1. Hypersensitivity
MBBS- Batch 16 Remya

2. Learning Objectives The objectives of this lecture are to :
explain with suitable examples how hypersensitivity reactions are classified
explain with suitable examples the mechanism of each of the hypersensitivity reactions
discuss the role of T lymphocytes and antibody as mediators of hypersensitivity

3. Learning outcomes At the end of the lecture, students should be
able to:
classify hypersensitivity reactions.
specify the role of the initiators and mediators of each of the hypersensitivity reaction
discuss with appropriate examples, the mechanism of each of the hypersensitivity reactions.

4. Hypersensitivity (Allergy): An abnormal response to
antigens.
Hypersensitivity reactions differ from protective
immune reactions only in that they are exaggerated or
inappropriate and damaging to the host.
It requires a pre-sensitized (immune) state of the host
It can be divided into 4 types:
-based on the mechanisms involved
-time taken for the reaction

5. Gell and Coombs classification (1960)
Four Types of Hypersensitivity Reactions:
Type I (Anaphylactic) Reactions
Type II (Cytotoxic) Reactions
Type III (Immune Complex) Reactions
Type IV (Delayed type/Cell-Mediated) Reactions

6. Type I (Anaphylactic) Reactions
Antigens are called “allergens”
Atopy (out of place) is the immediate hypersensitive reactions in people with a strong hereditary pre disposition
-they have abnormally high levels of IgE
-high levels of circulating eosinophils

8. Anaphylaxis – rapid and severe reaction developed within minutes.
a) systemic (generalised):
itching, erythema, vomiting, abdominal cramps, diarrhea, breathing difficulties, laryngeal edema, angioedema, vascular collapse, shock, death
b) cutaneous (localised):
signs of local inflammation

9. Mechanism of Type I hypersensitivity
Sensitization phase
Activation phase

10. 10 10

11. Occur within minutes of exposure to antigen.
Antigens combine with IgE antibodies.
IgE binds to mast cells and basophils, causing them to undergo degranulation and release several mediators:
Histamine: Dilates and increases permeability of blood vessels (swelling and redness), increases mucus secretion (runny nose), smooth muscle contraction (bronchi).
Prostaglandins: Contraction of smooth muscle of respiratory system and increased mucus secretion.
Leukotrienes: Bronchial spasms.

12. Anaphylactic shock: Massive drop in blood pressure
Anaphylactic shock: Massive drop in blood pressure. Can be fatal in minutes.
The most severe type of anaphylaxis, occurs when an allergic response triggers a quick release of large quantities of immunological mediators (histamines, prostaglandins and leukotrienes) from mast cells, leading to systemic vasodilation (associated with a sudden drop in blood pressure) and edema (resulting in bronchoconstriction and difficulty breathing).

13. Anaphylactic shock can lead to death in a matter of minutes if left untreated.
Anaphylaxis may occur after ingestion, skin contact, injection of an allergen or, in some cases, inhalation.

15. Type II (Cytotoxic) Reactions
Involve activation of complement by IgG or IgM binding to an antigenic cell.
Antigenic cell is lysed.
Transfusion reactions:
ABO Blood group system: Type O is universal donor. Incompatible donor cells are lysed as they enter bloodstream.
Hemolytic disease of newborn: Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta.

16. B cell proliferation will take place and
B cell proliferation will take place and antibodies to the antigen are produced.
IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation to eliminate cells presenting foreign antigens.
That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death.

17. Drug-induced hemolytic anemia
Drugs react with RBC surface
molecules to make new Ags.
Penicillin, quinidine, methyldopa.
Not the same as a drug allergy.

18. Antibody-dependent cell-mediated cytotoxicity (ADCC)
Another form of type II hypersensitivity
Antibodies bind to organisms via their Fab region.
Large granular lymphocytes (Natural Killer cells - NK cells)/ polymorphs, attach via Fc receptors, and kill these organisms not by phagocytosis but by release of toxic substances called perforins.

20. Type III (Immune Complex) Reactions
Sometimes antibody- (soluble) antigen complexes are not cleared like how they should be.
When deposited in tissue, they cause damage complement activation- produces inflammatory mediators - neutrophils are attracted.

22. Involve reactions against soluble antigens circulating in serum.
Antibody-Antigen immune complexes are deposited in organs, activate complement, and cause inflammatory damage.
Occurs when antigens and antibodies (IgG or IgM) are present in roughly equal amounts, causing extensive cross-linking.

23. It is characterized by soluble antigens that are not bound to cell surfaces (which is the case in type II hypersensitivity).
When these antigens bind antibodies, immune complexes of different sizes form.
Large complexes can be cleared by macrophages but they have difficulty binding to small immune complexes for clearance.

24. These immune complexes insert themselves into small blood vessels, joints, and glomeruli, causing symptoms.
They deposit in tissues and induce an inflammatory response, and can cause damage wherever they precipitate.

25. Type IV (Cell-Mediated) Reactions
Involve reactions by TD memory cells.
First contact sensitizes person.
Subsequent contacts elicit a reaction.
Reactions are delayed by two or more days (delayed type hypersensitivity).
Delay is due to migration of macrophages and T cells to site of foreign antigens.
Reactions are frequently displayed on the skin: itching, redness, swelling, pain.