Hypersensitivity reactions immunology

1. Hypersensitivity Reactions
HAFIZ M WASEEM
UE LAHORE

2. Hypersensitivity
– Immune system is generally protective in nature
– Protective mechanisms may result in severe
damages to tissues and may lead to even death
when the immune system respond in exaggerated
or inappropriate form.
– This inappropriate immune response is termed as
hypersensitivity or allergy

3. Classification
Gell and Coombs classification of hypersensitivity reactions:
Humoral mediated types
-Type I – IgE mediated or immediate type (atopic, or
anaphylactic)
-Type II - antibody-dependent type
-Type III - immune complex mediated type
Cell mediated types
-Type IV - cell-mediated or delayed type

4. Classification
– Humoral hypersensitivity is mediated by antibody or
antigen-antibody complexes:
• IgE-mediated (type I),
• Antibody-mediated (type II),
• Immune complex–mediated (type III).
– Cell mediated hypersensitivity depends on reactions where
T-lymphocytes (cytokines) are involved
• Delayed type hypersensitivity, or DTH (type IV).

6. Mechanism of hypersensitivity type-I
reactions
Type 1 reactions involve:
– Allergens and antigens
– Reaginic antibody (IgE)
– Binding of IgE to Fc receptors
– Mast cells and Basophils
– Allergic mediators

7. – A type I hypersensitive reaction is induced by certain
types of antigens which are referred as allergens
– Allergens induce a humoral antibody response
resulting in the generation of antibody-secreting
plasma cells and memory cells.
– What distinguishes a type I hypersensitive response
from a normal humoral response is that the plasma
cells secrete IgE.
– This class of antibody binds with high affinity to Fc
receptors on the surface of tissue mast cells and
basophils.
Mechanism of hypersensitivity type-I
reactions

8. – Mast cells and Basophils coated with IgE are said
to be sensitized.
– A later exposure to the same allergen cross-links
the membrane-bound IgE on sensitized mast cells
and basophils, causing degranulation of the cells .
– Pharmacologically active mediators released from
the granules act on the surrounding tissues.
– Principle effects—vasodilation and smooth-muscle
contraction—may be either systemic or localized,
depending on the extent of mediators release.
Mechanism of hypersensitivity type-I
reactions

9. Mechanism of hypersensitivity type-I
reactions

10. Hypersensitivity type-I
allergens

11. Hypersensitivity type-I
mediators

12. Hypersensitivity type-I
• Can be:
– Systemic - shock-like and often fatal state whose
onset occurs within minutes of a type I
hypersensitive ( e:g Anaphylaxix)
– Localized - the reaction is limited to a specific
target tissue or organ, often involving epithelial
surfaces at the site of allergen entry (e:g Allergic
Rhinitis, Asthma, Atopic Dermatitis)

13. Hypersensitivity type-II
• Antibody mediated cytotoxic hypersensitivity:
– In type II hypersensitivity, the antibodies produced by the immune
response bind to antigens on the patient's own cell surfaces.
– The antigens recognized in this way may either be intrinsic ("self"
antigen, innately part of the patient's cells) or extrinsic (absorbed onto
the cells during exposure to some foreign antigen, possibly as part of
infection with a pathogen
– IgG and IgM antibodies bind to these antigens to form complexes that
activate the classical pathway of complement activation for
eliminating cells presenting foreign antigens (which are usually, but
not in this case, pathogens).
– As a result mediators of acute inflammation are generated at the site
and membrane attack complexes cause cell lysis and death. The
reaction takes hours to a day.

14. • Examples Of ADCC:
– Autoimmune haemolytic anaemia
– Pernicious anemia
– Immune thrombocytopenia
– Transfusion reactions
– Hashimoto's thyroiditis
– Graves' disease
– Myasthenia gravis
– Farmer's Lung
– Hemolytic disease of the newborn
Hypersensitivity type-II

15. Hypersensitivity type-II

16. Hypersensitivity type-II

17. • Also known as immune complex disease occurs when immune
complex (Ag-Ab) are not removed from circulation
• These complexes are deposited in various tissues and organs
such as:
- Kidneys
- Joints
- Lung
- Skin
• The reaction takes hours to days to develop
• This may trigger an immune response according to the
classical pathway of complement activation.
Hypersensitivity type-III

18. Hypersensitivity type-III
• Immune complex formation may occur as a result of :
– Autoimmune diseases (RA)
– Persistence infection (Hepatitis virus)
– Repeated inhalation of antigenic materials
Examples:
– Immune complex glomerulonephritis
– Rheumatoid arthritis
– Serum sickness
– Subacute bacterial endocarditis
– Systemic lupus erythematosus
– Arthus reaction

19. Localized depositions of immune complexes within a tissue cause
type III hypersensitivity

20. Delayed type hypersensitivity (DTH)
– Type IV hypersensitivity is often called delayed type as the
reaction takes two to three days to develop.
– A type of cell-mediated response.
– The mechanism includes T lymphocytes and monocytes
and/or macrophages.
– Cytotoxic T cells (Tc) cause direct damage whereas helper T
(TH1) cells secrete cytokines which activate cytotoxic T cells,
recruit and activate monocytes and macrophages, which
cause the bulk of the damage
– The delayed hypersensitivity lesions mainly contain
monocytes and a few T cells.
Hypersensitivity type-IV

21. Some clinical examples:
– Contact dermatitis
– Symptoms of leprosy
– Symptoms of tuberculosis
– Transplant rejection
Hypersensitivity type-III

22. Figure 12-2
The hypersensitivity reactions