The Immune System 1.The Innate System 2.The Adaptive System

The Innate Immune System “Nonspecific” system –Surface Barriers –Cell and Chemical Responses

Innate Immunity: Surface Barriers

Innate Immunity: Cell and Chemical Defenses They do not target specific pathogens – They target abnormal or foreign cells Six categories: –Phagocytes –Natural killer (NK) cells –Inflammation response –The complement system –Interferons –Fever

Phagocytes Macrophages, neutrophils, eosinophils 1.Adherence and endocytosis 2.Phagocytic endosome 3.Lysosome fuses with endosome, releases hydrolytic acids/enzymes 4.Microbe is killed and digested 5.Exocytosis

Natural Killer Cells Lymphocytes that destroy tumor cells and cells infected with viruses Not phagocytes, instead release chemicals onto cell membranes –Cytolytic, perforin complexes The target cell lyses & nucleus disintegrates NK cells also release substances to stimulate inflammation

Inflammation Response Redness Increased Temperature Swelling Pain

The Complement System > 20 plasma proteins Activation triggers cascade of chemical reactions Molecular Complexes form: –Membrane Attack Complex creates holes in bacterial cell membranes –C3b marks them for phagocytes –C3a and C5a stimulate mast cells to release histamines

Interferons - Interfere with viral replication - Block protein synthesis at ribosomes - Activate macrophages - Mobilize NK cells

Fever When macrophages attack foreign matter, they release chemicals called pyrogens into the blood –Endogenous: interleukins, tumor necrosis factors, macrophage inflammatory protein, interferons –Exogenous: Lipopolysaccharides of gram-negative bacteria trigger endogenous factors The hypothalamus is stimulated to increase body temperature – fever Liver and spleen sequester iron and zinc High temp. unfavorable for microbes

The Adaptive Immune System “Specific” defense mechanisms Three characteristics: –recognizes & targets specific foreign substances –protects the entire body, not a specific injury or infection site –has a "memory" to store information from past exposures

Cell Recognition Proteins, polysaccharides, glycoproteins signal the identity of the cell (host or foreign) Major histocompatibility complexes (MHC) –Molecular markers on host cells Antigens –Substances that mobilize the immune response Molecular markers on foreign cells, abnormal/infected or cancerous host cells Auto-immune diseases arise when our immune system cannot differentiate “host” from “foreign” cells

Key to Adaptive Immune System Lymphocytes Originate from stem cells in bone marrow 30% of circulating WBCs – B cells mature in Bone marrow – T cells mature in Thymus Gland – Both types are made in the bone marrow –Immune response may be antibody-mediated (humoral) or cell-mediated

Antibody-mediated Immunity Antibodies: Y-shaped proteins (4 polypeptides) –Made by mature B- lymphocytes Binds to antigens to form antigen-antibody complex

Antibody-mediated Immunity Immunoglobulin classes –IgD: antigen receptor of B cell –IgM: antigen receptor of B cell (monomer); released by plasma cells during primary response (pentamer) –IgG: most abundant and diverse; targets bacteria, viruses, toxins; main antibody for both primary and secondary response –IgA: found in exocrine secretions; prevents pathogens from attaching to epithelial surface –IgE: bound to mast cells and basophils; mediates inflammation and allergic reaction

Antibody-mediated Immunity

WBC detects a pathogen or abnormal cell –Attacks pathogen –Alerts Helper T cells and B cells T cells attracted by chemical signals B cells alerted by using the pathogen’s own antigens Antigen Pathogen MHC MHC+Antigen Signaling molecules Helper T cell B cell Macrophage

Antibody-mediated Immunity Antigens bind to specific antibodies on B cell surface Activation causes B cells to divide rapidly –Plasma cells produce antibodies 100 million antibodies/hour –Memory B cells Remain on “stand by” until activated by helper T cells Surveillance

Cell-mediated Immunity MHC + antigen complex waves a warning flag Class II MHC’s found on B cells, some T cells, and antigen- presenting cells Class I MHC’s found on most cells, except RBCs

Cell-mediated Immunity Antigen Pathogen MHC MHC + Antigen Signaling molecules Signaling molecules Macrophage Helper T cell Cytotoxic T cell Activated Cytotoxic T cell Memory T cell Perforin molecules form pores in pathogen cell membrane Helper T cells (CD4): –recognize class II MHC – stimulate other immune cells Cytotoxic T cells (CD8): –recognize class I MHC – kill infected, cancer, or foreign cells Memory T cells: – reactivate on re-exposure Suppressor T cells: – suppresses other immune cells

Cell-mediated Immunity Helper T-cells facilitate both cell- mediated and antibody-mediated immune responses Cytotoxic T cells function similar to NK cells, however they only see specific MHC I + antigen complexes

Memory B and T Cells are Like…

Immune Memory Primary immune response –first exposure to pathogen –recognition, production of B & T cells 3 to 6 day lag time antibodies peak in 10 to 12 days –B & T memory cells created –basis for "immunity" from the disease Secondary immune response –Memory B & T cells immediately identify the pathogen –faster, longer lasting, more effective than the first –at subsequent infection, new legions of B & T cells form in a few days –often no symptoms are noticed