Lymphatic and Immune Systems

Part 1: Body defensed

• Two mechanisms that make up the immune system defend us from foreign materials

  • Innate (nonspecific) 

    • Mechanisms protect against a variety of invaders

    • Responds immediately to protect from foreign materials

  • Adaptive (specific)

    • Fights invaders that get past the innate system

    • Specific defense is required for each type of invader

    • The highly specific resistance to disease is immunity

• Immunity - specific resistance to disease

• Immune system is a functional system rather than an organ system in an anatomical sense 

• Inflammatory response

  • Triggered when body tissues are injured

  • Four most common indicators (cardinal signs) of acute inflammation

    • Redness

    • Heat

    • Pain

    • Swelling 

  • Damaged cells releases inflammatory chemicals

    • Histamine

    • Kinin

  • These chemicals cause

    • Blood vessels to dilate

    • Capillaries to become leaky

    • Phagocytes and white blood cells to move into the area (called positive chemotaxis) (towards chemical response) 

• Functions of the inflammatory response

  • Prevents spread of damaging agents

  • Dispose of cell debris and pathogens through phagocytosis

  • Sets stage for repair 

• Phagocytes

  • Cells such as neutrophils and macrophages engulf foreign material by phagocytosis 

  • The phagocytic vesicle is fused with a lysosome and enzymes digest the cells contents 

• Antimicrobial proteins

  • Enhance innate defenses by

    • Attacking microorganisms directly

    • Hinterding reproduction of microorganisms

  • Most important types

    • Complement proteins

    • Interferon 

•  Antimicrobial proteins: complement  proteins

  • Complement refers to a group of at least 20 plasma proteins that circulate in the plasma

  • Complement is activated when these plasma proteins encounter and attack to cells (known as complement fixation)

  • Membrane attack complexes (MACs) one result of complement fixation produce holes or pores in cells

    • Pores allow water to rush into the cell

    • Cell bursts (lyses)

  • Activated complement enhances the inflammatory response

• Antimicrobial proteins: interferons

  • Interferons are mall proteins secreted by virus infected cells

  • Interferons bind to membrane receptor on healthy cell surfaces to interfere with the ability of viruses to multiply 

• Fever

  • Abnormally high body temperature is a systemic response to invasion by microorganisms

  • Hypothalamus regulates body temperature at 37C (98.6F)

  • The hypothalamus thermostat can be reset higher by pyrogens (secreted by white blood cells)

  • High temps inhibit the release of iron and zinc (needed by bacteria) from the liver and spleen

  • Fever also increases the speed of repair processes

• Adaptive body defenses

  • Adaptive body defenses are the body’s specific defense system or the third line of defense

  • Antigens are targeted and destroyed by antibodies or leukocytes 

  • Three aspects of adaptive defense

    • Antigen specific - the adaptive defense system recognized and acts against particular foreign substances 

    • Systemic - immunity is not restricted to the initial infection site

      • Systemic means whole body 

    • Memory - the adaptive defense system recognizes and mounts a stronger attack on previously encountered pathogens

  • Two arms of adaptive defense system

    • Humoral immunity = antibody-mediated immunity

      • Provided by antibodies present in body fluid

    • cellular immunity = cell-mediated immunity

      • Targets virus-infected cells, cancer cells, and cells of foreign grafts

  • Antigens are any substance capable of exciting the immune system and provoking an immune response 

    • Example of common nonself antigens

      • Foreign proteins provoke the strongest response

      • Nucleic acid

      • Large carbohydrates

      • Some lipids

      • Pollen grains

      • Microorganisms (bacteria, fungi, viruses)

  • Self-antigens 

    • Human cells have many proteins and carbohydrate molecules

    • Self-antigens do not trigger an immune response in us 

    • The presence of our cells in another person’s body can trigger an immune response because they are foreign 

      • Restricts donors for transplants

  • Haptens, or incomplete antigens, are not antigenic by themselves

    • When they link up with our own proteins, the immune system may recognize the combination as foreign and respond with an attack

    • Found in poison ivy, animal dander, detergents, hair, dyes cosmetics

  • Crucial cells of the adaptive system

    • Lymphocytes - respond to specific antigens

      • B lymphocytes (B cells) produce antibodies and oversee humoral immunity

      • T lymphocytes (T cells) constitute the cell-mediated arm of the adaptive defenses; do not make antibodies

      • Arise from hemocytoblasts of bone marrow

      • Whether a lymphocyte matures into a B cell or T cells

      • Depends on where it becomes immunocompetent 

      • T cells develop immunicompetence in the Thymus and oversee cell-mediated immunity

        • Identify foreign antigens

        • Those that bind self-antigens are destroyed

        • Self-tolerance is an important part of lymphocyte “education”

      • Antigen-presenting cells 

        • Engulf and then present fragments of antigens on their own surface, where they can be recognized by T cells

        • Major types of cells behaving as APCs 

          • Dendritic cells

          • Macrophages

          • B lymphocytes

        • When they present antigens, dendritic cells and macrophages activate T cells, which release chemicals 

    • Antigen-presenting cells (APCs) help the lymphocytes but do not respond to specific antigens

    • B cells develop immunocompetence in bone marrow and provide humoral immunity 

  • Immunocompetence

    • The capability to respond to a specific antigen by binding to it with antigen-specific receptors that appear on the lymphocyte’s surface

  • Immunocompetent T and B lymphocytes migrate to the lymph nodes and spleen, where encounters with antigens occur

  • Differentiation from naive cells into mature lymphocytes is competent when they bind with recognized antigens

  • Mature lymphocytes (especially T cells) circulate continuously throughout the body 

• Humoral (antibody-mediated) Immune Response

  • B lymphocytes with specific receptors bind to a specific antigen 

  • The binding event sensitizes, or activates, the lymphocyte to undergo clonal selection

  • A large number of clones is produced (primary humoral response) 

  • Most of the B cells clone members (descendants) become plasma cells

    • Produce antibodies to destroy antigens

    • Activity lasts from 4 to 5 days 

    • Plasma cells begin to die 

  • Some B cells become long-lived memory cells capable of mounting a rapid attack against the same antigens in subsequent meetings (secondary humoral response)

    • These cells provide immunological memory 

  • Active immunity

    • Occurs when B cells encounter antigens and produce antibodies

    • Active immunity can be:

      • Naturally acquired during bacterial and viral infections

      • Artificially acquired from vaccines

  • Passive immunity 

    • Occurs when antibodies are obtained from someone else

      • Naturally acquired from a mother to her fetus or in the breast milk

      • Artificially acquired from immune serum or gamma globulin (donated antibodies)

    • Immunological memory does not occur

    • Protection is short-lived (2–3 weeks)

    • Monoclonal antibodies 

      • Antibodies prepared for clinical testing for diagnostic services

      • Produced from descendants of a single cell line

      • Exhibit specificity for only one antigen

      • Examples of uses for monoclonal antibodies

        • Cancer treatment

        • Diagnosis of pregnancy

        • Treatment after exposure to hepatitis and rabies

    • Antibodies (immunoglobulins, Igs)

      • Constitute gamma globulin part of blood proteins

      • Soluble proteins secreted by activated B cells (plasma cells)

      • Formed in response to a huge number of antigens 

• Antibody structure

  • Four polypeptide chains, two heavy and two light linked by disulfide bonds to form a T- or Y-shaped molecule 

  • Each polypeptide chain has a variable (V) region and a constant (C) region 

    • Variable regions form antigen-binding sites, one on each arm of the T or Y

    • Constant regions determine the type of antibody formed (antibody class)

• Antibody Classes

  • Antibodies of each class have slightly different roles and differ structurally and functionally

  • Five major immunoglobulin classes (MADGE)

    • IgM can fix complement

    • IgA found mainly in secretions, such as mucus or tears

    • IgD important in activation of B cell

    • IgG can cross the placental barrier and fix complement; most abundant antibody in plasma 

    • IgE involved in allergies 

• Antibody Functions

  • Antibodies inactivate antigens in a number of ways 

  • Complement Fixation: Chief antibody ammunition used against cellular antigens

  • Neutralization: antibodies bind to specific sites on bacterial exotoxins or on viruses that can cause all injury

  • Agglutination: antibody-antigen reaction that causes clumping of cells

  • Precipitation: cross-lining reaction in which antigen-antibody complex settles out of solution

• Cellular (cell mediated) Immune Response

               -Main Difference: B cells secrete antibodies and T cells fight antigens directly

     -Like B Cells: immunocompetent T cells are activated to form a clone by                                                                                                                                                                                                                                              binding with a recognized antigen

               -Unlike B Cells, T cells are unable to bind to free antigens 

               -Antigens must be presented by a macrophage, and double recognition must occur

                  -APC engulfs and presents the processed antigen in combination with a protein from the APC

• Different Classes of effector T Cells

  • Helper T Cells and Cytotoxic T Cells (Killer)

• T Cells must recognize nonself and self through the process of antigen presentation

  • Nonself: the antigen fragment presented by the APC

  • Self-coupling with a specific glycoprotein on the APC’s surface at the same time

• Cytotoxic T Cells

  • Specialize in killing infected cells

  • Inserts a toxic chemical (perforin or granzyme) 

  • The perforin enters the foreign cell’s plasma membrane (like being stabbed)

  • Pores now appear in the target cell’s membrane

  • Granzymes (protein-digesting enzyme) enters and kills the foreign cell

• Helper T Cells

  • Recruit other cells to fight invaders

  • Interacts directly with B Cells bond to an antigen, prodding the B Cells into clone production

  • Releases cytokines (can summon or activate more leukocytes) chemicals that act directly to rid the body of antigens