Overview of Hypersensitivity , understanding mechanism of action

Brief explain of hypersensitivity, about it's types and its action

1. Hypersensitivity
Immune response is generally a protective process but it may sometimes be injurious to
the host. Hypersensitivity refers to a condition in which immune response results in
excessive reactions leading to tissue damage, disease or even death in the sensitized host.
Hypersensitivity is defined as exaggerated state of normal immune response which results
in adverse effects on the body. Understanding these types is crucial for diagnosing and
managing allergic and autoimmune conditions.

2. TYPES:
Immediate type
· Immediately ( within seconds to
minutes).
· Mediated by humoral antibodies
· Type I, II, III.
Delayed type:
· Slower in onset and develops within
24-48 hours.
· Mediated by cellular response( T cell
mediated)
· Type IV reaction.

3. CLASSIFICATION:
· Type I (Anaphylactic)
· Type II (Cytotoxic)
· Type III (Immune complex)
· Type IV (Delayed or cell mediated)

4. Type I Hypersensitivity
It is rapidly developing immunological reaction occurring within minutes. it is commonly
refers to as allergy.
Mediated by IgE antibodies produced by plasma cells in response to stimulation of Th2 cells
by an antigen.
The antigens that stimulate it are called allergens( house dust, pollens, cosmetics, insects,
clothing and drug)
Exposure may be ingested, inhalational, injection or direct contact.

5. Type I hypersensitivity reactions can be systemic ( eg., systemic anaphlaxis) or localized to a
specific target tissue or organ (eg., allergy rhinitis, asthma)
Symptoms :
Symptoms range from mild (sneezing, itching) to severe (difficulty breathing, shock),
requiring immediate medical attention.

6. PATHOGENESIS:
During 1st contact of the host with the antigen
Antigen is captured by antigen presenting cells
Presented to T cell which differentiates into TH2
TH2 cell releases IL- 3, IL- 4 and IL- 5
IL - 4 causes activation of B- cell
Activated B cells differentiate to form IgE- secreting plasma cells.
IgE antibodies formed
Bind to the Fc receptors present on mast cells
Mast cells are now fully sensitised for the next event

7. During the second contact with the same antigen (shocking dose)
IgE antibodies on the surface of mast cells- basophils are activated
Causes cell damage- membrane lysis, influx of sodium and water
Degranulation of mast cells- basophils

9. The released granules contain important chemicals and enzymes with proinflammatory
properties
· Histamine
· Serotonin
· Vasoactive intestinal peptide (VIP)
· Chemotactic factors of anaphylaxis for neutrophils and eosinophils
· Leukotrienes B4 and D4
· Prostagladins ( thromboxane A2, prostaglandin D2 and E2)
· Platelet activating factor

10. The effects of these agents are:
Increased vascular permeability
Smooth muscle contraction
Early vasoconstriction followed by vasodilation
Shock
Increased gastric secretion
Increased nasal and lacrimal secretions

11. Examples

1 2
3
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Asthma( atopy) Eczema
Hay fever
Urticaria Anaphylactic shock
Acute dermatitis

12. Other examples:
Theobald smith phenomenon
PK ( Prusnitz kunster) reaction
Casoni’s skin test
Schultz Dale phenomenon

13. TYPE II HYPERSENSITIVITY
Type II hypersensitivity is also known as cytotoxic hypersensitivity and may affect a variety of
organs and tissues
It is mediated by antibodies directed towards antigen on cell surfaces or extracellular matrix.
The antigens are normally endogenous, although exogenous chemicals that can attach to
cell membranes can also leads to type II hypersensitivity.

14. 1
2
3
Mechanism
This type occurs when
IgG or IgM antibodies
bind to antigens on cell
surfaces, leading to cell
destruction via
complement activation.
Common Examples
Conditions such as
hemolytic anemia and
autoimmune diseases like
Graves' disease exemplify
Type II reactions.
Symptoms
Symptoms may include
fatigue, jaundice, and other
organ-specific issues
resulting from the
destruction of affected cells.

15. PATHOGENESIS:
Antigen on the surface of target cells
Circulating B lymphocytes get activated
Differentiate to form plasma cells
Antibodies formed ( IgG or IgM)
Ag - Ab complex formed
Activation of classical pathway of serum complement
Generates activated complement component C3b
Activated C3b bound to the target cell acts an opsonin
Phagocytosis

17. EXAMPLES:
Myasthenia gravis
Blood transfusion reactions
Graves’ disease
Insulin resistant disease
Rheumatic fever
Hyper graft rejection
Pernicious anaemia

18. TYPE III HYPESENSITIVITY
It is a reactions result from deposition of antigen- antibody complexes on tissue, which is
followed by activation of the complement system and inflammatory reaction, resulting in cell
injury.
The reaction may take 3- 10 hours after exposure to the antigen.
Excess amounts of antibodies like IgG or IgM are produced in this type.

19. Mechanism
Involves the formation of
immune complexes that
deposit in tissues, causing
inflammation and tissue
damage through
complement activation.
Common Examples
Diseases such as systemic
lupus erythematosus and
rheumatoid arthritis
showcase Type III
hypersensitivity.
Symptoms
Symptoms often include
joint pain, skin rashes, and
systemic effects depending
on the location of immune
complex deposition.

20. PATHOGENESIS:
Soluble antigen
Circulating B lymphocytes get activated
Differentiate to form plasma cells
Antibodies formed
Immune complexes are formed by interaction of soluble antibody and antigen
Fc component of antibody links with complement and activates the complement
Formation of C3a, C5a and membrane attack complex
Accumulated neutrophils and macrophages in the tissue release cytokines
Inflammation and tissue destruction

22. EXAMPLES:
Serum sickness
Henoch- Schonlein Purpura
Arthus reaction
Reactive arthritis

23. Type IV Hypersensitivity
Type IV hypersensitivity is a form of immune response characterized by T cell-mediated
activation, differing from antibody-mediated responses. Commonly seen in conditions like
contact dermatitis and graft-versus-host disease, the symptoms develop over 24-72 hours
after exposure, leading to noticeable skin reactions.
Type IV or delayed hypersensitivity reaction is tissue injury by T cell- mediated immune
response without formation of antibodies (contrary to type I, II and III).It is a slow and
prolonged response.
Treatment includes anti- inflammatory agents.

24. Mechanism
This delayed-type
hypersensitivity is
mediated by T cells rather
than antibodies, leading to
tissue damage after a
sensitization period.
Common Examples
Contact dermatitis and
graft-versus-host disease
are typical examples of
Type IV hypersensitivity.
Symptoms
Symptoms usually appear
24-72 hours after exposure
and can include redness,
swelling, and blistering at
the site of contact.

25. PATHOGENESIS:
Antigen is recognised and processed by antigen presenting cells
Antigen- presenting cells migrate to lymph node where antigen is presented to helper T cells
(TH1 cells)
TH1 cells release cytokines (TNF-α, IFN- γ, IL- 2 and IL-12)
Cell destruction and granuloma formation

27. EXAMPLES:
John mote reaction
Tuberculin reaction
Lepromin reaction
Pernicious anaemia
Contact dermatitis

28. Diagnosis and Testing
1
2
3
Skin Tests
Skin prick tests or intradermal
tests are commonly used to
identify allergens causing Type
I hypersensitivity.
Blood Tests
Specific IgE tests and complement
activation tests can help diagnose
Type II and Type III
hypersensitivities.
Patch Tests
Used for diagnosing Type IV
hypersensitivity, these tests involve
applying allergens to the skin and
monitoring for reactions.

29. Treatment Strategies
Avoidance
The primary strategy for
managing hypersensitivity is to
avoid known allergens to prevent
reactions.
Medications
Antihistamines, corticosteroids,
and immunomodulators can help
manage symptoms and reduce
inflammation.
Immunotherapy
Allergen desensitization therapy
may be beneficial for some
patients, particularly those with
Type I hypersensitivity.

30. Conclusion on Hypersensitivity
Hypersensitivity encompasses a range of immune responses that can lead to significant health issues.
Understanding the types, mechanisms, symptoms, and treatment options is crucial for effective management and
improving patient outcomes.
Immune Responses
Hypersensitivity includes a range
of immune responses.
Health Issues
It can lead to significant health
issues.
Effective Management
Understanding types and
treatment options aids in
management.