Immunopathology Student Lecture 1 PDF

Immunodeficiency: ◼ Can result from a partial or total loss of function of one or more components of the immune system. ◼ a. Primary deficiencies - involve a basic developmental failure somewhere in the system (e.g., bone marrow or thymus) or in the synthesi...

Immunodeficiency: ◼ Can result from a partial or total loss of function of one or more components of the immune system. ◼ a. Primary deficiencies - involve a basic developmental failure somewhere in the system (e.g., bone marrow or thymus) or in the synthesis of antibodies. ◼ Usually the result of genetic or congenital abnormality which is first noticed in infants and children. ◼ b. Secondary (acquired) deficiencies - refer to loss of the immune response due to specific causes ◼ (e.g., viral infection, malnutrition, splenectomy, liver disease, use of immunosuppressive drugs)  Hypersensitivity ◼ is an altered immunologic reactivity to an antigen that results in a pathologic immune response after re- exposure. (results in tissue injury) ◼ is the inappropriate responses of allergy, autoimmunity, and alloimmunity. ◼ i. Allergy - is the deleterious effects of hypersensitivity to environmental (exogenous) antigens  Hypersensitivity ◼ ii. Autoimmunity – ◼ is a disturbance in the immunologic tolerance of self- antigens. ◼ produce autoimmune disorders. ◼ iii. Alloimmune diseases – ◼ immune system of one individual produces an immunologic reaction against tissue of another individual. ◼ e.g., during transfusions, grafted tissue, fetus during pregnancy Type I Hypersensitivity: (Immediate) ◼ Allergens: ◼ proteins in plants, pollens, dust mites, animal dander, foods, chemicals ◼ Exposure: ◼ Inhalation, ingestion, injection, skin contact ◼ Outcomes: ◼ Discomfort ◼ Severe debilitation ◼ Anaphylaxis (systemic and potentially life threatening)  Type 1 Hypersensitivity ◼ Allergic reaction to allergen ◼ Involves two cell types: ◼ Type 2 Helper T (TH2) & granule-containing cells (e.g., mast, basophils) ◼ Released cytokines cause B cell differentiation into IgE producing plasma cells and cause growth of mast cells and blood basophils ◼ IgE in this situation is considered a cytotropic antibody because of its avid and specific binding  Type 1 Hypersensitivity ◼ Priming Stage: ◼ Exposure to allergen ◼ Sensitization of mast cell or basophil ◼ Allergen specific IgE binds to these cells ◼ Subsequent Exposure: ◼ Allergen to cell-associated IgE (same allergen) and triggers degranulation of preformed mediators ◼ e.g., histamines, prostaglandins, leukotrienes, IL, enzymes which produce kinins Location of the sensitized mast cells determines the signs that will be manifested.  Type I Hypersensitivity ◼ There appears to be a genetic link for hyper- responders. These individuals have lowered numbers and depressed activity of suppresser T cells.  Type I Hypersensitivity ◼ Phase I: ◼ Mast cells degranulate releasing primarily preformed histamine (& enzymes that activate kinin system). ◼ Results in increased vascular permeability, constriction of bronchial muscles and narrowing of airways, increased secretion from nasal, bronchial and gastric glands. ◼ Antihistamines and epinephrine blocks mass cell degranulation.  Type I Hypersensitivity ◼ Phase II: ◼ Occurs in 2-8 hours and may last for 2-3 days. ◼ Other mediators are released (Those responsible for cellular infiltration and tissue damage) ◼ e.g., prostaglandins, platelet-activating factor, protein- digesting enzymes, chemotactic factors, leukotrienes ◼ The use of corticosteroids and NSAID blocks second phase.  Type I Hypersensitivity ◼ Importance: ◼ Plays a protective role in the control of parasitic intestinal infections (especially late phase) ◼ IgE antibodies can directly damage spread of parasites/ recruit inflammatory cells and stimulate antibody-dependent cell-mediated cytotoxicity ◼ Important in developing countries  Clinical Signs: ◼ a. Hay Fever or Allergic Rhinitis ◼ allergic reaction to pollen, grasses, trees, animal dander, etc. ◼ Perennial or Seasonal ◼ frequent sneezing, copious watery secretions from the nose and eyes (rhinoconjunctivitis), possible sinusitis and bronchial asthma ◼ if severe: malaise, fatigue, muscle soreness, headache (fever is usually absent) ◼ Oral antihistamines, intranasal corticosteroids, intranasal cromolyn (stabilizes mast cells) ◼ Allergy shots (producing increasing amounts of IgG to block IgE binding)  Clinical Signs ◼ b. Food allergies – ◼ targets skin, GI and/or respiratory tract mucosa ◼ milk, eggs, peanuts, soybeans, tree nuts, fish, and shellfish ◼ Produces an inflammatory response that results in: ◼ nausea, vomiting, or diarrhea ◼ Urticaria or hives in the skin ◼ Hives in the pharyngeal mucosa which can obstruct airway flow.  Clinical Signs: ◼ c. Asthma - results in bronchospasm of the large and small airways of the lower respiratory tract, edema, thick secretions, and hyperplasia of smooth muscle and mucus-secreting glands. ◼ Leads to ventilatory insufficiency, wheezing, and difficult or labored breathing. ◼ Anaphylaxis or Anaphylactic Shock ◼ - is a severe, life threatening, systemic hypersensitivity reaction. ◼ - Characterized by: ◼ a. General vasodilation ◼ b. Edema of the lung mucosa  Treatment ◼ Epinephrine injection: ◼ Produces relaxation of bronchial smooth muscle ◼ Inhibits the immediate life-threatening cardiovascular effects  Types of Hypersensitivity ◼ 2. Type II Hypersensitivity: Cytotoxic Type ◼ - caused by an antigen-antibody reaction but the antibodies formed are often cytotoxic and are directed against antigens on cell surfaces or connective tissue. ◼ - IgG and IgM are the classes of antibody usually involved in these reactions.  Type II Hypersensitivity ◼ Antibody-mediated mechanisms: ◼ Complement- Antibody-Medicated Cell Destruction ◼ Complement- and Antibody-Mediated Inflammation ◼ Antibody-Medicated Cellular Dysfunction Type II Hypersensitivity: Cytotoxic Type ◼ Circulating IgG or IgM react with the cell surface antigen (e.g., on a RBC) causing destruction of the cell ◼ Activation of the complement system. ◼ (e.g., Autoimmune hemolytic anemia – incompatible blood transfusion) ◼ Destroys the cell either by: ◼ Activating complement products (directly lyse the target cell or ◼ Indirectly through the process of opsonization and phagocytosis..  Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) ◼ Does not require the participation of the complement system. ◼ Leukocytes attack an antibody-coated target cell. ◼ May be involved in the pathogenesis of some autoimmune diseases. ◼ thyroiditis/Grave’s disease ◼ myasthenia gravis - form IgG auto antibodies to Ach receptors at the motor end plate of muscle Mechanism of Type II Hypersensitivity  Types of Hypersensitivity ◼ 3. Type III Hypersensitivity: Immune Complex Diseases ◼ - involves tissue injury mediated by immune complexes ◼ (are simply aggregations of antigen and their corresponding antibodies). ◼ - IgM, IgG, or IgA is formed against a circulating antigen or one derived from tissue ◼ - The antigen-antibody complex formed in the circulation are deposited in tissues ◼ (e.g., renal glomerulus, skin capillary venules, lung, joint synovium, etc.)  Types of Hypersensitivity ◼ 3. Type III Hypersensitivity: Immune Complex Diseases cont. ◼ Once deposited, immune complexes call forth an inflammatory response by activating complement. ◼ Produces chemotactic recruitment of neutrophils or macrophages to the site. (Therefore, an indirect effect) ◼ These cells are then activated and release their tissue- damaging substances (e.g., proteases, oxygen radicals) ◼ Examples: ◼ Autoimmune diseases of connective tissue, such as systemic lupus erythematosus and rheumatoid arthritis ◼ Some types of vasculitis ◼ Most varieties of acute glomerulonephritis Immune-Complex Hypersensitivity ◼ Generally two types of antigens that cause immune-complex mediated injury: ◼ 1. Exogenous antigens such as viral and bacterial (e.g., acute glomerulonephritis can follow a streptococcal infection) ◼ 2. Endogenous antigens such as self-antigens associated with autoimmune disorders (e.g., systemic lupus erythematosus)  Immune-Complex Hypersensitivity ◼ “Serum Sickness” ◼ The syndrome consists of rash, lymphadenopathy, arthralgias (joint pain), and occasionally neurologic disorders. ◼ May be caused by allergic reactions to penicillin, various foods, drugs, and insect venoms. ◼ Caused by the deposition of insoluble antigen-antibody (IgM and IgG)complexes in blood vessels, joints, heart, and kidney tissue. Type IV Hypersensitivity: Cell-Mediated Immunity an antigen-elicited cellular immune reaction that results in tissue damage ◼ does not require the participation of antibodies. ◼ Mediated by sensitized T lymphocytes ◼ Two Basic Types: ◼ Direct cell-mediated cytotoxicity ◼ Delayed-Type Hypersensitivity Disorders  Type IV Hypersensitivity ◼ Direct Cell-Mediated Cytotoxicity ◼ CD8+ cytotoxic T lymphocytes directly kill target cells that expressed peptides on MHC class 1 molecules ◼ e.g., virally infected cells ◼ (seen with certain types of hepatitis)  Type IV Hypersensitivity ◼ Delayed Type Hypersensitivity Disorders ◼ delayed response (24-72 hours after exposure of a sensitized individual) by sensitized T lymphocytes to antigens ◼ resulting in release of lymphokines or other chemical mediators that cause an inflammatory response and destruction of the antigen. (e.g., Contact dermatitis, response to poison ivy).  Type IV Hypersensitivity ◼ Is the principle mechanism of damage in tuberculosis, contact dermatitis, many fungal, viral, and parasitic infections and acute and chronic transplant rejection. ◼ The mediating cells are TC, activated macrophages, K cells, and NK cells all orchestrated by TH cells. ◼ Must have antigen presentation and TH sensitization.