Primary Immunodeficiencies Flashcards
DiGeorge syndrome is due to what failure of development?
Failure of formation of the 3rd and 4th pharyngeal pouch
What is the gene mutation with DiGeorge syndrome?
22q11 microdeletion
What are the three classic findings of patients with DiGeorge syndrome?
Abnormalities of the face
Hypocalcemia
T-cell deficiency
What is the pathophysiology behind the T cell deficiency seen in DiGeorge syndrome?
Lack of a thymus
What is the pathophysiology behind the hypocalcemia seen in DiGeorge syndrome?
No parathyroids thus no PTH
What two types of pathogens are pts with DiGeorge syndrome susceptible to?
Viruses
Fungi
(these are T cell mediated defenses)
Which types of immunity are affected in SCID: humoral or cell mediated?
Both
What are the three major etiologies of SCID?
- Cytokine receptor defects
- Adenosine deaminase deficiency
- MHC class II deficiency
Why does an adenosine deaminase deficiency result in SCID?
Inability to deaminate adenosine results in accumulation of toxic adenosine in lymphocytes
Why does MHC class II deficiency result in SCID?
No CD4+ Th cell activation, thus no helper cells (T-helper cells are the conductors of the immune system)
What is the treatment for SCID?
Stem cells transplant in bone marrow
What is the pathophysiology behind X-linked agammaglobinemia?
Disordered B cell maturation, leading to a complete lack of immunoglobin
What is the protein that is mutated in X-linked agammaglobinemia?
Bruton Tyrosine Kinase
What are the three infections that pts with X-linked agammaglobinemia are susceptible to?
Bacterial
Enterovirus
Giardia
What patients must avoid live vaccines? (2)
X-linked agammaglobinemia
SCID
Why is it that pts with X-linked agammaglobinemia do not present with symptoms before 6 months of age?
Still have maternal antibodies
What is the pathophysiology behind common variable deficiency?
Low immunoglobin d/t B cell or Th cell defects
What are the three infections that CVID pts are susceptible to?
- Bacterial
- Giardia
- Enterovirus
What is the malignancy that CVID pts are susceptible to? Why?
B cell lymphoma d/t proliferation of B cells
What is the pathophysiology behind IgA deficiency?
Low serum IgA, leading to an increased risk for mucosal infections
What is the most common immunoglobin deficiency?
IgA deficiency
Which GI disease is associated with IgA deficiency?
Celiac disease
What type of infections are patients with IgA deficiencies susceptible to?
Mucosal infections, especially viral
What is the mutation involved in hyper IgM syndrome?
Second cell signals to B cells (CD40 ligand) do not function, thus no class switching from IgM
What are the two ways in which B cells are activated?
Antigen binds IgM on cell surface
B cell internalizes antigen, and presents to CD4+ Th cells
When CD4+ T cells are activated by B cells, what two cytokines do they produce to induce B cells to switch from IgM to other immunoglobin classes?
IL-4
IL-5
Why is there still adequate amounts of IgM in hyper IgM syndrome?
B cells can still be activated via IgM binding to antigens on cell surface receptor
What are the three symptoms of Wiskott-Aldrich syndrome?
- Thrombocytopenia
- Eczema
- Recurrent infx
What is the mutation involved in Wiskott-Aldrich syndrome (what gene on what chromosome)?
Defect in the WASP gene on the X chromosome
Deficiency if C5-C9 pose an increased risk with what infection in particular?
Neisseria (gonorrhea, meningitis etc)
C1 inhibitor deficiency causes what physical symptoms?
Hereditary angioedema
What is the pathophysiology behind C1 inhibitor deficiency?
Not inhibiting C1 will lead to chronic edema and inflammation d/t no inactivation of complement
C1 inhibitor deficiency causes what physical symptoms?
Hereditary angioedema–periorbital edema especially
