ch 20&21

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1

Lymphatic and Immune Systems

A. The ability to ward off the pathogens that produce disease is called resistance.
B. Lack of resistance is called susceptibility.
C. Resistance to disease can be grouped into two broad areas.
1. Nonspecific resistance or innate immunity are present at birth and includes defense mechanisms that provide general protection against invasion by a wide range of pathogens.
2. Immunity involves activation of specific lymphocytes that combat a particular pathogen or other foreign substance.
D. The body system that carries out immune responses is the lymphatic system.

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II. LYMPHATIC SYSTEM STRUCTURE AND FUNCTION

A. The lymphatic system functions to drain interstitial fluid, return leaked plasma proteins to the blood, transport dietary fats, and protect against invasion by nonspecific defenses and specific immune responses.
B. The lymphatic system consists of a fluid called lymph flowing within lymphatic vessels, several structures and organs that contain lymphatic tissue (specialized reticular tissue containing large numbers of lymphocytes), and bone marrow, which is the site of lymphocyte production.
1. Interstitial fluid and lymph are basically the same - The major difference is location.

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C. Lymphatic Vessels and Lymph Circulation

Lymph Trunk and Ducts:formed from the exiting vessels of lymph nodes, are the lumbar, intestinal, bronchomediastinal, subclavian, and jugular trunks.
b.The thoracic duct begins as a dilation called the cisterna chili and is the main collecting duct of the lymphatic system.
c.Right Lymphatic Duct:The right lymphatic duct drains lymph from the upper right side of the body.
1.Interstitial fluid drains into lymphatic capillaries, thus forming lymph.
2.Lymph capillaries merge to form larger vessels, called lymphatic vessels, which convey lymph into and out of structures called lymph nodes.
3.Lymphatic Capillaries:Lymphatic capillaries are found throughout the body except in avascular tissue, the CNS, portions of the spleen, and red bone marrow.
4.Lymphatic capillaries have a slightly larger diameter than blood capillaries and have overlapping endothelial cells which work as one-way valves for fluid to enter the lymphatic capillary.
5.A lymphatic capillary in the villus of the small intestine is the lacteal. It functions to transport digested fats from the small intestine into blood.

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D. Formation and Flow of Lymph

1. Interstitial fluid drains into lymph capillaries.
2. The passage of lymph is from arteries and blood capillaries (blood) to interstitial spaces (interstitial fluid) to lymph capillaries (lymph) to lymphatic vessels to lymph trunks to the thoracic duct or right lymphatic duct to the subclavian veins (blood).
a. Lymph flows as a result of the milking action of skeletal muscle contractions and respiratory movements.
b. It is also aided by lymphatic vessel valves that prevent backflow of lymph.

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E. Lymphatic Organs and Tissues

The primary lymphatic organs are those in which cells become immunocompetent (capable of mounting an immune response) the red bone marrow (B cells) and the Thymus gland (T cells).
a.The secondary lymphatic organs are the lymph nodes and spleen.
b.Included as secondary lymphatic tissues are lymphatic nodules.
c.Most immune responses occur in secondary lymphatic organs and tissues.
2.Thymus Gland-The thymus gland lies between the sternum and the heart and functions in immunity as the site of T cell maturation.
3.Lymph Nodes-Lymph nodes are encapsulated oval structures located along lymphatic vessels,contain T cells, macrophages, follicular dendritic cells, and B cells.
c.Lymph enters nodes through afferent lymphatic vessels, and exits through efferent lymphatic vessels.1.Foreign substances filtered by the lymph nodes are trapped by nodal reticular fibers. 2.Macrophages then destroy some foreign substances and cells by phagocytosis. 3.Lymphocytes bring about the destruction of other cells by immune responses.

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4. Spleen

a. The spleen is the largest mass of lymphatic tissue in the body and is found in the left hypochondriac region between the fundus of the stomach and the diaphragm.
b. The spleen consists of white and red pulp
1. The white pulp is lymphatic tissue.
2. Its T lymphocytes directly attack and destroy antigens in blood, primarily via cytolysis.
3. Its B lymphocytes develop into antibody producing plasma cells, and the antibodies inactivate antigens in blood.
4. Macrophages destroy antigens in blood by phagocytosis.
c. The red pulp consists of venous sinuses filled with blood and splenic cords consisting of RBCs, macrophages, lymphocytes, plasma cells, and granulocytes.
1. Macrophages remove worn-out or defective RBCs, WBCs, and platelets by phagocytosis
2. The spleen stores blood platelets in the red pulp.
3. The red pulp is involved in the production of blood cells during the second trimester of pregnancy.

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5. Lymphatic Nodules

a. Lymphatic nodules are oval-shaped concentrations of lymphatic tissue.
1. They are scattered throughout the lamina propria of mucous membranes lining the GI tract, respiratory airways, urinary tract, and reproductive tract.
2. This is the mucosa-associated lymphatic tissue (MALT).
3. Peyer’s patches are lymphatic nodules in the ileum of the small intestine.
4. Tonsils are multiple aggregations of large lymphatic nodules embedded in a mucous membrane at the junction of the oral cavity and the pharynx.
5. They include the pharyngeal (adenoid), palatine, and lingual tonsils.
6. They are situated strategically to protect against invasion of foreign substances and participate in immune responses by producing lymphocytes and antibodies.

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III. INNATE IMMUNITY – NONSELECTIVE IMMUNITY
A. First Line of Defense: Skin and Mucous Membranes

1. Innate immunity (nonselective resistance) refers to a wide variety of body responses against a wide range of pathogens (disease producing organisms) and their toxins that are present at birth.
2. Mechanical protection includes the intact epidermis layer of the skin, mucous membranes, the lacrimal apparatus, saliva, mucus, cilia, the epiglottis, and the flow of urine. Defecation and vomiting also may be considered mechanical processes that expel microbes.
3. Chemical protection is localized on the skin, in loose connective tissue, stomach, and vagina.
a. The skin produces sebum, which has a low pH due to the presence of unsaturated fatty acids and lactic acid.
b. Lysozyme is an enzyme component of sweat that also has antimicrobial properties.
c. Gastric juice renders the stomach nearly sterile because its low pH (1.5-3.0) kills many bacteria and destroys most of their toxins; vaginal secretions also are slightly acidic.

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III. INNATE IMMUNITY – NONSELECTIVE IMMUNITY
B. Second Line of Defense: Internal Defenses

1. Antimicrobial Proteins
a. Lymphocyte and macrophage cells infected with viruses produce proteins called interferons (IFNs).
1. Once produced and released from virus-infected cells, IFN diffuses to uninfected neighboring cells and binds to surface receptors, inducing uninfected cells to synthesize antiviral proteins that interfere with or inhibit viral replication.
b. A group of about 20 proteins present in blood plasma and on cell membranes comprises the complement system; when activated, these proteins “complement” or enhance certain immune, allergic, and inflammatory reactions.
c. Iron-binding proteins remove iron from the body fluids thereby inhibiting microbial growth.
d. Anti-microbial substances are peptides that produce anti-microbial activity and attract dendritic and mast cells.

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III. INNATE IMMUNITY – NONSELECTIVE IMMUNITY
2. Natural Killer Cells and Phagocytes

a. Natural killer (NK) cells are lymphocytes that lack the membrane molecules that identify T and B cells.
1. They have the ability to “kill” a wide variety of infectious microbes.
2. NK cells sometimes release perforins that insert into the plasma membrane of a microbe and make the membrane leaky so that cytolysis occurs
3. Phagocytes are cells specialized to perform phagocytosis and include neutrophils and macrophages.
4. The steps of phagocytosis include
i. Chemotaxis
ii. Adherence
iii. Ingestion
iv. Digestion - After phagocytosis has been accomplished, a phagolysosome is formed (filled with digestive enzymes/oxidants)
v. Killing
5. Some of the reasons why a microbe may evade phagocytosis include: capsule formation (e.g. Bacillus anthracis), toxin production, interference with lysozyme secretion, and the microbe’s ability to counter oxidants produced by the phagocytes (Clinical Connection).

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III. INNATE IMMUNITY – NONSELECTIVE IMMUNITY
3. Inflammation

a. Inflammation occurs when cells are damaged by microbes, physical agents, or chemical agents. The injury may be viewed as a form of stress.
b. Inflammation is usually characterized by four symptoms: redness, pain, heat, and swelling. Loss of function may be a fifth symptom, depending on the site and extent of the injury.
c. The three basic stages of inflammation are:
1. vasodilation and increased permeability of blood vessels
2. phagocyte migration
3. tissue repair
d. Substances that contribute to inflammation are histamines, kinins, prostaglandins, leukotrienes, and complement.
4. Fever is usually caused by infection from bacteria (and their toxins) and viruses. The high body temperature inhibits some microbial growth and speeds up body reactions that aid repair.

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IV. ADAPTIVE IMMUNITY

A. Immunity is the ability of the body to defend itself against specific invading agents.
1. Antigens are substances recognized as foreign by the immune responses.
2. The distinguishing properties of immunity are specificity and memory.
3. The branch of science that deals with the responses of the body when challenged by antigens is called immunology.

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B. Antigens and Antigen Receptors

1. Antigens are chemical substances that are recognized as foreign by antigen receptors when introduced into the body. Antigens are both immunogenic and reactive. An antigen that gets past the nonspecific defenses can get into lymphatic tissue by entering an injured blood vessel and being carried to the spleen, penetrating the skin and entering lymph vessels leading to lymph nodes, or penetrating mucous membranes and lodging in mucosa-associated lymphoid tissue.
2. Antigens are large, complex molecules. They are most often proteins, but sometimes are nucleoproteins, lipoproteins, glycoproteins, and certain large polysaccharides.
3. Specific portions of antigen molecules, called antigenic determinants, or epitopes, trigger immune responses.
4. Antigen receptors exhibit great diversity due to genetic recombination.
5. Major histocompatibility complex (MHC) antigens (also called human leucocyte associated, or HLA, antigens) are unique to each person’s body cells. These self-antigens aid in the detection of foreign invaders. All cells except red blood cells display MHC class I antigens. Some cells also display MHC class II antigens.

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C. Pathways of Antigen Processing

1. For an immune response to occur, B and T cells must recognize that a foreign antigen is present.
2. B cells can recognize and bind to antigens in extracellular fluid.
3. T cells, however, can only recognize fragments of antigenic proteins that first have been processed and presented in association with MHC self-antigens.
4. Peptide fragments from foreign antigens help stimulate MHC molecules.
5. Processing of Exogenous Antigens
a. 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
b. APCs include macrophages, B cells, and dendritic cells.
c. Steps in processing and presenting an exogenous antigen by an APC include ingestion of the antigen, digestion of antigen into peptide fragments, fusion of vesicles, binding of peptide fragments to MHC-II molecules, and insertion of antigen-MHC-II complex into the plasma membrane.

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D. Maturation of T Cells and B Cells

1. Both T cells and B cells derive from stem cells in bone marrow.
a. B cells complete their development, becoming immunocompetent, in bone marrow.
b. T cells develop from pre-T cells that migrate to the thymus where they become immunocompetent under the influence of thymic hormones
c. Before T cells leave the thymus or B cells leave bone marrow, they acquire several distinctive surface proteins; some function as antigen receptors, molecules capable of recognizing specific antigens.

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E. Types of Adaptive immunity

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

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F. Clonal selection

1. Clonal selection is the process by which an immune cels proliferates and differentiates in response to a specific antigen.
2. Two major types of cells result from clonal selection; 1) effector cells; and 2) memory cells.
3. Effector cells are the cells that actually do the work to destroy the antigen and include: cytotoxic T cells, helper T cells and plasma cells (a clone of B cells)
4. Memory cells, with long life spans, provide a faster second invasion response by proliferating and differentiating into effector cells.

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G. Cytokines

1. Cytokines are small protein hormones needed for many normal cell functions.

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V. CELL-MEDIATED IMMUNITY

A. In a cell-mediated immune response, an antigen is recognized (bound), a small number of specific T cells proliferate and differentiate into a clone of effector cells (a population of identical cells that can recognize the same antigen and carry out some aspect of the immune attack), and the antigen (intruder) is eliminated.

B. Activation of T Cells

C. Activation and clonal selction of helper T Cells

D. Activation and clonal selction of helper T Cells

E. Elimination of invaders

F. Immunological Surveillance

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VI. ANTIBODY-MEDIATED IMMUNITY

A. The body contains not only millions of different T cells but also millions of different B cells, each capable of responding to a specific antigen.

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B. Activation and clonal selection of B Cells

1. During activation of a B cell, an antigen binds to antigen receptors on the cell surface
2. B cell antigen receptors are chemically similar to the antibodies that will eventually be secreted by their progeny.
3. Some antigen is taken into the B cell, broken down into peptide fragments and combined with the MHC-II self-antigen, and moved to the B cell surface.
4. Helper T cells recognize the antigen-MHC-II combination and deliver the costimulation needed for B cell proliferation and differentiation.
5. Some activated B cells become antibody-secretion plasma cells. Others become memory B cells.

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C. Antibodies

1. An antibody is a protein that can combine specifically with the antigenic determinant on the antigen that triggered its production.

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D. Antibody Structure

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

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E. Antibody actions

1. The functions of antibodies include neutralizing antigen, immobilization of bacteria, agglutination and precipitation of antigen, activation of complement and enhancing phagocytosis.

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F. Role of Complement system in immunity

1. A group of about 20 proteins present in blood plasma and on cell membranes comprises the complement system; when activated, these proteins “complement” or enhance certain immune, allergic, and inflammatory reactions.

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G. Immunological Memory

1. Immunological memory is due to the presence of long-lived antibodies and very long-lived lymphocytes that arise during proliferation and differentiation of antigen-stimulated B and T cells.
2. Immunization against certain microbes is possible because memory B cells and memory T cells remain after the primary response to an antigen.

The secondary response (immunological memory) provides protection should the same microbe enter the body again. There is rapid proliferation of memory cells, resulting in a far greater antibody titer (amount of antibody in serum) than during a primary response.

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Homeostatic Imbalances
The 4 basic types of hypersensitivity reactions.

-Type I (anaphylaxis) reactions are the most common and occur with a few minutes after a person sensitized to an allergen is reexposed to it. Anaphylaxis results from the interaction of allergens with IgE antibodies on the surface of mast cells and basophils. In anaphylactic shock, which may occur in a susceptible individual who has just received a triggering drug or been stung by a wasp, wheezing and shortness of breath as airways constrict are usually accompanied by shock due to vasodilation and fluid loss from blood. This is a life-threatening emergency.
-Type II (cytotoxic) reactions are caused by antibodies (IgG or IgM) directed against a person’s blood cells or tissue cells. The reaction of antibodies and antigens usually leads to activation of complement. Type II reaction, which may occur in incompatible blood transfusion reactions, damage cells by causing lysis.
-Type III (immune complex) reactions involve antigens (not part of a host tissue cell), antibodies (IgA or IgM), and complement. Some type II conditions include glomerulonephritis, systemic lupus erythematosus, and rheumatoid arthritis.
-Type IV (cell-mediated) reactions or delayed hypersensitivity reactions usually appear 12-72 hours after exposure to an allergen and occur when allergens are taken up by antigen-presenting cells that migrate to lymph nodes and present the allergen to T cells. Intracellular bacteria, such as the one that causes tuberculosis, trigger this type of cell-mediated immune response.