Nonspecific Defenses Species resistance – species develop diseases that are unique to it Mechanical barriers – skin and mucous membranes Chemical barriers – enzymes in body fluids, lysozyme and pepsin – gastric acid – interferons blocks viral replication – defensins create holes in bacterial membranes – collectins make pathogens easier to phagocytize

Fever Infection stimulates lymphocyte production of endogenous pyrogen. Endogenous pyrogen raises the thermoregulatory set point in the hypothalamus. Fever causes the liver and spleen to sequester iron and make it less available to bacteria.

Inflammation Blood vessels dilate, redness occurs. Capillary and venule permeability increase. White blood cells invade region. Tissue fluids seep into area. Fibroblasts appear. Phagocytes are active. Cells divide.

Phagocytosis Neutrophils and monocytes leave the bloodstream by diapedesis. Chemicals released from injured tissue attract these cells by chemotaxis. Monocytes give rise to macrophages. Phagocytosis removes foreign particles from the lymph.

Specific Defenses Immunity is a specific defense mechanism. It is resistance to a particular pathogen or its toxin or metabolic by-product. Immunity is based upon the ability to distinguish self molecules from nonself. Molecules that can elicit an immune response are antigens.

Antigens The lymphatic system responds to nonself or foreign antigens, but not to self antigens. Antigens may be proteins, polysaccharides, glycoproteins, or glycolipids. They are usually large and complex. Small molecules, haptens, can elicit an immune response if they combine with a larger molecule.

Lymphocytes Origin Red bone marrow releases undifferentiated lymphocytes into the circulation. Some become T lymphocytes or T cells in the thymus. Figure 16.16

Lymphocytes Origin Some stay in the bone marrow and become B lymphocytes or B cells. B cells and T cells circulate in the blood and settle into lymphatic organs.

Antigen-Presenting Cells Macrophages alert lymphocytes by displaying antigens from engulfed cells. Foreign antigens are attached to the macrophage surface by a self protein, part of the major histocompatibility complex (MHC). This group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances. The MHC protein complex is also called the human leukocyte antigen (HLA) system. Figure 16.18

Cellular Immune Response T cells attach to foreign, antigen-bearing cells, cell-to-cell contact. This is cellular immune response or cell mediated immunity. Cytokines or lymphokines enhance cellular response to antigens.

Types of T Cells Helper T cells – stimulate B cells to produce antibodies – CD4 cells are prime targets of HIV Memory T cells – produced upon initial antigen exposure and protect against delay in future exposure Cytotoxic T cells – release perforin to destroy cells that present foreign antigens

Humoral Immunity B cells secrete antibodies into the blood. This is humoral or antibody-mediated immunity. Helper T cells activate B cells in response to macrophage presentation of antigens. Stimulated B cells produce plasma cells or memory cells. Plasma cells produce antibodies.

B Cell Activation Activated helper T cell releases cytokines. Cytokines stimulate B cell proliferation. Figure 16.19

B Cell Activation Some B cells become plasma cells that secrete antibodies that bind antigens. Antibodies (immunoglobulins) are globular proteins composed of four chains. Ends of the molecule contain antigen- binding sites.

Immunoglobulins Immunoglobulin G – IgG, gamma globulin, 80% of antibodies – defends against bacteria, viruses, toxins – found in blood plasma and tissue fluid – activates complement Figure 16.20

Immunoglobulins Immunoglobulin A – IgA, 13% of antibodies – found in exocrine secretions – defends against bacteria and viruses

Immunoglobulins Immunoglobulin M – IgM, 6% of antibodies, found in plasma – activates complement Immunoglobulin D – IgD, found on mast cells – activates B cells Immunoglobulin E – IgE, found in exocrine secretions – promotes inflammation and allergic reactions

Antibody Actions Antibodies attach directly to antigens – agglutination, precipitation, neutralization Antibodies activate complement – Combination with antigens exposes reactive sites on complement which results in opsonization increasing phagocytosis susceptibility chemotaxis attracting neutrophils and macrophages inflammation to prevent spread of antigens lysis of cell membranes

Figure 16.21

Figure 16.22

Immune Responses Primary Immune Response – Activation of B or T cells upon a first exposure – IgG and IgM are produced and released – Some B cells remain dormant, memory cells Figure 16.23

Immune Responses Secondary Immune Response – Exposure to an antigen to which B or T cells were previously sensitized – occurs more rapidly and lasts longer than primary response

Immunity Classification Naturally acquired active immunity – exposure to live pathogens creating immunity Naturally acquired passive immunity – antibodies passed from mother to fetus Artificially acquired active immunity – vaccination resulting in immunity Artificially acquired passive immunity – injection of antibodies or antitoxin

Allergic Reactions An immune attack against a nonharmful substance can damage tissue. Antigens that trigger allergic responses are allergens. Delayed-reaction allergy (type IV) results from repeated exposure. It usually takes 48 hours to occur and can affect anyone.

Allergic Reactions Hypersensitivities that take 1 to 3 hours to develop – Antibody-dependent cytotoxic reactions type II, ex: transfusion reaction antigen stimulates phagocytosis and lysis – Immune complex reactions type III, ex: autoimmunity widespread antigen-antibody complex block vessels

Allergic Reactions Immediate-reaction allergy – type I or anaphylactic – occurs within minutes after allergen contact in individuals with an inherited tendency to overproduce IgE antibodies – activates B cells which become sensitized – IgE attaches to mast cells which release histamine, prostaglandin D 2 and leukotrienes resulting in a severe inflammatory reaction

Figure 16.24

Transplantation Recipient’s immune system recognizes donor tissue as foreign and attempts to destroy transplanted tissue (tissue rejection) Types of grafts – isograft: tissue from a genetically identical twin – autograft: tissue from elsewhere on the body – allograft: tissue from genetically different individual of the same species – xenograft: tissue from a different species

Autoimmunity Immune system fails to distinguish self from nonself producing autoantibodies and cytotoxic T cells that attack the body Autoimmunity is an attack against self – GlomerulonephritisRheumatic fever – Grave’s diseaseHemolytic anemia – Juvenile diabetesMyasthenia gravis – Systemic lupus erythematosus

Life-Span Changes The immune system begins to decline early in life. T cell numbers decline only slightly and B cells not at all, but activity levels of the cells is diminished. Antibody response is slower. More autoantibodies are produced.