Pathology bootcamp

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the most likely underlying condition in this infant?

Hyper IgE syndrome
Severe combined immunodeficiency
Leukocyte adhesion deficiency (correct)
Chronic granulomatous disease

What is the significance of the positive nitroblue tetrazolium dye reduction test?

It confirms the diagnosis of chronic granulomatous disease (correct)
It indicates a defect in phagocytosis
It suggests a deficiency in superoxide production
It rules out a defect in the ubiquitin-proteasomal pathway

What is the likely cause of the infant's omphalitis?

Impaired migration of leukocytes to the site of infection (correct)
Impaired opsonization of bacterial pathogens
An abnormality in the ubiquitin-proteasomal pathway
Defective production of reactive oxygen species

What is the classification of the genetic defect in leukocyte adhesion deficiency?

Autosomal recessive (C) Signup and view all the answers

What is the role of CD18 (LFA-1) in leukocyte function?

Adhesion to endothelial cells (B) Signup and view all the answers

Which of the following is NOT a feature of leukocyte adhesion deficiency?

Elevated immunoglobulin E levels (C) Signup and view all the answers

What is the likely consequence of a defect in superoxide production?

Impaired killing of bacterial pathogens (D) Signup and view all the answers

Which of the following is a complication of leukocyte adhesion deficiency?

Omphalitis (B) Signup and view all the answers

What is the function of C5a in the complement system?

Neutrophil chemotaxis and histamine release from mast cells (D) Signup and view all the answers

What is the function of LFA-1 (CD11a/CD18) in neutrophils?

Tight adhesion (C) Signup and view all the answers

What is the result of a defect in the LYST gene?

Chediak-Higashi Syndrome (D) Signup and view all the answers

Which cytokine is secreted by Th1 cells and activates macrophages to increase the inflammatory response?

IFN-γ (A) Signup and view all the answers

What is the result of a defect in CD18?

Leukocyte adhesion deficiency type 1 (B) Signup and view all the answers

What is the function of PECAM-1 (CD31) in neutrophils?

Transmigration (A) Signup and view all the answers

What is the function of C3b in the complement system?

Opsonization (C) Signup and view all the answers

What is the result of a defect in the LFA-1 (CD18) adhesion molecule?

Leukocyte adhesion deficiency type 1 (D) Signup and view all the answers

What is the function of CD14 in the recognition of LPS?

Co-receptor for TLR4 (A) Signup and view all the answers

What is the result of a granuloma?

Chronic inflammation (C) Signup and view all the answers

What is the primary function of Toll-Like Receptors (TLRs)?

To recognize and respond to pathogens and damaged cells (D) Signup and view all the answers

What is the result of Leukocyte Adhesion Deficiency?

Impaired neutrophil migration (B) Signup and view all the answers

Which of the following is NOT a component of the acute inflammatory response?

Granulomas (D) Signup and view all the answers

What is the role of Hageman Factor XII in the inflammatory response?

Activation of bradykinin (A) Signup and view all the answers

What is the primary characteristic of chronic inflammatory response?

Formation of granulomas (A) Signup and view all the answers

What is the result of Chediak-Higashi Syndrome?

Defective lysosomal function (D) Signup and view all the answers

Study Notes

Physical Examination

Tenderness and erythema at the umbilical stump with serosanguinous drainage
Umbilical cord remains attached from birth
Induration along the surrounding tissues
Bulging right tympanic membrane with opacification and loss of light reflex

Laboratory Evaluation

Hemoglobin: 16.5 g/dL
Leukocyte count: 45,500/mm3
Platelet count: 185,000/mm3
C-reactive protein: Elevated
Nitroblue tetrazolium dye reduction test: Positive

Inflammatory Response

Toll-Like Receptors (TLRs) recognize PAMPs and DAMPs, triggering an inflammatory response
Arachidonic acid: lipooxygenase pathway à leukotrienes à ↑ neutrophil chemotaxis
Bradykinin, Hageman Factor XII: ↑ vasodilation, vascular permeability, and pain sensitivity
Inflammatory cytokines: IL-1, TNF-⍺, IL-6 à acute inflammatory process
Damaged endothelial cells: ↑ nitric oxide à ↑ vasodilation

Neutrophil Migration

Margination: ↑ vascular permeability à hemoconcentration à ↑ neutrophil contact with endothelium
Rolling: Neutrophil: Sialyl LewisX; Endothelium: E-selectin, P-selectin
Tight Adhesion: Neutrophil: LFA-1 (CD11a/CD18), Mac1 (CD11b/CD18); Endothelium: ICAM-1 (CD54)
Transmigration: Neutrophil: PECAM-1 (CD31); Endothelium: PECAM-1 (CD31); driven by chemotaxis (LTB4, IL-8, C5a)

Disorders of Leukocyte Migration

Leukocyte Adhesion Deficiency (LAD): absence of LFA-1 (CD18) à impaired tight adhesion
Chediak-Higashi Syndrome: impaired microtubule polymerization à ↓ neutrophil chemotaxis; LYST gene defect

Chronic Inflammation

Fibrosis and angiogenesis
Granulomas: maintained by IL-12 and TNF-⍺; composed of multinucleated giant cells, fibroblasts, lymphocytes, and epithelioid cells