2. 1. Definition: It is excessive immune response which leads to undesirable consequences, i.e. tissue or organ damage/ dysfunction. immune responses which are damaging rather than helpful to the host. Excessive immune response in a sensitized individual (atopic) leading to tissue damage.
3. Why hypersensitivity occurs in somepeople? (not all) Allergins Low immunity from childhood Host factors include heredity, gender, race, and age, with heredity being by far the most significant. However, there have been recent increases in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes.
4. Types of Hypersensitivity:Nearly 45 years ago Gell andCoombs proposed a classificationscheme which defined 4 types of Hypersensitivity type Ihypersensitivity reactions.Ab mediated: type:Ⅰ, Ⅱ, Ⅲ Hypersensitivity type II(Immediate)T-cell mediated: type Ⅳ (Delayed) Hypersensitivity type III Hypersensitivity type IV
5. Hyper sensitivity type I:IgE mediated, immediatehypersensitivity/ allergyMajor features:React and disappear quicklyon re-exposure to AgDysfunction rather thansevere tissue and cell damageoccursObvious individualdifference and geneticcorrelationBy mast cells and basophils
6. MECHANISM OF ACTIONBASIC ELEMENTS ARE: 1. MEDIATOR = IgE2. PRIMARY CELLULAR COMPONENT = MAST CELL AND BASOPHILS 3. AMPLIFIER = PLATELETS, NEUTROPHILS AND EIOSINOPHILS
7. MECHANISM OF ACTION
8. MECHANISM OF ACTIONSTEP 1: EXPOSURE OF ANTIGEN TO ANTIGEN PRESENTING CELL
9. MECHANISM OF ACTIONSTEP 2: RECOGNITION BY T- HELPER CELLSACTIVATION OF B-CELLS INTO PLASMA AND MEMORY CELLS SECRETION OF ANTIBODIES (IgE)
10. MECHANISM OF ACTIONSTEP 3: IgE BINDS TO HIGH AFFINITY RECEPTORS (FC EPSILONRI) ON THE SURFACE OF MAST CELLS
11. MECHANISM OF ACTIONSTEP 4: SUBSEQUENT EXPOSURE OF ANTIGENANTIGEN BINDS WITH IgE ON THE SURFACE OF MAST CELLS
12. Mechanism of action
13. MECHANISM OF ACTIONSTEP 5: RELEASE OF PRIMARY INFLAMMATORY METABOLTESACTIVATION OF SECONDARY METABOLITES
14. SYMPTOMS 1. May vary from minor inconvenience to death2. Usually take 10 to 30 mins to appear after exposure to antigen3. Sometimes delayed onset of reaction (10- 12h)
16. CLINICAL"a serious allergic reaction that is rapidAnaphylaxis is defined as DISEASESin onset and may cause death". It typically results in a number ofsymptoms including an itchy rash, throat swelling, and low bloodpressure. Common causes include insect bites, foods, andmedications. AnaphylaxisAsthma (from the Greek, "panting") is thecommon chronic inflammatory disease ofthe airways characterized by variable and recurringsymptoms, reversible airflow obstruction, etcAllergic rhinitis is an allergic inflammation of the nasal airways. It Asthmaoccurs when an allergen, such as pollen, dust or animal dander(particles of shed skin and hair) is inhaled by an individual with asensitized immune system.The protein in the food is the most common allergic component.These kinds of allergies occur when the bodys immune systemmistakenly identifies a protein as harmful. Some proteins or Allergic Rhinitisfragments of proteins are resistant to digestion and those thatare tagged by the IgE. The immune system, thinking theorganism (the individual) is under attack, triggers an allergicreaction. These reactions can range from mild to severe. Allergicresponses include dermatitis, gastrointestinal and respiratorydistress, including such life-threatening anaphylacticresponses and vasodilation; these require immediate emergencyintervention. Individuals with protein allergies commonly avoidcontact with the problematic protein. Some medications mayprevent, minimize or treat protein allergy reactions. injectableform of epinephrine such as an EpiPen
18. TREATMENT1. ANTIHISTAMINES2. Chromolyn sodium3. leukotriene receptor blockers4. use of IgG antibodies
19. Hyper sensitivity type II:Definition:A hypersensitivity resulting fromantibodies mistakenly reacting withnormal self antigens on body cells.Binding of the antibodies to thesenormal cells results in immunedestruction.
20. MEDIATORS IgG OR IgMIN THIS CASE1. MADE AGAINST SELF ANTIGENS2. ATTACH TO THE SURFACES OF CELLS HAVING SELF EPITOPSSELF ANTIGEN=Any constituent of the bodys own tissues capable of stimulating autoimmunity
21. FACTORS FOR RELEASE OF MEDIATORS1. FAILURE IN IMMUNE TOLERANCE2. ENTERANCE OF FOREIGN ANTIGEN RESEMBLING SOME MOLECULE ON THE SURFACE OF HOST CELLS IMMUNE TOLERANCE is the process by which the immune system does not attack an antigen
22. MECHANISM OF ACTIONTHESE FACTORS LEAD TO:1. OPSONIZATION2. MAC LYSIS3. ADCC
23. 1- OPSONIZATIONDEFINITION:The attachment of microbes and other foreign cells to phagocytes by antibody molecules such as IgG and complement proteins such as C3b. Also called enhanced attachment or immune adherence.
24. OPSONIZATIONMECHANISM THE OPSONIZATION IS OF THE HOST CELLPHAGOCYTES STICK TO MEMBRANES OF HOST CELL VIA IgG, C3B, C4B PHAGOCYTES DISCHARGE THEIR LYSOSOMES
25. OPSONIZATIONRESULT: LYSIS OF HOST CELL
26. 2- MAC LYSISDEFINITION A protein complex produced during the complement pathways. C5b6789 (MAC or membrane attack complex) puts pores into lipid bilayer membranes of human cells to which antibodies have bound. This results in cell lysis.
27. MAC LYSISMECHANISM IgG / IgM BINDS WITH EPITOPS ON CELL SURFACES ACTIVATE CLASSICAL PATHWAY OF COMPLEMENT SYSTEM MAC CAUSES LYSIS OF CELL
28. MAC LYSISMECHANISM
29. 3-ANTI-BODY DEPENDENT CYTOTOXICITY (ADCC)DEFINITION The process of NK cells binding to the Fc portion of antibodies that have bound to epitopes of cells recognized as nonself such as infected cells and tumor cells. Once bound to the Fc portion of the antibody, the NK cell will then lyse that cell with perforins.
30. ADCCMECHANISM IgG / IgM BINDS WITH EPITOPS ON CELL SURFACESNK CELLS ATTACH TO THE Fc PORTION OF IgG/IgM RELEASE OF PERFORINS AND GRANZYMES BY NK APOPTOSIS
33. EXAMPLES OF TYPE 2 HYPERSENSITIVITY AB AND RH BLOOD GROUP REACTIONS; AUTOIMMUNE DISEASES SUCH AS: RHEUMATIC FEVER where antibodies result in joint and heart valve damage; IDIOPATHIC THROMBOCYTOPENIA PURPURA where antibodies result in the destruction of platelets; MYASTHENIA GRAVIS where antibodies bind to the acetylcholine receptors on muscle cells causing faulty enervation of muscles; GOODPASTURES SYNDROME where antibodies lead to destruction of cells in the kidney;
34. EXAMPLES OF TYPE 2 HYPERSENSITIVITY SOME DRUG REACTIONS. TYPE II HYPERSENSITIVITY ALSO PARTICIPATES IN EARLY TRANSPLANT REJECTIONS.
35. DIAGNOSTIC TESTS1. DETECTION OF CIRCULATING ANTIBODY AGAINST THE TISSUES INVOLVED2. THE PRESENCE OF ANTIBODY AND COMPLEMENT IN THE LESION (BIOPSY) BY IMMUNOFLUORESCENT STAINING (PATTERN = LINEAR).
37. Hyper sensitivity type III:(THE IMMUNE COMPLEX HYPERSENSITIVITY)Definition:A hypersensitivity resulting fromlarge quantities of soluble antigen-antibody complexes passingbetween endothelial cells of theblood vessels and becoming trappedon the surrounding basementmembrane.
38. COMPOSITION OF IMMUNE COMPLEX 1. SELF OR NON-SELF ANTIGEN 2. ANTIBODIES MOSTLY IgG RARELY IgM PATHOLGY OCCURS AT THE SITE OF DEPOSITION
39. CAUSE OF TYPE 3 HYPERSENSITIVITYNORMALLY SOLUBLE ANTIGEN-ANTIBODY COMPLEX FORMATION REMOVED BY MACROPHAGES IN SPLEEN AND LIVER
40. CAUSE OF TYPE 3 HYPERSENSITIVITYABNORMALLY INCREASED SOLUBLE ANTIGEN-ANTIBODY COMPLEX FORMATION NOT ALL REMOVED BY MACROPHAGES IN SPLEEN AND LIVER DEPOSITION OF COMPLEXES VIA BLOOD VESSELS
41. MECHANISM OF ACTIONSTEP 1 Large quantities of soluble antigen-antibody complexes form in the blood and are not completely removed by macrophages.
42. MECHANISM OF ACTIONSTEP 2 These antigen-antibody complexes lodge in the blood vessels between the endothelial cells and the basement membrane.
43. MECHANISM OF ACTIONSTEP 3These antigen-antibody complexes activate the classical complement pathway leading to vasodilation
44. MECHANISM OF ACTIONSTEP 4 The complement proteins and antigen- antibody complexes attract leukocytes to the area.
45. MECHANISM OF ACTIONSTEP 5 The leukocytes discharge their killing agents and promote massive inflammation. This can lead to tissue death and hemorrhage.
46. EXAMPLES OF TYPE 3 HYPERSENSITIVITY1. SERUM SICKNESS, A COMBINATION TYPE I AND TYPE III HYPERSENSITIVITY2. AUTOIMMUNE ACUTE GLOMERULONEPHRITIS3. RHEUMATOID ARTHRITIS4. SOME CASES OF CHRONIC VIRAL HEPATITIS
47. DIAGNOSTIC TESTS1. Examination of tissue biopsies for deposits of immunoglobulins and complement by immunofluorescence (pattern = granular)2. The presence of immune complexes in serum3. Depletion in the level of complement
48. TRAETMENT ANTI-INFLAMMATORY DRUGS
49. Hyper sensitivity type IV:(THE CELL MEDIATED OR DELAYEDTYPE HYPERSENSITIVITY)Definition:A hypersensitivity resulting fromcell-mediated immunity (cytotoxicT-lymphocytes and cytokines)causing harm to the body.
50. CAUSE OF TYPE 4 HYPER- SENSITIVITY CAUSED BY T-CELLS1. T-HELPER CELLS BY SECRETION OF CYTOKINES2. MAINLY BY CYTOTOXIC T-CELLS BY DIRECT DAMAGE
51. MECHANISM OF ACTION T-H CELLS INDUCEDSTEP 1 ANTIGEN ENTERS THE BODY ENGULFED BY MACROPHAGES PRESENTED TO T-H CELLS T-H CELLS BECOMES ACTIVATED AND INCREASED IN NUMBER
52. MECHANISM OF ACTION T-H CELLS INDUCEDSTEP 2 SECOND EXPOSURE ENGULFED BY MACROPHAGES PRESENTED TO T-H CELLS T-H CELLS RELEASE CYTOKINES
53. MECHANISM OF ACTION T-H CELLS INDUCEDSTEP 3 T-H 2 CELLS RELEASE T-H 1 or TD CELLS IL-4 AND IL-5 RELEASE CYTOKINES ATTRACTION FOR MORE PROMOTE MACROPHAGES AT THE EXTRACELLULAR SITE OF ATTACK KILLING BY EOSINOPHILS MORE INFLAMMATION TISSUE DAMAGE SKIN LESIONS
54. MECHANISM OF ACTION CTOTOXICT CELLS INDUCEDSTEP 1 ANTIGEN BINDS TO NORMAL CELL EPITOPE PRESENTED WITH MHC-1 CTL ATTACHED BY TCR/CD8+ ACTIVATION OF T-CELL
55. MECHANISM OF ACTION CTOTOXICT CELLS INDUCEDSTEP 2 ACTIVATION OF CYTOTOXIC T-CELL RELEASE OF 1. PORE-FORMING PROTEINS CALLED PERFORINS 2. PROTEOLYTIC ENZYMES CALLED GRANZYMES 3. CHEMOKINES
56. MECHANISM OF ACTION CTOTOXICT CELLS INDUCEDSTEP 3 PERFORINS FORM PORES GRANZYMES PASS THROUGH PORES ACTIVATE ENZYMES OF CELLS APOPTOSIS
57. MECHANISM OF ACTION CTOTOXICT CELLS INDUCED
58. EXAMPLES OF TYPE 4 HYPERSENSITIVITY THE CELL OR TISSUE DAMAGE done during diseases like tuberculosis, leprosy, smallpox, measles, herpes infections. THE SKIN TEST REACTIONS seen for tuberculosis and other infections CONTACT DERMATITIS like poison ivy TYPE -1 INSULIN-DEPENDENT DIABETES where CTLs destroy insulin-producing cells
59. DIAGNOSTIC TESTS1. IN VIVO 1. Mantoux test 2. Patch test2. INVITRO 1. Lympho-cytotoxicity 2. IL-2 production