Type 1

Etiology of type 1 hypersensitivity

Exposure to allergens which is normally harmless lead to allergic reaction and may lead to anaphylaxis

Pathophysiology: -

On first exposure to the allergen the IgE antibodies are released and bind to mast cell

On second exposure , degranulation happens lead to release of histamine and cytokines

Treatment
Management and Treatment:

1 . Avoidance of Allergen.

2.Medications

-Antihistamines. -Corticosteroids -Bronchodilator -Epinephrine.

3.Immunotherapy (Desensitization)

Emergency Management of Anaphylaxis:

1 . Epinephrine (intramuscular injection) 2.Oxygen and IV fluids. 3.Antihistamines and corticosteroids

Clinical picture

Medical history alone is not sufficient to diagnose an allergic response. A complete physical examination
should also be performed. In general, a patient that presents with a type I hypersensitivity usually develops a
reaction within one hour after exposure to an antigen. The most common complaint and symptoms include
rash, erythema, pruritis, edema, flushing, bronchospasm, wheezing, rhinitis, and gastrointestinal symptoms
such as abdominal cramping. The presence of "wheal and-flare" (skin bump and redness) reactions are the
hallmark of IgE mediated reactions. Patients that present with anaphylaxis may also experience episodes of
loss of consciousness, nausea, vomiting, angioedema, hypotension, tachycardia ,tachypnea, etc .

Investigations
1. Skin Prick Test (SPT): . 2. Serum IgE Levels. 3. Radioallergosorbent Test (RAST)

4. Basophil Activation Test (BAT). 5. Challenge Tests:

 Type 2
Etiology of type 2 hypersensitivity:-

Excessive immune response against harmless substance lead to tissue damage and destruction mediated by antibody
this is why this type called cytotoxic hypersensitivity reaction

Pathophysiology:-

There is 3 main mechanisms of type 2 :-

1) Antibody and complement mediated structure

A) Formation membrane attack complex. B) opsonization

Examples :- autoimmune hemolytic anemia , mismatch blood transfusion

2) antibody dependant cell mediated cytotoxicty

Examples :- -medication induce hemolytic anemia or thrombocytopenia or neutropenia

3) target cell dysfunction

Graves disease:- presence of antibodies binds on TSH receptors lead to production of thyroid hormone without
negative feed back

Management and Treatment:

1 . Identify and Avoid Triggers

2. Medications:

-Corticosteroids -Immunosuppressive Agents. -Plasmapheresis. - Intravenous Immunoglobulin

3. Supportive Care: If hemolytic anemia is present, blood transfusions may be necessary.

Clinical pic

History and physical examination findings differ based on the disease category. presented. With type II
hypersensitivity reactions, during the history taking, the. patient might report repeated blood transfusions,
blood group or rhesus incompatibility, or a history of recent drug intake. The patient might clinically

present with features of autoimmunity, e.g., immune thrombocytopenia (characterized by bleeding disorders),
autoimmune hemolytic anemia (characterized by jaundice), and other blood dyscrasias (autoimmune
neutropenia) .In myasthenia gravis, the patient could have symptoms suggestive of generalizedmuscle
weakness with difficulty in mobilizing, eating, speech, and carrying out routine activities

investigation

1. Direct Coombs Test (Direct Antiglobulin Test) 2. Indirect Coombs Test.

3. Antinuclear Antibody (ANA) Test. 4. Enzyme-Linked Immunosorbent Assay (ELISA)

5. Complement Levels:
 type 3
Type III hypersensitivity, also known as immune complex-mediated hypersensitivity, occurs when antigen-
antibody complexes (immune complexes) are not adequately cleared by the immune system. This leads to an
inflammatory response and tissue damage.

Etiology:
1) Serum Sickness: Caused by drugs containing heterologous proteins (e.g., antivenins, vaccines, ).
Monoclonal and polyclonal antibodies from rabbit, horse, or mouse serum can also trigger this reaction.
2) Serum Sickness-Like Reactions (SSLR): Seen with synthetic monoclonal antibodies (chimeric proteins)
like infliximab (for rheumatoid arthritis and Crohn’s disease) and omalizumab (for asthma).
3) Insect Stings and Bites: Stings from insects, ticks, and mosquito bites can cause serum sickness
4) Infectious Diseases: Conditions like hepatitis B and bacterial endocarditis provide a continuous source
of antigens, forming circulating immune complexes.
5) Medications: Various drugs, including cephalosporins, penicillin, sulfonamides, tetracycline, and more,
are implicated in type III hypersensitivity reactions.

Pathophysioloy
1. Immune Complex Formation: The reaction begins when antibodies (mainly IgG and IgM) bind to soluble
antigens, forming immune complexes.
2. Deposition in Tissues: These immune complexes can deposit in various tissues, including blood vessel
walls, kidneys, and joints.
3. Complement Activation: The deposited immune complexes activate the complement system, a part of
the immune system that enhances the ability to clear microbes and damaged cells.
4. Inflammatory Response: Activation of the complement system attracts neutrophils and other
inflammatory cells to the site, leading to inflammation and tissue damage.
 Common conditions associated with Type III hypersensitivity include systemic lupus erythematosus
(SLE), rheumatoid arthritis (RA), and post-streptococcal glomerulonephritis.

Clinical Picture:

-Systemic Lupus Erythematosus (SLE). --Post-Streptococcal Glomerulonephritis

-Arthus Reaction. --Serum Sickness

Investigation

Blood tests:

• CBC. - Urine tests

•ESR OR CRP . - Tissue biopsy

•Complement Tests. - •Autoantibody Tests

Treatment

● Removal of the offending agent is the mainstay

● Antihistamines and NSAID can provide symptomatic relief.

● Corticosteroids are used in severe cases to suppress inflammation.

● treatment of SLE

● The patient must be hospitalized in cases of hemodynamic instability, or life-threatening symptoms,

 type 4
Type IV hypersensitivity, also known as delayed-type hypersensitivity, is a cell-mediated immune response
that typically takes 24-72 hours to develop.

Etiology:
1. Normal Physiological Events: These reactions help fight infections but can predispose to opportunistic
infections if dysfunctional.
2. Adverse Events: Occur when undesirable interaction between the immune system and an allergen
happens(e.g., poison ivy causing contact dermatitis).
3. Drug Triggers: Antibiotics, anticonvulsants, allopurinol, and more recently ,lamotrigine can trigger type IV
hypersensitivity reactions.
4. Viral Infections exposed to certain drugs: Certain viral infections (e.g., cytomegalovirus with antibiotics,
Epstein Barr virus with amoxicillin , herpesvirus 6 with anticonvulsant) can trigger reactions when exposed to
specific drugs.
5. Latex Exposure: Can cause both type I and type IV hypersensitivity reactions in susceptible individuals.

pathophysiology:
1. Antigen Presentation: When an antigen enters the body, it is processed and presented by antigen-presenting
cells (APCs) such as dendritic cells and macrophages.
2. T Cell Activation: The presented antigen is recognized by T cells, specifically CD4+ helper T cells and CD8+
cytotoxic T cells. These T cells become activated and proliferate.
3. Cytokine Release: Activated T cells release cytokines, which are signaling molecules that recruit and
activate other immune cells.
4. Inflammatory Response: The recruited immune cells, including macrophages and additional T cells, migrate
to the site of antigen exposure. They release enzymes and reactive oxygen species that cause local tissue
inflammation and damage.
 Examples of conditions involving Type IV hypersensitivity include contact dermatitis (e.g., reaction to poison
ivy), the tuberculin skin test, and chronic transplant rejection

Clinical Picture:

-Contact Dermatitis. -Tuberculosis. -Granulomatous Diseases -Multiple Sclerosis

Investigation

• Patch testing. •Skin prick test. • T-Cell Assays.

Contact dermatitis: Removing the offending agent ,topical steroids.

For Steven Johnson syndrome/toxic epidermolysis, aggressive life-saving therapy would be required, including
admission to an intensive care unit, optimal fluid therapy, antibiotics if there is a secondary infection.

For granulomatous conditions, therapy depends on the type of clinical condition. In both systemic and ocular
sarcoidosis, steroid therapy is the standard treatment.In addition to steroids, methotrexate has shown
efficacy in pulmonary sarcoidosis .In Crohn's disease, anti-tumor necrosis factor (TNF) monoclonal
antibodies can be used as an effective way to manage the disease.In schistosomiasis, praziquantel can be
used.Once the tuberculin test has revealed a positive result, the treatment of tuberculosis must be started,
and one of the commonest regimens is to give rifampin, isoniazid.

reference
 References :

https://www.ncbi.nlm.nih.gov/books/NBK560561/

https://www.ncbi.nlm.nih.gov/books/NBK563264/

Justiz Vaillant AA, Vashisht R, Zito PM. StatPearls [Internet]. StatPearls Publishing; Treasure Island
(FL): May 29, 2023. Immediate Hypersensitivity Reactions (Archived) [PubMed] Bach JF. The effect
of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002 Sep
19;347(12):911-20. [PubMed] Tomasiak-Łozowska MM, Klimek M, Lis A, Moniuszko M, Bodzenta-
Łukaszyk A. Markers of anaphylaxis - a systematic review. Adv Med Sci. 2018 Sep;63(2):265 277.
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