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Immunity is defined as resistance to disease, specifically infectious disease. It has the ability to differentiate between the individual`s own cells and harmful invading organisms. Active immunity is the immunity induced in an individual by infection or vaccination. Passive immunity is the immunity conferred on an individual by transfer of antibodies or lymphocytes from an actively immunized individual. Immune System is the collection of cells, tissues, and molecules that mediate resistance to infections (prevent infections and to eradicate established infections) The coordinated reaction of these cells and molecules to infectious microbes is the Immune Response. Immunology is the study of the physiological functioning of the immune system in states of health, diseases and malfunctions of the immune system in immunological disorders (Autoimmunity & Immunodeficiency). The Primary lymphoid organs of the immune system are the thymus and bone marrow. The secondary lymphatic tissues include spleen, tonsils, lymph vessels, lymph nodes, adenoids, and skin and liver.
TYPES OF IMMUNITY: A. INNATE IMMUNITY The epithelial barriers, specialized cells and natural antibiotics present in epithelia, function to block the entry of microbes. If microbes do breach epithelia and enter the tissues or circulation, they are attacked by phagocytes, natural killer cells, and several plasma proteins, including the proteins of the complement system. All of these agents specifically recognize and react against microbes but do not react against non-infectious foreign substances. Innate immunity recognizes antigens & enhances adaptive immune responses against the infectious agents. B. ADAPTIVE IMMUNITY The adaptive immune system consists of lymphocytes and their products, such as antibodies. Adaptive immune responses are triggered only if microbes or their antigens pass through epithelial barriers and are delivered to lymphoid organs where they can be recognized by lymphocytes. Adaptive immune responses are specialized to combat different types of infections. Types of adaptive immunity: Humoral immunity (provide defense against extracellular microbes) It is mediated by proteins called antibodies, which are produced by cells called B lymphocytes. Antibodies are secreted into the circulation and mucosal fluids, and they neutralize and eliminate microbes and microbial toxins. These antibodies are able to recognize many different types of molecules, including proteins, carbohydrates, and lipids. Cell-mediated immunity (provide defense against intracellular microbes) Antibodies cannot gain access to microbes that live and divide inside infected cells. Defense against such intracellular microbes is called cell-mediated immunity because it is mediated by cells called T lymphocytes. T cells recognize only protein antigens. Properties of adaptive immune responses Feature Functional Significance Specificity Ensures that distinct antigens elicit specific responses Diversity Enables immune system to respond to a large variety of antigens Memory Leads to enhanced responses to repeated exposures to the same antigens Clonal expansion Increases number of antigen-specific lymphocytes to keep pace with microbes Specialization Generates responses that are optimal for defense against different types of microbes Contraction and Allows immune system to respond to newly encountered antigens Homeostasis Nonreactivity to Prevents injury to the host during responses to foreign antigens self
8. Soluble components of blood or tissue fluids include many antimicrobial peptides & proteins
9. Major cells include Phagocytes (monocytes, macrophages, neutrophils), natural killer (NK) cells, dendritic cells
Hypersensitivity reactions:
These diseases result from normal immune responses and not because of excessive or Hyper responses. Both exogenous and endogenous antigens may elicit hypersensitivity reactions. The development of hypersensitivity diseases is often associated with the inheritance of particular susceptibility genes.
Mechanism: It occurs when an already sensitized individual is re-exposed to the same foreign substance. Hypersensitivity reflects an imbalance between the effector mechanisms of immune responses and the control mechanisms that serve to normally limit such responses. These reactions result in tissue injury or other pathophysiological changes. The response may be immediate or delayed depending upon the type of reaction involved. Types & related mechanisms of hypersensitivity diseases: In 1964, Gell and Coombs classified four types of immunologically mediated hypersensitivity states.
Autoimmune diseases:
Autoimmune diseases are a group of disorders in which tissue injury is caused (due to misrecognition of bodys own constituent parts (healthy body tissues) as non self) by humoral (by auto-antibodies) or cell mediated immune response (by auto-reactive T cells) to self antigens. Autoimmunity can be caused by immunological, genetic (HLA gene is the most important autoimmune susceptibility gene), viral, drug-induced, and hormonal factors.
General Features of Autoimmune diseases: Epitope spreading: Autoimmune reactions initiated against self antigen that injure tissues may result in the release and alterations of other tissue antigens, activation of lymphocytes specific for these other antigens, and exacerbation of the disease. Once induced it tends to be progressive, sometimes with sporadic relapses and remissions, and the damage becomes inexorable. The clinical and pathologic manifestations of an autoimmune disease are determined by the nature of the underlying immune response. Some autoimmune diseases may have a genetic component and are triggered by external factors (e.g., infection) or injury. Others are probably strictly caused by external factors (e.g., infection) or injury.
Possible Mechanisms of infections break tolerance: Mechanism Disruption of cell or tissue barrier Infection of antigenpresenting cell Binding of pathogen to self protein Molecular mimicry Effect Release of sequestered self antigen; activation of nontolerized cells Induction of co-stimulatory activity on antigen-presenting cells Pathogen acts as carrier to allow anti-self response Production of cross-reactive antibodies or T cells Polyclonal activation of autoreactive T cells Example Sympathetic opthalmia Effect of adjuvants in induction EAE interstitial nephritis Rheumatic fever Diabetes Multiple sclerosis Rheumatoid arthrirtis
Superantigen
Types of Autoimmune Diseases: 1. Haemolytic Autoimmune Diseases This can be any clinical disorder causing destructions of blood components. Auto Ab are formed against ones own RBCs, Platelets or Leucocytes, e.g. Haemolytic anaemia, Leucopenia, Thrombocytopenia, etc 2. Organ-Specific Autoimmune Diseases A particular organ is affected due to auto Abs. Type of Immune Autoimmune Disease Response Antibody to Myasthenia gravis receptors Graves disease Antibody to cell Pernicious anemia components Goodpastures synd. other than IDDM receptors Addisons disease Male infertility Pemphigus Hashimotos thyroiditis Primary myxedema
Target of Immune Response Acetylcholine receptor TSH receptor Intrinsic factor and parietal cells BM of kidney & lung Islet cell Adrenal cortex Sperm Desmoglein in tight junctions of skin Thyroglobulin Thyroid peroxidase
Hashimotos thyroiditis Hypothyroidism & destruction of thyroid cells. Characterised by Goitre, enlarged thyroid gland. Characterized by Type IV hypersensitive reactions. It is a T-cell associated auto immune disease. Myasthenia Gravis Caused by auto antibody against muscle antigen & acetylcholine receptor antigen. Characterized by muscular weakness Eventually death from respiratory failure. Neuromuscular junction is severely affected 3. Multisystem or Non-Organ Specific Autoimmune Diseases Immune complexes accumulate in many tissues and cause inflammation and damage. Type of Immune Autoimmune Disease Target of Immune Response Response Antibody to cell Rheumatoid arthritis IgG in joints components SLE dsDNA, histones other than Sjogrens syndrome (Sicca RNP antigens (SS-A/Ro and SS-B/La) receptors syndrome) Guillain-Barre synd. Myelin protein Systemic Lupus Erythematosus (SLE) Multisystem disease: Skin, kidneys, serosal surfaces, joints, CNS & heart Unknown etiology, genetic & non-genetic factors (drugs, UV light, estrogen enhance, androgen decrease) Pathogenesis: Due to the production of antinuclear factor (ANF). In these patients, LE cell (a mature neutrophil) appears in blood & bone marrow Function Phagocytosis in the presence of ANF. Rheumatoid Arthritis Disease of the joints. Caused by the auto Antibody of IgM type, called as rheumatoid factors. Activation of T-helper cells cytokines activate B cells Abs Non-suppurative proliferative synovitis (destruction of articular cartilage & progressive disabling arthritis) Marked by inflammatory changes in the synovial membrane. In later stage, deformity develops.
Immunodeficiency Disorders:
These are of two main types of immunodeficiencies; Primary: Almost always genetically determined. Affect the humoral and/or cellular arms of adaptive immunity or the defense mechanisms of innate immunity. Secondary: May arise as complications of cancers, infections, malnutrition, or side-effects of immunosuppressive drugs, irradiation, or chemotherapy for cancer and other diseases.
Simplified scheme of lymphocyte development and sites of block in primary immunodeficiency diseases
Amyloidosis:
Amyloid is a pathologic proteinaceous substance, deposited in between cells in various tissues and organs of the body in a wide variety of clinical settings. It appears as an amorphous, extracellular substance that, with progressive accumulation, encroaches on and produces pressure atrophy of adjacent cells. Affected organs are often enlarged and firm and have a waxy appearance. Chemical Nature: 95% consist of fibril proteins, 5% P component and other glycoproteins. 3 most common amyloid proteins 1. AL (amyloid light chain) derived from plasma cells and contains Ig light chains. 2. AA (amyloid-associated) non-Ig protein synthesized by the liver. 3. A amyloid found in Alzheimer disease.
Organs mostly affected by amyloidosis: Kidney, spleen, liver and heart are the key organs affected with amyloidosis. Other organs may include adrenal, thyroid and pituitary glands, GIT, tongue, respiratory tract and brain.