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The Lymphatic System The Immune System Innate

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									Chapter 22: The Lymphatic System and Immunity

Chapter Objectives

   1. Describe the organization of lymph vessels.
   2. Describe the general cellular structure, distribution, and operation of lymphatic
      capillaries; then note the special location and duty of lacteals.
   3. Identify the primary and secondary lymphatic organs and their distributions and general
   4. Discuss the location of the thymus gland and its effect on T-lymphocyte maturation.
   5. Describe the structure and locations of lymph nodes.
   6. Describe the overall structure of the spleen and the functions of the red and white pulp.
   7. Specify the names and locations of the different mucosa-associated lymphoid tissues.
   8. List the primary mechanisms that are responsible for Nonspecific resistance.
   9. List the major means by which the skin and mucous membranes act as the first line of
      defense against pathogens.
   10. List and describe the effects of the antimicrobial proteins: interferons, transferrins, and
      complement proteins.
   11. List the phases of phagocytosis and describe what is occurring in each step.
   12. Discuss Natural Killer cells locations and functions.
   13. Describe the symptoms and basic stages of inflammation, and the substances that
      contribute to the inflammatory process.
   14. Discuss the initiating factors and beneficial physiological responses thought to be
      attributable to fever.
   15. Define adaptive (specific) immunity and discuss its properties of specificity and memory.
   16. Distinguish the difference between cell-mediated and antibody-mediated immunity and
      which uses T cells and which uses B cells. Determine which is better against intracellular
      pathogens and which is better against extracellular pathogens.
   17. Discuss the characteristics of antigens, epitopes and haptens and give some examples of
   18. Describe the roles of the major histocompatibility complex (MCH) in foreign antigen
      recognition and the type of cells in the body that possess the two different classes of
   19. Give the details in the sequence of processing of exogenous antigens by antigen
       presenting cells (APCs) from endocytosis to MHC-antigen display on the cell membrane.
   20. Describe the processing of endogenous antigens
   21. List the names of some cytokines and give their general functions.
   22. Describe the components needed to achieve costimulation of a T cell.
   23. Determine which T cell displays CD4 and which displays CD8
   24. Determine which T cell will be stimulated best by intracellular pathogens and which by
       extracellular pathogens.
   25. Discuss the activation and activity of helper T cells, including memory helper T cells
   26. Discuss the activation and activity of cytotoxic T cells.
   27. Describe the mechanisms used by cytotoxic T cells to destroy body cells that have been
       invaded by pathogens.
   28. Discuss the general locations and response of specific B cells to specific antigens.
   29. Describe the scheme through which B cells are activated and costimulated to increase the
       number, transformation, and output of antibodies which will attack only the antigen that
       initially activated each specific B cell.
   30. Define an antibody.
   31. Describe the five functional classes of antibodies.
   32. Discuss the five actions provided by antibodies in the elimination of pathogenic antigens.
   33. Describe the three ways that the complement system may be activated and the results of
       the complement system activation.
   34. Describe the four different types of acquired immunity.
   35. Define autoimmune diseases, infectious mononucleosis, lymphomas, and systemic lupus

Chapter Lecture Notes


The lymphatic system is comprised of a network of vessels that transport body fluids, the cells

       and chemicals in those vessels, and the organs and glands that produce them.
Lymphatic vessels collect and carry away excess fluid from interstitial spaces and special vessels

        called lacteals transport fats to the circulatory system.

The organs of the lymphatic system help defend against disease. (Fig 22.1)

    red bone marrow



    lymph nodes

    diffuse lymphatic tissue

        tonsils, adenoids & peyers patches in digestive system

                                  Lymphatic Vessels & Circulation

Lymphatic vessels begin as blind-ended lymph capillaries in tissue spaces between cells

Combine to form lymphatic vessels (Fig 22.4)

    resemble veins with thin walls & more valves

Fluid flows through lymph nodes towards large veins above the heart

    The same forces that move blood in veins will also propel lymph through lymphatic vessels

    A condition that interferes with the flow of lymph will result in edema (swelling)

                                        Lymphatic Capillaries

Lymphatic capillaries have a slightly larger diameter than blood capillaries (Fig 22.2)

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)

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

                                      Lymph Trunk and Ducts

Lymph vessels unite to form trunks & then ducts
Right side head, arm & chest empty into right lymphatic duct and rest of body empties into

       thoracic duct (Fig 22.3)

   The right lymphatic duct and the thoracic duct drain lymph into venous blood via the

           subclavian veins (Fig 22.1)

                                  Lymphatic Organs & Tissues

Primary lymphatic organs

   Provide environment for stem cells to divide & mature into B and T lymphocytes

   Red bone marrow - gives rise to mature B cells

   Thymus (Fig 22.5)

       pre-T cells from red marrow mature

       large organ in infants (70 g) but atrophied as adult (3 g)

Secondary lymphatic organs & tissues

   site where most immune responses occur

   Lymph nodes (Fig 22.6)

       bean-shaped organs, up to 1 inch long, located along lymphatic vessels

       scattered throughout body but concentrated near mammary glands, axillae & groin

       lymph enters nodes through afferent lymphatic vessels, is filtered to remove damaged

              cells and microorganisms, and exits through efferent lymphatic vessels

       location where B lymphocytes proliferate into antibody-secreting plasma cells

   Spleen (Fig 22.7)

       5 inch organ between stomach & diaphragm

       Interior of white pulp and red pulp

           White pulp is lymphocytes & macrophages around branches of splenic artery

              Macrophages remove worn-out or defective RBCs, WBCs, and platelets.

           Red pulp has RBCs, macrophages, lymphocytes, plasma cells, and granulocytes

              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 fetal development

   Lymphatic nodules

       Mucosa-associated lymphoid tissue (MALT)

       Peyer’s patches in the ileum of the small intestine


       Tonsils form ring at top of throat

           adenoids (pharyngeal tonsil)

           palatine tonsils (on each side wall)

           lingual tonsil in the back of the tongue

                               Function of the Lymphatic System

Resistance is the ability to ward off disease and can be grouped into two broad areas.

   Nonspecific resistance to disease (Innate defenses)

       general defensive mechanisms effective on a wide range of pathogens (disease producing


   Specific resistance or immunity is ability to fight a specific pathogen (Adaptive defenses)

       cell-mediated immunity

       antibody-mediated immunity (humoral)

                               Nonspecific Resistance (Table 22.1)

The first line of defense is the skin and the mucous membranes

   Mechanical protection

       skin (epidermis) closely packed, keratinized cells

           shedding helps remove microbes

       mucous membrane secretes viscous mucus

           cilia & mucus trap & move microbes toward throat

       washing action of tears, urine and saliva
       defecation and vomiting also may be considered mechanical processes

   Chemical protection

       The skin produces sebum, which has a low pH that inhibits the growth of bacteria &


       Lysozyme is an enzyme component of sweat that also has antimicrobial properties

       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

The second line of defense involves internal antimicrobial proteins, phagocytic and natural killer

       cells, inflammation, and fever

   Antimicrobial proteins discourage microbial growth

       Body cells infected with viruses produce proteins called interferons (IFNs)

           IFN interfere with or inhibit viral replication, enhance the activity of phagocytes and

                   natural killer (NK) cells, inhibit cell growth, and suppress tumor formation

       A group of about 30 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

       Transferrins limits available iron which inhibits certain bacteria

   Phagocytes (neutrophils & macrophages)

       macrophages developed from monocytes

           fixed macrophages stand guard in specific tissues

               histiocytes in the skin, kupffer cells in the liver, alveolar macrophages in the lungs,

                        microglia in the brain & macrophages in spleen, red marrow & lymph


           wandering macrophages in most tissue
   ingest microbes or particulate matter by phagocytosis

   The four phases of phagocytosis (Fig 22.9)


           attraction to chemicals from damaged tissues, complement proteins, or microbial



           attachment to plasma membrane of phagocyte


           engulf by pseudopods to form phagosome

       Digestion & killing

           merge with lysosome containing digestive enzymes

           exocytosis residual body

   Some of the reasons why a microbe may evade phagocytosis include: capsule formation,

           toxin production, interference with lysozyme secretion, and the microbe’s ability

           to counter oxidants produced by the phagocytes

Natural Killer cells kill a variety of microbes & tumor cells

   found in blood, spleen, lymph nodes & red marrow

   attack cells displaying abnormal MHC antigens

Damaged cells initiate inflammation (Fig 22.10)

   Signs of inflammation





       Loss of function may be a fifth symptom, depending on the site and extent of the

       Function is to trap microbes, toxins or foreign material & begin tissue repair

       The three basic stages of inflammation

           Vasodilation & increased permeability of vessels

               caused by histamine from mast cells, kinins from precursors in the blood,

                       prostaglandins from damaged cells, and leukotrienes from basophils &

                       mast cells

           Phagocyte emigration (Diapedesis)

               within an hour, neutrophils and then monocytes arrive and leave blood stream


           Tissue repair

   Fever is abnormally high body temperature that occurs because the hypothalamic thermostat

           is reset

       Occurs during infection & inflammation

           bacterial toxins trigger release of fever-causing cytokines such as interleukin-1


           intensifies effects of interferons, inhibits bacterial growth, speeds up tissue repair

                                    Specific Resistance: Immunity

Immunity is the ability of the body to defend itself against specific invading agents.

Differs from nonspecific defense mechanisms

   Specificity - recognize self & non-self

   Memory - 2nd encounter produces even more vigorous response

                                    Specific Resistance: Immunity

Types of immune responses (Fig 22.11)

   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


       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


Molecules or bits of foreign material (Fig 22.12)

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

Large, complex molecules, usually proteins

   simple repeating subunits are not usually antigenic (plastics in joint replacements)

   entire microbes, parts of microbes, bacterial toxins, pollen, transplanted organs, incompatible

           blood cells

   small part of antigen that triggers the immune response is epitope

   hapten is smaller substance that can not trigger an immune response unless attached to body


       lipid of poison ivy

Immune system can recognize and respond to a billion different epitopes - even artificially made


Explanation for great diversity of receptors is genetic recombination of few hundred small gene


Each B or T cell has its own unique set of gene segments that codes its unique antigen receptor

       in the cell membrane

Major Histocompatibility Complex Antigens
   All our cells have unique integral membrane proteins (1000s molecules)

       Also called human leukocyte antigens (HLA)

   MHC-I molecules are built into cell membrane of all cells except red blood cells


       if cell is infected with virus (intracellular pathogen), MHC-I and a bit of the virus is sent

              to the cell surface, marking the cell so T cells recognize a problem

   Some cells also display MHC class II antigens.

       MHC-II markers seen only on membrane of antigen presenting cells (macrophages, B

              cells, dendritic cells)


       if antigen presenting cells (macrophages or B cells) ingest foreign proteins (extracellular

              pathogens), 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 (Fig 22.13)

   Cells called antigen-presenting cells (APCs) encounter foreign (extracellular) antigens in

          body fluid and phagocytize them

       APCs include macrophages, B cells, and dendritic cells

   Antigen is digested and fragments are bound to MHC-II molecules which travels to the cell

   APC migrates to lymphatic tissue to find T cells

   The presentation of exogenous antigens together with MHCII molecules on antigen

           presenting cells alerts T cells that “intruders are present”

Processing of Endogenous Antigens (Fig 22.14)

   Endogenous antigens are synthesized within the body (intracellular) 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 MHCI molecules inside the cell

   The antigen MHCI complex moves to the cell’s surface where it alerts T cells


Chemicals released by the body that promote the function of immune system cells. (Table 22.2)

   Il-1- proliferation of T cells

   Il-2 – co-stimulation of T and B cells, proliferation of T and B cells, activates natural killer


   Il-4 – co-stimulation of B cells

   Tumor necrosis factor – stimulates phagocyte accumulation and digestion

                                      Cell-Mediated Immunity

T cell receptors recognize antigen fragments associated with MHC molecules on the surface of a

       body cell.

Activation and proliferation of T cells requires costimulation

       MHC-CD pair

       T cell receptor (TCR)-antigen pair


Helper T Cells (Fig 22.15)

   Display CD4 on surface - T4 cells or TH cells
   Recognize antigen fragments associated with MHC-II molecules & activated by APCs


   Costimulates all other lymphocytes by secreting cytokines (interleukin-2 & 4)

       it will co-stimulate itself to proliferate and secrete more interleukin (positive feedback

               effect causes formation of many more helper T cells)

Cytotoxic T Cells (Fig 22.16)

   Display CD8 on surface; known as T8, Tc or killer T cells

   Recognize antigen fragments associated with MHC-I molecules (intracellular)

       cells infected with virus

       tumor cells

       tissue transplants

   Costimulation by cytokine from helper T cell

       prevents accidental immune response

   Proliferates & differentiates into population (clone) of Tc cells and memory Tc cells

Memory T Cells (Fig 22.15 & 22.16)

   Cytotoxic or Helper T cells from a clone that are available for swift response if a 2nd

   exposure should occur

Elimination of Invaders

   Cytotoxic T cells migrate to site of infection or tumor formation

   Recognize, attach & attack (Fig 22.17)

       secrete granules containing perforin that punch holes in target cell

       secrete lymphotoxin that activates enzymes in the target cell causing its DNA to fragment

       secrete gamma-interferon to activate phagocytic cells

                                   Antibody-Mediated Immunity

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.
B cells sit still and let antigens be brought to them

   stay put in lymph nodes, spleen or Peyer’s patches

B Cell Function (Fig 22.18)

   B cell receptors bind to antigen

       Can bind to unprocessed antigens in fluids but response more intense if antigen is

               processed by an APC

       B cell antigen receptors are chemically similar to the antibodies secreted by their progeny

   Some antigen is taken into the B cell, broken down into peptide fragments, combined with

           MHC-II and moved to the B cell surface

   Helper T cell costimulates

    Rapid cell division & differentiation occurs

       long-lived memory cells

       clone of plasma cells

           produce antibody at 2000 molecules/sec for 4-5 days

           secrete only one kind antibody

   Antibody enters the circulation to attack antigen


An antibody is a protein that can combine specifically with the epitope on the antigen that

       triggered its production.

Antibodies are glycoproteins called immunoglobulins

Based on chemistry and structure, antibodies are grouped into five principal classes each with

       specific biological roles (IgG, IgA, IgM, IgD, and IgE). (Table 22.3)

Antibody Structure (Fig 22.19)

   4 polypeptide chains -- 2 heavy & 2 light chains with variable and constant portions

       hinged midregion lets the molecule assume T or Y shape

       tips are variable regions - rest is constant region
          5 different classes (IgG, IgA, IgM, IgD and IgE) based on constant region

          tips form antigen binding sites

Antibody Actions

   Neutralization of antigen by blocking effects of toxins or preventing its attachment to body


   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)

                               Complement System in Immunity

Complement system is made up of over 30 proteins

Many complement proteins are inactive and must be activated.

Activated complement acts in a cascade that causes

   inflammation: dilation of arterioles, release of histamine & increased permeability of


   opsonization/phagocytosis: protein binds to microbe making it easier to phagocytized

   cytolysis: a complex of several proteins can form holes in microbe membranes causing

          leakiness and cell rupture

Complement may be activated by the classical pathway, alternative pathway, and the lectin

       pathway (Fig 22.20)

   Classical pathway begins when antibodies bind to antigens and activate C1 which leads to

          activation of C3

   Alternate pathway begins when microbial lipid-carbohydrate complexes interact with

          complement factors B, D and P leading to activation of C3

   Liver produced lectins bind to microbes leading to activation of C3
                                    Immunological Memory

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.

   Immunization against certain microbes is possible because memory B cells and memory T

           cells remain after the primary response to an antigen (Table 22.4)

   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. (Fig 22.21)

                                        Immune Disease

In an autoimmune disease the immune system fails to display self-tolerance and attacks the

       person’s own tissue

Infectious mononucleosis is a contagious disease primarily affecting lymphatic tissue throughout

       the body but also affecting the blood. It is caused by the Epstein-Barr virus which

       multiplies in B cells. There is no cure, and treatment consists of watching for and treating

       complications. Usually the disease runs its course in a few weeks

Lymphomas are cancers of the lymphatic organs especially the lymph nodes. The two main

       types are: Hodgkin disease and non-Hodgkin lymphoma

Systemic lupus erythematosus is a chronic autoimmune, inflammatory disease that affects

       multiple body systems

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