Types Of Hypersensitivity Reactions

When inappropriate immunologic responses occur in response to an antigen or allergen, they are known as hypersensitivity reactions. 

Hypersensitivity reactions are extremely important for your Pathology preparation. Read this blog till the end to understand this topic thoroughly and elevate your NEET PG preparation.

Immunity - Hypersensitivity Reactions

Gell & coomb classification

• Type I- Anaphylaxis 
• Type II- Cytotoxic
•  Type III- Immune Complex
• Type IV- Delayed Type     → Cell mediated

Type I Hypersensitivity Mechanism

• The first exposure: allergen. 
• Antigen-presenting cells pick up the allergen & going to keep the allergen on MHC and present it to the T cell. 
• T cells have alpha-beta receptors. 
• T cells differentiates into TH2 cells. 
• TH2 cells produce interleukin 4, interleukin 5, and interleukin 13. 
• Interleukin 4: isotype switching → antibody production 
• Interleukin 5: eosinophils activation happens.
• Interleukin 13: mucus production will occur. 
• Interleukin 4, 5, and 13 → forms IgE. 
• IgE sits on a mast cell in a distributed manner known as a sensitized mast cell. 
• When the second exposure happens, it will bridge the gap in the mast cell & undergoes polymerization. This will cause degranulation of the mast cell. 
• As a result, the mast cell bursts, will release histamine as the mast cell is a rich source of histamine. 

. What is the special stain for mast cells and basophils?

• Toluidine blue

Type I Hypersensitivity Early Phase

• Occurs within 2 hours
• Preformed mediators  - release of histamine & Tryptase.
  • Patients with allergies have a rise in serum tryptase.
• Newly formed mediators
  • PG
  • Leukotrine
  • Platelet Activating Factor
• All of these above mediators cause bronchoconstriction.
• Histamine causes vasodilation in the blood, and it causes bronchoconstriction in the lungs.

Type I Hypersensitivity Delayed Phase

• Occurs after 2 to 24 hours.
• Due to eosinophils
• Interleukin 5 is associated with it.
• Eosinophils release MBP (Major Basic Protein)

Difference between Anaphylaxis and Anaphylactoid

• Anaphylaxis: IgE is involved here
• Anaphylactoid reaction: IgE is not involved

Type I Hypersensitivity Examples

1. All kinds of allergies (allergic dermatitis, rhinitis, conjunctivitis.)
   • Other names of allergic conjunctivitis - VKC (Vernal KeratoConjunctivitis)
   • Drug of choice for VKC - Olapatadine
   • Olapatadine is a mast cell stabilizer. That means the cell will not burst. It also has antihistamine properties. 
   • ATOPY - Allergy with a genetic determinant - Cases where allergy runs in the family.
     • 5 chromosomes associated with ATOPY.
2. Bronchial Asthma
3. Casoni Test
   • The test is done for Echinococcus Granulosus.
4. Drugs (Penicillin - Test dose)
   • Some other hypersensitivity reaction examples include
     • PK reaction
     • Theobald smith phenomenon

Type II Hypersensitivity Mechanisms

Mechanisms
Opsonization and Phagocytosis	Antibody and antigen reactionsIgG will opsonize it, and phagocytosis will occur.
ADCC	Once the antigen is covered with IgG, it will be identified by NK cells and macrophage and all resulting in ADCC (Antibody dependent cellular cytotoxicity.)
Complement activation and inflammation	Antigen and antibody reactions activate the complement system.

Type II Hypersensitivity Examples

• My blood group is Rh+ve (mnemonic)
  • My: Myasthenia Gravis
  • Blood: blood transfusion reaction
  • Group: Good pasture syndrome and Graves disease
  • Is: Immune hemolytic anemia (IHA) - RBCs will break down
    • Immune thrombocytopenic purpura (ITP) - platelet will break down
  • Rh: Rh incompatibility/RHD
  • Positive: Pemphigus (Bullous) and Pernicious Anemia
• Myasthenia Gravis and Graves disease are now classified as Type V hypersensitivity.
  • In Myasthenia Gravis, Antibody is against acetylcholin receptor
  • In Graves disease, the antibody is against the TSH receptor
  • Graves disease is a classical hyperthyroidism
  • Antibodies are like stimulators
  • Antibodies against cellular receptor → type V hypersensitivity
  • They are also called thyroid-stimulating antibodies. They were previously known as LATS (Long-acting Thyroid stimulators). 

Type III Hypersensitivity - Phases

• Immune complex
• Occurs in 3 phases:
  • Immune complex formation - Here antigen and antibody are mobile and after some time they combine. 
  • Immune complex Deposition - These go and sit in some organs (joints, skin & serosa) 
  • Complement Activation - The patient will end up with signs and symptoms.
  • Duration - 10 to 14 days 
• Difference with Type II
  • In Type II, the antigen is fixed.
  • In Type III, both antibodies and antigens are roaming about.

Type III Hypersensitivity – Examples

• S - SLE
  • Serum sickness (anti-tetanus / anti-rabies serum)
  • Schick test (C. Diphtheriae)
• H - Henoch Schonlein Purpura (IgA Vasculitis in children)
• A - Arthus reaction (localized immune complex disease)
• R - Raji Assay, Reactive Arthritis
• P - PSGN (Poststreptococcal Glomerulonephritis) cola color urine
  • PAN, Parasitic diseases (eg, malaria → nephrotic syndrome → affecting kidneys)

Type IV Hypersensitivity 

• Delayed type hypersensitivity
• Only cell-mediated
• It has CD4 T cells and CD8 T cells
• Antigen presenting cell is the first one that picks up an antigen
• Then gives it to the T cell to form TH1 cells.
• TH1 releases interferon-gamma, forms granuloma. 
• CD8 T cells work as well in apoptosis and perform granzyme pathways.

Type IV Hypersensitivity – Examples

• Granuloma
• Skin test
  • Mantous test
  • Lepromin test
• IBD (Inflammatory Bowels Disease)
• Multiple sclerosis
• Contact dermatitis 
  • In contact to poison ivy in the world
  • Detergent and artificial jewelry in India
  • Women suffer from these more in India.

 Type V Hypersensitivity – Examples

• Myasthenia Gravis and Graves disease.
• There are antibodies against cellular receptors.

Controversial Hypersensitivity

• Rheumatoid arthritis. - Type 3 and Type 4
• Hypersensitivity pneumonitis - Type 3 and Type 4
• Transplant rejection
  • Hyperacute - Type 2
  • Acute - Type 2 and Type 4
  • Chronic - Type 4
• SLE: combination of type 2 <<< type 3 hypersensitivity. 

Ques. A 30-year-old HBsAg positive female complaints of feeling generally ill and fatigued, having fever, and loss of appetite and weight loss. Occasional episodes of muscle and or joint pains are reported. On GPE, the skin sores are noted. There is no cardiopulmonary discomfort noted. Her BP is raised. On arteriography, irregular narrowing and dilation of the blood vessels is noted. Biopsy of the vessels show fibrinoid necrosis. Which of the following hypersensitivity reactions play a role in this disease? Type I Type II Type III Type IV Ans -Type III Ques. A 42-year-old patient presents with cough and sputum. He also complains of weight loss, fever, and night sweats. On sputum examination, there are multinucleated giant cells along with lymphocytes , and macrophages. Numerous scattered cells with slipped shaped nuclei are noted. Which of the following hypersensitivity reactions play a role in this disease? Type I Type II Type III Type IV Ans- Type IV

And that is it! You have read everything you need to know about Hypersensitivity reactions and its types for your Pathology paper. For more interesting and informative posts like this, download the PrepLadder App and keep reading our blog!