IMMUNOLOGIC FUNCTION The immune system functions as the bodys defense mechanism against invasion and allows a rapid

response to foreign substances in a specific manner. Immunity refers to the bodys specific protective response to an invading foreign agent or organism. Immunopathology refers to the study of dses that result from dysfunctions w/ the immune system Immune System Disorders: Autoimmunity normal protective immune response paradoxically turns against or attacks the body, leading to tissue damage Hypersensitivity body produces inappropriate or exaggerated responses to specific antigens Gammopathies immunoglobulins are overproduced Immune deficiencies a. b. primary deficiency results from improper development of immune cells or tissues; usually congenital or inherited secondary deficiency results from some interference w/ an already developed immune system; usually acquired later in life

B-lymphocytes (B-cells) cells that are important for producing a humoral immune response; are those that migrate directly into the tissues w/o passing through the thymus. It matures in the bone marrow and then enter circulation T-lymphocytes (T-cells) cells that are important for producing a cellular immune response; move from the bone marrow to the thymus, where they mature into several kinds of cells with different functions. Stem cells precursors of all blood cells; reside primarily in bone marrow

Lymphoid Tissues

The spleen, composed of red and white pulp, acts as a filter. The red pulp is the site where old and injured RBCs are destroyed. The white pulp contains concentrations of lymphocytes. The lymph nodes are distributed throughout the body. They are connected by lymph channels and capillaries, w/c remove foreign material from the lymph system before it enters the bloodstream. They also serve as centers for immune cell proliferation. o Axillary o inguinal

epitopes any component of an antigen molecule that functions as an antigenetic determinant by permitting attachment of certain antibodies inflammatory response lysis of microbial agents disposal of foreign toxins

Immune Function 2 general types of immunity: a. b. natural (innate) is a nonspecific immunity that is present at birth acquired (adaptive) develops after birth

Natural (Innate) Immune System provides rapid specific immunity and is present at birth it has a broad spectrum of defense against and resistance to an infection provides a non-specific response to any foreign invader regardless of composition the basis of this defense mechanism is the ability to distinguish between self or non-self coordinates the initial response to pathogens through the production of cytokines and other effector molecules, w/c either activate cells for control of the pathogen (elimination) or promote the development of acquired immune response. o Macrophages o Dendritic cells o Natural killer cells Can be divided into 2 stages: o Immediate (occurring w/in 4h) o Delayed (occurring b/ 4 to 96h after exposure)

The major component of the immune system include: bone marrow WBC Lymphoid tissues o Thymus gland o Spleen o Lymph nodes o Tonsils o Adenoids o Tissues in the GI, Respi and Repro systems

Bone Marrow Produces WBC Lymphocytes are generated from stem cells, w/c are undifferentiated cells Lymphocyte a variety of WBC formed in the lymphoid tissues of the body; round, colorless, somewhat motile, with a single nucleus and no cytoplasmic granules. They make up 20 to 30% of all WBC and serve as a defense mechanism for the body. Their function is to produce antibodies.

WBC Action

Granular leukocytes or granulocytes fight invasion by foreign bodies or toxins by releasing cell mediators (e.g. histamine, bradykinin, prostaglandins) and engulfing foreign bodies or toxins.

Neutrophils (also called polymorphonuclear leukocytes, PMNs) are the first cells to arrive at the site where inflammation occurs. o Eosinophils and Basophils increase in number during allergic reactions and stress responses Non-granular leukocytes (monocytes or macrophages and lymphocytes) o Monocytes function as phagocytic cells, engulfing, ingesting and destroying greater numbers and quantities of foreign bodies or toxins o Lymphocytes (B-cells and T-cells) play major roles in humoral and cell-mediated immune responses

Passive temporary immunity transmitted from a source outside the body that has developed immunity through previous dse or immunization

Response to invasion: The phagocytic immune response The humoral or antibody immune response The cellular immune response

Phagocytic Immune Response Involves WBCs (granulocytes and macrophages) which have the ability to ingest foreign particles. Apoptosis programmed cell death; is the bodys way of destroying worn-out cells. It involves the digestion of DNA by endonucleases, w/c results in targeting of the cells for phagocytosis. Phagocytosis the engulfment and usually the isolation or destruction by phagocytes, or foreign or other particles or cells harmful to the body

Inflammatory Response Elicited in response to tissue injury or invading organisms. Chemical mediators assist this response by: o Minimizing blood loss o Walling off invading organisms o Activating phagocytes o Promoting formation of fibrous scar tissue o Promoting regeneration of injured tissue

Physical and Chemical Barriers Physical surface barriers: o Intact skin o Mucous membrane o Cilia Chemical barriers: o Mucus o Acidic gastric secretions o Enzymes in tears o Saliva o Substances in sebaceous and sweat secretions Viruses are countered by interferon Interferon one type of biologic response modifier; is a non-specific viricidal CHON that is naturally produced by the body and is capable of activating other components of the immune system.

Humoral Immune Response Antibody response The bodys second line of defense Is characterized by the production of antibodies by B-lymphocytes in response to a specific antigen. Begins with B-lymphocytes, w/c can transform themselves into plasma cells that manufacture antibodies. These antibodies are highly specific CHON that are transported in the bloodstream and attempt to disable invaders. Antibodies are large CHON called immunoglobulins (because they are found in the globulin portion of the plasma). They help defend against foreign invaders in several ways, and the type of defense depends on the structure and composition of bothe the antigen and immunoglobulin. The antibody molecule has at least 2 combining sites, or Fab fragments. One antibody can act as a crosslink b/w 2 antigens causing them to bind or clump together (agglutination). This helps clear the body of the invading organism by facilitating phagocytosis. Opsonization in this process, the antigen-antibody molecule is coated with a sticky substance that also facilitates phagocytosis. Antibodies also promote the release of vasoactive substances such as histamine and slow-reacting substance, two of the chemical mediators of the inflammatory response. Antibodies do not function in isolation: they mobilize other components of the immune system to defend against the invader. The typical role of antibodies is to focus components of the natural immune system on the invader. Antigenic determinant the portion of the antigen involved in binding w/ the antibody All immunoglobulins are glycoproteins and contain a certain amount of CHO The body can produce 5 different types of immunoglobulins: o IgA (75%) Appears in serum and tissues (interstitial fluid)

Immune Regulation The immune systems recognition of ones own tissues as foreign rather than as self is the basis for many autoimmune disorders Immunoregulation complex system of checks and balances that regulates or controls immune responses

Acquired (Adaptive Immunity) Immunologic responses acquired during life but not present at birth usually develops as a result of prior exposure to an antigen through immunization or by contracting a dse, both of w/c generate a protective immune response. The acquired immune response is divided into 2 mechanisms: o Cell-mediated response (T-cell) o Effector mechanisms (B-cell) Two types of acquired immunity: o Active the immunologic defenses are developed by the persons own body

Assumes a major role in bloodborne and tissue infections Activates the complement system Enhances phagocytosis Crosses the placenta IgD (15%) Appears in body fluids (blood, saliva, tears, breastmilk, and pulmonary, GI, prostatic and vaginal secretions) Protects against respiratory, GI and GU infections Prevents absorption of antigens from food Passes to neonate in breastmilk for protection IgE (10%) Appears mostly in intravascular system Appears as the first immunoglobulin produced in response to bacterial or viral infections Activates the complement system IgG (0.2%) Appears in small amounts in serum Possibly influences B-lymphocytes differentiation IgM (0.004%) Appears in serum Takes part in allergic and some hypersensitivity reactions Combats parasitic infections

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Cytotoxic T-cells killer T-cells; attack the antigen directly by altering the cell membrane and causing cell lysis (disintegration) and by releasing cytolytic enzymes and cytokines. Cytokines non-antibody proteins that act as intercellular mediators, as in the generation of immune response. Lymphokines substances released by sensitized lymphocytes when they come in contact with specific antigens. Lysis dissolution or disintegration of bacteria and cells by the action of a lysin. Lysin an antibody that has the capability of causing dissolution of cells. Null Lymphocytes destroy antigens directly coated with antibody Natural killer cells defend against microorganisms and some types of malignant cells

Cellular Immune Response The bodys third line of defense; involving the attack of pathogen by T-cells Involves T-lymphocytes w/c can turn into special cytotoxic (or killer) T-cells that can attack the pathogens Stem cells constantly migrate from the bone marrow to the thymus gland, where they develop into T-cells Antigen the structural part of the invading or attacking organism that is responsible for stimulating antibody production Cellular reactions are initiated by the binding of an antigen receptor located on the surface of a T-cell. The T-cells then carry the antigenic message or blueprint, to the lymph nodes, where the production of other T-cells is stimulated Role of T-Lymphocytes: o T-cells include:

Lymphocytes Involved in Immune Responses Type of Immune Response Cell Type Function Humoral B-lymphocyte Produces antibodies or immunoglobulins Cellular T-lymphocyte Helper T

Helper T1 Helper T2 Suppressor T Memory T

Cytotoxic T (killer T) Nonspecific Non-T or Non-B Lymphocyte Null cell Natural killer (NK) cell (granular lymphocyte)

Attacks foreign invaders (antigens) directly Initiates and augments inflammatory response Increases activated cytotoxic T-cells Increases B-cell antibody production Suppresses the immune response Remembers contact with an antigen and on subsequent exposures mounts an immune response Lyses cells infected with virus; plays a role in graft rejection

Effector T-cells participate in the destruction of foreign organisms Suppressor T-cells has the ability to decrease B-cell production, thereby keeping the immune response at a level that is compatible with health.

Memory T-cells are responsible for recognizing antigens from previous exposure and mounting and immune response Effector T-cells

Destroys antigen already coated with antibody Defends against microorganisms and some types of malignant cells; produces cytokines

Helper T-cells are activated on recognition of antigens and stimulate the rest of the immune system. When activated, they secrete cytokines, which attract and activate B-cells, cytotoxic T-cells, NK cells, macrophages and other cells of the immune system. They also produce lymphokines, w/c activate other Tcells, natural and cytotoxic T-cells and other inflammatory cells)

Stages of Immune Response: Recognition stage o Recognition of antigens as foreign or non-self by the immune system. o The body accomplishes recognition using lymph nodes and lymphocytes

Lymphocytes patrol the tissues and vessels that drain the areas served by the lymph nodes. They recirculate from the blood to the lymph nodes and from the lymph nodes back into the bloodstream, in a never-ending series of patrols. o Macrophages and neutrophils have receptors for antibodies and complement; as a result, they coat microorganisms with antibodies, complement, or both, enhancing phagocytosis. Proliferation stage o Enlargement of the lymph nodes o T and B-lymphocytes enlarge, divide and proliferate o T-lymphocytes differentiate into cytotoxic T-cells o B-lymphocytes produce and relese antibodies Response stage o The differentiated lymphocytes function in either a humoral or cellular capacity o The production of antibodies by the B-lymphocytes begins the humoral response. o Humoral refers to the fact that the antibodies are released into the bloodstream and therefore reside in the plasma o With the initial cellular response, the returning sensitized lymphocytes migrate to areas of the lymph node o Transformation of lymphocytes to cytotoxic T-cells Effector stage o Either the antibody of the humoral response or the cytotoxic T-cell of the cellular response reaches and connects with the antigen on the surface of the invader. o The connection initiates the total destruction of the invading microbes or the complete neutralization of the toxin. It involves the interplay of antibodies (humoral immunity), complement and action by the cytotoxic T-cells (cellular immunity) o

Disposing of immune complexes and byproducts associated with inflammation Activating the complement system: o Classic pathway activated by antigen-antibody complexes; it begins with when antibody binds to a cell surface and ends with lysis of the cell o Alternative and Lectin pathway initiated with the release of bacterial products (endotoxins) Complement components, prostaglandins, leukotrienes and other inflammatory mediators all contribute to the recruitment of inflammatory cells o

Complement-Mediated Immune Responses Complement Response Products Effects Cytolysis Opsonization C5b C9 C3b, C5b Lysis and destruction of cell membranes of bodys cells or of pathogens Targeting of the antigen so that it can be easily engulfed and digested by macrophages and other phagocytic cells Chemical attraction of neutrophils and phagocytic cells to the antigen Activation of mast cells and basophils with release of inflammatory mediators that produce smooth muscle contraction and increased vascular permeability

Differences in Cellular and Humoral Immune Responses: HUMORAL IMMUNE RESPONSE (B-CELLS) Bacterial phagocytosis and lysis Anaphylaxis Allergic hay fever and asthma Immune complex dse Bacterial and some viral infection

Chemotaxis Anaphylaxis

C3a, C5a C3a, C5a

CELLULAR RESPONSES (T-CELLS) Transplant rejection Delayed hypersensitivity (tuberculin reaction) Graft vs. host dse Tumor surveillance or destruction Intracellular infections Viral, fungal, and parasitic infections

Complement System

Complement series of enzymatic proteins in the serum that, when activated, destroy bacteria and other cells. 3 major fxns: o Defending the body against bacterial infection o Bridging natural and acquired immunity