This document discusses the four types of hypersensitivity reactions: 1. Type I reactions are immediate and mediated by IgE antibodies. They include allergic reactions and anaphylaxis. 2. Type II reactions are cytotoxic and mediated by IgG and IgM antibodies attacking cell surfaces, causing cell lysis. Examples include autoimmune hemolytic anemia. 3. Type III reactions involve antigen-antibody complex deposition, complement activation, and inflammatory cell injury. Examples are immune complex glomerulonephritis. 4. Type IV reactions are delayed, cell-mediated responses without antibodies. Examples include tuberculin reactions and transplant rejection.

1. Diseases of
Immunity-
Hypersensitivity
Presented by :
Dr. Ajay Kirti Jain ,MD (Ayurveda)
Asso. Professor and H.O.D
Govt. Dhanwantari Ayurveda College , Ujjain

2. HYPERSENSITIVITY REACTIONS
(IMMUNOLOGIC TISSUE INJURY)
Hypersensitivity is defined as an exaggerated or inappropriate state of normal
immune response with onset of adverse effects on the body. The lesions of
hypersensitivity are a form of antigen antibody reaction. These lesions are termed
as hypersensitivity reactions or immunologic tissue injury, of which 4 types are
described: type I, II, III and IV

3. Types of hypersensitivity reactions
Depending upon the rapidity, duration and type of the immune response, these 4
types of hypersensitivity reactions are grouped into immediate and delayed type:
1. Immediate type in which on administration of antigen, the reaction occurs
immediately (within seconds to minutes). Immune response in this type is mediated
largely by humoral antibodies (B cell mediated). Immediate type of hypersensitivity
reactions includes type I, II and III.
2. Delayed type in which the reaction is slower in onset and develops within 24-48
hours and the effect is prolonged. It is mediated by cellular response (T cell
mediated) and it includes Type IV reaction.

4. Comparative Features of 4 Types of
Hypersensitivity Reactions

5. ETIOLOGY
Type I reaction is mediated by humoral antibodies of IgE type or reagin antibodies in response to
antigen. Although definite cause for this form of immediate reaction to allergen is not known,
following are the possible hypotheses:
1. Genetic basis : There is evidence that ability to respond to antigen and produce IgE are both
linked to genetic basis. For example, there is a 50% chance that a child born to both parents
allergic to an antigen, may have similar allergy.
2. Environmental pollutants: Another proposed hypothesis is that environmental pollutants
increase mucosal permeability and thus may allow increased entry of allergen into the body, which
in turn leads to raised IgE level.
3. Concomitant factors: An alternate hypothesis is that allergic response in type I reaction may be
linked to simultaneous occurrence of certain viral infections of upper respiratory tract in a
susceptible individual.

6. PATHOGENESIS – Type 1
Type I reaction includes participation by B lymphocytes and plasma cells, mast cells and basophils,
neutrophils and eosinophils.
i) During the first contact of the host with the antigen, sensitisation takes place
ii) During the second contact with the same antigen, IgE antibodies on the surface of mast cells-basophils
are so firmly bound to Fc receptors that it sets in cell damage—membrane lysis, influx of sodium and
water and degranulation of mast cells-basophils.
iii) 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, prostaglandins (thromboxane A2, prostaglandin
D2 and E2) and platelet activating factor
iv) The effects of these agents are:
• increased vascular permeability;
• smooth muscle contraction;
• early vasoconstriction followed by vasodilatation;
• shock;
• increased gastric secretion;
• increased nasal and lacrimal secretions; and
• Increased migration of eosinophils and
neutrophils at the
• site of local injury as well as their rise in blood
(eosinophilia and neutrophilia)

7. PATHOGENESIS – Type 1
EXAMPLES OF TYPE I REACTION. The manifestations of type I reaction may be variable in severity and
intensity. It may manifest as a local irritant (skin, nose, throat, lungs etc), or sometimes may be severe and
life-threatening anaphylaxis. Common allergens which may incite local or systemic type I
reaction are as under-
I. Systemic anaphylaxis:
 Administration of antisera e.g. anti-tetanus serum (ATS).
 Administration of drugs e.g. penicillin.
 Sting by wasp or bee.
The clinical features of systemic anaphylaxis include itching, erythema, contraction of respiratory
bronchioles, diarrhoea, pulmonary oedema, pulmonary haemorrhage, shock and death.
II. Local anaphylaxis:
 Hay fever (seasonal allergic rhinitis) due to pollen sensitisation of conjunctiva and nasal passages.
 Bronchial asthma due to allergy to inhaled allergens like house dust.
 Food allergy to ingested allergens like fish, cow’s milk, eggs etc.
 Cutaneous anaphylaxis due to contact of antigen with skin characterised by urticaria, wheal and flare.
 Angioedema, an autosomal dominant inherited disorder characterised by laryngeal oedema, oedema
of eyelids, lips, tongue and trunk.

8. Type 2-Cytotoxic (Cytolytic) Reaction
Type II or cytotoxic reaction is defined as reactions byhumoral antibodies that attack cell surface antigens on
the specific cells and tissues and cause lysis of target cells. Type II reaction too appears generally within 15-
30 minutes after exposure to antigen but in myasthenia gravis and thyroiditis it may appear after longer
duration.
ETIOLOGY AND PATHOGENESIS
The mechanism involved is as under-
i. The antigen on the surface of target cell (foreign cell) attracts and binds Fab portion of the antibody (IgG
or IgM) forming antigen-antibody complex.
ii. The unattached Fc fragment of antibodies (IgG or IgM) forms a link between the antigen and
complement.
iii. The antigen-antibody binding with Fc forming a link causes activation of classical pathway of serum
complement which generates activated complement component, C3b, by splitting C4 and C2 by C1.
iv. Activated C3b bound to the target cell acts as an opsonin and attracts phagocytes to the site of cell
injury and initiates phagocytosis.
v. Antigen-antibody complex also activates complement system and exposes membrane attack complex
(MAC) that attacks and destroys the target cell.

9. I. Cytotoxic antibodies to blood cells. Most common examples of type II reaction are on blood cells.
i. Autoimmune haemolytic anaemia
ii. Transfusion reactions due to incompatible or mismatched blood transfusion.
iii. Haemolytic disease of the new-born (erythroblastosis foetalis)
iv. Idiopathic thrombocytopenic purpura (ITP)
v. Leucopenia with agranulocytosis
vi. Drug-induced cytotoxic antibodies
II. Cytotoxic antibodies to tissue components
i. In Graves’ disease (primary hyperthyroidism), thyroid autoantibody is formed which reacts with the
TSH receptor to cause hyperfunction and proliferation.
ii. In myasthenia gravis, antibody to acetylcholine receptors of skeletal muscle is formed which blocks
the neuromuscular transmission at the motor end-plate, resulting in muscleweakness.
iii. In male sterility, antisperm antibody is formed which reacts with spermatozoa and causes impaired
motility as well as cellular injury.
iv. In type 1 diabetes mellitus, islet cell autoantibodies are formed which react against islet cell tissue.
v. In hyperacute rejection reaction, antibodies are formed against donor antigen.
EXAMPLES OF TYPE II REACTION.

10. Type III reactions result from deposition of antigen-antibody complexes on tissues, which is followed by
activation of the complement system and inflammatory reaction, resulting in cell injury. The onset of type III
reaction takes place about 6 hours after exposure to the antigen.
ETIOLOGY
Type III reaction is not tissue specific and occurs when antigen-antibody complexes fail to get removed by
the body’s immune system. There can be 3 types of possible etiologic factors precipitating type III reaction
i. Persistence of low-grade microbial infection
ii. Extrinsic environmental antigen
iii. Autoimmune process.
Type III: Immune Complex Mediated (Arthus)
Reaction

11. Common examples of cell injury by type III injury are as under:
i. Immune complex glomerulonephritis in which the antigen may be GBM or exogenous agents (e.g.
Streptococcal antigen).
ii. Goodpasture syndrome having GBM as antigen.
iii. SLE in which there is nuclear antigen (DNA, RNA) and there is formation of anti-nuclear and anti-DNA
autoantibodies.
iv. Rheumatoid arthritis in which there is nuclear antigen.
v. Farmer’s lung in which actinomycetes-contaminated hay acts as antigen.
vi. Polyarteritis nodosa and Wegener’s granulomatosis with antineutrophil cytoplasmic antigen.
vii. Henoch-Schönlein purpura in which respiratory viruses act as antigen.
viii. Drug-induced vasculitis in which the drug acts as antigen.
EXAMPLES OF TYPE III REACTION

12. Type IV or delayed hypersensitivity reaction is tissue injury by cell mediated immune response without
formation of antibodies (contrary to type I, II and III) but is instead a slow and prolonged response of
specifically-sensitised T lymphocytes. The reaction occurs about 24 hours after exposure to antigen and the
effect is prolonged which may last up to 14 days.
ETIOLOGY AND PATHOGENESIS
Type IV reaction involves role of mast cells and basophils, macrophages and CD8+ T cells.
Briefly, the mechanism of type IV reaction is as under
i. The antigen is recognised by CD8+ T cells (cytotoxic T cells) and is processed by antigen presenting
cells.
ii. Antigen-presenting cells migrate to lymph node where antigen is presented to helper T cells (CD4+ T
cells).
iii. Helper T cells release cytokines that stimulate T cell proliferation and activate macrophages.
iv. Activated T cells and macrophages release proinflammatory mediators and cause cell destruction.
Type IV: Delayed Hypersensitivity (Cell-
Mediated) Reaction

13. EXAMPLES OF TYPE IV REACTION
Type IV reaction can explain tissue injury in following common examples:
1. Reaction against mycobacterial infection e.g. tuberculin
reaction, granulomatous reaction in tuberculosis, leprosy.
2. Reaction against virally infected cells.
3. Reaction against malignant cells in the body.
4. Reaction against organ transplantation e.g. transplant
rejection, graft versus host reaction.

14. Thank you