1. Chapter 15 Hypersensitivity Reactions, Allergies Dr. Capers
immunology

2. Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 15
Hypersensitivity Reactions
Copyright © 2007 by W. H. Freeman and Company

3. Hypersensitivity – responding inappropriately to an antigen
Inflammatory response can have deleterious effects
Tissue injury
Disease
death

4. Hypersensitivity Reactions
May develop in course of humoral OR cell-mediated response
Immediate hypersensitivity
Anaphylactic
Antibody-antigen complexes
Manifests in minutes
Delayed-type hypersensitivity
May occur in days

6. Type I – IgE-Mediated Hypersensitivity
Induced by antigens referred to as allergens
Induces humoral response but induces high secretion of IgE
Fc portion of IgE binds with Fc receptors on mast cells and basophils
Degranulation occurs

7. Type I

8. Type 1 Common components Allergens IgE Mast cells and basophils
Atopy – hereditary predisposition to development of immediate hypersensitivity reactions to common antigens
Allows nonparasitic antigens to induce IgE response
IgE
Normally lowest of all antibody classes in serum
Half-life is 2-3 days but once bound to mast cells or basophils, can last for weeks
Mast cells and basophils
IgE binding receptors
High affinity
Low affinity
Atopic individuals have higher amount of soluble IgE receptor that has been shown to increase IgE production by B cells

10. IgE cross-linkage initiates degranulation
Once cross-linkage of antigen has occurred, intracellular signaling result in mast cell degranulation
Cooperation among protein and lipid kinases, phosphatases, rearrangement of the cytoskeleton

11. Pharmacologic agents that mediate Type I
Primary mediators
Made before and stored in granules
Histamine, proteases, eosinophil chemotactic factor, heparin
Secondary mediators
Synthesized after
Platelet-activating factor, leukotrienes, prostaglandins, bradykinins, some cytokines and chemokines

13. Histamine Formed by decarboxylation of amino acid Histidine
Major component of granules
Effects observed in minutes
Contraction of smooth muscle (intestinal and bronchial), increase permeability of venules, increased mucus secretion by goblet cells

14. Leukotrienes and prostaglandins
Effects longer to become apparent
Effects longer lasting than histamine
Bronchoconstriction, vascular permeability, mucus production

15. Type 1 can be systemic or localized
Systemic anaphylaxis
Quick, can be fatal
Respiration labored, blood pressure drops, bronchiole constriction, edema, shock
Epinephrine treats, relaxes smooth muscle and increases cardiac output (prevents vascular collapse)

16. Type 1 can be systemic or localized
Localized Hypersensitivity Reactions (Atopy)
Allergic Rhinitis
Most common, “hay fever”
Asthma
Triggered like hay fever but doesn’t happen in nasal cavity, happens in lower respiratory tract
Food allergies
Hives, vomiting
Atopic dermatitis
Allergic eczema

17. Asthma Inflammatory disease
Induce expression of adhesion molecules on endothelial cells for eosinophils and neutrophils
Cause significant injury because of toxic enzymes, cytokines
Notice sloughing of the pseudostratified ciliated columnar epithelial cells lining the bronchiole

18. Clinical Methods to detect Type 1
Skin testing
Checking serum level of IgE

19. Control of Type 1 Avoiding contact Immunotherapy Drug therapies
Subcutaneous injections of allergens
Causes shift to IgG production instead of IgE
Monoclonal anti-human IgE
Drug therapies

20. Type II – Antibody-Mediated Cytotoxic Hypersensitivity
Transfusion Reactions
Due to exposure to microorganisms in gut, individuals have antibodies to blood types not their own
Antibody attaches to RBC and initiates complement system to lyse RBC
After lysis:
Hemoglobin detected in plasma, starts to filter through kidneys and found in urine (hemoglobinuria)
Hemoglobin converted to bilirubin – toxic at high levels
Fever, chills, blood clotting

21. Type II – Antibody-Mediated Cytotoxic Hypersensitivity
Hemolytic disease of newborn
Rh+ fetus, Rh- mother
IgG antibodies cross placenta
Some of these antibodies may be anti-Rh antibodies
Can have severe consequences
Antibodies against ABO blood groups produce less consequences, can be easily treated
Rhogam shot
Given to mother
Anti-Rh antibodies bind to fetal cells that might have entered mother’s system during birthing process, facilitates clearing before there is a B cell response

23. Type III – Immune complex-mediated hypersensitivity
Complexing of antigen plus antibody facilitates phagocytosis and clearing of antigen
Large amounts of these complexes can lead to tissue damage

25. Type III can be localized
Injection of antigen intradermally or subcu into animal that has high level of antibody for that antigen
Arthus reaction
Bug bites

26. Type III can be generalized
Serum sickness
After receiving antiserum (serum from another animal that may contain antitoxins for treatment)
Use of monoclonal antibodies for use of cancer treatment
Patient developed antibody against mouse monoclonal antibody
Autoimmune diseases
Lupus, Rheumatoid arthritis
Drug reactions
Penicillin, sulfonamides
Infectious disease

27. Type IV – Delayed-type Hypersensitivity
Some subpopulations of TH cells encounter antigen, secrete cytokines and induce localized inflammatory response
Most cases are not detrimental

28. Type IV Sensitization phase and Effector phase of DTH

29. Prolonged DTH can lead to formation of granuloma Tuberculosis test is done this way

30. Type IV – contact dermatitis

31. Chronic Inflammation Causes: Infections
Continuing physical damage to tissue
Obesity
autoimmunity