2.3 Primary Immunodeficiency Flashcards
What is the cause of DiGeorge syndrome?
Developmental failure of the 3rd and 4th pharyngeal pouches d/t microdeletion of chr 22q11
What are the s/sx of DiGeorge syndrome? (CATCH-22)
- Cleft palate
- Abnormal Facies
- Thymic aplasia
- Cardiac Defects
- Hypocalcemia from hypoparathyroidism
What part of lymph nodes will be underdeveloped in DiGeorge syndrome?
Paracortex
SCID is a term for a variety of diseases that have what in common?
Defect in cell mediated and humoral immunity
What are the three major etiologies of SCID?
- Cytokine receptor defects
- Adenosine deaminase deficiency
- MHC class II deficiency
What is the inheritance pattern of adenosine deaminase deficiency SCID?
AR
What is the inheritance pattern of IL-2 Receptor deficiency SCID?
XLR
What is the usual presentation of SCID pts?
FTT
- diarrhea
- Thrush
- Recurrent infx
What is the treatment for SCIDs?
Sterile isolation and Bone marrow transplant
Where is there a mixed humoral and T cell deficiency in SCID d/t MHC class II deficiency?
CD4+ T cells are involved in maturation of both arms of adaptive immunity
True or false: live vaccines are absolutely contraindicated in SCID pts
True
What is X-linked (Bruton’s) agammaglobulinemia?
Defect in BTK (Y kinase gene) which prevents B cell maturation
True or false: there are no B cells in X-linked (Bruton’s) agammaglobulinemia
False–no Mature B cells, but there are B cells
What is the usual presentation of X-linked (Bruton’s) agammaglobulinemia?
Recurrent bacterial, enteroviral, and giardia infections AFTER 6 months
When do kids with X-linked (Bruton’s) agammaglobulinemia present with s/sx? Why?
After 6 months, when maternal Ig falls
What parasitic infection are patients with B cell deficiencies at risk for?
Giardia
True or false: Live vaccines are absolutely contraindicated in X-linked (Bruton’s) agammaglobulinemia
True
What is CVID?
Low Ig d/t B cell or Th cell defects d/t a variety of causes, and presents later in life (can be acquired).
What are the three major infections that CVID pts are susceptible to?
Bacterial
Enteroviruses
Giardia
What noninfectious diseases are CIVD pts susceptible to?
Lymphoma
Autoimmune diseases
What is the most common primary immunodeficiency?
IgA deficiency
What type of infections are patients with IgA deficiency more susceptible to?
Mucosal, especially viral infections
What autoimmune GI diseases is associated with IgA deficiency?
Celiac disease
What is hyper-IgM syndrome?
Defect on CD40L on Th cells, leading to the inability to switch ab classes
What is the usualy presentation of hyper-IgM syndrome?
Severe pyogenic infections early in life; opportunistic infections with pneumocystis, cryptosporidium, CMV
What are the two ways in which B cells can be activated?
- Direct binding of antigen to IgM
- Antigen presentation via MHC II + CD40
Why is IgM high in hyper-IgM syndrome?
-Direct binding of IgM via antigen is intact, but no CD40 interaction on Th cells to induce switching
Why is there a predisposition to pyogenic infections with hyper-IgM syndrome?
No IgG for opsonization
What is Wiskott-Aldrich syndrome? What is the classic triad of symptoms (TIE)?
-Mutation in WASP gene, leading to the inability of T cells to reorganize actin cytoskeleton
Triad:
- Thrombocytopenia
- Infections
- Eczema
What are the classic Ig findings in Wiskott-Aldrich syndrome?
- Decreased IgG and IgM
- Increased IgE and IgA
What is the inheritance pattern of Wiskott-aldrich syndrome?
XLR
Deficiencies in C5-C9 components of complement predisposes patients to what infectious bacteria?
Neisseria infections
C1 inhibitor deficiency leads to what? What is the classic presentation of this?
Hereditary angioedema d/t overactivation of C1 and inflammatory response
Periorbital edema
What is the defect in Ataxia-Telangiectasia? What is the classic triad of symptoms?
- ATM gene, which is responsible for repairing double stranded breaks, is defective
- Ataxia
- Telangiectasia
- IgA deficiency
What are the brain findings of Ataxia-Telangiectasia?
Cerebellar atrophy
What sort of imaging should never be done on pts with Ataxia-Telangiectasia?
Anything involving x-rays, d/t inability to repair double stranded breaks
What are the Ig findings of Ataxia-Telangiectasia?
Decreased IgG, IgA, and IgE
What is IL-12 receptor deficiency?
Low IL-12 decreased Th1 cells response, leading to disseminated mycobacterial and fungal infections
When does IL-12 receptor deficiency classically present?
After BCG vaccination
What is the inheritance pattern of IL-12 receptor deficiency?
AR
What happens to IFN-gamma with IL-12 receptor deficiency?
Decreased d/t no Th1 cells to produce it
What is AD hyper IgE-syndrome (Job syndrome)?
Deficiency of Th17 cells d/t STAT3 mutation.
-Leads to impaired recruitment of PMNs
What are the classic features of Hyper IgE syndrome? (DRAFT)
Dermatological problems Respiratory infx Abscesses Facies are coarse Two rows of Teeth
What is the hallmark characteristic abscesses in Job syndrome?
They are cold (lacking typical s/sx of inflammation) d/t a lack of PMN chemotaxis
What is the inheritance pattern of Job syndrome? Hyper IgE syndrome?
Job = AD
Hyper IgE = AR
What is chronic mucocutaneous candidiasis?
T cell dysfunction 2/2 a variety of causes leads to recurrent, non invasive candidal infections
