IMMUNOLOGIC DISORDERS

The term immunity refers to the ability of the body to resist damage from an invading foreign agent such as microorganisms, and harmful chemicals such as toxins released by microorganisms.

Factors affecting immune function 1.Age 2.Emotional status 3.Medications 4.Stress of illness 5.Trauma and surgery

Immune response serves three functions: 1.Defense involves resisting infection 2.Homeostasis Involves removing worn out self components 3.Surveillance deals with the identification and destruction of mutant cells

Unique Characteristics of the immune system: 1.Self or Non- Self recognition - normally recognizes host cells as non-antigenic and responds only to foreign and potentially harmful agents, living or non-living as antigens 2.Antibody production Produces specific antibodies for specific antigens for destruction 1.Memory Remembers antigens that have invaded the body in the past allowing a quicker response 1.Self- Regulation Monitor its own performance, turning itself on when antigens invade and turning itself off when infection is eradicated In AUTOIMMUNE Response, there is a breakdown in this distinction because of the damage in the immune system due to pathologic changes, an autoimmune response may occur in response to certain bodys own protein resulting in the production of autoanitbodies.

ANATOMY OF THE IMMUNE SYSTEM

Major components include: 1.Bone marrow 2.White blood cells (WBCs) 3.Lymphoid tissues.

Bone Marrow - the production site of the WBCs involved in immunity. - Like other blood cells, lymphocytes are generated from stem cells, which are undifferentiated cells. - Descendants of stem cells become lymphocytes, the B lymphocytes (B cells), and the T lymphocytes (T cells) - B lymphocytes mature in the bone marrow and then enter the circulation. - T lymphocytes move from the bone marrow to the thymus, where they mature into several kinds of cells capable of different functions.

Lymphoid Tissues The spleen, composed of red and white pulp, acts somewhat like a filter. The red pulp is the site where old and injured red blood cells 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, which remove foreign material from the lymph before it enters the bloodstream. The lymph nodes also serve as a center for immune cell proliferation. The remaining lymphoid tissues, such as the tonsils and adenoids and other mucoid lymphatic tissues, contain immune cells that defend the bodys mucosal surfaces against microorganisms.

IMMUNE FUNCTION: DEFENSES AND RESPONSES

There are two general types of immunity: natural (innate) and acquired (adaptive). Natural immunity is a nonspecific immunity present at birth. Acquired or specific immunity develops after birth. Natural immune responses to a foreign invader are very similar from one encounter to the next regardless of the number of times the invader is encountered; in contrast, acquired responses increase in intensity with repeated exposure to the invading agent (Delves & Roitt, 2000a). Although each type of immunity plays a distinct role in defending the body against harmful invaders, the various components usually act in an interdependent manner.

FIRST LINE OF DEFENSE PHYSICAL BARRIERS Physical surface barriers include intact skin and mucous membranes, which prevent pathogens from gaining access to the body,and the cilia of the respiratory tract along with coughing and sneezing responses, which act to filter and clear pathogens from the upper respiratory tract before they can invade the body further.

CHEMICAL BARRIERS Chemical barriers, such as acidic gastric secretions, mucus, enzymes in tears and saliva, and substances in sebaceous and sweat secretions, act in a nonspecific way to destroy invading bacteria and fungi. Viruses are countered by other means, such as interferon. Interferon, one type of biologic response modifier, is a nonspecific viricidal protein naturally produced by the body that is capable of activating other components of the immune system.

SECOND LINE OF DEFENSE Non-specific Response 1.WHITE BLOOD CELL ACTION WBCs, or leukocytes, participate in both the natural and the acquired immune responses. Granular leukocytes, or granulocytes (so called because of granules in their cytoplasm), fight invasion by foreign bodies or toxins by releasing cell mediators, such as histamine, bradykinin, and prostaglandins, and engulfing the foreign bodies or toxins. Granulocytes include neutrophils, eosinophils, and basophils. Neutrophils are the first cells to arrive at the site where inflammation occurs. Eosinophils and basophils, other types of granulocytes, increase in number during allergic reactions and stress responses.

Nongranular leukocytes include monocytes or macrophages (referred to as histiocytes when they enter tissue spaces) and lymphocytes. Monocytes also function as phagocytic cells, engulfing, ingesting, and destroying greater numbers and quantities of foreign bodies or toxins than granulocytes.

1.INFLAMMATORY RESPONSE The chemicals mediators (histamine, prostaglandins, leukotrienes, complement, and kinins) produce several effects: 1.Vasodilation increases blood flow and brings phagocytes and other white blood cells to the area 2.Chemotactic attraction of phagocytes leave the blood and enter the tissue 3.Increased vascular permeability allowing fibrinogen and complement to enter the tissue from the blood

The inflammation can be localized or systemic Local Inflammation is an inflammatory response confined to a specific area of the body. Symptoms include redness (rubor), heat (calor), swelling (tumor), pain (dolor) and loss of function (function laesa) Redness, heat and swelling result from increased blood flow and increased vascular permeability. Pain is caused by swelling and by chemical mediators acting on pain receptors. Loss of function results from tissue destruction, swelling and pain

Systemic Inflammation is an inflammatory response that is generally distributed throughout the body. With three additional features can be present. Red Bone marrow produces and releases large number of neutrophils which promote phagocytosis Pyrogens is a chemical released by microorganisms, neutrophils and other cells stimulate fever production. It affects the body temperature-regulating mechanism in the hypothalamus. Fever promotes the activities of the immune system such as phagocytosis, and inhibits the growth of some microorganisms. In severe cases, vascular permeability can increase so much that large amount of fluid are lost from the blood into the tissue. The decreased blood volume can cause shock and death.

Acquired Immunity
Acquired (adaptive) immunityimmunologic responses acquired during life but not present at birthusually develops as a result of prior exposure to an antigen through immunization (vaccination) or by contracting a disease, both of which generate a protective

Cell Mediated Immunity T Cell Lymphokines Humoral Mediated Immunity B Cell - Antibodies

Response to Invasion
When the body is invaded or attacked by bacteria, viruses, or other pathogens, it has three means of defending itself: The phagocytic immune response The humoral or antibody immune response The cellular immune response

CONSEQUENCES OF ANTIBODY BINDING

Types of Active Immunity

A. Naturally Acquired Active Immunity: Antigens or pathogens enter body naturally. Body generates an immune response to antigens. Immunity may be lifelong (chickenpox or mumps) or temporary (influenza or intestinal infections). B. Artificially Acquired Active Immunity: Antigens are introduced in vaccines (immunization). Body generates an immune response to antigens. Immunity can be lifelong (oral polio vaccine) or temporary (tetanus toxoid).

Types of Passive Immunity

A. Naturally Acquired Passive Immunity: Antibodies pass from mother to fetus via placenta or breast feeding (colostrum). No immune response to antigens. Immunity is usually short-lived (weeks to months). Protection until childs immune system develops. B. Artificially Acquired Passive Immunity: Preformed antibodies (antiserum) are introduced into body by injection.
Snake antivenom injection from horses or rabbits.

Immunity is short lived (half life three weeks). Host immune system does not respond to antigens.

Serum: Fluid that remains after blood has clotted and cells have been removed. Antiserum: Serum containing antibodies to a specific antigen(s). Obtained from injecting an animal (horse, rabbit, goat) with antigen (snake venom, botulism or diphtheria toxin). Serology: The study of reactions between antibodies and antigens. Gamma Globulins: Fraction of serum that contains most of the antibodies. Serum Sickness: Disease caused by multiple injections of antiserum. Immune response to foreign proteins. May cause fever, kidney problems, and joint pain. Rare today.

I. Humoral (Antibody-Mediated) Immunity

Involves production of antibodies against foreign antigens. Antibodies are produced by a subset of lymphocytes called B cells. B cells that are stimulated will actively secrete antibodies and are called plasma cells. Defense against bacteria, bacterial toxins, and viruses that circulate freely in body fluids, before they enter cells.

Immunoglobulin Classes I. IgG Monomer Enhances phagocytosis, neutralizes toxins and viruses, Can cross placenta: protects fetus and newborn. II. IgM Pentamer First antibodies produced during an infection. Effective against microbes and agglutinating antigens. III. IgA Dimer Secretions such as tears, saliva, intestine, milk Provides immunity to infant digestive tract. IV. IgD Monomer In serum function is unknown. On B cell surface, initiate immune response. V. IgE Monomer Allergic reactions

T Cells and Cell Mediated Immunity T cells are key cellular component of immunity. T cells have an antigen receptor that recognizes and reacts to a specific antigen (T cell receptor). T cell receptor only recognize antigens combined with major histocompatability (MHC) proteins on the surface of cells. MHC Class I: Found on all cells. MHC Class II: Found on phagocytes. Clonal selection increases number of T cells.

Types
1.Helper (CD4+T cells)
T helper cell (TH cells) assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and activation of cytotoxic T cells and macrophages, among other functions. 2. Cytotoxic (CD8+T cells) Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection.

3. Memory
Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers upon re-exposure to their cognate antigen, thus providing the immune system with "memory" against past infections

4. Regulatory (Suppressor T Cells)

Regulatory T cells (Treg cells), are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus.