Learning Objectives 1. Name the four types of hypersensitivity reactions. 2. Cite six examples of allergens. 3. Outline the steps in hypersensitivity reactions. 4. Discuss the principles in autoimmune diseases. 5. Explain the concept of immuno-suppression 6. Discuss the principles of immunodiagnostic procedures. Overview of the Immune System Immune System
Innate Adaptive (Nonspecific) (Specific)
Anatomical Humoral Cellular Humoral Cell-mediated
Barriers Components Components Immunity Immunity Immunopathology Allergy, hypersensitivity – an exaggerated, misdirected expression of immune responses Involves the same types of immune reactions as those at work in protective immunities. Autoimmunity – abnormal responses to self Ag Immunodeficiency – deficiency or loss of immunity Cancer – results from a lack of surveillance Type I Hypersensitivity Atopy – any chronic local allergy such as hay fever or asthma Anaphylaxis – a systemic, often explosive reaction that involves airway obstruction and circulatory collapse Mechanism of Type I sensitizing dose – on first contact with allergen, specific B cells form IgE which attaches to mast cells and basophils provocative dose - subsequent exposure with the same allergen binds to the IgE-mast cell complex degranulation releases mediators with physiological effects such as vasodilation and bronchoconstriction symptoms are rash, itching, redness, increased mucous discharge, pain, swelling, and difficulty breathing Role of Mast Cells & Basophils Mast cells are located in the connective tissue of virtually all organs; high conc. in lungs, skin, GI and genital tract Basophils circulate in blood, migrate into tissues each cell can bind 10,000-40,000 IgE cytoplasmic granules contain physiologically active cytokines, histamine, etc cells degranulate when stimulated by allergen Chemical mediators Systemic Anaphylaxis Sudden respiratory and circulatory disruption that can be fatal in a few minutes Allergen and route are variable Bee stings, antibiotics or serum injection Strategies for circumventing allergic attacks Blocking Ab Type II Hypersensitivity Reactions that lyse foreign cells Involve antibodies, complement, leading to lysis of foreign cells Transfusion reactions ABO blood groups Rh factor – hemolytic disease of the newborn Type III Hypersensitivity A large quantity of soluble foreign Ag stimulates Ab that produce small, soluble Ag- Ab complexes Immune complexes become trapped in tissues & incite a damaging inflammatory response Arthus reaction – local reaction to series of injected Ag to same body site Serum sickness – systemic disease resulting from repeated injections of foreign proteins Autoimmunity In certain type I & II hypersensitivities, the immune system has lost tolerance to self molecules and forms autoantibodies and sensitized T cells against them. More common in females Disruption of function can be systemic or organic specific Systemic lupus erythematosus Rheumatoid arthritis Endocrine autoimmunities Myasthenia gravis Multiple sclerosis Type IV Hypersensitivity Cell-mediated A delayed response to Ag involving activation of and damage by T cells Delayed allergic response – skin response to allergens – tuberculin skin test, contact dermititis from plants, metals, cosmetics Graft rejection – reaction of cytotoxic T cells directed against foreign cells of a grafted tissue; involves recognition of foreign HLA Immune Diseases Autoimmune diseases • Immunologic tolerance and autoimmunity • Specific diseases Primary immune deficiencies • Basic concepts • Specific diseases Immunologic Tolerance “Tolerance” = unresponsiveness to an antigen “Self-tolerance” = unresponsiveness to one’s own antigens In generating billions of B and T cells, some will react against self antigens! There are two ways of muzzling these cells: central tolerance and peripheral tolerance Autoimmunity
“Autoimmunity” = immune reaction against self
Self-tolerance breaks down, causing disease Two main reasons for breakdown: • Genes • HLA-DR4: ↑ risk of rheumatoid arthritis • HLA-B27: ↑ risk of ankylosing spondylitis • Environmental triggers • Expose hidden self-antigens • Activate APCs • Mimic self antigens Lupus Rheumatoid Arthritis Sjögren Syndrome Oral changes in Sjögren Syndrome
atrophic papillae, missing teeth and
angular cheilitis deeply fissured multiple caries epithelium Scleroderma Immunodeficiency diseases Components of the immune response system are absent. Deficiencies involve B and T cells, phagocytes, and complement Primary immunodeficiency – genetically based congenital lack of B-cell and/or T cell activity B cell defect – agammaglobulinemia – patient lacks antibodies T cell defect – thymus is missing or abnormal Severe combined immunodeficiency - both limbs of lymphocyte system are missing or defective; no adaptive immune response Secondary (acquired) immune deficiency – due to damage after birth (infections, drugs, radiation) AIDS Types of serological tests 1. Agglutination tests 2. Double diffusion precipitation tests 3. Immunoelectrophoresis 4. Western blot tests 5. Complement fixation tests 6. Immunofluorescence testing 7. Immunoassays Types of serological tests 1. Agglutination tests – Ab cross-links whole cell Ag, forming complexes that settle out and from visible clumps in the test chamber blood type, some bacterial & viral diseases 2. Double diffusion precipitation tests involve the diffusion of Ags and Abs in a soft agar gel, forming zones of precipitation where they meet 3. Immunoelectrophoresis – migration of serum proteins in gel is combined with precipitation by Ab 4. Western blot test – separates Ag into bands. After the gel is affixed to a blotter, it is reacted with a test specimen and developed by radioactivity or with dyes 5. Complement fixation tests detect lysins- Ab that fix complement and can lyse target cells. Involves mixing test Ag and Ab with complement and then with sensitized sheep RBCs. If complement is fixed by the Ag-Ab, the RBCs remain intact and the test is positive. If RBCs are hemolyzed, specific Ab are lacking and the test is negative. 6. Immunofluorescence testing uses fluorescent Ab either directly or indirectly to visualize cells or cell aggregates that have reacted with the FAbs 7. Immunoassays are highly sensitive tests for Ag and Ab. Radioimmunoassay –Ag or Abs are labeled with radioactive isotopes and traced Enzyme-linked immunosorbent assay (ELISA) can detect unknown Ag or Ab by direct or indirect means. A positive result is visualized when a colored product is released by an enzyme-substrate reaction. Tests can differentiate B cells from T cells and their subtypes. Other IDP Quellung reaction Skin testing