Pharm immuno17-18 hypersensitivity por

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  • Allergy: Disease with immune response to an Ag Clinical symptoms are independent of physical & chemical characteristics of Ag
  • 5. Type V: Stimulatory Hypersensitivity
  • ITAM = IMMUNORECEPTOR TYROSINE-BASED ACTIVATION MOTIF ITIM = IMMUNORECEPTOR TYROSINE-BASED INHIBITION MOTIF
  • anaphylaxis an c^ -f U -lak c sis An induced systemic or generalized sensitivity; at times the term anaphylaxis is used for anaphylactic shock. The term is commonly used to denote the immediate, transient kind of immunologic (allergic) reaction characterized by contraction of smooth muscle and dilation of capillaries due to release of pharmacologically active substances (histamine, bradykinin, serotonin, and slow-reacting substance), classically initiated by the combination of antigen (allergen) with mast-cell–fixed, cytophilic antibody (chiefly IgE); the reaction can be initiated, also, by relatively large quantities of serum aggregates (antigen-antibody complexes, and others) that seemingly activate complement leading to production of anaphylatoxins. Syn: anaphylactic reaction. Origin [G. ana, away from, back from, + phylaxis, protection Forms of Type I disease: Urticaria , hives Eczema Conjunctivitis Rhinitis, hay fever Asthma Anaphylaxis : Bronchioconstriction & hypotension can be life threatening
  • epinephrine A catecholamine that is the chief neurohormone of the adrenal medulla of most species; also secreted by neurons. The L-isomer is the most potent stimulant (sympathomimetic) of adrenergic  - and  -receptors, resulting in increased heart rate and force of contraction, vasoconstriction or vasodilation, relaxation of bronchiolar and intestinal smooth muscle, glycogenolysis, lipolysis, and other metabolic effects; used in the treatment of bronchial asthma, acute allergic disorders, open-angle glaucoma, cardiac arrest, and heart block, and as a topical and local vasoconstrictor. Generally used salts are epinephrine hydrochloride and epinephrine bitartrate, the latter most frequently used in topical preparations. Syn: adrenaline cromolyn sodium Used for the prevention of asthmatic attack. Stabilizes mast cell membranes to prevent the release of leukotrienes and other bronchospasm-inducing substances. Syn: sodium cromoglycate. Corticosteroid A steroid mad by adrenal cortex
  • urticaria er c ti-kar c i- ^ An eruption of itching wheals, usually of systemic origin; it may be due to a state of hypersensitivity to foods or drugs, foci of infection, physical agents (heat, cold, light, friction), or psychic stimuli. Syn: hives (1), urtication (2). Syn: hives, urtication L. a nettle Urtica dioica , fr. uro, pp. ustus, to burn
  • Bathmotropic state refers to the irritability of the myocardium Chronotropic state refers to the cardiac frequency Dromotropic state refers to the conduction velocity of the myocardial conduction system
  • Leukotrienes are the main mediators of bronchoconstriction of asthma and are not treatable by antihistamines
  • Serotonin ( 5-hydroxytryptamine , or 5-HT ) is a monoamine neurotransmitter synthesised in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract . In the central nervous system, serotonin is believed to play an important role in the regulation of mood , sleep , emesis (vomiting), sexuality and appetite . Serotonin has been thought to play a part in many disorders, notably as part of the biochemistry of depression , migraine , bipolar disorder and anxiety . The name "serotonin" is something of a misnomer and reflects the circumstances of the compound's discovery. It was initially identified as a vasoconstrictor substance in blood serum - hence serotonin , a serum agent affecting vascular tone. This agent was later chemically identified as 5-hydroxytryptamine (5-HT), and, as the broad range of physiological roles were elucidated, 5-HT became the preferred name in the pharmacological field Serotonin was first isolated from blood in 1948 by Page and coworkers and was later identified in the central nervous system. As is the case for most neurotransmitters, it has a relatively simple chemical structure but displays complex pharmacological properties. Based on the similarity of this structure to the structures of norepinephrine and dopamine, it is not surprising that serotonin, like its catecholamine counterparts, possesses a diversity of pharmacological effects, both centrally and peripherally. It is found in three main areas of the body: the intestinal wall (where it causes increased gastrointestinal motility); blood vessels (where large vessels are constricted); and the central nervous system (CNS).
  • Prausnitz-Kustner Reaction This test was used in the past to determine the cutaneous anaphylaxis In this test serum from atopic patient was taken and injected into the skin of a normal person A few hours later the test antigen was injected into the sensitized site Positive test gave an immediate type of wheal-and-flare reaction Not used; danger of transmitting viral infections
  • a·top·ic ( ³ -t ¼ p “¹ k) adj. Of, relating to, or caused by a hereditary predisposition toward the development of certain hypersensitivity reactions, such as hay fever, asthma, or chronic urticaria, upon exposure to specific antigens: atopic dermatitis. [From Greek atopia , unusualness, from atopos , out of the way : a- , not; see A- 1 + topos , place.] --at “ o·py ( ² t “… -p ¶ ) n.
  • Graves disease 1. toxic goiter characterized by diffuse hyperplasia of the thyroid gland, a form of hyperthyroidism; exophthalmos is a common, but not invariable, concomitant; 2. thyroid dysfunction and all or any of its clinical associations; 3. an organ-specific autoimmune disease of the thyroid gland. See: goiter, myxedema, Hashimoto thyroiditis, thyrotoxicosis. Syn: Basedow disease, Parry disease, ophthalmic hyperthyroidism Hashimoto thyroiditis diffuse infiltration of the thyroid gland with lymphocytes, resulting in diffuse goiter, progressive destruction of the parenchyma and hypothyroidism. Syn: Hashimoto disease, Hashimoto struma, struma lymphomatosa, autoimmune thyroiditis, chronic lymphadenoid thyroiditis, chronic lymphocytic thyroiditis, lymphocytic thyroiditi All three mechanisms are seen with antibodies that bind directly to their target antigens
  • IgG and IgE antibodies in subjects allergic to penicillins recognize different parts of the penicillin molecule. Torres MJ , Gonzalez FJ , Mayorga C , Fernandez M , Juarez C , Romano A , Blanca M . Department of Internal Medicine, Carlos Haya Hospital, Malaga, Spain. BACKGROUND: IgE and IgG antibodies to penicillins can have different specificities. However, this response, including the recognition of the different parts of penicillin, has never been studied in the same subject. OBJECTIVE: Study of the specificity of IgE and IgG antibodies and the relevant parts of the penicillin molecule that contribute to the hapten binding site in sera from human. METHODS: Specific IgE antibodies were determined by RAST and specific IgG antibodies by ELISA. The recognition of the different molecules was studied by inhibition studies. RESULTS: Seven sera with IgG and IgE antibodies to amoxicillin and benzyl penicillin were analyzed. IgE antibodies recognized mainly two different epitopes: in one, the side chain was a relevant part of the epitope, in the other, it was the nuclear portion. IgG antibodies recognized the nuclear portion in all instances. In the same subject, antibodies of different isotype and specificity were found. CONCLUSIONS: Subjects who develop simultaneously IgE and IgG antibodies to penicillins show different specificities. This proves that different populations of antibodies recognize different epitopes.
  • pemphigus (p µ m “ f ¹ -g … s, p µ m-f º“ g … s) n. Any of several acute or chronic skin diseases characterized by groups of itching blisters. [New Latin, from Greek pemphix , pemphig-, pustule.] --pem “ phi·gous adj.
  • hyperthyroidism hU-per-thUcroyd-izm An abnormality of the thyroid gland in which secretion of thyroid hormone is usually increased and is no longer under regulatory control of hypothalamic-pituitary centers; characterized by a hypermetabolic state, usually with weight loss, tremulousness, elevated plasma levels of thyroxin and/or triiodothyronine, and sometimes exophthalmos; may progress to severe weakness, wasting, hyperpyrexia, and other manifestations of thyroid storm; often associated with exophthalmos (Graves disease). See Also: thyrotoxicosis. Syn: hyperthyrea, thyroidism (1), thyrointoxication. hereditary hyperthyroidism iodine-induced hyperthyroidism masked hyperthyroidism ophthalmic hyperthyroidism primary hyperthyroidism secondary hyperthyroidism
  • Fig 11-10: Human immune complex diseases
  • Although it takes several days for the symptoms to develop, serum sickness is classified as immediate reaction due to the fact symptoms develop promptly after immune-complexes are formed. The symptoms gradually subside as the antigen is excreted from the body. Serum sickness is rare because foreign serum is rarely used. Now a day’s serum sickness is due to drugs
  • The reaction consists of mononuclear cell infiltration, e.g., macrophages and CD4 cells and induration. Examples of delayed type hypersensitivity include contact hypersensitivity and tuberculin type hypersensitivity
  • Infected person does not always give a positive skin test. Overwhelming infections, use of immunosuppressive drugs and disorders suppress cell-mediated immunity ( anergy ). Cell-mediated immunity also develops in many viral infections. However, serologic tests are more specific than skin tests for the assessment of immunity Infected person does not always give a positive skin test. Overwhelming infections, use of immunosuppressive drugs and disorders suppress cell-mediated immunity ( anergy ). Cell-mediated hypersensitivity also develops in many viral infections . However, serologic tests are more specific than skin tests for the assessment of immunity
  • urushiol oocroo-shT-bl A mixture of nonvolatile hydrocarbons, derivatives of catechol with unsaturated C15 or C17 side chains, constituting the active allergen of the irritant oil of poison ivy, Toxicodendron radicans , poison oak, T. diversilobum , and the Asiatic laquer tree, T. verniciferum . Origin [Jap. urushi, lac, + L. oleum, oil] urushiol oxidase
  • Pharm immuno17-18 hypersensitivity por

    1. 1. Pharmacy-Immunology 17 – 18 Hypersensitivity Saber Hussein
    2. 2. Objectives <ul><li>1. Define: </li></ul><ul><ul><li>i. Allergy </li></ul></ul><ul><ul><li>ii. Anaphylaxis </li></ul></ul><ul><ul><li>iii. Atopy </li></ul></ul><ul><ul><li>iv. Sensitization </li></ul></ul><ul><ul><li>v. Desensitization </li></ul></ul><ul><ul><li>Shocking dose </li></ul></ul><ul><li>2.Know the four types of hypersensitivity, their immunological bases; give examples of each: </li></ul><ul><ul><li>i. Type I: immediate (anaphylactic) hypersensitivity </li></ul></ul><ul><ul><li>ii. Type II: antibody-dependent cytotoxic hypersensitivity </li></ul></ul><ul><ul><li>iii. Type III: immune complex-mediated hypersensitivity </li></ul></ul><ul><ul><li>ii. Type IV: cell-mediated (delayed type) hypersensitivity. </li></ul></ul>
    3. 3. Objectives <ul><li>3. Understand that in immediate hypersensitivity reactions , the immune system itself provokes tissue damage by responding to false alarm. </li></ul><ul><li>  4.Differentiate between primary and secondary exposure to antigen in immunity and in hypersensitivity </li></ul><ul><li>  5.Explain the structure-function relationship of IgE ; discuss the cytotropism of IgE </li></ul><ul><li>6. Describe the role of mast cells in immediate hypersensitivity reactions ; explain degranulation; distinguish between and give examples for preformed and newly formed mediators released by mast cells </li></ul>
    4. 4. Allergen <ul><li>Antigen that causes allergy: The term is used to refer to the antigen molecule itself or its source, such as pollen grain, animal dander, and insect venom or food products. </li></ul><ul><li>Many naturally occurring and synthetic chemicals have been considered allergens </li></ul><ul><li>Any foreign substance, which can elicit an immune response, is a potential allergen </li></ul>
    5. 5. Hypersensitivity (Allergy) <ul><li>Harmful, inappropriate or exaggerated immune response </li></ul><ul><li>The first contact of the Ag with the host is necessary for sensitization </li></ul><ul><ul><li>During this phase the Ag induces the Ab formation </li></ul></ul><ul><li>The second contact of the same Ag will result in allergic response </li></ul><ul><ul><li>Such an individual is hypersensitive to that specific Ag </li></ul></ul><ul><ul><li>The clinical manifestation of the typical symptoms depends on the individual </li></ul></ul>
    6. 6. Sensitization & Acute desensitization <ul><li>Sensitization </li></ul><ul><ul><li>Immunization, especially with reference to Ags not associated with infection </li></ul></ul><ul><ul><li>The induction of acquired sensitivity or of allergy </li></ul></ul><ul><li>Acute desensitization </li></ul><ul><ul><li>This involves the administration of very small amounts of Ag at 15 minutes intervals </li></ul></ul><ul><ul><li>Few Ag-IgE complexes are formed, so mediator release is so low that it cannot give major allergic reaction </li></ul></ul><ul><ul><li>Used for administering drugs in sensitive patients </li></ul></ul><ul><ul><li>This is a temporary situation </li></ul></ul><ul><ul><li>Hypersensitivity is restored after a few days </li></ul></ul>
    7. 7. Chronic desensitization <ul><li>Involves long-term weekly administration of the Ag to the sensitive patient </li></ul><ul><li>This leads to the production of IgG-blocking Abs in the serum , which can prevent subsequent Ag from reaching IgE on mast cells </li></ul><ul><li>Hence under these conditions, no immediate hypersensitive reaction would occur </li></ul>
    8. 8. Types of hypersensitivity <ul><li>Type I, II, III reactions are antibody-mediated </li></ul><ul><li>Type IV reactions are cell mediated </li></ul><ul><ul><li>Type I: Immediate/ Anaphylactic Hypersensitivity </li></ul></ul><ul><ul><ul><li>IgE is involved </li></ul></ul></ul><ul><ul><li>Type II:Cytotoxic Hypersensitivity: IgG or IgM </li></ul></ul><ul><ul><li>T ype III:Immune-Complex Hypersensitivity </li></ul></ul><ul><ul><li>Type IV:Cell-mediated Hypersensitivity (Delayed) </li></ul></ul>
    9. 9. Fig 11-1: Immune effector mechanisms of the four types of hypersensitivity
    10. 10. Fig 11-1
    11. 11. Type I hypersensitivity <ul><li>Ag binds IgE on surface of mast cells & basophil </li></ul><ul><li>Degranulation & Release of mediators </li></ul><ul><li>cAMP, cGMP and Ca ++ </li></ul><ul><li>High [ cGMP ]  increase degranulation </li></ul><ul><li>High [ cAMP ]  decrease mediators release </li></ul><ul><li>Epinephrine increases intracellular cAMP </li></ul>Allergen
    12. 12. Fig 11-2: The sequence of events in immediate hypersensitivity
    13. 13. Fig 11-2: The sequence of events in immediate hypersensitivity Fig 11-2: The sequence of events in immediate hypersensitivity
    14. 14. Activation of mast cells <ul><li>A . Mast cells are sensitized by the binding of IgE to Fc  RI receptors </li></ul><ul><li>B. Binding of the allergen to the IgE cross-links the Fc  receptors and activates the mast cells </li></ul>Fig 11-3
    15. 15. The activation of mast cells <ul><li>C & D: Mast cell activation leads to degranulation , as seen in the light micrographs in which the granules are stained with a red dye </li></ul><ul><li>E, F: Degranulation in the electron micrographs of a resting and an activated mast cell </li></ul>Fig 11-3
    16. 16. Biochemical events in mast cell activation <ul><li>Cross-linking of IgE on a mast cell by an allergen initiates multiple signaling pathways from the signaling chains of the IgE Fc receptor ( Fc  RI ), including the phosphorylation of ITAMs . </li></ul><ul><li>These signaling pathways stimulate the: </li></ul><ul><ul><li>release of mast cell granule contents (amines, proteases) </li></ul></ul><ul><ul><li>synthesis of arachidonic acid metabolites (prostaglandins, leukotrienes), </li></ul></ul><ul><ul><li>synthesis of various cytokines </li></ul></ul><ul><li>These mast cell mediators stimulate the various reactions of immediate hypersensitivity </li></ul>ITAM Fig 11-4 Immunoreceptor tyrosine-based activation motif
    17. 17. Mediators of Type I hypersensitivity <ul><li>Preformed mediators </li></ul><ul><ul><li>Histamine </li></ul></ul><ul><ul><li>Heparin </li></ul></ul><ul><ul><li>Eosinophil chemotactic factor of anaphylaxis (ECF-A) </li></ul></ul><ul><ul><li>Neutrophil chemotactic factor </li></ul></ul><ul><ul><li>Serotonin </li></ul></ul><ul><li>Newly synthesized mediators </li></ul><ul><ul><li>Prostaglandins </li></ul></ul><ul><ul><li>Thromboxanes </li></ul></ul><ul><ul><li>Leukotrienes </li></ul></ul><ul><ul><ul><li>Slow reacting substance of anaphylaxis (SRS-A) </li></ul></ul></ul>Allergen
    18. 18. Clinical manifestations of immediate hypersensitivity Fig 11-5
    19. 19. Treatment of immediate hypersensitivity reactions Various drugs & their principal mechanisms of action cAMP ↑ Fig 11-6
    20. 20. Urticaria & Eczema <ul><li>An eruption of itching wheals </li></ul><ul><li>of systemic origin </li></ul><ul><li>It may be due to allergic reaction to: </li></ul><ul><ul><li>foods </li></ul></ul><ul><ul><li>drugs </li></ul></ul><ul><ul><li>foci of infection </li></ul></ul><ul><ul><li>physical agents (heat, cold, light, friction) </li></ul></ul><ul><ul><li>psychic stimuli </li></ul></ul>
    21. 21. Histamine <ul><li>Present in the preformed state in granules of tissue mast cells and basophil </li></ul><ul><li>It causes: </li></ul><ul><ul><li>Vasodilatation </li></ul></ul><ul><ul><li>Increased capillary permeability, and </li></ul></ul><ul><ul><li>Smooth muscle contraction </li></ul></ul>
    22. 22. Slow reacting substance of anaphylaxis (SRS-A) <ul><li>It is composed of several leukotrienes , which do not exist in the preformed state and are released during anaphylactic reactions </li></ul><ul><li>This explains in part the slow action of SRS-A </li></ul><ul><li>Leukotrienes are synthesized from arachidonic acid by the lipoxygenic pathway </li></ul><ul><li>Leukotrienes also cause increase vascular permeability and smooth muscle contraction </li></ul><ul><li>Leukotrienes are the main mediators of bronchoconstriction of asthma </li></ul>
    23. 23. Eosinophil chemotactic factor of anaphylaxis (ECF-A) <ul><li>A tetrapeptide exists in preformed state in mast cell granules </li></ul><ul><li>When released, it attracts eosinophils that are prominent in immediate allergic reactions </li></ul><ul><li>The role of eosinophil in Type I hypersensitivity is unknown </li></ul><ul><li>Eosinophils do release </li></ul><ul><ul><li>Histaminase , which degrades histamine </li></ul></ul><ul><ul><li>Arylsulphatase , which degrades SRS-A </li></ul></ul><ul><li>Eosinophil may be involved in reducing the severity of the type I response </li></ul>
    24. 24. Serotonin (5-hydroxytryptamine, 5HT) <ul><li>O ccurs preformed in mast cells and blood platelet </li></ul><ul><li>When released during anaphylaxis, it causes: </li></ul><ul><ul><li>Vasoconstriction of large blood vessels </li></ul></ul><ul><ul><li>Capillary dilatation </li></ul></ul><ul><ul><li>Increased vascular permeability </li></ul></ul><ul><ul><li>smooth muscle contraction </li></ul></ul><ul><li>Its role is minor in human anaphylaxis </li></ul><ul><li>Major effects on the CNS </li></ul>5-HT
    25. 25. Prostaglandin & Thromboxane <ul><li>Related to leukotrienes </li></ul><ul><li>Derived from arachidonic acid via cyclooxygenase pathway </li></ul><ul><li>The effects of prostaglandin are: </li></ul><ul><ul><li>Dilation </li></ul></ul><ul><ul><li>Increased permeability </li></ul></ul><ul><ul><li>Bronchoconstriction </li></ul></ul><ul><li>Thromboxanes aggregate platelets </li></ul>
    26. 26. Anaphylactoid Reaction <ul><li>Clinically, they are similar to anaphylactic reactions </li></ul><ul><li>The mechanism is different </li></ul><ul><li>They are not IgE mediated </li></ul><ul><li>The drugs or iodinated chemicals directly induce the mast cells to release the mediators </li></ul>
    27. 27. Drug Hypersensitivity <ul><li>Antimicrobial agents are among the most common agents of this type of reactions </li></ul><ul><li>Usually the metabolic product of the drug acts as a hapten and binds to body protein and act as a sensitizing antigen </li></ul><ul><li>On Re-exposure to the drug, the resulting antibody reacts either with the intact drug or hapten to cause type I hypersensitivity </li></ul><ul><li>Clinical symptoms include rashes, fever, local or systemic anaphylaxis with varying severity </li></ul><ul><li>The skin test can be used to test the drug sensitivity </li></ul>
    28. 28. Atopy <ul><li>This includes type I reactions that exhibit familial predisposition </li></ul><ul><li>Associated with high levels of IgE </li></ul><ul><li>Genetically based disorders </li></ul><ul><li>Induced by exposure to specific allergens; e.g., pollens, dust; or in the foods such as shellfish and nuts </li></ul><ul><li>Common symptoms: Urticaria, eczema, asthma and hay fever </li></ul><ul><li>The skin tests for the individuals with atopy are immediately positive when specific antigens are used </li></ul><ul><li>Atopic allergy is transferable by serum only </li></ul><ul><li>It is antibody-mediated </li></ul><ul><li>Probable cause: </li></ul><ul><ul><li>Reduced numbers of suppressor T cells </li></ul></ul><ul><ul><li>Predisposition to an abnormally high IgE response have been proposed as cause </li></ul></ul>Atopia = unusualness = out of place: propensity to IgE production
    29. 29. IgE, IgG, mast cell & eosinophilia in parasite purging <ul><li>Mast cell in the mucosa are coated with IgE specific for worm Ags </li></ul><ul><li>IgE bind worm Ags  Trigger degranulation </li></ul><ul><li>ECF-A & NCF & histamine  Eosinophilia, blood vessel permeability ↑  IgG & eosinophils leak to the lumen where the worm is located  Abs opsonize the worm  Eosinophils bind the Fc γ  degranulate  kill and purge the worm </li></ul>
    30. 30. Type II: Ab-Mediated <ul><li>Ab, other than IgE , directed towards the cell surface Ags, especially on RBCs . </li></ul><ul><li>In this case, the IgG or IgM antibody attaches to the antigen via Fab region, and acts as a bridge to complement via the Fc region. </li></ul><ul><li>This results in complement-mediated lysis </li></ul><ul><li>Killer cells can be involved with ADCC </li></ul><ul><li>Examples: </li></ul><ul><ul><li>hemolytic anemia </li></ul></ul><ul><ul><li>ABO transfusion reactions </li></ul></ul><ul><ul><li>Rh hemolytic disease </li></ul></ul>Start here 3/6/08
    31. 31. Types of antibody-mediated diseases A: Type II hypersensitivity <ul><li>Antibodies (other than IgE) may cause tissue injury and disease by binding directly to their target antigens in cells and extracellular matrix </li></ul>Fig 11-7A
    32. 32. Type III hypersensitivity <ul><li>Abs (other than IgE) may cause tissue injury & disease by forming immune complexes that deposit in blood vessels </li></ul>Fig 11-7B
    33. 33. Effector mechanisms of Ab-mediated diseases <ul><li>Abs may cause disease by inducing inflammation at the site of deposition </li></ul><ul><li>All three mechanisms are seen with antibodies that bind directly to their target antigens, but immune complexes cause disease mainly by inducing inflammation </li></ul>Fig 11-8
    34. 34. Effector mechanisms of Ab-mediated diseases <ul><li>Abs may cause disease by opsonizing cells for phagocytosis </li></ul><ul><li>Opsonins involved: </li></ul><ul><ul><li>IgG antibody </li></ul></ul><ul><ul><li>C3b complement fragment </li></ul></ul>Fig 11-8
    35. 35. Effector mechanisms of Ab-mediated diseases <ul><li>Abs may cause disease by interfering with normal cellular functions , such as hormone receptor signaling </li></ul><ul><li>Examples: </li></ul><ul><ul><li>Graves disease </li></ul></ul><ul><ul><li>Myasthenia gravis </li></ul></ul><ul><li>TSH = thyroid-stimulating hormone </li></ul><ul><li>Ach = acetylcholine </li></ul>Fig 11-8C: Myasthenia gravis Graves disease
    36. 36. Type II: Drugs adverse reactions <ul><li>Penicillins (haptens): </li></ul><ul><ul><li>Can attach to surface proteins on RBCs, </li></ul></ul><ul><ul><li>Become immunogenic & elicit Ab synthesis including </li></ul></ul><ul><ul><ul><li>IgE (type I) </li></ul></ul></ul><ul><ul><ul><li>Autoimmune IgG Abs interact with the cell surface and hemolysis occurs </li></ul></ul></ul><ul><ul><ul><li>IgG and IgE antibodies in subjects allergic to penicillins recognize different parts of the penicillin molecule </li></ul></ul></ul><ul><li>Quinine : </li></ul><ul><ul><li>Can attach to platelets </li></ul></ul><ul><ul><li>Induce autoantibodies formation </li></ul></ul><ul><ul><li>Lead to thrombocytopenia with bleeding tendency </li></ul></ul><ul><li>Hydralazine : </li></ul><ul><ul><li>May modify host tissues </li></ul></ul><ul><ul><li>Favoring the production of autoantibodies directed at DNA, </li></ul></ul><ul><ul><li>Resulting disease resembles SLE </li></ul></ul>
    37. 37. Type II: Autoimmune diseases <ul><li>In rheumatic fever , antibodies against Group A streptococci cross-react with cardiac tissue </li></ul><ul><li>In Mycoplasma pneumoniae infection, antibodies are formed that cross-react with RBCs, which results in hemolytic anemia </li></ul><ul><li>In Goodpasture syndrome , Abs to basement membrane of the kidneys and lungs are formed, which lead to severe damage to the membrane via complement-attracted leukocytes </li></ul>
    38. 38. Human antibody-mediated diseases Itching blisters Fig 11-9
    39. 39. Human antibody-mediated diseases Fig 11-9
    40. 40. Type III: Immune-complex Hypersensitivity <ul><li>Ag-Ab complexes induce an inflammatory response in tissues. </li></ul><ul><li>Normally, the Ag-Ab complexes are removed. </li></ul><ul><li>Occasionally, they persist and are deposited in the tissues . </li></ul><ul><li>In persistent bacterial and viral infections , immune complexes may be deposited in the organs such as kidneys and result in damage </li></ul>
    41. 41. Type III hypersensitivity <ul><li>Abs (other than IgE) may cause tissue injury & disease by forming immune complexes that deposit in blood vessels </li></ul>Fig 11-7B
    42. 42. Type III: Immune-complex hypersensitivity & immune complex Disease <ul><li>In autoimmune diseases, &quot;self&quot; Ags may produce antibodies that bind to an organ antigen or deposit in organs as complexes </li></ul><ul><li>This can occur in: </li></ul><ul><ul><li>Joints  arthritis </li></ul></ul><ul><ul><li>Kidneys  nephritis </li></ul></ul><ul><ul><li>Blood vessels  vasculitis </li></ul></ul><ul><li>Deposited immune complexes activate the complement system </li></ul><ul><li>Attracted PMNs cause inflammation and tissue injury </li></ul>Fig 11-10
    43. 43. Type III: Arthus Reaction & Serum Sickness <ul><li>Arthus Reaction </li></ul><ul><li>Local inflammatory reaction with necrosis </li></ul><ul><li>Few hours after intradermal Ag inoculation </li></ul><ul><li>The inoculated animal was previously </li></ul><ul><li>immunized to the same Ag </li></ul><ul><li>Immunized animal has high titers of precipitating IgG Abs </li></ul><ul><li>Serum Sickness </li></ul><ul><li>After injection of a foreign serum or certain drugs, Ag is excreted slowly leading to Ab production </li></ul><ul><li>Ag + Ab  Ag-Ab complex </li></ul><ul><li>These complexes may circulate or be deposited at various sites. </li></ul><ul><li>Symptoms: fever , urticaria & lymphadenopathy </li></ul><ul><li>Symptoms develop after few days to 2 weeks </li></ul><ul><li>Serum sickness is classified as immediate reaction due to the fact that symptoms develop promptly after immune-complexes are formed </li></ul>Arthus Reaction
    44. 44. Type IV: Delayed; Cell-mediated <ul><li>It is called delayed because it starts hours or days after contact with the Ag and lasts for days </li></ul><ul><li>DH can be elicited by many innocuous substances and can result in damage in the responding individual </li></ul><ul><li>DTH is the prime defense against intracellular bacteria and fungi </li></ul><ul><li>It is a function of helper (CD4) T lymphocytes </li></ul><ul><li>It can be transferred by sensitized T cells </li></ul><ul><li>Rxn: Macrophages and CD4 cells and induration </li></ul>
    45. 45. Mechanisms of T cell-mediated tissue injury <ul><li>T cells may cause tissue injury and disease by two mechanisms: </li></ul><ul><li>A: Delayed hypersensitivity reactions, which may be triggered by CD4 + and CD8 + T cells and in which tissue injury is caused by activated macrophages and inflammatory cells </li></ul><ul><li>B: Direct killing of target cells, which is mediated by CD8 + CTLs </li></ul>Fig 11-11
    46. 46. Mechanisms of T cell-mediated tissue injury <ul><li>T cells may cause tissue injury and disease by two mechanisms: </li></ul><ul><ul><li>A: Delayed hypersensitivity reactions, which may be triggered by CD4 + and CD8 + T cells and in which tissue injury is caused by activated macrophages and inflammatory cells </li></ul></ul><ul><ul><li>B: Direct killing of target cells, which is mediated by CD8 + CTLs </li></ul></ul>Fig 11-11
    47. 47. T-cell mediated diseases Fig 11-12
    48. 48. Type IV: Tuberculin test <ul><li>A patient previously exposed to Mycobacterium tuberculosis is injected intradermally with a small amount of tuberculin (PPD) </li></ul><ul><li>Gradually, induration and redness develop and peak in 48 to 72 hours. </li></ul><ul><li>Positive test indicates previous infection/exposure </li></ul><ul><li>It does not confirm the presence of current disease </li></ul><ul><li>If a person with previously negative test gives a positive test, it indicates that the person has been recently infected </li></ul><ul><li>PPD injected intradermal  Induration & redness after 48-72 hours </li></ul><ul><li> Positive test </li></ul>PPD Test
    49. 49. Type IV: Contact allergy <ul><li>It occurs after sensitization with certain chemicals (formaldehyde), plant material (poison ivy), topically applied drugs (neomycin), cosmetics, soaps etc. </li></ul><ul><ul><li>Poison ivy’s allergen is Urushiol </li></ul></ul><ul><li>In all cases the molecules act as hapten , enter the skin, attach to body proteins and become complete antigens (allergens) </li></ul><ul><li>Cell-mediated reaction develops in the skin </li></ul><ul><li>Sensitized person develops erythema, itching, eczema and necrosis of the skin within 12-48 h </li></ul>Contact dermatitis (poison ivy)

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