PRIMARY IMMUNODEFICIENCY Flashcards
What is DiGEORGE Syndrome? What is the genetic etiology?
Dvlm failure of 3rd and 4th pharyngeal pouches
22q11 microdeletion
What are the lab findings of DiGEORGE SYNDROME?
HYPOCALCEMIA - Lack of Parathyroids
DECREASED T-cell count: Lack of Thymus (More susceptible to viral and fungal infections)
What other structural abnormalities do you see with DiGeorge Syndrome other than lack of thymus/parathyroids?
SUPERIOR aspect of heart + great vessels + face
What are 3 possible causes of SCID (Defective HUMORAL + T-cell mediated immunity)?
1) ADA DEFICIENCY - Lack of ADA -> Buildup of ADENOSINE and DEOXYADENOSINE that are toxic to lymphocytes
2) COMPLEMENT RECEPTOR DEFECTS
3) MHC CLASS II DEFICIENCY
Which infections are SCID pts most susceptible to?
1) Increased susceptibility to FUNGAL/VIRAL infections - Defective T-cell function
2) Increased susc to PROTOZOAL/BACTERIAL infections - Defective B-cell function
3) Increased susc to OPPORTUNISTIC infections (almost like AIDS) - Defective CD4+ required for both B-cell and T-cell function
What is the short-term Tx of SCID? What is the long-term Tx of SCID?
SHORT TERM: Sterile isolation (bubble baby)
LONG TERM: Stem cell Tx of donor intact HSC that can become B cells and T cells
What is the etiology of X-LINKED AGAMMAGLOBULINEMIA? What is the pathology?
X-linked mutation of BRUTON TYR KINASE
Defective B-cell maturation into plasma B cells -> Lack Igs in the blood
What infections (3) are X-linked AGAMMAGLOBULINEMIA pts susceptible to?
- BACTERIAL - Lack IgG -> Can NOT opsonize bacteria
- ENTEROVIRUS (Polio, Coxsackie) - Lack IgA
- GIARDIA LAMBLIA - Lack IgA
When do recurrent infections present themselves in a X-LINKED AGAMMAGLOBULINEMIA pt?
After 6mo of life - First 6mo, dependent on mother’s Igs
What is the pathology of CVID?
Low Igs due to either:
1) B-cell defect
2) Th cell defect
What infections are CVID pts most susceptible to? When do they tend to present? How is that different from X-linked agammaglobulinemia?
1-3) Low Igs (like X-linked agammaglobulinemia) - BACTERIAL, ENTEROVIRUS, GIARDIA
ASYMPTOMATIC until late childhood (unlike X-linked agammaglobulinemia - presents 6mo after birth)
What two other conditions are CVID pts more susceptible to acquiring?
AUTOIMMUNE DISEASE
LYMPHOMA
What is the most common Ig Deficiency? What infections are they most susceptible to?
IgA DEFICIENCY
MUCOSAL, viral infections
What are the two possible etiologies of HYPER IgM SYNDROME?
- Mutation in CD40L (CD4+Th2 cell)
2. Mutation in CD40R (B cell - APC)
What is the pathology of HYPER-IgM SYNDROME?
No second signal of CD4+ Th2 cell - No IL-4, IL-5 produced NO IL-4: No class switching to IgG, IgE NO IL-5: No class switching to IgA Elevated pre-class switching IgM
What infections are HYPER-IgM SYNDROME most susceptible to?
Low IgE, Low IgA - Mucosal, viral infections
Low IgG - Low opsonization of bacteria, Pyogenic infections
BACTERIAL + ENTEROVIRUS + GIARDIA
What is the etiology of WISKOTT-ALDRICH SYNDROME?
X-linked mutation in WASP gene (Cytoskeleton re-arrangement)
What is the clinical triad of WISKOTT-ALDRICH SYNDROME?
THROMBOCYTOPENIA - Petechiae, increased bleeding
ECZEMA
RECURRENT INFECTIONS - Defective humoral and cellular immunity
What is a major cause of death in WISKOTT ALDRICH SYNDROME pts?
Bleeding
Which infection is C5-C9 COMPLEMENT DEFICIENT pts most susceptible to?
NEISSERIA infection - N. gonorrhoeae + N. meningitidis
Explain the pathophysiology of C1 INHIBITOR DEFICIENCY.
Deficiency in C1 inhibitor -> HIGH C1 -> HIGH activation of CLASSICAL COMPLEMENT PATHWAY -> Extreme vasodilation + Increased capillary permeability
What is the classic presentation of C1 INHIBITOR DEFICIENCY?
HEREDITARY ANGIOEDEMA: Edema of skin (PERIORBITAL**) + Skin
Puffy eyes/face of baby/lips
(Also puffy larynx, extremities)
**UW: Pt is a celiac disease pt with a recurrent history of pneumonia. Receives blood transfusion with O- RBC, and during the transfusion develops facial swelling, generalized hives (URTICARIA), and SB. What is the diagnosis? Why?
IgA Deficiency
Has Anaphylaxis during transfusion because of the IgE Ab directed against IgA
IgE = anti-IgA (from the RBC transufsions) -> Fatal anaphylaxis
**UW: NODULAR LYMPHOID HYPERPLASIA OF THE INTESTINE is commonly seen in which immunodeficiency?
CVID (Low Igs)