1. Hypersensitivity reactions

2. Hypersensitivity reactions
In some individuals certain
innocuous molecules stimulate an
adaptive immune response and the
development of memory
The over reactions of the
immune system to these antigens
are called hypersensitivity reactions
The environmental
antigens that cause these
reactions are termed
allergen

3. 4 types of Hypersensitivity Reactions
Type I: Caused by binding of antigen to IgE, principally on mast cells.
Type II: Caused by molecules that bind and modify cell surface components to which IgG then binds
Type III: Caused by small immune complexes (IgG + Antigen) which becomes deposited in blood vessel wall.
Immune complex activates complement and WBCs leading to inflammation
Type IV: Caused by antigens presented by APC to T cells which results in production of cytokines, activation of
phagocytes (macrophages) and inflammation

4. 4 types of Hypersensitivity Reactions

5. Type I hypersensitivity reactions (allergy, immediate)
Caused by binding of antigen to antigen specific IgE bound to its Fc receptor,
principally on mast cells.

6. IgE binds irreversibly to Fc receptors on mast cells, basophils and activated eosinophils
When receptors are crosslinked by antigen binding to IgE on the surface of a mast
cell, a signal is transmitted that leads to the release of preformed granules
containing histamine and other inflammatory mediators

7. Tissue mast cells orchestrate IgE-mediated allergic rxns through the release of inflammatory mediators

8. Tissue mast cells orchestrate IgE-mediated allergic rxns through the release of inflammatory mediators

9. Eosinophils and basophils are specialized granulocytes that release toxic mediators in IgE-mediated responses

10. IgE mediated allergic reactions consist of an immediate response followed by a late response
Substances to which a person is sensitive produce a characteristic inflammatory
reaction called a wheal and flare at the site of the injection within a few minutes. Due
to IgE-mediated mast cell degranulation in skin e.g. histamine release
About 6-8 hours after second reaction (late phase reaction) occurs due to
leukotrienes, chemokines and cytokines synthesized by mast cells after IgE-
mediated activation

11. The effects of IgE-mediated allergic reactions vary with the site of mast cell activation
Inhaled allergens activate mast cells in respiratory tract which can lead to
rhinitis and asthma
Insect stings deliver antigens into skin where mast cells mediators can
cause urticaria (hives), angioedema, atopic dermatitis (eczema)
Allergens in food trigger mast cells in GI tract resulting in vomiting and
diarrhea
Allergens in blood causes systemic mast cell activation resulting in effects
such as anaphylaxis

12. Urticaria (hives)
Atopic dermatitis (eczema)
Angioedema)

14. People with parasite infections and high levels of IgE rarely develop allergic disease
For the populations of western Europe and North America, helminth and many other
parasitic infections have largely been eradicated
In these populations the prevalence of IgE-mediated allergy and asthma has been
steadily increasing
The hygiene hypothesis proposes that this increase has been caused by better
hygiene, vaccination to prevent infection, and the increased use of antibiotics and
other drugs to stop infections
A lack of practice in dealing with real infections can reveal a propensity to perceive
danger where it does not exist
Family studies have shown that exposure of children to more infections, and at a
younger age, reduces the likelihood that they will develop atopic allergic reactions

15. Type II hypersensitivity reactions
Caused by antibodies specific for altered components of human cells
Chemically reactive drug molecules can bind surface components of RBCs or platelets and create new epitopes to which the immune system is not tolerant
These epitopes stimulate the formation of IgM and IgG antibodies that are specific for the conjugate of drug and cell-surface component

16. Type II hypersensitivity reactions

17. Type III hypersensitivity reactions
Caused by immune complexes formed from IgG and soluble antigens
Complexes of soluble protein antigens and their high-affinity IgG antibodies are
generated in almost all immune responses and in most situations they are cleared
without causing tissue damage
The larger aggregates fix complement efficiently and are readily taken up by
phagocytes and removed from the circulation
Smaller immune complexes are less efficient at fixing complement, they tend to
circulate in the blood and become deposited in blood vessel walls
When these complexes accumulate at such sites they become capable of fixing
complement and initiate tissue-damaging inflammatory reactions through their
interactions with the Fc receptors and complement receptors on circulating
WBCs.

18. Type III hypersensitivity reactions

19. Complement receptors remove immune complexes from the circulation.
Complement receptors on red blood cells bind immune complexes.
During circulation these complexes are removed and degraded in the spleen and liver.
If immune complexes are not removed they can accumulate in small blood vessels particularly in the kidneys.

20. Type IV hypersensitivity reactions (delayed-type hypersensitivity)
Caused by effector TH1 cells specific for the sensitizing antigen
Macrophage activation
On activation, the TH1 cells release cytokines that cause accumulation and
activation of macrophages, which, in turn, cause local damage.
Occurs 1-3 days after contact with antigen
Best studied example is the tuberculin test in which a small amount of protein
antigen from M. Tuberculosis is injected in the skin. Inflammatory rxn hours
later.
Other example: Dermatitis from contact with Poison Ivy and Poison oak

21. Type IV hypersensitivity reactions
(delayed-type hypersensitivity)