WBR0691

Author	[[PageAuthor::Twinkle Singh, M.B.B.S. [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	USMLE Step 1
Main Category	Immunology
Sub Category	Pulmonology, Renal
Prompt	A 20-year-old man presents with complaints of chronic dry cough that has recently become associated with bloody sputum. His cough is associated with intermittent low-grade fever, malaise, shortness of breath, chest pain, and bloody urine. Chest X ray demonstrates bilateral patchy areas of consolidation. Urine examination is remarkable for the presence of red blood cell casts and protein. Serologic assays are positive for anti-GBM antibodies and negative for ANCAs. Which of the following types of hypersensitivity reactions is responsible for this patient’s condition?
Answer A	Type I hypersensitivity
Answer A Explanation	Type I hypersensitivity involves IgE-mediated reaction in which an antigen crosslinks two IgE antibody molecules on pre-sensitized mast cells. Subsequently, mast cells release histamines, leukotrienes, and prostaglandins. Anaphylaxis is an example of type I hypersensitivity.
Answer B	Type II hypersensitivity
Answer B Explanation	Type II hypersensitivity reactions are either IgM- or IgG-mediated, where antibodies attach to antigens on cell surfaces followed by complement-mediated lysis of cells. In Goodpasture’s syndrome, antibodies against antigen present in type IV collagen target GBM and alveolar basement membrane, both of which are rich in type IV collagen.
Answer C	Type III hypersensitivity
Answer C Explanation	Type III hypersensitivity involves antigen-antibody immune complexes. In this reaction, the antigen is not attached to tissues. Immune complexes circulate in blood and are deposited in various tissues where they activate complement and induce an inflammatory reaction.
Answer D	Type IV hypersensitivity
Answer D Explanation	Type IV hypersensitivity (delayed type hypersensitivity) is a cell-mediated response unlike other antibody-mediated hypersensitivity reactions. CD-4 helper T cells recognize antigens presented by antigen-presenting cells (APC) on major histocompatibility complex type II. Activated helper T cells release lymphokines and interferon gamma, which lead to the activation of macrophages.
Answer E	Mixed hypersensitivity
Answer E Explanation	Goodpasture's syndrome is a type II hypersensitivity. it is not a mixed hypersensitivity. An example of mixed hypersensitivity is hypersensitivity pneumonitis (type III and type IV).
Right Answer	B
Explanation	[[Explanation::Goodpasture’s syndrome is a pulmonary-renal syndromes that is characterized by the presence of auto-antibodies against type IV collagen. These auto-antibodies target the glomerular basement membrane and result in the development of rapidly progressive glomerulonephritis. Simultaneously, these auto-antibodies also target alveolar basement membrane leading to diffuse pulmonary haemorrhage. Goodpasture's syndrome is a classic example of type II hypersensitivity. Diagnosis is made by immunofluorescence, in which a linear pattern of staining is present along the renal glomerular basement membrane. Educational Objective: Type II hypersensitivity reactions are either IgM- or IgG-mediated, where antibodies attach to antigens on cell surfaces followed by complement-mediated lysis of cells. In Goodpasture’s syndrome, antibodies against antigen present in type IV collagen target GBM and alveolar basement membrane, both of which are rich in type IV collagen. References: First Aid 2015 page 212.]]
Approved	Yes
Keyword	Hypersensitivity, Goodpasture's syndrome, anti-GBM antibodies, Type II hypersensitivity, Auto-antibodies
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