primary immunodeficiencies

Question 1

DiGeorge syndrome: what is it? What is it’s cause?

Answer 1

developmental failure of the 3rd and 4th pharyngeal pouches d/t 22q11 microdeletion

Question 2

What is the presentation of DiGeorge syndrome?

Answer 2

1. T cell deficiency: they have no thymus
2. Hypocalcemia: they have no parathyroid
3. Abnormalities of heart, great vessels, and face

Question 3

What is SCID? Definition, manifestation, and tx

Answer 3

severe combined immunodeficiency with defective cell mediated AND humoral immunity
causes susceptibility to fungal, viral, bacterial, and protozoal infections, including opportunistic infections and live vaccines
tx: sterile isolation (bubble boy) and stem cell transplantation

Question 4

What are the etiologies of SCID?

Answer 4

1. cytokine receptor defects: remember that cytokine signaling is necessary for the prolif and maturation of T and B cells
2. Adenosine deaminase deficiency: ADA is necessary to deaminate adenosine and deoxyadenosine for excretion as waste products. Build up of adenosine and deoxyadenosine is toxic to lymphocytes
3. MHC class II deficiency: MHC class II is necessary for CD4+ T cell activation and cytokine (which in turn supports CD 8+ T cells and B cells.

Question 5

What is X-linked agammaglobulinemia? What is the etiology of agammaglobulinemia?

Answer 5

complete lack of immunoglobulin d/t disordered B cell maturation (pre and pro B cells can’t mature)
etiology: mutated Bruton tyrosine kinase, which is X-linked (TK is a signaling molecule needed for a naive B cell to become a plasma cell)

Question 6

How does X-linked agammaglobulinemia present? Considerations in management of these pts?

Answer 6

after 6 mo of like of recurrent bacterial, enterovirus (polio and coxsackievirus), and Giardia lamblia infections (last 2 b/c they don’t have mucosla protection). Moms abs are protective for first 6 mo.
absent or scanty lymph nodes
Avoid live vaccines?

Question 7

What is common variable immunodeficiency?

Answer 7

disease characterized by low immunoglobulin d/t B cell or helper T cell defects

Question 8

Symptoms of common variable immunodeficiency

Answer 8

incr. risk of bacterial enterovirus (polio, coxsacchie), and giardia lamblia infections, esp. in late childhood. Also incr. risk for autoimmune disease and lymphoma

Question 9

What is IgA deficiency? What is it, clinical manifestations and important associations? Management considerations

Answer 9

low serum and mucosal IgA. most common immunodeficiency
incr. risk of mucosal infection, esp. viral- but most pts are asymptomatic
These pts will have an anaphylaxis to IgA containing products
may be associated with celiac disease

Question 10

What is hyper IgM syndrome?

Answer 10

characterized by elevated IgM levels
Due to mutated CD40 ligand (on helper T cells) or CD40 receptor (on B cells).  Therefore, the second signal can't be delivered to T cells.  This activation is needed for B cell class switching to IgA, IgG and IgE subtypes.
Patients have low IgA, IgG, and IgE, and are susceptible to recurrent pyogenic infections (from poor opsonization), esp. at mucosal sites.

Question 11

What is wiskott aldrich syndrome? What is its cause?

Answer 11

characterized by thrombocytopenia, eczema, and recurrent infections (from defective humoral and cellular immunity). Bleeding is a major cause of death.
D/t a muation in X-linked WASP gene

Question 12

What is the significance of a C1 inhibitor deficiency?

Answer 12

herediatary angioedema characterized by edema of the skin (esp. periorbital edema) and mucosal surfaces

Question 13

What is the significance of C5-9 deficiencies?

Answer 13

incr. risk of Neisseria infection (N gonorrhoeae and N meningitidis)

Question 14

What happens with IL-12 receptor deficiencies?

Answer 14

Decreased Th1 response. autosomal recessive.

Reduced IFN-gamma. Pts get disseminated mycobacterial and fungal infections. It may present after BCG vaccine

Question 15

What is hyper IgE syndrome?

Answer 15

autosomal dominant syndrome casued by a deficiency in Th17 cells due to a STAT3 mutation. These patiens have impaired recruitment of neutrophils to sites of infection. FATED: coarse facies, non-inflammed staph abscesses, retained primary teeth, incr. IgE, and Derm problems (eczema). they have high IgE and low IFN gamma

Question 16

What is ataxia telangiectasia? Etiology and clinical manifestations

Answer 16

increased AFPthis is a disease casued by defects in the ATM gene. Without ATM gene, DNA double stranded breaks cannot be repaired and there is cell cycle arrest. Triad of problems: cerebellar defects that cause ataxia, spider angiomas (telengiectasias), and IgA deficiency and other immunodeficiencies

Question 17

What are some biochemical findings in ataxia telangiactasia?

Answer 17

increased alpha fetal protein, decr. IgA, IgG, and IgE

Question 18

What is chronic mucocutaneous candidiasis?

Answer 18

T cell dysfunction with many causes. manifests as noninvasive candida infections of skin and mucous membranes. diagnostic testing: absent in vitro t cell prolif. in response to candida antigens; absent cutanoues rxn to candida antigens.