The body’s defenders

Core concepts Infectious diseases are caused by pathogens Nonspecific defenses against infection Plants and animals have mechanisms that are not targeted to specific pathogens that help them combat infection Skin and mucous membranes provide first-line barriers to infection Phagocytic cells, inflammation, and antimicrobial proteins function as the second line of defense Specific immunity arises from lymphocyte-antigen interactions Lymphocytes provide the specificity and diversity of the immune system Antigens interact with specific lymphocytes, inducing immune responses and immunological memory Lymphocyte development gives rise to an immune system that distinguishes self from nonself Immune responses take two forms: humoral and cell-mediated Helper T-lymphocytes function in both humoral and cell-mediated immunity Cytotoxic T-cells counter intracellular pathogens B-cells make antibodies against extracellular pathogens Memory B- and T-cells are responsible for faster and stronger secondary immune responses Immunity in health and disease Immunity can be achieved naturally or artificially The immune system limits blood transfusion and tissue transplantation Abnormal immune function can lead to disease AIDS is an immunodeficiency disease caused by a virus

Keywords memory cell chemokines monocytes class I MHC class II MHC natural killer cells neutrophils nonspecific defense opportunistic disease passive immunity pathogen perforin phagocytosis plasma cell primary immune response prostaglandins pyrogens Rh factor secondary immune response suppressor T cell T cell T cell receptor target cell tumor antigen vaccine Keywords chemokines class I MHC class II MHC clonal selection complement fixation complement system cytokine cytotoxic T cell effector cell eosinophils helper T cell histamine HIV humoral immunity immunity immunodeficiency disease immunoglobulin inflammatory response interferon interleukin lysozyme macrophages major histocompatibility complex mast cells membrane attack complex ABO blood groups active immunity agglutination AIDS allergy anaphylactic shock antibody antigen antigen receptor antigen-presenting cell apoptosis autoimmune disease B cell basophils CD4 CD8 cell-mediated immunity

Germ theory of disease Infectious diseases are caused by microorganisms or germs. Contradicts miasma and contagion theory Supported by Francesco Redi Anton van Leeuwenhoek Agostino Bassi (fungus attacks silkworms) Ignaz Semmelweis (childbed fever) John Snow (he knows something…about cholera) Louis Pasteur Robert Koch

Pathogens and disease Fungi Viruses Protozoa Large parasites Bacteria

Two major types of defenses INNATE (NONSPECIFIC) IMMUNITY Rapid responses to a broad range of microbes ACQUIRED (SPECIFIC) IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens)

Innate (nonspecific) immunity First line: External defenses Mucus, cilia Tears Mouth bacteria, saliva Skin, oil, sweat, acidity Intestinal flora Gastric juice Acid conditions

Q1 The germ theory of disease states that infectious diseases are caused by pathogenic microorganisms bad air inorganic (non-living particles) direct contact between individuals

Q2 Which contributor to the germ theory is properly matched with his contribution? Redi - disproved spontaneous generation through experiments involving swan neck flasks and sterile nutrient broth; also proved that microorganisms cause spoilage and decay. Koch - series of steps that that specific germs cause specific diseases Semmelweis - innovated on the design of the microscope and observed small "animalcules" in a drop of water. van Leeuwenhoek - observed that childbed fever was caused by particles transferred from dead women to healthy ones

Q3 Koch's Postulates are a series of steps that prove that a microorganism causes a disease. Place the following in the proper order: 1 - Microorganism from pure culture is inoculated in animals and disease symptoms are observed. 2 - Microorganism is found in all infected individuals. 3 - Microorganism is recovered from the inoculated animals and shown to be the same as the original microorganism. 4 - Microorganism is isolated and grown in pure culture. 3, 4, 1, 2 2, 1, 4, 3 2, 4, 1, 3 3, 1, 4, 2

Q4 Which pathogen type is correctly matched with the disease it causes? Viruses - anthrax, botulism, tetanus, tuberculosis, plague, typhoid Bacteria - Ebola, dengue, cold, influenza, Hepatitis A Protists - Creutzfeldt-Jakob disease, mad cow disease Fungi - athlete's foot, ringworm, jock itch

Q5 The third line of defense is associated with External innate and nonspecific responses Internal innate and nonspecific responses Internal acquired specific responses

Q6 Lysozyme, an enzyme present in tears and saliva is an example of an External innate and nonspecific response Internal innate and nonspecific response Internal acquired specific response

Q7 Phagocytes that attach to and ingest invading pathogens are part of the External innate and nonspecific response Internal innate and nonspecific response Internal acquired specific response

Q8 Which phagocytic WBCs are large eaters that are found in the bloodstream and in lymph organs, lungs, kidneys, and connective tissues Macrophages Neutrophils Basophils Eosinophils

Innate immunity Second line: Internal defenses Microbes MACROPHAGE Vacuole Lysosome containing enzymes Phagocytic cell Innate immunity Second line: Internal defenses 1 Phagocytes Attach to and ingest invading microorganisms Initiate the inflammatory response Macrophages – migrants or in lymph organs, lungs, kidneys, connective tissues Antimicrobial proteins Complement system – lysis of invading cells, triggers inflammation Interferons – activate macrophages, prevent cell-to-cell spread of viruses Defensins – secreted by macrophages to damage pathogens 2 3 4 5 6

70% chemotaxis 5% 1.5% histamine

Q9 These phagocytic WBCs are most abundant (~70%) and are often the first responders to an infection through chemotaxis. They die immediately following an infection. Macrophages Neutrophils Basophils Eosinophils

Q10 These phagocytic WBCs protect against large parasites like worms. Macrophages Neutrophils Basophils Eosinophils

Q11 These phagocytic WBCs secrete the vasodilator histamine and play roles in parasitic infections and allergies. Macrophages Neutrophils Basophils Eosinophils

Innate immunity Second line: Internal defenses (con’t.) Inflammatory response Chemicals involved Histamines Prostaglandins Chemokines Pyrogens http://www.sumanasinc.com/webcontent/anisamples/dynamicillustrations/inflammatory.html

Q12 Steps in an inflammatory response: 1 Capillaries dilate and become leaky 2 Complement proteins and chemokines attract WBCs to the area 3 Injury 4 Mast cells release histamine 5 Phagocytosis of dead cells and pathogens 6 Signalling stops, tissue heals 3, 4, 1, 2, 5, 6 3, 1, 4, 5, 6, 2

Q13 Which proteins raise the body’s temperature during an inflammatory response? Chemokines Histamines Prostaglandins Pyrogens

Innate immunity Second line: Internal defenses (con’t.) Natural killer (NK) cells Attack virus-infected body cells and cancer cells Apoptosis (cell death) in cells attacked Coelomocytes and hemocytes – phagocytes in invertebrates

Q14 Which phagocytes are present in invertebrates? Natural killer cells Coelomocytes and hemocytes Mast cells

Q15 Which phagocytes are highly similar to basophils? Natural killer cells Coelomocytes and hemocytes Mast cells

Q16 Which phagocytes are play an important role in tumor eradication and death of infected cells? Natural killer cells Coelomocytes and hemocytes Mast cells

Specific (acquired) immunity Third line of defense Lymphocytes In blood and lymph Types B – cells – mature in marrow T – cells – mature in thymus Helper Cytotoxic/Killer Regulatory/Suppressor Memory Activated by cytokines from phagocytes Display specificity to antigens (antibody generator) Have specific membrane-bound antigen-receptors

Three pathogens with antigens on their surfaces (puzzle pieces) 1 Three pathogens with antigens on their surfaces (puzzle pieces) 2 Pathogen A is engulfed by Antigen Presenting Cells like dendritic cells, macrophages, B cells 3 MHC class II proteins within the APCs (thumb and index finger) present antigens on the surface 4 Helper T cells with specific receptors bind to the MHC-Antigen complex (see if puzzle pieces fit) 5 APC releases cytokines that activate specific Helper Ts and cause them to multiply rapidly 6 Numerous Helper T clones are produced, some become memory Helper Ts cells

7 Pathogen B is broken up by proteins and antigens are engulfed by Antigen Presenting Cells like dendritic cells, macrophages, B cells 8 MHC class II proteins within the APCs (thumb and index finger) present antigens on the surface 9 Activated Helper T cells bind to the MHC-Antigen complex (see if puzzle pieces fit) 10 Helper Ts release cytokines to activate B cells and cause them to rapidly proliferate 11 Numerous B cell clones are produced 12 B cells differentiate into plasma cells and memory B cells 13 Plasma cells produce identical antibodies specific to the given antigen

14 Pathogen C infects normal body cells and is broken down by lysosomes 15 MHC class I proteins within the infected body cells (thumb and index finger) present antigens on the surface 16 Killer T cells recognize and bind to the MHC-Antigen complex (see if puzzle pieces fit) 17 Binding causes Killer T to release perforin that lyses the infected cell 18 Helper Ts release cytokines to activate Killer Ts and cause them to rapidly proliferate 19 Numerous Killer T cell clones are produced

Two types of specific immune responses B and T cells generate clones of short-lived activated effector cells long-lived memory cells

MHC molecules and T cell function Class I MHC molecules Most nucleated cells of the body Infected/cancerous cells display parts of foreign antigens on surfaces Recognized by cytotoxic T cells Class II MHC molecules Dendritic cells, macrophages, B cells (APCs) display phagocytized antigen fragments on surfaces Recognized by helper T cells T cells that have receptors for self-molecules are destroyed  self-tolerance

Clonal selection antigen-driven cloning of lymphocytes image/svg+xml \\ Clonal selection antigen-driven cloning of lymphocytes Antigen binds to receptor on lymphocyte Lymphocyte is activated Thousands of clones specific for the antigen are produced

Antibody action

Immunity – memory cells initiate a faster, more efficient response upon reinfection

Passive immunity Active immunity Own system develops antibodies Develops naturally in response to infection Develops following immunization (artificial immunity) Long-lasting protection but may take a long time Passive immunity Antibodies are passed from mother to fetus via the placenta Antibodies are passed from mother to infant via breast milk (colostrum) Antibodies may be injected into a nonimmune person (artificial immunity) Immediate, short-term protection

Blood groups and transfusions Problems with transfusions and transplants Antigens on RBC’s will determine a person’s blood type: A, B, AB, O blood Another RBC antigen: Rh factor  Rh+ or Rh-

Immune disorders/diseases Allergies – hypersensitive responses to antigens called allergens Autoimmune diseases – immune system loses tolerance for self and turns against certain molecules of the body (SLE, diabetes type I, rheumatoid arthritis) Immunodeficient diseases Inborn or primary (severe combined ID) Acquired or secondary AIDS – HIV attacks CD4 molecules on helper T cells, macrophages, dendritic cells

IgE antibodies bind to receptors or mast cells. 1 On subsequent exposure to the same allergen, IgE molecules attached to a mast cell recog- nize and bind the allergen. 2 Degranulation of the cell, triggered by cross-linking of adjacent IgE molecules, releases histamine and other chemicals, leading to allergy symptoms. 3 Allergen IgE Histamine Granule Mast cell

Innate immunity Second line: Internal defenses Microbes MACROPHAGE Vacuole Lysosome containing enzymes Phagocytic cell 1 Phagocytes Attach to and ingest invading microorganisms Initiates the inflammatory response Macrophages – migrants or in lymph organs Antimicrobial proteins Complement system – lysis of invading cells, triggers inflammation Interferons – activate macrophages, prevent cell-to-cell spread 2 3 4 5 6

Innate immunity Second line: Internal defenses (con’t.) Inflammatory response Chemicals involved Histamines Prostaglandins Chemokines Pyrogens http://www.sumanasinc.com/webcontent/anisamples/dynamicillustrations/inflammatory.html

Innate immunity Second line: Internal defenses (con’t.) Natural killer (NK) cells Patrol body Attack virus-infected body cells and cancer cells Apoptosis (cell death) in cells attacked Coelomocytes in invertebrates function in nonspecific immunity

Specific (acquired) immunity Third line of defense Lymphocytes Found in blood and lymph Types B – cells – mature in marrow T – cells – mature in thymus Helper Cytotoxic Display specificity to antigens (antibody generator) Have membrane-bound antigen-receptors

Two types of specific immune responses B and T cells generate clones of short-lived activated effector cells long-lived memory cells

Antibody action

Immunity – memory cells initiate a faster, more efficient response upon reinfection

Own system develops antibodies Active immunity Own system develops antibodies Develops naturally in response to infection Develops following immunization Long-lasting protection but may take a long time Passive immunity Antibodies are passed from mother to fetus via the placenta Antibodies are passed from mother to infant via breast milk (colostrum) Antibodies may be injected into a nonimmune person Immediate, short-term protection

Blood groups and transfusions Problems with transfusions and transplants Antigens on RBC’s will determine a person’s blood type: A, B, AB, O blood Another RBC antigen: Rh factor  Rh+ or Rh-

Immune disorders/diseases Allergies – hypersensitive responses to antigens called allergens Autoimmune diseases – immune system loses tolerance for self and turns against certain molecules of the body Immunodeficient diseases Inborn or primary Acquired or secondary AIDS – HIV attacks helper T cells 1µm