CHAPTER 43 THE BODYS DEFENSES I NONSPECIFIC DEFENSES

CHAPTER 43 THE BODY'S DEFENSES

I. NONSPECIFIC DEFENSES AGAINST INFECTION A. • 1. 2. 3. 4. 5. THE SKIN AND MUCOUS MEMBRANES PROVIDE FIRST-LINE BARRIERS TO INFECTION THE FIRST LINE OF NONSPECIFIC DEFENSE CONSISTS OF THE INTACT SKIN AND MUCOUS MEMBRANES MUCUS CILIATED CELLS: LINE THE UPPER RESPIRATORY SYSTEM (LUNGS) ANTIMICROBIAL PROTEINS: EX. LYSOZYME- BREAKS DOWN CELL WALLS OF BACTERIA GASTRIC JUICES: FOUND IN THE STOMACH

B. PHAGOCYTIC CELLS, INFLAMMATION, AND ANTIMICROBIAL PROTEINS FUNCTION EARLY IN INFECTION • THE SECOND LINE OF NONSPECIFIC DEFENSE DEPENDS PRIMARILY UPON NEUTROPHILS AND MACROPHAGES, PHAGOCYTIC WHITE CELLS IN THE BLOOD AND TISSUES. • NATURAL KILLER CELLS MEDIATE LYSIS OF VIRUS-INFECTED CELLS AND TUMOR CELLS.

• TISSUE DAMAGE TRIGGERS A LOCAL INFLAMMATORY RESPONSE. 1. 2. 3. 4. INJURED CELLS RELEASE HISTAMINE, A CHEMICAL SIGNAL VASODILATION AND INCREASED PERMEABILITY OF BLOOD VESSELS OCCURS (ALLOWS FLUID AND LARGE NUMBERS OT PHAGOCYTIC WHITE BLOOD CELLS TO ENTER THE TISSUES. ) PHAGOCYTES: ENGULF PATHOGENS AND DAMAGED CELLS COMPLEMENT PROTEINS: HELP PHAGOCYTES ENGULF FOREIGN CELLS, STIMULATE RELEASE OF HISTAMINE AND HELP LYSE FOREIGN CELLS

• THE MOST IMPORTANT ANTIMICROBIAL PROTEINS IN THE BLOOD AND TISSUES ARE THE PROTEINS OF THE COMPLEMENT SYSTEM, INVOLVED IN NONSPECIFIC AND SPECIFIC DEFENSE, AND INTERFERONS. • SECRETED BY VIRUS-INFECTED CELLS, INTERFERONS INHIBIT VIRUS PRODUCTION IN NEIGHBORING CELLS.

II. HOW SPECIFIC IMMUNITY ARISES A. • • • LYMPHOCYTES PROVIDE THE SPECIFICITY AND DIVERSITY OF THE IMMUNE SYSTEM A SUBSTANCE THAT ELICITS AN IMMUNE RESPONSE IS CALLED AN ANTIGEN. THE IMMUNE SYSTEM RECOGNIZES SPECIFIC ANTIGENS (MOLECULES BELONGING TO MICROBES, TOXINS, TRANSPLANTED TISSUE, OR CANCER CELLS) AND DEVELOPS AN IMMUNE RESPONSE THAT INACTIVATES OR DESTROYS THAT SUBSTANCE. B LYMPHOCYTES AND T LYMPHOCYTES RECOGNIZE ANTIGENS VIA SURFACE ANTIGEN RECEPTORS: MEMBRANE ANTIBODIES FOR B CELLS, AND T CELL RECEPTORS FOR T CELLS. LYMPHOCYTES CIRCULATE THROUGHOUT THE BLOOD AND LYMPH AND ARE FOUND IN HIGH NUMBERS IN LYMPHATIC TISSUES. THE GREAT DIVERSITY OF LYMPHOCYTES, EACH WITH RECEPTORS OF PARTICULAR SPECIFICITY, GIVES THE IMMUNE SYSTEM THE CAPACITY TO RESPOND TO VIRTUALLY ANTIGEN.

B. ANTIGENS INTERACT WITH SPECIFIC LYMPHOCYTES, INDUCING IMMUNE RESPONSES AND IMMUNOLOGICAL MEMORY • CLONAL SELECTION OCCURS WHEN AN ANTIGEN ACTIVATES A LYMPHOCYTE BY BINDING TO SPECIFIC RECEPTORS. • IN THE PRIMARY IMMUNE RESPONSE, THE BODY'S FIRST EXPOSURE TO AN ANTIGEN, THE LYMPHOCYTE PROLIFERATES AND DIFFERENTIATES, FORMING A CLONE OF SHORT-LIVED, INFECTION-FIGHTING EFFECTOR CELLS AND A CLONE OF LONG-LIVED MEMORY CELLS, ALL SPECIFIC FOR THE ANTIGEN. • SECONDARY IMMUNE RESPONSES TO THAT SAME ANTIGEN, WHICH INVOLVE MEMORY CELLS, ARE FASTER AND OFTEN PROTECTIVE.

B. LYMPHOCYTE DEVELOPMENT GIVES RISE TO AN IMMUNE SYSTEM THAT DISTINGUISHES SELF FROM NONSELF • LYMPHOCYTES DEVELOP FROM PLURIPOTENT STEM CELLS IN THE BONE MARROW. • B CELLS MATURE IN THE MARROW, WHILE T CELLS MATURE IN THE THYMUS. • SELF-TOLERANCE DEVELOPS AS LYMPHOCYTES BEARING RECEPTORS SPECIFIC FOR NATIVE MOLECULES ARE DESTROYED OR RENDERED NONRESPONSIVE. • MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) MOLECULES ARE CRUCIAL TO T CELL FUNCTION.

• CLASS I MHC MOLECULES, LOCATED ON ALL NUCLEATED CELLS OF THE BODY, PRESENT ANTIGEN FRAGMENTS TO CYTOTOXIC T CELLS. • CLASS II MHC MOLECULES, FOUND MAINLY ON MACROPHAGES AND B CELLS, PRESENT ANTIGEN FRAGMENTS TO HELPER T CELLS. • DEVELOPING T CELLS ARE EXPOSED TO CLASS I AND II MHC MOLECULES ON CELLS OF THE THYMUS • ONLY T CELLS BEARING RECEPTORS WITH AFFINITY FOR SELF-MHC REACH MATURITY.

III. IMMUNE RESPONSES

A. HELPER T LYMPHOCYTES FUNCTION IN BOTH HUMORAL AND CELL-MEDIATED IMMUNITY • HUMORAL, OR B CELL, IMMUNITY, BASED ON CIRCULATION OF ANTIBODIES IN THE BLOOD AND LYMPH, DEFENDS AGAINST FREE VIRUSES, BACTERIA, AND OTHER EXTRACELLULAR THREATS. • CELL-MEDIATED, OR T CELL IMMUNITY DEFENDS AGAINST INTRACELLULAR PATHOGENS BY DESTROYING INFECTED CELLS; • IT ALSO DEFENDS AGAINST TRANSPLANTED TISSUE AND CANCER CELLS.

43. 11 THE CENTRAL ROLE OF HELPER T CELLS

B. IN THE CELL-MEDIATED RESPONSE, CYTOTOXIC TCELLS DEFEND AGAINST INTRACELLULAR PATHOGENS • CYTOTOXIC T CELLS ARE ACTIVATED BY CYTOKINES AND SPECIFIC BINDING CLASS 1 MHC -ANTIGEN COMPLEXES ON A TARGET (INFECTED, TRANSPLANTED, OR CANCEROUS) CELL. • THE T CELL THEN SECRETES PERFORINS, WHICH FORM PORES IN THE TARGET CELL MEMBRANE, CAUSING THE CELL TO LYSE.

43. 14 EPITOPES (ANTIGENIC DETERMINANTS): ANTIBODIES BIND TO EPITOPES ON THE SURFACE OF AN ANTIGEN. IN THIS EXAMPLE, 3 DIFFERENT ANTIBODY MOLECULES REACT WITH DIFFERENT EPITOPES ON THE SAME LARGE ANTIGEN MOLECULE.

B. IN THE HUMORAL RESPONSE, B CELLS PRODUCE ANTIBODIES AGAINST EXTRACELLULAR PATHOGENS • B CELLS ARE ACTIVATED BY CYTOKINES AND SPECIFIC BINDING OF ITS MEMBRANE ANTIBODIES TO EXTRACELLULAR ANTIGENS. • MOST OF THESE ANTIGENS ARE PROTEINS OR LARGE POLYSACCHARIDES, EACH WITH MULTIPLE EPITOPES. • ANTIBODIES, ALSO CALLED IMMUNOGLOBULIN (IG) MOLECULES, ARE SERUM PROTEINS. • THE VARIABLE REGION OF AN IG MOLECULE BINDS TO A SPECIFIC EPITOPE; THE CONSTANT REGION DETERMINES THE ANTIBODY’S CLASS. • THE FIVE MAJOR IMMUNOGLOBULIN CLASSES ARE Ig. G, Ig. M, 1 g. D, Ig. A AND Ig. E. • AN ANTIBODY DOES NOT DESTROY AN ANTIGEN DIRECTLY, INSTEAD NEUTRALIZES IT OR TARGETS IT FOR ELIMINATION BY OPSONIZATION, AGGLUTINATION, PRECIPITATION, OR COMPLEMENT FIXATION.

43. 12 THE FUNCTIONING OF CYTOTOXIC T CELLS

43. 16 EFFECTOR MECHANISMS OF HUMORAL IMMUNITY: THE BINDING OF ANTIBODIES TO ANTIGENS TAGS FOREING CELLS AND MOLECULES FOR DESTRUCTION BY PHAGOCYTES OR THE COMPLEMENT SYSTEM OF PROTEINS.

IV. IMMUNITY IN HEALTH AND DISEASE A. • 1. 2. • • IMMUNITY CAN BE ACHIEVED NATURALLY OR ARTIFICIALLY ACTIVE IMMUNITY: THE IMMUNE SYSTEM RESPONDS TO A GOREIGN ANTIGEN AXQUIRED EITHER BY NATURAL INFECTION OR ARTIFICIALLY, AS BY IMMUNIZATION ANTIBIOTICS: CHEMICALS DERIVED FROM BACTERIA OR FUNGI THAT ARE HARMFUL TO OTHER BACTERIA VACCINES: SUBSTANCES THAT STIMULATE THE PRODUCTION OF MEMORY CELLS. INACTIVATED VIRUSES OR BACTERIA ARE USED AS VACCINES. IN IMMUNIZATION, A NONPATHOGENIC FORM OF A MICROBE OR PART OF A MICROBE GENERATES AN IMMUNE RESPONSE TO AN IMMUNOLOGICAL MEMORY FOR THAT MICROBE PASSIVE IMMUNITY: ANTIBODIES ARE TRANSFERRED FROM ONE INDIVIDUAL TO ANOTHER