic endothelial cells to surrounding tissues. Fingerlike projection (villi) of the small intestine contains blood capillaries and a specialized lymphatic capillary called lacteal. Formation and Flow of Lymph Most components of blood plasma freely move through the capillary walls to form interstitial fluid. More fluid seeps out of blood capillaries by filtration than returns to them by absorption. The excess fluid, about 3 liters per day, drains into lymphatic vessels and becomes lymph. Lymph drains into venous blood through the right and left lymphatic ducts at the junction of the internal jugular and subclavian veins. Sequence of Fluid Flow Arteries (blood plasma) blood capillaries (blood plasma) interstitial spaces (interstitial fluid) lymphatic capillaries (lymph) lymphatic vessels (lymph) lymphatic ducts (lymph) subclavian

6 6 veins (blood plasma) Since most plasma proteins are too large to leave blood vessels, interstitial fluid contains only small amounts of protein. Any protein that do escape, however, cannot return to the blood by diffusion. (The concentration gradient (high level of proteins inside blood capillaries, low level outside) prevent diffusion back to the blood). Important function of lymphatic vesel is to return leaked plasma proteins to the blood. Factor that maintain lymph flow: (1) Contracting of the skeletal muscle (milking action) (2) One-way valve (similar to those found in veins) within the lymphatic vessels prevent backflow of lymph. (3) Breathing movement; (With each inhalation, lymph flows from the abdominal region, where the pressure is higher, toward the thoracic region, where it is lower). Lymph Trunks and Ducts Lymph passes from lymphatic capillaries into lymphatic vessels and through lymph nodes. Lymphatic vessels exiting lymph nodes pass lymph toward another node of the same group or on to another group of nodes. From the most proximal group of each chain of nodes, the exiting vessels unite to form lymph trunks.

7 7 Principal Lymph Trunks: (1) Lumba trunk (2) Intestinal trunk (3) Bronchomediastinal trunk (4) Subclavian trunk (5) Jugular trunk Pricipal trunks pass their lymphs into two main channels: (1) Thoracic (Left Lymphatic) Duct (2) Right Lymphatic Duct Ducts pass lymphs into venous blood. Thoracic (Left Lymphatic) Duct Is about cm (15-18 in.) in length. Begins as a dilation called cisterna chyli (sis-ter-na Kile). Thoracic duct is the main collecting duct of the lymphatic system Receives lymph from the left side of the head, neck and chest, the left upper limb, and the entire body inferior to the ribs Right Lymphatic Duct Is about 1.25 cm (1/2 in.) in length. Drains lymph from the upper right side of the body LYMPHATIC TISSUES Primary Lymphatic (Lymphoid) Organs of the body are: (1) Bone Marrow (in flat bones and the epiphyses of long bones),

8 8 (2) Thymus gland Are both called primary lymphatic organs because they produce B and T cells, the lymphocytes that carry out immune responses. Hemopoietic stem cells in red bone marrow give rise to B cells and pre-t cells. The pre-t cells then migrate to the thymus gland. Secondary Lymphatic Organs of the body are: (1) Lymph nodes (2) Spleen (3) Lymphatic nodules (not discrete organs because they are not surrounded by a capsule). THYMUS GLAND A bilobed (2 lobes) lymphatic organ. Located in the superior mediastinum, posterior to the sternum and between the lungs. An enveloping layer of connective tissue holds the two thymic lobes closely together. Capsule, a connective tiisue, encloses each lobe. Trabeculae, extension given off by the capsule, divides the lobes into lobules. Each lobule consists of: (a) A deeply staining outer cortex, and (b) A lighter-staining central medulla.

9 9 Pre-T cells migrate (via the blood) from red bone marrow to the thymus, where they proliferate and develop into mature T cells. Thymus gland is large in the infant, reaches its maximum size of about 40 g (about 1.4 oz) at years of age. After puberty, much of the thymic tissue is replaced by fat and areolar connective tissue. By maturity, the gland has atrophied considerably (involution with age). Although most T cells arise before puberty, some continue to mature through out life. LYMPH NODES Are oval or bean-shaped structures located along the length of lymphatic vessels. They range from 1 to 25 mm (0.04 to 1 in.) in length. Are scattered throughout the body, usually in groups: Heavily concentrated in areas such the mammary glands, axillae, and groin. Each node is covered by capsule, and capsular extension is called trabeculae. The parenchyma of a lymph node is specialized into two regions: (a) Cortex, and (b) Medulla Cortex contains many follicles. The outer rim of each follicle contains T cells (T lymphocytes) plus macrophages and follicular dendritic cells). Follicles have germinal centers, where B cells (B lymphocytes) proliferate into antibody-secreting plasma cells.

10 10 Medulla is the inner region of a lymph node. Contain macrophages and plasma cells. Lymph flows through a node in one direction. Enter through afferent lymphatic vessels, which penetrate the convex surface of the node at several points. Contain valves that open toward the node so that the lymph is directed inward. Lymph flows through sinuses in the cortex (cortical sinuses) and then in the medulla (medullary sinuses). Exit through efferent lymphatic vessels through a depression called hilus. Blood vessels also enter and leave the node at the hilus. Among lymphatic tissues, only lymph nodes filter lymph by having it enter at one end and exit at other. Lymph is filtered of foreign substances, which are trapped by the reticular fibers within the node. Macrophages then destroy some foreign substance by phagocytosis and lymphocytes bring about destruction of others by immune responses. Cancerus lymph nodes feel enlarged, firm, and nontender. Most lymph nodes that enlarge during an infection, by contrast, are not firm and very tender. Structure: 1. Hilus or Hilium - a slight depression on one side of lymph node, where blood vessels and efferent lymphatic vessels leave the node 2. Capsule - covers each node

11 11 3. Cortex - contains densely packed lymphocytes arranged in masses called lymphatic nodules 4. Germinal Center - lighter-staining central areas, where the lymphocytes are produced 5. Medulla - the inner region of a lymph node 6. Afferent lymphatic vessels - contain valves that open toward the node so that lymph is directed inward 7. Efferent lymphatic vessels - contain valves that open away from the node to convey lymph out of the node Medical Application: Metastasis through the lymphatic system. SPLEEN: Is the largest single mass of lymphatic tissues in the body. Measures about 12 cm (5 inches) in length Situated in the left hypochondriac region between the fundus of the stomach and diaphragm lateral to the liver. Like lymph nodes, has a hilus, where the splenic artery and vein and the efferent lymphatic vessels pass through. (Note: There is no afferent lymphatic vessels or lymph sinuses, therefore does not filter lymph). A parenchyma of the spleen consists of two different kinds of tissue: (1) White pulp: Lymphatic tissue, mostly lymphocytes (B cells), arranged around central arteries. Functions in immunity as a site of B cell proliferation into antibody-producing plasma cells. (2) Red pulp: Consists of venous sinuses filled with blood and thin plates of tissue called splenic (Billroth's) cords between the sinuses.

12 12 Splenic cords consist of red blood cells, macrophages, lymphocytes, plasma cells, and granulocytes. Veins are closely associated with red pulps. Function - Carries out the main function of the spleen: Phagocytosis of bacteria and worn-out and damaged red blood cells and platelets. Other functions of the Spleen: Stores and releases the blood in case of demand, such as during hemorrhage. Participates in blood cell formation during early fetal development. Lymphatic Nodules Are oval-shape concentration of lymphatic tissue. Most are solitary, small, and discret. Are scattered throughout the lamina propria (connective tissue) of mucus membranes lining the gastrointestinal tract, respiratory airways, urinary tract, and reproductive tract. This lymphatic tissue is referred to as mucosa-associated lymphoid tissue (MALT). Some lymphatic nodules occur in multiple, large aggregations in specific parts of the body: (a) (b) (c) Tonsils in the pharyngeal region Aggregated lymphatic follicles (Peyer's patches) in the ileum of the small intestine. Aggregation of lymphatic nodules also occur in the appendix.

13 13 There are five tonsils, which form a ring at the junction of the oral cavity and oropharynx and at the junction of the nasal cavity and nasopharynx. Are strategically positioned to participate in immune response against foreign substances that are inhaled or ingested. Their T cells destroy foreign intruders directly; Their B cells develop into antibody-secreting plasma cells and the antibodies dispose of foreign substances. Pharyngeal tonsil or adenoid (single) is embedded in the posterior wall of the nasopharynx. Palatine tonsil (double) lie at the posterior region of the pral cavity, one on each side. Commonly removed by a tonsillectomy. Lingual tonsil (paired) are located at the base of the tongue, may also be removed by tonsillectomy. IMMUNITY Immunity Is the ability to resist damage from foreign substances such as microorganisms and harmful chemicals. Two Categories of Immunity: 1. Innate Immunity (Nonspecific Resistance) The body recognizes and destroys certain foreign substances, but the response to them is the same each time the body is exposed to them.

14 14 2. Adaptive Immunity (Specific Resistance) The body recognizes and destroys foreign substances, but the response to them improves each time the foreign substance is encountered. Are characterized by: (a) Specificity, and (b) Memory. Specificity Is the ability of adaptive immunity to recognize a particular substance. Memory Is the ability of adaptive immunity to remember previous encounters with a particular substance and, as a result, to respond to it more rapidly. Innate Immunity There are three main components of Innate Immunity. 1. Mechanical Mechanisms Prevent the entry of microbes into the body or that prevent the entry of microbes into the body or that physically remove them from body surfaces. 2. Chemical Mediators Act directly against microorganisms or activate others mechanisms, leading to the destruction of microorganisms. 3. Cells Involve in phagocytosis and the production of chemicals that participate in the response of the immune system. Inflammatory Response Inflammatory Response Is a complex sequence of events involving many of the chemical mediators and cell of innate immunity.

15 15 Types of Inflammatory Responses: 1. Local Inflammation Is an inflammatory response confined to a specific area of the body. 2. Systemic inflammation Is an inflammatory response that occurs in many parts of the body. Adaptive Immunity Adaptive Immunity involves the ability to recognize, respond to, and remember a particular substance. Antigens Are substances that stimulate adaptive immunity. Two Groups of antigens: 1. Foreign antigens Are not produced by the body but are introduced from outside it. 2. Self-antigens Are molecules produced by the body that stimulate an adaptive immune system response. Two Types of Adaptive Immunity Immunity results from the activity of lymphocytes called B and T cells. 1. Humoral (Antibody-mediated immunity) B cells give rise to cells that produce proteins called antibodies, which are found in the plasma. 2. Cell-mediated Immunity T cells are responsible for cellmediated immunity.

16 16 ORIGIN AND EVELOPMENT OF LYMPHOCYTES All blood cells, including lymphocytes, are derived from stem cells in the red bone marrow. - Some stem cells give rise to pre-t cells that migrate through the blood to the thymus, where they divide and are processed into T cells. - Other stem cells produce pre-b cells, which are processed in the red bone marrow into B cells. Positive selection process Results in the survival of pre-b and pre-t cells that are capable of an immune response. Clones - Are the B and T cells that can respond to antigens and are composed of small groups of identical lymphocytes. Negative selection process Eliminates or suppresses clones acting against self-antigens, thereby preventing the destruction of self-cells. - B cells are released from red bone marrow, T cells are released from the thymus, and both types of cells move through the blood to lymphatic tissue. - There are approximately five T cells for every B cell in the blood. Primary Lymphatic Organs Are the sites where lymphocytes mature into functional cells. - Red bone marrow - Thymus Secondary Lymphatic Organs and Tissues Are the sites where lymphocytes interact with each other, antigen-presenting cells, and antigens to produce an immune response.

17 17 - Diffuse lymphatic tissue - Lymphatic nodules - Tonsils - Lymph nodes - Spleen Activation of Lymphocytes Two general principles of Lymphocyte activation; 1. Lymphocytes must be able to recognize the antigen. 2. After recognition, the lymphocytes must increase in number to effectively destroy the antigen. Antigenic Determinants and Antigen Receptors Antigenic Determinants (Epitopes) Are specific regions of a given antigen recognized by a lymphocyte, and each antigen has many different antigen determinants. Antigen Receptors It is a surface identical protein found on all the lymphocytes of a given clone. T-Cell Receptor Consists of two polypeptide chains, which are subdivided into a variable and a constant region. B-Cell Receptor Consists of four polypeptide chains with two identical variables regions. Major Histocompatibility Complex Molecules

18 18 SUMMARY OF CELLS THAT ARE IMPORTANT IN IMMUNE RESPONSES 1. Macrophage: Phagocytosis; processing and presentation of foreign antigens to T cells; secretion of interleukin-1 that stimulated secretion of interleukin -2 by helper T cells (stimulates proliferation of cytotoxic T cells) and induces proliferation of B cells; secretion of interferons that stimulate T cell growth. 2. Cytotoxic (Killer) T Cell: Lysis of foreign cells by lymphotoxin and release of various other lymphokines that recruit and intensify cytotoxic T cell action (transfer factor), increase phagocytic activity of macrophages (macrophage activating factor), prevent macrophage migration from site of action *macrophage migration inhibitation factor), and proliferation of uncommitted or nonsensitized lymphocytes (mitogenic factor). Cytotoxic T cells also secrete interferons. 3. Helper T Cell: Cooperates with B cells to amplify antibody production by plasma cells and secretes interleukin-2, which stimulates proliferation of cytotoxic T cells. 4. Suppressor T Cell: Inhibits secretion of injurious substances by cytotoxin T cells and inhibits antibody production by plasma cells. 5. Delayed Hyper- Sensitivity T Cell: Secretes macrophage activation factor and macrophage migration inhibition factor, by substances related to hypersensitivity (allergy). 6. Amplifier T Cell: Stimulates helper T cells, suppressor T cells, and B cells to exaggerated levels of activity. 7. Memory T Cell: Remains in lymphoid tissue and recognizes original invading antigens, even years after infection.

19 19 8. Natural Killer (NK) Cell: Lymphocyte that destroys foreign cells by lysis and produces interferon. Interferon - A substance formed within a virus-infected cell which prevents the entrance of or replication of virus particles. 9. B Cell: Differentiates into antibody-producing plasma cell. 10. Plasma Cell: Descendant of B cell that produces antibodies. 11. Memory B Cell: Ready to respond more rapidly and forcefully than initially should the same antigen challenge the body in the future. SUMMARY OF LYMPHOKINE (CYTOKINES) CYTOTOXIC (KILLER) T CELLS SECRETE 1. Lymphotoxin (LT): Destroys antigens directly by lysis. 2. Perforin: Perforates cell membranes of target cells. 3. Transfer factor (TF): Recruits additional lymphocytes and converts them into sensitized cytotoxic cells. 4. Macrophage Chemotactic Factor: 5. Macrophage Activating Factor (MAF): Attracts macrophages to site of invasion to destroy antigens by phagocytosis. Increases activity of macrophages.

20 20 6. Macrophage Migration Inhibiting Factor: Prevents macrophages from migrating away from site of infection. 7. Mitogenic Factor: Induces uncommitted or nonsensitized lymphocytes to divide more rapidly. 8. Interleukin-1 (IL-1) (Lymphocyte-activating Factor): Produced by antigen-stimulated macrophages and stimulates T cell and B cell growth; stimulates secretion of interleukin-2 by helper cell. 9. Interleukin-2 (IL-2) (T cell growth Factor): Produced by helper T cells to stimulate the proliferation of cytotoxic (killer) T cells and natural killer cells. 10. Interleukin-3 (IL-3) (Multipotential CSF): Produced by activated T cells; supports to growth of bone marrow stem cells and is a growth factor for mast cells. 11. Interleukin-4 (IL-4) (B Cell Stimulating Factor 1): Produced by activated T cells; growth factor for activated B cells and resting T cells. 12. Colony Stimulating Factors (CSFs): Produced by white blood cells and function in their proliferation. 13. Interferons (IFNS): Produced by virus-infected cells to inhibit viral replication in uninfected cells; produced by antigen-stimulated macrophage to stimulate T cell growth. Produced by cytotoxic T cells to augment killing action of cytotoxic T cells; Produced by

21 Tumor Necrosis Factor (TNF) (Cachectic): natural killer cells to inhibit viral replication. Produced by macrophages in the presence of bacterial endotoxins; kills some tumor cells, stimulate synthesis of lymphokines, activates macrophages, and mediates inflammation. Immunology and Cancer Cancer cells contain tumor-specific antigens and are frequently destroyed by the body's immune system (Immunological surveillance). Some cancer cells escape detection and destruction, a phenomenon called immunologic Escape. *Immunotherapy - induction of the immune system against cancer. Aging and The Immune System 1. With advancing age, individuals become more susceptible to infections and malignancies, response to vaccines is decreased, and more antibodies are produced. 2. Cellular and humoral responses also diminish. Developmental Anatomy of The Lymphatic System 1. Lymphatic vessels develop from lymph sacs, which develop from veins. Thus, they are derived from mesoderm. 2. Lymph nodes develop from lymph sacs that become invaded by mesenchymal cells.

22 22 CLINICAL FOCUS Acquired Immunodeficiency Syndrome 1. Acquired Immune Deficiency Syndrome (AIDS) lowers the body's immunity by decreasing the number of helper T cells and reversing the ratio of Helper T cells to Suppressor T cells. - Aids victims frequently develop Kaposi's Sacroma (KS) and Pneumocystis carinii pneumonia (PCP). -HumanImmunodeficiencyy Virus (HIV) - the can satire agent of AIDS. 2. Autoimmune diseases result when the body does not recognize "self" antigens and produces antibodies against them. -Several human autoimmune diseases are rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), rheumatic fever, homolyctic and pernicious anemias, myatheria gravis, and multiple sclerosis (MS). 3. Severe Combined Immunodeficiency (SCID) is an immunodeficiency disease in which both B and T cells are missing or inactive in providing immunity. 4. Hypersensitivity (Allergy) - is overactivity to an antigen. - Localized anaphylactive reactions include hay fever, asthma, eczema, and hives; acute anaphylaxis is a severe reaction with systemic effects. 5. Tissue Rejection of a transplant tissue or organ involves antibody production against the proteins (antigens) in the transplant. -It may be overcome with immunosuppressive drugs. 6. Hodgkin's disease (HD) is a malignant disorder, usually arising in lymph nodes.