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					                                 Part 1
                                          Immune System




http://www.electroresponse.com
 Much of the text material is from, “Principles of Anatomy and
Physiology” by Gerald J. Tortora and Bryan Derrickson (2009).
 I don‟t claim authorship. Other sources are noted when they
                           are used.




                                                                 2
                               Outline
•   Introduction
•   Lymphatic system
•   Innate immunity, external defenses
•   Innate immunity, internal defenses
•   Inflammation and fever




                                         3
Introduction




               4
                               Immunity
•   Most people remain healthy despite constant exposure to pathogens;
    that is, disease-producing bacteria and viruses.
•   The body is also susceptible to abrasions and cuts, exposure to ultra-
    violet (UV) radiation from sunlight, exposure to chemical toxins, and
    burns.
•   Immunity or resistance involves the body‟s defenses that respond to
    diseases and other damage.
•   The two general types are called innate immunity and adaptive immu-
    nity.




    Chapter 22, page 831
                                                                             5
                                        Immunity (continued)




    http://www.rikenresearch.riken.jp
6
                         Innate Immunity
•   Innate or nonspecific immunity consists of defenses that are active
    as early as birth.
•   They can respond rapidly to provide protection against many dis-
    eases.
•   Innate immunity does not recognize specific microbes—its mech-
    anisms respond to all microbes in the same manner and with sim-
    ilar actions.


       Microbe = a very tiny form of life—microbes include bacteria,
         fungi, and protozoan parasites—best visualized under a
                 microscope. (www.emedicinehealth.com)
                  Also, another term for a microorganism.



    Chapter 22, page 831
                                                                          7
                  Innate Immunity (continued)
•   The first line of defense includes physical and chemical barriers of
    the skin and mucous membranes.
•   The second line includes anti-microbial substances, natural killer
    cells, phagocytes, inflammation, and fever.
•   Both help prevent microbes from entering the body and eliminate
    those that gain access.
•   Second-line responses serve as an „early-warning system‟ for the
    body.

         Natural killer (NK) cell = a type of white blood cell that can
                          kill microbial or tumor cells.
          Phagocyte = a cell that engulfs and digests debris and
                               invading microbes.


    Chapter 22, page 831
                                                                           8
                       Adaptive Immunity
•   Adaptive or specific immunity are defenses involving the recognition
    of specific microbes if they have breached the nonspecific defenses.
•   Adaptive immunity is slower to respond than innate immunity, but it
    has „memory‟ to facilitate the immune response if the microbe is ever
    encountered again.
•   The responses involve T lymphocytes (T cells) and B lymphocytes (B
    cells).



                  Lymphocyte = type of white blood cell.




    Chapter 22, page 831
                                                                            9
Lymphatic System




                   10
                       Lymphatic System
•   The lymphatic system mediates adaptive immunity and aspects of
    innate immunity.
•   It also works with the cardiovascular system, and with the digestive
    system in the absorption of lipids.




    Chapter 22, page 831
                                                                           11
                 Lymphatic System (continued)
•   The lymphatic system consists of:
      -   Fluid known as lymph,
      -   Lymphatic vessels that transport the lymph,
      -   Structures and organs containing lymphatic tissue, and
      -   Red bone marrow where stem cells develop into blood cells.
•   The lymphatic system, like the cardiovascular system, circulates body
    fluids.




    Chapter 22, page 832          Figure 22.1
                                                                            12
Lymphatic System (continued)




                   http://www.clinic-clinic.com




                                                  13
                                  Lymph
•   Most components of blood plasma filter through the blood capillary
    walls to form interstitial fluid.
•   Once interstitial fluid passes into lymphatic vessels, it is known as
    lymph.
•   The major differences between interstitial fluid and lymph are their
    locations.
•   Interstitial fluid is found between cells, and lymph in lymphatic ves-
    sels and lymphatic tissue.




    Chapter 22, page 832
                                                                             14
          Lymphatic Tissue and Lymphocytes
•   Lymphatic tissue is composed of reticular connective tissue that
    contains large numbers of lymphocytes.
•   Lymphocytes (T cells and B cells) are agranular white blood cells,
    as covered in the lecture on blood.


         Reticular connective tissue = a network of reticular fibers,
                         made of type III collagen.
          Agranular = lacking granules when viewed under a light
                                microscope.




    Chapter 22, page 832
                                                                         15
                                 Functions
•   The primary functions of the lymphatic system are to:
      -   Drain excess fluid from the interstitial spaces and return it to the
          blood.
      -   Transport lipid-soluble food molecules and lipid-soluble vitamins
          (A, D, E, and K) absorbed by the gastrointestinal tract.
      -   Initiate immune responses against microbes and abnormal cells.
•   These functions are covered in subsequent slides and the textbook.




    Chapter 22, page 832
                                                                                 16
                        Lymphatic Vessels
•   Lymphatic vessels begin as lymphatic capillaries in the interstitial
    space.
•   Lymphatic capillaries are closed at the end terminating in the inter-
    stitial space.
•   These capillaries converge to form larger lymphatic vessels, just as
    blood capillaries converge to form venules and then veins.
•   Although lymphatic vessels resemble veins, they have thinner walls
    and a greater number of valves to permit one-way flow of lymphatic
    fluid.




    Chapter 22, page 832           Figure 22.2
                                                                            17
               Lymphatic Vessels (continued)
•   Lymph passes through lymph nodes found at intervals along lym-
    phatic vessels.
•   Lymph nodes are encapsulated, bean-shaped organs consisting of
    masses of B cells and T cells.




    Chapter 22, page 832        Figure 22.2
                                                                     18
                Lymphatic Vessels (continued)
•   Lymphatic vessels in the subcutaneous tissue generally follow the
    same routes as veins.
•   Lymphatic vessels in the viscera typically follow arteries and form
    plexuses or networks.




    Chapter 22, page 832          Figure 22.2
                                                                          19
                 Lymphatic Vessels (continued)
•   Some tissues do not contain lymphatic capillaries—they include:
      -   Avascular tissues including cartilage, epidermis, and cornea
          of the eye
      -   Central nervous system
      -   Portions of the spleen
      -   Red bone marrow


                      Avascular = without blood vessels.




    Chapter 22, page 832           Figure 22.2
                                                                         20
                      Lymphatic Capillaries
•   Lymphatic capillaries have slightly larger diameters than blood capil-
    laries.
•   Their walls have a one-way structure to enable interstitial fluid to flow
    into, but not out of, the lumen.
•   The endothelial cells of the lymphatic capillary wall overlap to enable
    one-way flow.




    Chapter 22, page 832           Figure 22.2
                                                                                21
Lymphatic Capillaries (continued)




     http://www.web-books.com/elibrary/medicine/hysiology




                                                            22
              Lymphatic Capillaries (continued)
•   When the hydrostatic pressure is higher in the interstitial fluid than
    in the lymphatic capillary, the endothelial cells open slightly, as in a
    one-way swinging door.
•   Interstitial fluid enters the lymphatic capillary through the openings.
•   When the hydrostatic pressure is higher in the lymphatic capillary
    than in the interstitial fluid, the cells adhere more closely to „shut the
    door.‟
•   Therefore, lymph cannot re-enter the interstitial fluid since the open-
    ings are closed.




    Chapter 22, page 832            Figure 22.2
                                                                                 23
              Lymphatic Capillaries (continued)
•   Further inflow of interstitial fluid occurs as the pressure is reduced
    when lymph flows down the lymphatic capillary.
•   Lymphatic capillaries are attached to elastic anchoring filaments
    that connect the lymphatic endothelial cells to surrounding tissues.
•   The filaments are pulled when excess interstitial fluid accumulates
    and causes tissue swelling.
•   The openings widen between endothelial cells to permit even more
    interstitial fluid to flow into the lymphatic capillary.




    Chapter 22, page 832           Figure 22.2
                                                                             24
                                Lacteals
•   Lacteals—specialized lymphatic capillaries in the small intestine—
    transport dietary lipids into lymphatic vessels and into the blood.
•   The lipids make the lymphatic fluid, known as chyle juice, appear
    creamy-white.
•   Lymph is a clear, pale-yellow fluid in the other tissues of the body.




    Chapter 22, page 832
                                                                            25
                Digestive Tract




Note the centrally-located lacteal in the enlarged villus
                      to the right.


                                                            26
                         Lymph Production
•   Most components of the blood plasma can filter through the walls
    of blood capillary to produce interstitial fluid.
•   Formed elements (RBCs, WBCs, and platelets) usually cannot
    pass.
•   More fluid filters out of blood capillaries than is reabsorbed into the
    capillaries.
•   The excess fluid—about 3 liters per day—drains into the lymphatic
    vessels to produce lymph.




    Chapter 22, page 834           Figure 21.7
                                                                              27
                 Lymph Production (continued)
•   Interstitial fluid has only a small amount of proteins since most protein
    molecules are too large to pass from the blood plasma through blood
    capillary walls.
•   The smaller amount of proteins in interstitial fluid is not reabsorbed
    through the blood capillary walls because of the opposing concentra-
    tion gradient.
•   These proteins,therefore, pass into the more readily-permeable lym-
    phatic capillaries.
•   The proteins are returned to the blood through the lymphatic system.




    Chapter 22, page 834           Figure 22.4
                                                                                28
                          Lymphatic Flow
•   Lymph flows from lymphatic capillaries, into afferent lymphatic vessels,
    and then into lymph nodes.
•   Efferent lymphatic vessels exit the lymph nodes and converge to form
    lymph trunks.
•   Lymph then drains into the thoracic and right lymphatic ducts, and then
    into venous blood.
•   The anatomical relationships between the lymphatic system and cardio-
    vascular system are shown in Figure 22.4 in the textbook.




    Chapter 22, page 834          Figure 22.4
                                                                               29
                     Skeletal Muscle Pump
•   Lymphatic vessels, like veins in the cardiovascular system, have
    valves that permit one-way flow.
•   Skeletal muscle and respiratory pumps assist in the flow of lymph,
    just as they aid in the return of venous blood to the right atrium of
    the heart.
•   Skeletal muscle contractions compress the lymphatic vessel walls.
•   The compressions force lymph toward the junction of the internal
    jugular and subclavian veins where it empties into blood circulation.




    Chapter 22, page 834           Figure 21.9
                                                                            30
                        Respiratory Pump
•   During inhalation, lymph flows from the abdominal region where the
    pressure is higher to the thoracic region where the pressure is lower.
•   When a lymphatic vessel is distended, the smooth muscle in its wall
    contracts in response, which propels lymph from one segment of the
    vessel to the next.
•   Valves prevent the backflow of lymph when the pressure differential is
    reversed during exhalation.




    Chapter 22, page 834
                                                                             31
                Primary Lymphatic Organs
•   Lymphatic organs and tissues are either primary or secondary based
    on their functions.
•   Primary lymphatic organs are sites where stem cells can divide and
    become immunocompetent—that is, capable of an immune response.
•   The primary lymphatic organs are the red bone marrow and thymus.




    Chapter 22, page 834
                                                                         32
                      Red Bone Marrow
•   Pluripotent stem cells in red bone marrow form mature, immunocom-
    petent B cells, and pre-T cells.
•   Pre-T cells migrate to the thymus where they mature into immunocom
    petent T cells.




    Chapter 22, page 834
                                                                         33
Red Bone Marrow (continued)




             http://gardenrain.files.wordpress.com




                                                     34
    Secondary Lymphatic Organs and Tissues
•   Most immune responses occur in the secondary lymphatic organs
    and tissues.
•   They include the spleen, lymph nodes, and lymphatic nodules (or
    follicles).
•   The thymus, spleen, and lymph nodes are organs since each one
    is surrounded by a capsule of connective tissue.
•   Lymphatic nodules lack this capsule, and are not considered to be
    organs.




    Chapter 22, page 836
                                                                        35
                                Thymus
•   The thymus is a bilobed organ located in the mediastinum between
    the sternum and aorta.
•   A layer of connective tissue holds the two lobes closely together.
•   Each lobe is further divided by extensions of the connective tissue
    capsule to form smaller lobules.
•   A lobule has a darker-staining outer cortex and lighter-staining cen-
    tral medulla.


                      Bilobed = divided into two lobes.




    Chapter 22, page 836          Figure 22.5
                                                                            36
Thymus (continued)




              http://www.acm.uiuc.edu




                                        37
                         Thymus—Cortex
•   The cortex is composed of large numbers of T cells, and dendritic
    cells, epithelial cells, and macrophages.
•   Immature pre-T cells migrate from red bone marrow to the cortex
    where they proliferate and begin maturation.
•   Dendritic cells, derived from monocytes, assist in this maturation
    process.


          Proliferate = to increase in number or spread rapidly.
        Monocyte = large phagocytic white blood cell which, when it
               enters tissue, develops into a macrophage.
                         (http://thyroid.about.com)




    Chapter 22, page 836          Figure 22.5
                                                                         38
                 Thymus—Cortex (continued)
•   The epithelial cells have long processes that surround and form a
    framework for as many as 50 T cells.
•   They also produce thymic hormones for the maturation of T cells.
•   About 2 percent of the T cells survive in the cortex—the others die
    by apoptosis.
•   The surviving T cells enter the medulla of the thymus, and macro-
    phages dispose of the dead and dying T cells in the thymic cortex.

        Process = a natural prolongation or projection from a part of
             an organism. (http://wordnetweb.princeton.edu)
        Apoptosis = normal cellular process involving a genetically
        programmed series of events leading to the death of a cell.
                     (http://science.education.nih.gov)


    Chapter 22, page 836          Figure 22.5
                                                                          39
                         Thymus—Medulla
•   The medulla contains more-mature T cells, epithelial cells, dendritic
    cells, and macrophages.
•   Epithelial cells form concentric layers of flat cells that serve as sites
    for T cell death.
•   The surviving T cells eventually exit the medulla via the blood, and
    migrate to lymph nodes, spleen, and other lymphatic tissues to colo-
    nize these tissues.


                Concentric = circles sharing the same center.




    Chapter 22, page 837            Figure 22.5
                                                                                40
                 Thymus—Age Progression
•   The thymus is large in infants, weighing about 70 grams.
•   Adipose and areolar connective tissue begin replacing thymic tissue
    at puberty.
•   The thymus atrophies substantially by adulthood.
•   It can weigh as little as 3 grams later in life—a 96 percent decrease
    from infancy.


          Atrophy = wasting away of tissue or an organ due to the
             degeneration of cells. (http://medclinic.bli.uci.edu)




    Chapter 22, page 837
                                                                            41
         Thymus—Age Progression (continued)
•   The thymus populates the secondary lymphatic organs and tissues
    with T cells before it atrophies.
•   Small numbers of T cells, however, continue to proliferate in the thy-
    mus during an individual‟s lifetime.




    Chapter 22, page 837
                                                                             42
                           Lymph Nodes
•   About 600 lymph nodes are located among the lymphatic vessels.
•   Lymph nodes are found in both superficial and deep tissues of the
    body.
•   The nodes often form groups, including near the mammary glands
    and in the axillae and groin.


                   Axillae = plural for axilla; the armpits.




    Chapter 22, page 837           Figure 22.1
                                                                        43
Lymph Nodes (continued)




                 http://www.acm.uiuc.edu




                                           44
                  Lymph Nodes—Structure
•   Lymph nodes, ranging from 1-to-25 mm in length, are enclosed in
    capsules of dense connective tissue that extends into each node.
•   These trabeculae divide the node into compartments to provide
    structural support and a path for blood vessels into the node.
•   Collectively, the capsule, trabeculae, reticular fibers, and fibro-
    blasts form the stroma (supporting connective tissue) of a lymph
    node.




    Chapter 22, page 837           Figure 22.6
                                                                          45
Lymph Nodes—Structure (continued)




                   http://www.acm.uiuc.edu




                                             46
               Lymph Nodes—Outer Cortex
•   The functioning part of a lymph node is known as its parenchyma.
•   The parenchyma consist of an outer and inner cortex and a deeper
    medulla.
•   The outer region contains aggregates of B cells known as lymphatic
    nodules or follicles.




    Chapter 22, page 839         Figure 22.6
                                                                         47
                    Outer Cortex (continued)
•   A nodule consisting mostly of B cells is known as a primary lym-
    phatic nodule.
•   Secondary lymphatic nodules—the more common type—form in
    response to antigens.
•   These nodules are sites of plasma cell and memory B cell forma-
    tion.


            Antigen = any substance (as a toxin or enzyme) that
        stimulates an immune response in the body (especially the
       production of antibodies). (http://wordnetweb.princeton.edu)




    Chapter 22, page 839          Figure 22.6
                                                                       48
                          Germinal Center
•   The central region of a secondary lymphatic nodule has cells known
    as the germinal center.
•   The germinal center contains B cells, follicular dendritic cells, and
    macrophages.




    Chapter 22, page 839
                                                                            49
                        B Cell Responses
•   B cells proliferate into antibody-producing plasma cells or memory B
    cells when follicular dendritic cells present an antigen.
•   Memory B cells persist after the immune response ends to „remember‟
    a specific antigen if it is encountered again.
•   B cells that fail to develop properly undergo apoptosis and destruction
    by macrophages.
•   The region surrounding the germinal center has dense accumulations
    of B cells that migrated from their site or origin within the nodule.

       Antibody = any of a large variety of proteins normally present
        in the body or produced in response to an antigen which it
             neutralizes, thus producing an immune response.
                     (http://wordnetweb.princeton.edu)


    Chapter 22, page 839
                                                                              50
                              Inner Cortex
•   The inner cortex does not contain lymphatic nodules, but it does
    have T cells and dendritic cells that migrated from other tissues.
•   Dendritic cells present antigens to T cells, triggering proliferation
    of T cells.
•   Newly-formed T cells migrate from the lymph node to sites of anti-
    genic activity in the body.




    Chapter 22, page 839
                                                                            51
                                Medulla
•   The medulla contains B cells—antibody-producing plasma cells that
    migrated from the cortex, and macrophages.
•   The cells are embedded in a network of reticular fibers and reticular
    cells.




    Chapter 22, page 839
                                                                            52
                  Lymph Nodes and Lymph
•   Lymph enters lymphatic nodes though afferent lymphatic vessels.
•   The vessels have valves that direct lymphatic flow into the nodes.
•   The textbook describes the flow of lymph through the sinuses with-
    in a node.




    Chapter 22, page 839          Figure 22.6
                                                                         53
                        Filtration Function
•   The lymph nodes filter lymph—foreign substances entering a node are
    trapped by the reticular fibers within the sinuses.
•   Macrophages destroy some of the foreign substances through phago-
    cytosis, while lymphocytes destroy others through immune responses.
•   The filtered lymph exits the lymph node into efferent lymphatic vessels.


     Lymphocyte = a type of white blood cell or leukocyte that occurs
       in two forms; B-lymphocytes, which produce antibodies in the
    humoral immune response, and T-lymphocytes, which participates
     in the cell-mediated immune response. (http://en.wiktionary.org)




    Chapter 22, page 839
                                                                               54
                Efferent Lymphatic Vessels
•   The medullary sinuses drain into 1-or-2 efferent lymphatic vessels.
•   The vessels have one-way valves to convey lymph away from the
    lymph node.
•   Lymph exiting a lymph node contains activated T cells and anti-
    bodies from plasma cells.




    Chapter 22, page 839          Figure 22.6
                                                                          55
Spleen




         http://www.acm.uiuc.edu




                                   56
                                 Spleen
•   The spleen is the largest single mass of lymphatic tissue—it is oval
    in shape and measures about 12 cm in length.
•   It is located in the left hypochondriac region between the stomach
    and diaphragm.
•   The stomach, left kidney, and large intestine make impressions on
    the surface of the spleen due to their close proximity.
•   Anatomical details of the spleen are described in Chapter 22 of the
    textbook.




    Chapter 22, page 840          Figure 22.7
                                                                           57
                      Spleen—White Pulp
•   The functioning part of the spleen—its parenchyma—has two types
    of tissue known as white pulp and red pulp.
•   White pulp is lymphatic tissue arranged around the central arteries
    of the spleen.
•   Blood flowing into the spleen through the central arteries enters the
    white pulp.




    Chapter 22, page 841          Figure 22.7
                                                                            58
                             Functions
•                                                               •
    White pulp is composed mostly of lymphocytes and macrophages.•
•   The B cells and T cells (both lymphocytes) perform immune functions
    similar to those in lymph nodes.
•   Macrophages in the white pulp destroy pathogens by phagocytosis.




    Chapter 22, page 841
                                                                          59
                       Spleen—Red Pulp
•   Red pulp consists of blood-filled venous sinuses and cords of splenic
    tissue known as splenic cords.
•   The cords contain red blood cells, macrophages, lymphocytes, plasma
    cells, and granulocytes.
•   Veins are co-located with red pulp.




    Chapter 22, page 841          Figure 22.7
                                                                            60
                               Functions
•   Red pulp has three functions:
      -   Removal of ruptured, worn-out, and defective blood cells and
          platelets by macrophages.
      -   Storage of up to one-third of the body‟s supply of platelets.
      -   Production of blood cells (known as hemopoiesis) during fetal
          life.




    Chapter 22, page 841
                                                                          61
                        Lymphatic Nodules
•   Lymphatic nodules are small, egg-shaped masses of lymphatic tis-sue,
    but without a surrounding capsule.
•   They are also called mucosa-associated lymphatic tissue, or MALT.
•   The nodules are located in connective tissue of mucous membranes
    lining the respiratory airways, and in he digestive, urinary, and repro-
    ductive tracts.




    Chapter 22, page 841
                                                                               62
               Lymphatic Nodules (continued)
•   Some lymphatic nodules are small and single, but many form large
    aggregations.
•   Aggregations are found in the tonsils in the pharyngeal region of the
    throat, and in ileum of the small intestine and the appendix.
•   The five tonsils—two adenoid, two lingual, and one palatine—are
    involved in immune responses to inhaled and ingested foreign sub-
    stances.




    Chapter 22, page 841          Figure 23.2
                                                                            63
Innate Immunity, External Defenses




                                     64
                        External Defenses
•   Innate immunity consists of external barriers to provide a first line
    of defense against pathogens.
•   The barriers consist of the skin, mucous membranes, fluids, and
    chemicals.




    Chapter 22, page 842
                                                                            65
                                   Skin
•   The epidermis—the outer, epithelial layer of the skin—consists of
    layers of closely-packed, keratinized cells.
•   The epidermis is a barrier to microbes and other pathogens—
    bacteria, for example, can rarely penetrate an intact skin surface.
•   When the skin is cut, punctured or burned, pathogens can enter to
    invade tissues and circulate in the blood.
•   Periodic shedding of epidermal cells helps remove microbes at the
    skin surface.




    Chapter 22, page 842           Figure 5.1
                                                                          66
                       Mucous Membranes
•   The epithelial layer of the mucous membranes secretes mucus,
    a fluid that lubricates and moistens the cavity surface.
•   Mucous traps microbes and other foreign substances because it
    is slightly viscous.
•   The mucous membrane of the nose has mucous-coated hairs to
    trap and filter microbes, dust, and pollutants found in inhaled air.



                 Viscous = having a high resistance to flow.




    Chapter 22, page 842
                                                                           67
               Mucous Membranes (continued)
•   The mucous membranes of the upper respiratory tract contain many
    cilia.
•   Cilia are microscopic, hair-like projections on the surface of epithelial
    cells.
•   Their waving motion helps expel microbes and dust trapped in mucus
    toward the throat.




    Chapter 22, page 842
                                                                                68
        Coughing, Sneezing, and Swallowing
•   Coughing and sneezing accelerate the movement of mucus along
    with entrapped microbes and dust out of the body.
•   Swallowing mucus transports microbes to the stomach where many
    are destroyed by gastric acid.




    Chapter 22, page 842
                                                                     69
                      Tears and Lysozyme
•   The lacrimal apparatus of the eyes produces tears in response to
    environmental irritants and some emotional states.
•   Blinking spreads the tears over the surface of the eye to help dilute
    microbes and keep them from settling on the eye.
•   Tears contain lysozyme, an enzyme that breaks-down the cell walls
    of some bacteria.
•   Lysozyme is also found in saliva, perspiration, nasal secretions, and
    tissue fluids.




    Chapter 22, page 842          Figure 17.6
                                                                            70
                                 Saliva
•   Saliva, secreted by the salivary glands, washes microbes from the
    teeth and mucous membrane of the oral cavity (mouth).
•   Saliva helps reduce the over-colonization of microbes in the mouth.



        Colonization = proliferation of microorganisms on or within
       body sites without detectable host immune response, cellular
          damage, or clinical expression. (http://www.cdc.gov)




    Chapter 22, page 842
                                                                          71
                        Other Mechanisms
•   Cleansing of the urethra by urine inhibits microbial colonization of
    the urinary system.
•   Vaginal secretions sweep microbes out of the female reproductive
    tract.
•   Defecation and vomiting can expel many microbes from the body.
•   The lower gastrointestinal tract contracts vigorously in response to
    some microbes—diarrhea expels many of them through defecation.




    Chapter 22, page 842
                                                                           72
                              Chemicals
•   Sebaceous (oil) glands secrete sebum, an oily substance, to form
    a protective film on the surface of the skin.
•   Unsaturated fatty acids in sebum inhibit the growth of some path-
    ogenic types of bacteria and fungi.
•   The high acidity of the skin (pH 3-to-5)—which is inhospitable to
    some pathogens—results from fatty acids and lactic acid secre-
    tions.
•   Perspiration can help flush microbes from the surface of the skin.


                 Pathogenic = a disease-producing agent.




    Chapter 22, page 842
                                                                         73
                       Chemicals (continued)
•   Gastric juice—secreted by exocrine glands in the stomach wall—
    contains hydrochloric acid, enzymes, and mucus.
•   The high acidity (pH 1.2-to-3.5) destroys many bacteria and their
    toxins.
•   Vaginal secretions are slightly acidic, and hinder bacterial growth.




    Chapter 22, page 842
                                                                           74
Innate Immunity, Internal Defenses




                                     75
                        Internal Defenses
•   Innate immunity includes internal defenses that can respond when
    external defenses are breached.
•   These defenses include antimicrobial substances, natural killer cells,
    phagocytes, inflammation, and fever.




    Chapter 22, page 843
                                                                             76
                   Antimicrobial Substances
•   Antimicrobial substances that hinder microbial growth include:
      -   Interferons
      -   Complement system
      -   Iron-binding proteins
      -   Antimicrobial proteins




    Chapter 22, page 843
                                                                     77
                               Interferons
•   Lymphocytes, macrophages, and fibroblasts infected with viruses
    produce proteins known as interferons.
•   When released by infected cells, interferons diffuse to uninfected
    cells where they induce the synthesis of antiviral proteins to inter-
    fere with virus replication.
•   Interferons are a key defense mechanism because viruses are only
    effective when they can replicate.




    Chapter 22, page 843
                                                                            78
                     Complement System
•   The complement system consists of a group of normally-inactive
    proteins found in blood plasma and on the plasma membranes of
    cells.
•   The proteins complement, or enhance, some types of immune re-
    actions.
•   The system initiates cytolysis, promotes phagocytosis, and contri-
    butes to inflammation.


          Cytolysis = breakdown of a cell by the destruction of its
                           plasma membrane.




    Chapter 22, page 843
                                                                         79
                      Iron-Binding Proteins
•   Iron-binding proteins inhibit the growth of some types of bacteria
    by reducing the amount of available iron.
•   The proteins include:
      - Hemoglobin in red blood cells
      - Transferrin in blood and tissue fluids
      - Lactoferrin in milk, saliva, and mucus
      - Ferritin in the liver, spleen, and red bone marrow




    Chapter 22, page 843
                                                                         80
                     Antimicrobial Proteins
•   Antimicrobial proteins (AMPs) are short peptide chains that exert a
    broad spectrum, or range, of antimicrobial activity.
•   AMPs destroy many microbes, and attract dendritic cells and mast
    cells for participation in immune responses.
•   Antimicrobial proteins include:
      - Dermicidin secreted by sweat glands
      - Defensins and cathelicidins from neutrophils, macrophages
        and epithelium
      - Thrombocidin from platelets




    Chapter 22, page 843
                                                                          81
                       Natural Killer Cells
•   Microbes that have penetrated the skin or mucous membranes and
    by-passed antimicrobial substances in the blood may be destroyed
    by natural killer (NK) cells and phagocytes
•   About 5-to-10 percent of the lymphocytes in the blood are NK cells.
•   NK cells are also found in the spleen, lymph nodes, and red bone
    marrow.
•   NK cells lack the membrane molecules that identify B and T cells.




    Chapter 22, page 843
                                                                          82
                Natural Killer Cells (continued)
•   NK cells can destroy a wide variety of infected body cells and some
    tumor cells.
•   They attack body cells that display abnormal or unusual proteins on
    their plasma membranes.




    Chapter 22, page 843
                                                                          83
Natural Killer Cells (continued)




                    http://www.biotechnologie.de




NK cell (in yellow) attacking a cancer cell.


                                                   84
                                 Perforin
•   The binding of NK cells to an infected cell initiates the release of
    granules of toxic substances, including perforin and granzymes.
•   Perforin is a protein that inserts itself into the plasma membrane of
    infected cells to create channels or perforations.
•   Extracellular fluid flows into the cells, causing them to burst (cytoly-
    sis).




    Chapter 22, page 843
                                                                               85
                             Granzymes
•   Granzymes released by NK cells are protein-digesting enzymes that
    induce the infected cell to undergo apoptosis (self-destruction).
•   Apoptosis kills infected cells, but not the microbes contained within
    them.
•   Microbes released upon the death of the cell are destroyed by phago-
    cytes.




    Chapter 22, page 843
                                                                            86
                             Phagocytes
•   Phagocytes perform phagocytosis, the ingestion of microbes and
    cellular debris.
•   While phagocytes are an innate defense mechanism, they also have
    roles in active immunity, as will be discussed in part 2 of these notes.
•   The two main types of phagocytes are neutrophils and macrophages.
•   These monocytes migrate to the site of an infection or tissue damage.




    Chapter 22, page 843           Figure 3.13
                                                                               87
                             Macrophage




     http://www.itb.cnr.it
88
           Wandering and Fixed Macrophages
•   During migration, monocytes enlarge and develop into active phago-
    cytes known as wandering macrophages.• •
•   In comparison, fixed macrophages „stand guard‟ in tissues—examples
    include:
      -   Histiocytes in connective tissues.
      -   Stellate reticuloendothelial cells (also known as Kuppfer cells) in
          the liver.
      -   Alveolar macrophages in the lungs.
      -   Microglia in the nervous system.
      -   Tissue macrophages in the spleen, lymph nodes, and red bone
          marrow.




    Chapter 22, page 843
                                                                                89
                  Phases of Phagocytosis
•   Chemotaxis
•   Adherence
•   Ingestion
•   Digestion
•   Destruction




    Chapter 22, page 844   Figure 22.9
                                           90
Phagocytosis




               91
                            Chemotaxis
•   Chemotaxis involves chemically-stimulated movement of phagocytes
    to the site of infection or other tissue damage.
•   Chemicals that attract phagocytes are released from microbes, white
    blood cells, activated complement proteins, and damaged tissue cells.




    Chapter 22, page 844         Figure 22.9
                                                                            92
                            Adherence
•   Adherence is the physical attachment of the phagocyte to a microbe
    or other foreign substance.
•   The binding of complement proteins to the microbe enhances adher-
    ence.




    Chapter 22, page 844         Figure 22.9
                                                                         93
                             Ingestion
•   The plasma membrane of a phagocyte extends projections known as
    pseudopods to engulf the microbe in a process known as ingestion.
•   Pseudopods join and fuse to surround the microbe to form a phago-
    some.




    Chapter 22, page 844        Figure 22.9
                                                                        94
                               Digestion
•   The phagosomes enter the cytoplasm of the phagocyte and merge with
    lysosomes to form a large, single phagolysome.
•   Lysozyme destroys the cell walls of the engulfed microbe, and digestive
    enzymes breakdown the microbe‟s carbohydrates, proteins, lipids, and
    nucleic acids.
•   The phagocyte also forms lethal oxidants—including superoxide anion
    (O2-), hypochlorite anion (OCl-), and hydrogen peroxide (H2O2)—in an
    oxidative burst.


        Oxidative or respiratory burst = the rapid release of reactive
         oxygen (superoxide radical and hydrogen peroxide) from
             different types of cells. (http://en.wikipedia.org)



    Chapter 22, page 844          Figure 22.9
                                                                              95
                            Destruction
•   Lysozyme, digestive enzymes, and oxidants destroy many types of
    microbes.
•   Any remaining materials that cannot be completely digested remain
    in the phagocyte to form residual bodies.




    Chapter 22, page 844        Figure 22.9
                                                                        96
                        Microbial Evasion
•   Some microbes, such as bacteria that cause pneumonia, have extra-
    cellular structures known as capsules.
•   The capsules make if physically difficult for phagocytes to engulf the
    microbes.
•   Other toxin-producing microbes, such as those responsible for a type
    of food poisoning, produce leukocidins.
•   Leukocidins destroy phagocytes by causing the release of the phago-
    cyte‟s own enzymes into its cytoplasm.



                        Evasion = elude or escape.




    Chapter 22, page 843
                                                                             97
                 Microbial Evasion (continued)
•   Other microbes, such as the bacteria that cause tuberculosis, inhibit
    the fusion of phagosomes and lysosomes, and prevent exposure of
    the microbes to lysosomal enzymes.
•   The bacteria within the phagosomes multiplies, which can destroy the
    phagocyte.
•   Some bacteria contain chemicals in their cell walls can counteract the
    effects of lethal oxidants produced by phagocytes.


           Phagosome = membrane-bound vacuole within a cell
           containing foreign material captured by phagocytosis.
                          (http://en.wiktionary.org)
            Oxidant = compound that donate electrons to other
              compounds. (http://www.hepatitis-central.com)


    Chapter 22, page 843
                                                                             98
Inflammation and Fever




                         99
                            Inflammation
•   Inflammation is a non-specific, defensive response to tissue damage
    and infection.
•   Inflammation can be produced by microbes, abrasions, chemical
    irritation, various disturbances of cells, and extreme temperatures.
•   Inflammation is an attempt to dispose of microbes, toxins, or foreign
    materials at the site of an injury.
•   It also helps prevent spread to other tissues, and prepares the site
    for tissue repair.
•   The four basic signs of inflammation are: redness, pain, heat, and
    swelling.




    Chapter 22, page 844
                                                                            100
                     Inflammation (continued)
•   Inflammation can cause loss of function in the injured area depend-
    ing on the location and extent of the injury.
•   The response is similar to burns, radiation, and bacterial or viral in-
    fection.
•   The inflammatory response has three stages:
      - Vasodilation and increased permeability of blood capillaries,
      - Emigration of phagocytes from the blood into the interstitial fluid,
        and
      - Tissue repair.




    Chapter 22, page 844
                                                                               101
                       Vascular Responses
•   Increased diameter of the arterioles (vasodilation) and increased
    permeability of blood capillaries occur in the vicinity of the tissue
    injury.
•   The result is increased blood flow through the damaged area.
•   The increase in blood flow also helps remove microbes, their toxins,
    and dead tissue cells.
•   Increased permeability enables substances, including antibodies
    and clotting factors, to pass from the blood into the interstitial fluid.
•   A number of substances contribute to vasodilation and permeability.




    Chapter 22, page 844            Figure 22.10
                                                                                102
                            Contributors
•   Histamine is released by mast cells in connective tissue and baso-
    phils and platelets in the blood
•   This chemical promotes vasodilation and increased permeability of
    blood capillaries
•   Kinins, including bradykinin, are polypeptides formed in blood from
    inactive precursors known as kininogens.
•   These chemicals promote vasodilation, increase capillary membrane
    permeability, and serve as chemotaxic agents for migration of phago-
    cytes.




    Chapter 22, page 845
                                                                           103
                       Other Contributors
•   Prostaglandins are lipid molecules released by damaged cells.
•   They intensify the effects of histamine and kinins, and stimulate the
    emigration of phagocytes through the membranes of blood capillaries.
•   Leukotrienes are produced by basophils and mast cells to increase
    membrane permeability, promote adherence of phagocytes to path-
    ogens, and serve as chemotaxic agents for phagocytes.
•   The complement system stimulates histamine release, attracts neu-
    trophils via chemotaxis, promotes phagocytosis, and destroys bac-
    teria.




    Chapter 22, page 845
                                                                            104
                 Symptoms of Inflammation
•   Arteriole dilation and increased permeability of capillaries produce
    some of the symptoms of inflammation—heat, redness (erythema),
    and swelling (edema).
•   Heat and redness result from blood accumulating in the damaged
    area.
•   As the local temperature rises, metabolic reactions are more rapid
    and release even more heat.
•   Edema results from the increased permeability of blood capillaries,
    enabling more fluid to move from blood into the interstitial space.




    Chapter 22, page 845
                                                                           105
                    Inflammation and Pain
•   Pain is a prime symptom of inflammation—it results from injury to nerve
    fibers and release of microbial toxins.
•   Kinins can affect nerve endings, and can intensify the pain associated
    with inflammation.
•   Prostaglandins intensify and prolong the pain associated with an inflam-
    mation.
•   Pain can also result from the increased mechanical pressure on tissues
    due to edema.




    Chapter 22, page 845
                                                                             106
                          Clotting Factors
•   An increase in capillary permeability enables blood-clotting factors,
    including fibrinogen, to emigrate into tissues.
•   Fibrinogen is converted to an insoluble, thick mesh of fibrin threads
    that localizes and trap microbes and hinders their spread to other
    tissues.
•   The clotting sequence is described in Chapter 19 of the textbook.



                Emigrate = to leave and generally not return.




    Chapter 22, page 845
                                                                            107
                  Emigration of Phagocytes
•   Phagocytes, including neutrophils, emigrate to the site of a tissue
    injury within about an hour of the start of the inflammation process.
•   Emigration depends on chemotaxis.
•   Neutrophils stick to the endothelium or lining of blood vessels as
    blood accumulates in the injured area.
•   They squeeze through the blood vessel wall to reach the damaged
    area.




    Chapter 22, page 845          Figure 22.10
                                                                            108
          Emigration of Phagocytes (continued)
•   Neutrophils destroy microbes in the damaged tissue by phago-
    cytosis.
•   A steady stream of neutrophils is assured through the production
    and release of additional neutrophils from the red bone marrow.
•   This increase in the production of neutrophils is known as leuko-
    cytosis.




    Chapter 22, page 845         Figure 22.10
                                                                        109
               Monocytes and Macrophages
•   Neutrophils rapidly die-off after predominating in the early stages of
    an infection.
•   Monocytes move into the damaged tissue to prolong the inflamma-
    tory response.
•   Upon entering the tissue, monocytes are transformed into wander-
    ing macrophages to supplement the activity of fixed macrophages.
•   Macrophages are much more potent phagocytes that neutrophils—
    they are large enough to engulf damaged tissue, dead neutrophils,
    and microbes.




    Chapter 22, page 845
                                                                             110
                                  Pus
•   Macrophages eventually die-off as the inflammatory response pro-
    gresses.
•   A pocket of dead macrophages and damaged tissue forms within a
    few days—the collection of dead cells and fluids is known as pus.
•   Pus forms in many inflammatory responses, and usually continues
    until the infection subsides.




    Chapter 22, page 845
                                                                        111
                     Abcesses and Ulcers
•   Pus may reach the surface of the body, drain into an internal cavity,
    or remain in the tissue to be gradually absorbed.
•   An abscess can result if pus cannot drain out of the inflamed region.
•   Pimples and boils are examples of abcesses.
•   An open sore, called an ulcer, results when inflamed tissue sloughs
    off the surface of the tissue.




    Chapter 22, page 846
                                                                            112
           Ulcerations in Diabetic Individuals
•   Individuals with poor blood circulation, such as diabetics who have
    advanced atherosclerosis, are susceptible to ulcers in the tissues of
    their legs.
•   These are known as statis ulcers, which are due to diminished oxy-
    gen and nutrient supply to tissues.
•   The result is that the tissues become even more susceptible to mild
    injury or infection.

          Atherosclerosis = a type of arteriosclerosis in which the
         vessels that supply oxygen-rich blood to the heart become
           clogged with plaque (a fatty substance) and calcium,
        depriving the heart muscle of the oxygen it needs for normal
                functioning. (http://www.cardiogenesis.com)



    Chapter 22, page 846
                                                                            113
                                 Fever
•   Fever is an abnormally-high body temperature that occurs due to
    changes in the thermoregulatory mechanism in the hypothalamus.
•   Fever can occur during infection and inflammation.
•   Many bacterial toxins can elevate body temperature by triggering the
    release of fever-causing cytokines, such as interleukin-1, from macro-
    phages.
•   An elevated body temperature accelerates the effects of interferons,
    inhibits the growth of some microbes, and speeds-up cellular actions
    for tissue repair.




    Chapter 22, page 846
                                                                             114

				
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