TYPE III AND TYPE IV HYPERSENSITIVITY REACTIONS SEMNAR.pptx

Pharmacology

1. TYPE III AND TYPE IV HYPERSENSITIVITY REACTIONS BARATH KUMAR D I YEAR MDS DEPARTMENT OF ORTHODONTICS AND DENTOFACIAL ORTHOPAEDICS

2. INTRODUCTION Immune responses that normally are protective also are capable of causing tissue injury. Injurious immune reactions are grouped under hypersensitivity , and the resulting diseases are called hypersensitivity diseases.

3. Gell Coombs classified the hypersensitivity reactions into four types based on mechanism involved and time taken for hypersensitivity reaction into four types 1. TYPE I HYPERSENSITIVITY 2. TYPE II HYPERSENSITIVITY 3. TYPE III HYPERSENSITIVITY 4. TYPE IV HYPERSENSITIVITY

4. TYPE III HYPERSENSITIVITY REACTION Antigen–antibody (immune) complexes that are formed in the circulation may deposit in blood vessels, leading to complement activation and acute inflammation. The antigens that form immune complexes may be exogenous, such as a foreign protein that is injected or produced by an infectious microbe, or endogenous, if the individual produces antibody against self antigens (autoimmunity). Th e reaction may be general (e.g., serum sickness) or may involve individual organs including or other organs. Unlike type I hypersensitivity reaction, a single injection acts as both priming and shocking doses.

5. COMMON DISEASE IN TYPE III HYPERSENSITIVITY REACTION SERUM SICKNESS POST STREPTOCOCCAL GLOMERULONEPHRITIS SYSTEMIC LUPUS ERYTHROMATOSIS FARMERS LUNG RHEUMATOID ARTHRITIS

6. MECHANISM The process take place in three steps PHASE 1 – IMMUNE COMPLEX FORMATION PHASE 2 – IMMUNE COMPLEX DEPOSITION PHASE 3 – INFLAMMATION AND TISSUE INJURY

7. IMMUNE COMPLEX FORMATION Endogenous or exogenous antigen exposure triigers and antibody formation Exogenous antigens are foreign proteins Endogenous antigens are self antigens In both case Ag bind to Ab which led to circulating immune complex bodies Later migrate out of plasma cells and deposit in host tissue

8. IMMUNE COMPLEX DEPOSITION Excess of Ag cause formation numerous small sized aggregates of immune complexes They are difficult to remove by phagocytosis and get deposited in various tissue spaces and activate immune system by complements

9. INFLAMMATORY REACTION The final step is the activation of classical complement pathway Leading to the release of C3a and C5a Which release macrophage and neutrophils and cause inflammatory damage to tissue Depending on the site and symptom – VASCULITIS , ARTHRITIS, GLOMERULONEPHRITIS

10. ARTHUS REACTION An example of local immune complex diseases is the Arthus reaction, in which an area of tissue necrosis appears as a result of acute immune complex vasculitis. The reaction is produced experimentally by injecting an antigen into the skin of a previously immunized animal with preformed antibody. Immune complexes form as the antigen diffuses into the vascular wall at the site of injection, triggering the same inflammatory reaction and histologic appearance as in systemic immune complex disease. Arthus lesions evolve over a few hours and reach a peak 4 to 10 hours after injection, when the injection site develops edema and hemorrhage, occasionally followed by ulceration.

11. Serum sickness Serum sickness is a systemic inflammatory reaction caused by deposition of immune complexes at many sites of the body. The condition manifests after a single injection of a high concentration of foreign serum. It appears a few days to 2 weeks after injection of foreign serum or certain drugs. Unlike type I hypersensitivity reaction, a single injection acts as both priming and shocking doses. Fever, lymphadenopathy, rashes, arthritis, splenomegaly, and eosinophilia are the typi-cal manifestations. Disease is self-limited and clears without sequelae.

12. Autoimmune diseases Drug reactions Infectious diseases Systemic lupus erythematosus (SLE) Allergies to penicillin and sulfonamides Poststreptococcal glomerulonephritis Rheumatoid arthritis Meningitis Hepatitis Infectious mononucleosis Malaria

13. DIAGNOSIS BLOOD INVESTIGATIONS URINE ANALYSIS X RAY AND CT SKIN PRICK TEST CULTURES

14. TREATMENT REMOVING THE OFFENDING AGENT ANTIHISTAMINES NSAIDS CORTICOSTEROIDS In case of hemodynamic stability, life threatening symptoms – patients were hospitalized AUTOIMMUNE DISORDER – Hydroxychloroquine , NSAIDS, Azathioprine, Methotrexate, Tacrolimus

15. TYPE IV HYPERSENSITIVITY REACTION Delayed hypersensitivity is a function of T Lymphocytes , not by antibody. It starts hours ( or Days) after contact with the antigen and often lasts for days. Two types of T cell reactions are capable of causing tissue injury and disease: C ytokine-mediated inflammation, in which the cytokines are produced mainly by CD4+ T cells, and D irect cell cytotoxicity, mediated by CD8+ T cells

16. CD4+ T cell- mediated hypersensitivity reactions 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 (DTH), a tissue reaction to antigens given to immune individuals. In this reaction, an antigen administered into the skin of a previously immunized individual results in a detectable cutaneous reaction within 24 to 48 hours.

17. CD8+ T cell mediated hypersensitivity In this type of T cell–mediated reaction, CD8+ CTLs kill antigen-expressing target cells. In a virus infected cell, viral peptides are displayed by class I MHC molecules and the complex is recognized by the TCR of CD8+ T lymphocytes. The killing of infected cells leads to elimination of the infection, but in some cases, it is responsible for cell damage that accompanies the infection (e.g., in viral hepatitis).

18. EXAMPLES OF CD4 T CELL MEDIATED HYPERSENSITIVITY TUBERCULIN REACTION – intra cutaneous injection of PPD in a previously sensitized individual ( accumulation of CD4 cells and macrophages ) GRANULOMATOUS INFLAMMATION CONTACT DERMATITIS RHEUMATOID ARTHRITIS MULTIPLE SCLEROSIS INFLAMMATORY BOWEL DISEASE PSORIASIS

19. EXAMPLES OF CD8 T CELL MEDIATED HYPERSENSITIVITY GRAFT VERSUS HOST DISEASE GRAFT VERSUS LEUKEMIA REACTION TYPE 1 DIABETES MELLITUS – DESTRUCTION OF ISLET CELLS HEPATIC INJURY DUE TO HBV INFECTION ARTHRITIS HEMAPHAGOCYTIC LYMPHOHISTIOCYTOSIS

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21. REFERENCE Tripathi, K. (2008) Essentials of medical Pharmacology . Jaypee Brothers, Medical Publishers Pvt. Limited. Garg, G.Rai.G . (2020) REVIEW OF PHARMACOLOGY. Katzung , B.G. and Trevor, A.J. (2020) Basic and Clinical Pharmacology 15E . McGraw Hill Professional.