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Chapter 22: Lymphatic System and Immunity Objectives: ● To learn about the organization and components of the lymphatic system. ● To gain information about its role in keeping us healthy. The Lymphatic System, Disease Resistance, and Homeostasis The lymphatic system contributes to homeostasis by draining interstitial fluid as well as providing the mechanisms for defense against disease. The lymphatic system is one of the principal body systems that helps to defend us against disease-producing microbes. Question #1: Did you ever wonder how cancer can spread from one part of the body to another? 22.1 The Concept of Immunity Objectives: ● Define immunity. ● Compare the two basic types of immunity. Pathogens (PATH-ô-jens)-disease-producing microbes such as bacteria and viruses-most people remain healthy. Immunity (i-MÜ-ni-te) or resistance is the ability to ward off damage or disease through our defenses. Susceptibility is vulnerability or lack of resistance. Innate (nonspecific) immunity refers to defenses that are present at birth. Components of Innate Immunity
- The first line of defense (the physical and chemical barriers of the skin and mucous membranes)
- The second line of defense (antimicrobial substances, natural killer cells, phagocytes, inflammation, and fever) Adaptive (specific) immunity refers to defenses that involve specific recognition of a microbe once it has breached the innate immunity defenses. Adaptive immunity involves lymphocytes (a type of white blood cell) called T lymphocytes (T cells) and B lymphocytes (B cells). The body system responsible for adaptive immunity (and some aspects of innate immunity) is the **lymphatic system. Checkpoint
- What is a pathogen?
- Now are innate and adaptive immunity different? 22.2 Overview of the Lymphatic System Objectives: ● List the components of the lymphatic system. ● Describe the functions of the lymphatic system.**
Components of the Lymphatic System The lymphatic or lymphoid system (lim-FAT-ik) consists of a fluid called lymph , vessels called lymphatic vessels that transport the lymph , a number of structures and organs containing lymphatic tissue (lymphocytes within a filtering tissue), and red bone marrow. Functions
- Drains excess interstitial fluid.
- Transports dietary lipids from the gastrointestinal tract to the blood.
- Protects against invasion through immune responses. Question #2: What tissue contains stem cells that develop into lymphocytes? After interstitial fluid passes into lymphatic vessels, it is called lymph (LIMF = clear fluid). Lymphatic tissue is a specialized form of reticular connective tissue (see Table 4.4) that contains large numbers of lymphocytes. **Functions of the Lymphatic System The lymphatic system has three primary functions:
- Drains excess interstitial fluid.** Lymphatic vessels drain excess interstitial fluid from tissue spaces and return it to the blood. This function closely links it with the cardiovascular system. In fact, without this function, the maintenance of circulating blood volume would not be possible. 2. Transports dietary lipids. Lymphatic vessels transport lipids and lipid-soluble vitamins (A, D, E, and K) absorbed by the gastrointestinal tract. 3. Carries out immune responses. Lymphatic tissue initiates highly specific responses directed against particular microbes or abnormal cells. **Checkpoint
- What are the components and functions of the lymphatic system? 22.3 Lymphatic Vessels and Lymph Circulation Lymphatic Capillaries Organization of Lymphatic Vessels ● Lymphatic Capillaries ● Lymphatic Collecting Vessels ● Lymphatic Trunks ● Lymphatic Ducts Lymphatic Capillaries** ● They have greater permeability than blood
FORMATION AND FLOW OF LYMPH
The sequence of fluid flow is blood capillaries (blood) - interstitial spaces (interstitial fluid) - lymphatic capillaries (lymph) - lymphatic vessels (lymph) - lymphatic trunks or ducts (lymph) - junction of the internal jugular and subclavian veins (blood). Schematic diagram showing the relationship of the lymphatic system to the cardiovascular system. Two "pumps" that aid the return of venous blood to the heart maintain the flow of lymph.
1. Respiratory Pump. Lymph flow is also maintained by pressure changes that occur during inhalation (breathing in). Lymph flows from the abdominal region, where the pressure is higher, toward the thoracic region, where it is lower. 2. Skeletal Muscle Pump. The "milking action" of skeletal muscle contractions compresses lymphatic vessels and forces lymph toward the junction of the internal jugular and subclavian veins. 22.4 Lymphatic Organ and Tissues Classifications of Lymphatic Organ and Tissue: 1. Primary Lymphatic Organs are the sites where stem cells divide and become immunocompetent, that is, capable of mounting an immune response. The primary lymphatic organs are the red bone marrow in flat bones and the epiphyses of long bones of adults and the thymus. 2. Secondary Lymphatic Organs and tissues are the sites where most immune responses occur. They include lymph nodes, the spleen, and lymphatic nodules (follicles). The thymus, lymph nodes, and spleen are considered organs because each is surrounded by a connective tissue capsule; lymphatic nodules, in con-trast, are not considered organs because they lack a capsule. ***** An enveloping layer of connective tissue holds the two lobes closely together, but a connective tissue capsule encloses each lobe separately. Extensions of the capsule, called trabeculae , penetrate inward and divide each lobe into lobules. · Dendritic cells are derived from monocytes that assist the maturation process. · Epithelial cells help "educate" the pre-T cells in a process known as positive selection
· Thymic macrophages help clear out the debris of dead and dying cells. · Medulla consists of widely scattered, more mature T cells, epithelial cells, dendritic cells, and macrophages. Lymph Nodes - are located along lymphatic vessels that are scattered throughout the body, both superficially and deep, and usually occur in groups.
- They are 1-25 mm (0.04-1 in.) long and, like the thymus, are covered by a capsule of dense connective tissue that extends into the node. · Trabeculae are the capsular extensions that divide the node into compartments, provide support, and provide a route for blood vessels into the interior of a node. · Parenchyma of a lymph node is divided into a superficial cortex and a deep medulla. Outer cortex contains lymphatic nodules. Inner cortex does not contain lymphatic nodules. · Lymphatic Nodules are egg shaped aggregate of B-cells · The medulla of a lymph node contains B cells, antibody-producing plasma cells that have migrated out of the cortex into the medulla, and macrophages. · Afferent Lymphatic Vessels contain valves that open toward the center of the node, directing the lymph inward. · Sinuses , a series of irregu- the lymph node. Since there are many afferent lymphatic vessels that lar channels that contain branching reticular fibers, lymphocytes, and bring lymph into a lymph node and only one or two efferent lymphatic macrophages. Metastasis through Lymphatic Vessels Metastasis (me-TAS-ta-sis; meta- = beyond; -stasis = to stand), the spread of a disease from one part of the body to another, can occur via lymphatic vessels. All malignant tumors eventually metastasize. Spleen is the largest single mass of lymphatic tissue in the body. SPLEEN Spleen is the largest single mass of lymphatic tissue in the body. It is a soft, encapsulated organ of variable size, but on average it fits in a person's open hand and measures about 12 cm (5 in.) in length.
cisterna chyli and lose their connections with adjacent veins. 22.6 Innate Immunity Innate Immunity includes the external physical and chemical barriers provided by the skin and mucous membrane. First Line of Defense: Skin and Mucous Membranes PHYSICAL FACTORS: Epidermis of skin - Forms physical barrier to entrance of microbes. Mucous membranes - Inhibit entrance of many microbes, but not as effective as intact skin. Mucus – Traps microbes in respiratory and gastrointestinal tracts. Hairs – Filter out microbes and dust in the nose. Cilia – Together with mucus, trap and remove microbes and dust from the upper respiratory tract. Lacrimal apparatus – Tears dilute and wash away irritating substances and microbes. Saliva – Washes microbes from surfaces of teeth and mucous membranes of mouth. Urine – Washes microbes from urethra. Defecation and vomiting – Expel microbes from body. CHEMICAL FACTORS Sebum – Forms protective acidic film over the skin surface that inhibits growth of many microbes. Lysozyme – Antimicrobial substance in perspiration, tears, saliva, nasal secretions, and tissue fluids. Gastric Juice – Destroys bacteria and most toxins in the stomach. Vaginal Secretions – Slightly acidity discourages bacterial growth; flush microbes out of vagina Second Line of Defense: Internal Defense Antimicrobial Substances (4 main types)
- Interferons (IFN). Once released by virus-infected cells, IFs diffuse to uninfected neighboring cells, where they induce synthesis of antiviral proteins that interfere with viral replication.
- Complement System. When activated, these proteins "complement" or enhance certain immune reactions. The complement system causes cytolysis (bursting) of microbes, promotes phagocytosis, and contributes to inflammation.
- Iron-binding Proteins. They inhibit the growth of certain bacteria by reducing the amount of available iron.
- Antimicrobial Proteins. These are short peptides that have a broad spectrum of antimicrobial activity. NATURAL KILLER CELLS – kill infected target cells by releasing granules
that contain perforin and granzymes; phagocytes then kill released microbes. PHAGOCYTOSIS – These are specialized cells that perform phagocytosis, the ingestion of microbes or other particles such as cellular debris. FIVE PHASES OF PHAGOCYTOSIS Chemotaxis. Phagocytosis begins with chemotaxis (ke-mo-TAK-sis), a chemically stimulated movement of phagocytes to a site of damage. Chemicals that attract phagocytes might come from invading microbes, white blood cells, damaged tissue cells, or activated complement proteins. Adherence. Attachment of the phagocyte to the microbe or other foreign material is termed adherence (ad-HER-ents). The binding of complement proteins to the invading pathogen enhances adherence. Ingestion. The plasma membrane of the phagocyte extends projections, called pseudopods (S00-do pods), that engulf the microbe in a process called ingestion. When the pseudopods meet they fuse, surrounding the microorganism with a sac called a phagosome (FAG-o•som). Digestion. The phagosome enters the cytoplasm and merges with lysosomes to form a single, larger structure called a phagolysosome. The lysosome contributes lysozyme, which breaks down microbial cell walls, and other digestive enzymes that degrade carbohydrates, proteins, lipids, and nucleic acids. The phagocyte also forms lethal oxidants, such as superoxide anion (0, ), hypochlorite anion (OCI), and hydrogen peroxide (H,O,), in a process called an oxidative burst. Killing. The chemical onslaught provided by lysozyme, digestive enzymes, and oxidants within a phagolysosome quickly kills many types of microbes. Any materials that cannot be degraded further remain in structures called residual bodies. 22.7 Adaptive Immunity OBJECTIVES
- Describe how T cells and B cells arise and function in adaptive immunity.
- Explain the relationship between an antigen and an antibody.
- Compare the functions of cell-mediated immunity and antibody- mediated immunity. adaptive (specific) immunity The ability of the body to defend itself against specific invading agents such as bacteria, toxins, viruses, and foreign tissues antigens (Ags) Substances that are recognized as foreign and pro- voke immune responses Two properties distinguish adaptive immunity from innate immunity: (1) specificity for particular foreign molecules (antigens), which also involves distinguishing self from nonself mol- ecules, and
it is also referred to as humoral immunity cell-mediated and antibody-mediated immune responses often work together to eliminate the large number of copies of a particular antigen from the body. Clonal Selection: The Principle Clonal selection It is the process by which lympho-cyte proliferates (divides) and differentiates (forms more highly special- ized cells) in response to a specific antigen. Clone formation of a population of identical cells Clonal selection of lymphocytes occurs in the secon-dary lymphatic organs and tissues. two major types of cells in the clone: effector cells and memory cells Effector cells · result in the destruction or inactivation of the antigen. · active helper T cells, · active cytotoxic T cells · plasma cells Memory cells · do not actively participate in the initial immune response to the antigen. · Memory helper T cells · Memory cytotoxic T cells · Memory B cells Antigens and Antigen Receptors Antigens have two important characteristics: immunogenicity and reactivity. Immunogenicity is the ability to provoke an immune response by stimulating the production of specific antibodies, the proliferation of specific T cells, or both. Reactivity is the ability of the antigen to react specifically with the antibodies or cells it provoked. epitopes or antigenic determinants certain small parts of a large antigen molecule act as the triggers for immune responses. Chemical Nature of Antigens Antigens are large, complex molecules. hapten A smaller substance that has reactivity but lacks immunogenicity. hapten-stimulated immune responses responsible for some allergic reactions to drugs and other substances in the environment.
Diversity of Antigen Receptors its ability to recognize and bind to at least a billion (109) different epitopes. Question: What is the difference between an epitope and a hapten? Major Histocompatibility Complex (MHC) Antigens Located in the plasma membrane of body cells are “self-antigens,” transmembrane glycoproteins are also called human leukocyte antigens (HLA) because they were first identified on white blood cells. two types of major histocompatibility complex antigens are class I and class II. Class I MHC (MHC-I) molecules are built into the plasma membranes of all body cells except red blood cells. Class II MHC (MHC-II) molecules appear on the surface of antigen-presenting cells (described in the next section). Pathways of Antigen Processing antigen processing antigenic proteins are broken down into peptide fragments that then associate with MHC molecules. antigen presentation insertion of the complex into the plasma membrane Processing of Exogenous Antigens exogenous antigens Foreign antigens that are present in fluids outside body cells are termed A special class of cells called antigen-presenting cells (APCs) process and present exogenous antigens. The steps in the processing and presenting of an exogenous anti-gen by an antigen-presenting cell occur as follows: 1.) Ingestion of the antigen Antigen-presenting cells ingest exogenous antigens by phagocytosis or endocytosis. 2.) Digestion of antigen into peptide fragments Within the phagosome or endosome, protein-digesting enzymes split large antigens into short peptide fragments. 3.) Synthesis of MHC-II molecules At the same time, the APC synthesizes MHC-II molecules at the endoplasmic reticulum (ER). 4.) Packaging of MHC-II molecules Once synthesized, the MHC-II molecules are packaged into vesicles. 5.) Fusion of vesicles. The vesicles containing antigen peptide fragments and MHC-II molecules merge and fuse.
**- Distinguish between the action of natural killer cells and cytotoxic T cells.
- Define immunological surveillance. Activation of T Cells** Antigen receptors on the surface of T cells, called T-cell receptors (TCRs), Antigen recognition also involves other surface proteins on T cells, the CD4 or CD proteins A T cell becomes activated only if it binds to the foreign antigen and at the same time receives a second signal, a process known as costimulation. 20 known costimulators, some are cytokines, such as interleukin-2 (IL-2). recognition (antigen binding to a receptor) without costimulation leads to a prolonged state of inactivity called anergy (AN-er-je) in both T cells and B cells. Activation and Clonal Selection of Helper T Cells helper T cells, also known as CD4 T cells. hours after costimulation, active helper T cells start secreting a variety of cytokines the memory helper T cells of a helper T cell clone are not active cells.
Activation and Clonal Selection of
Cytotoxic T Cells
cytotoxic T cells , also termed CD8 T cells. Cytotoxic T cells recognize foreign antigens combined with major histocompatibility complex class I (MHC-|) molecules on the
surface of (1) body cells infected by microbes, (2) some tumor cells, and (3) cells of a tissue transplant Active cytotoxic T cells attack other body cells that have been infected with the antigen. Memory cytotoxic T cells do not attack infected body cells. Elimination of Invaders Cytotoxic T cells recognize and attach to target cells. Then, the cytotoxic T cells deliver a "lethal hit" that kills the target cells. natural killer cells can destroy a wide variety of microbe-infected body cells. Cytotoxic T cells have two principal mechanisms for killing infected target cells.
- Cytotoxic T cells, using receptors on their surfaces, recognize and bind to infected target cells that have microbial antigens displayed on their surlace.
- Alternatively, cytotoxic T cells bind to infected body cells and release cells infected with one particular type of microbe; natural killer cells two proteins from their granules: perforin and granulysin. cytotoxic cells may also destroy target cells by releasing a toxic molecule called lym-photoxin
Antibody Structure Antibodies belong to a group of glycoproteins called globulins, and for this reason they are also known as immunoglobulins (Igs) Most antibodies contain four polypeptide chains. Two of the chains are identical to each other and are called heavy (H) chains: each consists of about 450 amino acids Short carbohydrate chains are attached to each heavy polypeptide chain. The two other polypeptide chains, also identical to each other, are called light (L) chains and each consists of about 220 amino acids. A disulfide bond S-S holds each light chain to a heavy chain. Two disulfide bonds also link the mid region of the two heavy chains; this part of the antibody displays considerable Hexibity and is called the hinge region. The tips of the H and L chains, called the variable (V) regions, constitute the antigen-binding site. The remainder of each H and L chain, called the constant (C) region , is nearly the same in all antibodies of the same class and is responsible for the type of antigen-antibody reaction that occurs. Antibody Actions The actions of the five classes of immunoglobulins differ somewhat, but all of them act to disable antigens in some way, Actions of antibodies include the following Neutralizing antigen The reaction of antibody with antigen blocks or neutralizes some bacterial toxins and prevents attachment of sme viruses to body cells immobilizing bacteria If antibodies form against andeens on the cilia or flagella of motile bacteria, the antigen-antibody reaction may cause the bacteria to lose their motility. which limits their spread into nearby tissues. Agglutinating and precipitating antigen. Because antibodies have two or more sites for binding to antigen, the antigen-antibody reaction may cross-link pathogens to one another, causing agglutination (clumping together). Phagocytic cells ingest agglutinated microbes more readily. Likewise, soluble antigens may come out of solution and form a more easily phagocytized precipitate when cross-linked by antibodies.
Activating complement Andren-antibody complexes initiate the classical pathway of the complement system Enhancing phagocytosis The stem region of an antibody acts as a tag that attracts phagocytes once antigens have bound to the antibody's variable region. Role of the Complement System in Immunity complement system (KOM-ple-ment) is a defensive system made up of over 30 proteins produced by the liver and found circulating in blood plasma and within tissues throughout the body. Most complement proteins are designated by an uppercase letter C, numbered C1 through C9, named for the order in which they were discovered. The C1-C9 complement proteins are inactive and become activated only when split by enzymes into active fragments, which are indicated by lowercase letters a and b. For example, inactive complement protein C3 is split into the activated fragments, C3a and C3b. The active fragments carry out the destructive actions of the C1-C9 complement proteins. Other complement proteins are referred to as factors B, D, and P (properdin). C3 can be activated in three ways: The classical pathway starts when antibodies bind to antigens microbes. The alternative pathway does not involve antibodies lectin pathway Macrophages digest microbes and release chemicals that cause the liver to produce proteins called lectins. Lectins Bind to the carbohydrates on the surface of microbes, ultimately causing the activation of C Immunological Memory the presence of long lasting antibodies and very long-lived lymphocytes that arise
AIDS: Acquired Immunodeficiency Syndrome Acquired immunodeficiency syndrome (AIDS) is a condition in which a person experiences a telltale assortment of infections due to the progressive destruction of immune system cells by the human immunodeficiency virus (HIV). HIV Transmission because HIV is present in the blood and some body fluids, it is most effectively transmitted (spread from one person to another) by actions or practices that involve the exchange of blood or body fluids between people. HIV is transmitted in semen or vaginal fluid during unprotected (without a condom) anal, vaginal, or oral sex. HIV also is transmitted by direct blood-to-blood contact such as occurs among intravenous drug users who share hypodermic needles or health-care professionals who may be accidentally stuck by HIV-contaminated hypodermic needles. HIV can be transmitted from an HIV-infected mother to her baby at birth or during breast-feeding. 22.12 Aging and the Immune System Infectious Mononucleosis ● Infectious Mononucleosis or "mono" is a contagious disease caused by the Epstein-Barr virus (EBV). It occurs mainly in children and young adults, and more often in females than in males. The virus most commonly enters the body through intimate oral contact such as kissing, which accounts for its common name, the "kissing dis-ease." ● EBV then multiplies in lymphatic tissues and filters into the blood, where it infects and multiplies in B cells, the primary host cells. Because of this infection, the B cells become so enlarged and abnormal in appearance that they resemble monocytes, the primary reason for the term mononucleosis. Lymphomas ● Lymphomas (lim-FÖ-mas; lymph- = clear water; -oma = tumor) are cancers of the lymphatic organs, especially the lymph nodes. Most have no known cause. The two main types of lymphomas are Hodgkin disease and non-Hodgkin lymphoma. ● Hodgkin disease (HD) (HOJ-kin) is characterized by a painless, nontender enlargement of one or more lymph nodes, most commonly in the neck, chest, and axilla. If the disease has metastasized from these sites, fever, night sweats, weight loss, and bone pain also occur. HD primarily affects individuals between
ages 15 and 35 and those over 60, and it is more common in males. If diagnosed early, HD has a 90-95% cure rate. ● Non-Hodgkin lymphoma (NHL), which is more common than HD, occurs in all age groups, the incidence increasing with age to a maximum between ages 45 and 70. NHL may start the same way as HD but may also include an enlarged spleen, anemia, and general malaise. Up to half of all individuals with NHL are cured or survive for a lengthy pe-riod. Treatment options for both HD and NHL include radiation therapy, chemotherapy, and bone marrow transplantation. Systemic Lupus Erythematosus ● Systemic lupus erythematosus or simply lupus is a chronic autoimmune, inflammatory disease that affects multiple body systems. Lupus is characterized by periods of active disease and remission; symptoms range from mild to life-threatening. Severe Combined Immunodeficiency Disease ● Severe combined immunodeficiency disease (SCID) is a rare inherited disorder in which both B cells and T cells are missing or inactive. MEDICAL TERMINOLOGIES ● Adenitis (ad'-e-Ni-tis; aden- = gland; -itis = inflammation of) Enlarged, tender, and inflamed lymph nodes resulting from an infection. ● Allograft (AL-∞-graft; allo- = other) A transplant between genetically distinct individuals of the same species. Skin transplants from other people and blood transfusions are allografts. ● Autograft (AW-to-graft; auto- = self) A transplant in which one's own tissue is grafted to another part of the body (such as skin grafts for burn treatment or plastic surgery). ● Chronic fatigue syndrome (CFS) A disorder, usually occurring in young adults and primarily in females, characterized by (1) extreme fatigue that impairs normal activities for at least 6 months and (2) the absence of other known diseases (cancer, infections, drug abuse, toxicity, or psychiatric dis-orders) that might produce similar symptoms. ● Gamma globulin (GLOB-ü-lin) Suspension of immunoglobulins from blood consisting of antibodies that react with a specific pathogen. It is prepared by injecting the pathogen into animals, removing blood from the animals after antibodies have been produced, isolating the antibodies, and injecting them into a human to provide short-term immunity. ● Hypersplenism (hi-per-SPLEN-izm; hyper- = over) Abnormal splenic activity due to splenic enlargement and associated with an increased rate of destruction of normal blood cells. ● Lymphadenopathy (lim-fad'-e-NOP-a-the; lymph- =
