Hypersensitivity reactions. Mpharm pharmacology 2nd semester advanced pharmacology

Advanced pharmacology 2

1. HYPERSENSITIVITY REACTIONS ADVANCED PHARMACOLOGY-II PRESENTED BY, A.CHIFORA, M.PHARM-2 ND SEMESTER, DEPARTMENT OF PHARMACOLOGY, SRIPMS-COP.

2. TABLE OF CONTENTS

3. HYPERSENSITIVITY REACTIONS A hypersensitivity reaction is an inappropriate or overreactive immune response to an antigen resulting in undesirable effects. The symptoms typically appear in individuals who had at least one previous exposure to the antigen.

4. HISTORY Paul Portier and Charles Richet Physalia physalis - stings contain the toxic agent. Injected low doses of toxin into dogs To elicit an immune response Instead of generating a protective antibody, the dog died. Deadly overreaction called Anaphylaxis

5. IMMUNOGLOBULINS

6. CLASSIFICATION

7. INFLAMMATORY MEDIATORS TYPE IMMUNE CELLS INVOLVED INFLAMMATORY MEDIATORS DURATION OF ONSET ANAPHYLACTIC Mast cells Basophils Th2 cells Histamine Leukotrienes Prostaglandins Cytokines Within minutes to 2 hours CYTOLYTIC IgG, IgM, NK Cells, Neutrophils C3a, C5a Reactive Oxygen Species Lytic enzymes Inflammatory cytokines Minutes to hours ARTHUS Neutrophils Monocytes C3a, C5a Reactive Oxygen Species Lysosomal enzymes Cytokines 4 to 12 hours CELL-MEDIATED CD4+ cells, CD8+ cells, Macrophages Interferon gamma, tumor necrosis factor alpha, interleukin-2 , IL-12, IL-17,IL-1 48 to 72 hours

8. MECHANISMS: 1]B-Cell mediated mechanism 2] Antibody dependent cell mediated toxicity 3] Immune complex formation 4] Cell- mediated mechanism

9. MECHANISMS 1)B-CELL MEDIATED MECHANISM:

10. 2] ADCC [ ANTIBODY DEPENDENT CELL-MEDIATED CYTOTOXICITY] Ab CD4 CD4+Fc Cell lysis

11. 3] IMMUNE COMPLEX FORMATION

12. 4] CELL- MEDIATED MECHANISM

13. ANAPHYLACTIC REACTION CAUSES CHEMICAL MEDIATORS

14. CLINICAL MANIFESTATIONS

15. TREATMENT: Drug Receptor Activity Pharmacological effect   Epinephrine  1 receptor Constrict blood vessels ↑BP  reduces swelling  1 receptor Strengthen heart contraction Opens airways  eases breathing  2 receptor Relaxes bronchial smooth muscles Reduces inflammation  2 receptor Reduces the release of histamine Maintains circulation     Anti-Histamines     H 1 receptor Constrict the blood vessels ↓vasodilation Reduces wheal, flare & flush ↓ swelling Inhibits degranulation of mast cells ↓ itching Dilates the bronchial smooth muscles ↓bronchoconstriction   Corticosteroids Phospholipase A 2 and leukotrienes     ↓cytokines ↓inflammation ↓swelling ↓late-phase allergic response

16. CYTOLYTIC REACTION CAUSES CHEMICAL MEDIATORS

17. CLINICAL MANIFESTATIONS

18. TREATMENT: Drug class Binding site Pharmacological effect Corticosteroids Glucocorticoid receptor inside the nucleus Suppress cytokine production   Calcineurin inhibitors Cyclophilin/ FKBP+ Calcineurin enzyme Prevents dephosphorylation of nuclear factor of activated T cells Azathioprine Purine synthesis enzyme Blocks nucleotide production Mycophenolate mofetil IMPDH enzyme Inhibits guanine nucleotide synthesis cyclophosphamide DNA Causes apoptosis in rapidly dividing B and T cells Immunosuppressants like systemic glucocorticoids

19. ARTHUS REACTION CAUSES CHEMICAL MEDIATORS

20. CLINICAL MANIFESTATIONS

21. TREATMENT Drug Receptors Activity Pharmacological effects Anti-Histamines   H 1 receptor Reduces triple response ↓ local swelling (edema) ↓ redness ↓itching Inhibits degranulation of mast cells ↓ pain due to vascular effects NSAIDs COX-1 &COX-2 Reduce prostaglandin synthesis ↓edema ↓pain ↓Fever           Corticosteroids   Glucocorticoid receptors ↓cytokine production ↓recruitment and activation of immune cells Phospholipase A 2 Blocks the release of arachidonic acid ↓inflammation & chemotaxis Lysosomal membranes Prevent macrophage release & free radicals ↓ tissue damage Blood vessels Reduce leakage from blood vessels ↓ edema and swelling Immune cell Impairs lymphocyte and macrophage functions ↓ chronic inflammation Azathioprine Bind to enzymes in purine synthesis pathway Inhibits DNA synthesis in rapidly dividing lymphocytes ↓antibody production Cyclophosphamide DNA Apoptosis of proliferating cells ↓inflammation Mycophenolate mofetil Inosine monophosphate dehydrogenase (IMPDH) Inhibits guanine nucleotide synthesis ↓B and T cell proliferation Calcineurin inhibitors Bind to immunophilins Prevents T cell activation ↓antibody production

22. TYPE 4 HYPERSENSITIVITY CAUSES

23. CLINICAL MANIFESTATIONS

24. TREATMENT Removing the triggering allergen Managing the symptoms with glucocorticoids and immunosuppressants. Allergen immunotherapy: It is a preventative treatment that aims to reduce a person’s sensitivity to specific allergens.it involves gradually exposing the individual to increasing doses of the allergen, over time, to help the immune system build tolerance and reduce allergic reactions .

25. TYPE NAME MECHANISM KEY IMMUNE COMPONENTS ONSET DURATION EXAMPLES INFLAMMATORY MEDIATORS Type 1 Anaphylactic Allergen binds to IgE on mast cells  degranulation IgE , mast cells, Basophils Minutes to 2 hours Asthma, anaphylaxis, food allergy, hay fever Histamine, prostaglandins, leukotrienes Type 2 Cytotoxic IgG or IgM bind to cell surface antigens  complement activation IgG, IgM, Complement proteins, NK cells Minutes to hours Haemolytic anaemia, Goodpasture syndrome, Rh incompatibility Complement (C3a, C5a), ROS Type 3 Immune complex mediated Immune complexes deposit in tissues  inflammation via complement activation IgG, IgM, Complement proteins, Neutrophils 4 to 12 hours or days Serum sickness, Arthus rection, SLE C3a, C5a, Neutrophils, ROS Type 4 Delayed Sensitized T cells release cytokines  macrophage recruitment and inflammation CD4+ and CD8+ cells, macrophages 48 to 72 hours Contact dermatitis, graft rejection IFN- , TNF-, IL-2, IL-17, Nitric oxide, ROS

26. CONCLUSION Each type involves different immune components, mechanisms, onset durations, and clinical manifestations, making accurate classification essential for diagnosis and treatment. A thorough understanding of these mechanisms not only helps in identifying allergic and autoimmune diseases but also guides effective therapeutic strategies using antihistamines, immunosuppressants, or desensitization therapies. Thus, hypersensitivity reactions exemplify the fine balance of the immune system, where protective responses can become pathological if not properly regulated.

27. REFERENCES Brunton LL, Hilal‑Dandan R, Knollmann BC, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw‑Hill Education; 2023. p. 103–4. Tripathi KD. Essentials of Medical Pharmacology. 6th ed. New Delhi: Jaypee Brothers Medical Publishers; 2008. p. 86–7. Punt J, Stranford SA, Jones PP, Owen JA. Allergy, hypersensitivities, and chronic inflammation. Kuby Immunology. 8th ed. New York: Macmillan Learning; 2023. p. 1048–109. Selvaraj P. Hypersensitity and types of hypersensitivity I–IV [Internet]. SlideShare; 2013 Jun [cited 2025 Jun 16]. Available from: https://www.slideshare.net/slideshow/hypersensitity-and-types-of-hypersensitivity-i-ii-iii-iv/30181758 Rutgers New Jersey Medical School. Hypersensitivity Reactions (Types I, II, III, IV) [Internet]. Newark (NJ): Rutgers New Jersey Medical School; 2009 Apr 15 [cited 2025 Jun 16]. Available from: https://njms.rutgers.edu/sgs/olc/mci/prot/2009/Hypersensitivities09.pdf Jiwaji University. Hypersensitivity Type I for MSc 2nd Semester Microbiology [Internet]. Gwalior: Jiwaji University; [date unknown] [cited 2025 Jun 16]. Available from: https://www.jiwaji.edu/pdf/ecourse/microbiology/Hypersensitivity%20Type%20I%20%20for%20MSc%202%20sem.%20Microbiology.pdf Pharmacy Department, SDBiDoon . Pharmaceutical Biotechnology Unit III: Hypersensitivity Reactions [Internet]. 31 Mar 2020 [cited 2025 Jun 17]. Available from: https://www.sdbidoon.com/document/b‑pharma‑3rd‑year‑biotechnology‑31‑03‑2020.pdf Usman N, Annamaraju P. Type III Hypersensitivity Reaction [Internet]. In: StatPearls . Treasure Island (FL): StatPearls Publishing; Jan 2025 [cited 2025 Jun 17]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559122/ Bajwa S F. Type II Hypersensitivity Reaction [Internet]. In: StatPearls . Treasure Island (FL): StatPearls Publishing; 2023 [cited 2025 Jun 20]. Available from: https://europepmc.org/article/NBK/nbk563264 MicrobeOnline . Hypersensitivity Type I [Internet]. [place unknown]: MicrobeOnline ; [date unknown] [cited 2025 Jun 21]. Available from: https://microbeonline.com/hypersensitivity-type-i/ Online Biology Notes. Type II hypersensitivity reaction: mechanism and examples [Internet]. ~2018 [cited 2025 Jun 21]. Available from:  https://www.onlinebiologynotes.com/type-ii-hypersensitivity-reaction-mechanism-and-examples/