Disorders of the Immune System Flashcards
In which patients should immunodeficiency be considered?
In infants presenting with unexplained failure to thrive, diarrhea, recurrent or chronic infections, or unexplained hepatosplenomegaly.
Recurrent bacterial infection suggests…, whereas unusual susceptibility to viral infection is indicative of….
- Humoral (B-cell) deficiency
2. Deficiency in cell-mediated immunity
Defects in complement C3 can cause failure of opsonization of bacteria, causing susceptibility to bacteria, especially…
Neisseria.
What is the pathophysiologic basis of hereditary angioedema?
Hereditary angioedema involves fluid accumulation in soft tissues and airways due to uncontrolled activation of the classical complement pathway, caused by deficiency of C1 inhibitor. It exhibits an autosomal dominant inheritance pattern.
How is hereditary angioedema managed medically?
With infusion of fresh frozen plasma or recombinant C1 inhibitor and daily therapy with attenuated androgens such as danazol.
Describe the pathophysiologic basis of chronic granulomatous disease (CGD).
In CGD, phagocytes ingest foreign pathogens, but fail to destroy them, causing a persistent cellular immune response. Consequently, granulomatous lesions form in a variety of tissues; patients with CGD develop pneumonia, lymph node infections, and abscesses in the skin, liver, etc.
Describe the inheritance pattern of CGD.
Most cases of CGD are transmitted in a recessive manner as a mutation on the X chromosome. The affected gene on the X chromosome codes for the gp91 protein p91-PHOX. CGD can also be transmitted in an autosomal recessive fashion (via CYBA and NCF1) and affects other PHOX proteins. The type of mutation that causes both types of CGD are varied and may be deletions, frame-shift, nonsense, and missense.
A low level of NADPH, the cofactor required for superoxide synthesis, can lead to CGD. This has been reported in women who are homozygous for the genetic defect causing glucose-6-phosphate dehydrogenase deficiency (G6PD), which is characterised by reduced NADPH levels.
The X-linked recessive form of CGD involves defective cytochrome b that confers failure to generate….
Hydrogen peroxide.
How does leukocyte adhesion deficiency commonly present?
As a life-threatening, acute infection of skin and mucus membranes, with impaired pus formation.
Describe the inheritance pattern and pathophysiologic basis of leukocyte adhesion deficiency.
Leukocyte adhesion deficiency is an autosomal recessive disease in which absence of the beta2 component of the leukocyte integrin molecule involved in cell adhesion produces phagocytes impaired in their ability to engage in diapedesis and thus ingestion of microorganisms in peripheral tissues.
Chediak-Higashi syndrome
Autosomal recessive
Partial albinism, recurrent bacterial infections, and malignant lymphoma
A defect in lysosome assembly causes deficiency in lysosomal killing of phagocytosed bacteria
How can leukocyte adhesion deficiency be cured?
Bone marrow transplantation.
Which HLA haplotype is very strongly associated with ankylosing spondylitis?
HLA-B27
