Hypersensitivity pathology by urooj umer

hypersensitivity and allergy relation and difference and the types and diseases related to each type of of hypersensitivity are discussed here.

1. HYPERSENSTIVITY (ALLERGY ) PRESENTED BY : UROOJ UMER RIPHAH INTERNATIONAL UNIVERSITY

2. CONTENTS Hypersensitivity Types of hypersensitivity Types of hypersensitivity reactions. TYPE -1 (anaphylactic / immediate hypersensitivity) TYPE -2 (cytotoxic hypersensitivity) TYPE -3 (immune complex hypersensitivity) TYPE -4 ( Cell-mediated / delayed hypersensitivity)

3. HYPERSENSITIVITY “The term hypersensitivity is used to describe the immune responses which are damaging rather than helpful to the host .” It denotes a term in which an immune results in exaggerated or inappropriate reactions that are harmful to the host. Also referred to as over reaction of immune system and these reactions may be damaging , uncomfortable or occasionally fatal. It require a pre-sensitized (immune ) state.

4. FEATURES OF HYPERSENSITIVITY DISORDERS The features of hypersensitivity disorders are as follows : Reactions can be elicited by exogenous environmental antigens (microbial or non microbial) and endogenous self antigens Usually result from imbalance between effector mechanism and control mechanism of immune system. Hypersensitivity disease is associated with HLA and non HLA genes. Mechanism of tissue injury is same as the effector mechanism of defense against infectious pathogens

5. TYPES OF HYPERSENSITIVITY There are two types of hypersensitivity IMMUNOLOGIC HYPERSENSITIVIY (allergy) Non-immunologic hypersensitivity (non- allergic) ALLERGIC NON-ALLERGIC Immunological reaction No immunological reaction Cross reaction to structurally related compounds Cross reaction due to function of drug Highly specific Not specific

6. RELATION BETWEEN ALLERGY AND HYPERSENSITIVITY Allergy is also called hypersensitivity reaction or hypersensitivity response. Allergy is a clinical syndrome Hypersensitivity is a descriptive term for immunological process , it is due to external stimuli. Allergy is evacuated with hypersensitivity but should be limited to immunoglobulin IgE mediated reactions

7. TYPES OF HYPERSENSITIVITY REACTIONS Types of hypersensitivity reactions is classified in two classes: Antibody mediated (type 1 , 2 , 3) Cell- mediated (type 4)

8. TYPE -1 HYPERSENSITIVITY (antibody –mediated) Also known as immediate (anaphylactic hypersensitivity). Immediate hypersensitivity occur as a systemic disorder or local reaction. Local reactions are diverse , depending upon the portal of entry of allergen. It is also called IgE mediated allergy An immediate hypersensitivity reaction occurs when antigen (allergen) binds to IgE on the surface of mast cells and basophils with a subsequent release of several mediators.

9. ACTIVATION OF Th-2 CELLS AND PRODUCTION OF ANTIBODY: The first step is the generation of Th-2 cells is the presentation of antigen to naïve CD4+ helper cells . Th-2 cells produce chemokines that attract more Th-2 cells to reaction site.

10. MEDIATORS CYTOKINES TNF IL-4 IL-13 IL-5 IL-1

11. PHASES IN TYPE -1 Two phases occur: IMMEDIATE PHASE : Reaction occurs in minutes after exposure and include release of vasoactive amines and lipid mediators . Characterized by vasodilation , vascular leakage , glandular secretions. hi stamine is mediator LATE – PHASE Late –phase of IgE – mediated inflammation occurs approximately 6 hours after exposure to the antigen . Eosinophils are mediators

12. PROCESS OF LATE – PHASE

13. CLINICAL MENIFESTATIONS CLINICAL SYNDORME CHARACTERIZATION PATHOLOGICAL MENIFESTATION ANAPHYLAXIS Vascular shock , bronchoconstriction Fall in blood pressure Vascular dilation Airway obstruction BRONCHIAL ASTHMA Shortness of breath. Tightness of chest. Wheezing Airway obstruction caused by bronchial smooth muscle hyperactivity ALLERGIC RHINITIS , SINUSITIS (hay fever) runny nose itchy eyes Congestion sinus pressure Increased mucous secretion Inflammation in upper airways FOOD ALLERGIES mouth itching swelling of the lips, face, throat, mouth ,tongue, rashes, asthma Increased peristalsis due to contraction of intestinal muscles.

14. Type – 2 (CYTOTOXIC HYPERSENSITIVITY) MECHANISMS FOR TYPE -2 Opsonization and phagocytosis Inflammation Cellular dysfunction. Antibodies that react with antigens on cell surfaces or in extracellular matrix causes disease by destroying cells (tissue damage) , triggering inflammation or interfering normal functions

15. 1.. OPSONIZATION AND PHAGOCYTOSIS

16. 2.. INFLAMMATION

17. 3.. CELLULAR DYSFUNCTION Antibodies directed against cell surface receptors impair or dysregulate function without causing injury or inflammation . MYSTHENIA GRAVIS

18. CLINICAL MENIFESTATION DISESE MECHANISM CLINICAL MENIFESTATION HHEMOLYTIC ANEMIA Opsonization and phagocytosis of RBCS Hemolysis anemia THROMBO- CYTOPENIC PURPURA Opsonization and phagocytosis of platelets bleeding GOODPASTURE SYNDROME Complement and Fc mediated inflammation Nephritis Lung hemorrhage ACUTE RHEUMATIC FEVER inflammation Myocarditis Arthritis MYSTHENIA GRAVIS Cellular dysfunction Muscle weakness paralysis GRAVES DISESE Cellular dysfunction Hyperthyroidism

19. TYPE -3 (IMMUNE COMPLEX MEDIATED ) The principal morphologic manifestation of immune complex injury is acute vasculitis, associated with necrosis of the vessel wall. The necrotic tissue and deposits of immune complexes , complement, and plasma protein appear as a smudgy eosinophilic area of tissue destruction, an appearance termed fibrinoid necrosis It is also antibody mediated . PATHOGENESIS OF SYSTEMIC IMMNE COMPLEX DISEASE Formation of immune complexes Deposition of immune complexes Inflammation Antigen-antibody complexes produce tissue damage mainly by eliciting inflammation at the sites of deposition

20. LOCAL IMMUNE COMPLEX DISEASE ARTHUS REACTION : The Arthus reaction is a localized area of tissue necrosis resulting from acute immune complex vasculitis, usually elicited in the skin.

21. CLINICAL MENIFESTATIONS DISESAE CLINICAL MENIFESTATION SYSTEMIC LUPUS ERYTHEMATOUS Nephritis Skin lesions arthritis REACTIVE ARTHRITIS Acute arthritis SERUM SICKNESS Arthritis Vasculitis nephritis ARTHUS REACTION Cutaneous vasculitis

22. TYPE -4 (T – CELL MEDIATED ) CD4+ T cell–mediated hypersensitivity induced by environmental. CD8+ cells may also be involved in some of these autoimmune diseases . MECHANISMS OF TYPE -4 : CD4+ T cell mediated inflammation CD8+ T cell mediated cytotoxicity The cell-mediated type of hypersensitivity is caused by inflammation resulting from cytokines produced by CD4+ T cells and cell killing by CD8+ T cell.

23. CD4 + T cell mediated inflammation In CD4+ T cell–mediated hypersensitivity reactions, cytokines produced by the T cells induce inflammation that may be chronic and destructive. The prototype of T cell–mediated inflammation is delayed-type hypersensitivity .

24. CD8+ T CELL MEDIATED CYTOTOXICITY In this type , CD8+ CTLs kill antigen – expressing target cells . CTLs direct cell surface histocompatibility antigens and play important role in graft rejection. In virus infected cell , viral peptides are displayed by Class 1 MHC molecules and complex is recognized by TCR of CD8+T lymphocytes.

25. Process: CTLs that recognize the target cells secrete a complex consisting of granzymes , perforins and other proteins that enter target cell by endocytosis. In target cell cytoplasm , perforins facilitates the release of granzymes from complex. Granzymes are proteases that cleaves and activate caspases which induce APOPTOSIS .

26. CLINICAL MENIFESTATIONS DISEASE SPECIFIC PATHOGENIC T CELL CLINICAL MANIFESTATIONS RHEMATOID ARTHRITIS Collagen Chronic arthritis with inflammation , destruction of acicular cartilage MULTIPLE SECLEROSIS Protein antigen in myelin Demyelination in CNS with inflammation TYPE 1 DIABETIES Antigens of pancreatic islet beta cells Insulitis Destruction of beta cells INFLAMMATORY BOWL DISEASE Enteric bacteria Chronic intestinal inflammation , obstruction CONTACT SENSITIVITY Various environmental chemicals Epidermal necrosis , dermal inflammation causing skin rash , blisters

27. REFRENCES Robins and cartons pathological basis Medical microbiology and immunology