Primary Immunodeficiency

Question 1

Primary Immunodeficiency Disorders

Answer 1

DiGeorge Syndrome
SCID
X-Linked Agammaglobulinemia
CVID
IgA Deficiency
Hyper-IgM Syndrome
Wiskott-Aldrich Syndrome
Complement Deficiencies

Question 2

DiGeorge Syndrome

Answer 2

22q11 microdeletion
Developmental failure of 3rd & 4th pharyngeal pouches

Presents with:
Lack of Thymus → T Cell Deficiency
Lack of Parathyroids → Hypocalcemia
Abnormalities of the heart, great vessels, face

Question 3

SCID - Etiologies

Answer 3

Severe Combined Immunodeficiency
(Both cell-mediated & humoral)

3 Etiologies:
Adenosine Deaminase Deficiency (Highest Yield)
Cytokine Receptor Defects
MHC-II Deficiency

Question 4

SCID - Adenosine Deaminase Deficiency

Answer 4

Can’t deaminate adenosine or deoxyadenosine.
Build-up of adenosine & deoxyadenosine in lymphocytes.
This is toxic to lymphocytes

Question 5

SCID - Cytokine Receptor Defects

Answer 5

Can’t mature B cells or activate CD8 cells

Question 6

SCID - MHC-II Deficiency

Answer 6

CD4s can’t get activated

Can’t mature B cells or activate CD8 cells

Question 7

SCID - Characteristics

Answer 7

No T Cells → Fungal & Viral infections
No B Cells → Bacterial & Protozoal infections
Opportunistic infections
Please avoid live vaccines

Question 8

SCID - Treatment

Answer 8

Sterile isolation (Bubble Baby)
Stem cell transplant

Question 9

X-Linked Agammaglobulinemia

Answer 9

X-Linked Bruton’s Tyrosine Kinase (BTK) mutation → Disordered B Cell Maturation → Naive B Cells can’t mature to Plasma Cells → Complete LACK of Ig

After 6 months of life, recurrent infections:
Bacterial (Can't opsonize)
Enterovirus (No IgA)
Giardia (No IgA)
Please avoid live vaccines eg Polio

Question 10

Enterovirus

Answer 10

Affects mucosal surface of GI tract

IgA protects mucosa normally

Question 11

Giardia

Answer 11

Usually leads to GI infection

IgA normally protects GI mucosa

Question 12

Which GI disease is associated with IgA deficiency?

Answer 12

Celiac Disease

Question 13

CVID

Answer 13

Common Variable Immune Deficiency
B Cell or Th defects → LOW levels of Ig

Recurrent infections (usually late in childhood):
Bacterial (Poor opsonization)
Enterovirus (Low IgA)
Giardia (Low IgA)

Increased risk (later in life):
Autoimmune disease
Lymphoma

Question 14

IgA Deficiency

Answer 14

Most common Ig deficiency
Low serum & mucosal IgA
Increased risk for mucosal infections (especially viral)

Question 15

Hyper IgM Syndrome

Answer 15

Mutated CD40L or CD40R
Characterized by elevated IgM

B Cell activation through binding Ag is intact → IgM production is intact
B Cell activation through phagocytosis, MHC-II presentation & CD40 coactivation is not intact → IL-4 & IL-5 are not secreted → No Class Switching → Low levels of:
IgA (Recurrent mucosal infections)
IgG (Recurrent pyogenic infections)
IgE

Question 16

Wiskott-Aldrich Syndrome

Answer 16

X-Linked Mutation in Wiskott-Aldrich Syndrome Protein (WASP) gene

Classic Triad:
Thrombocytopenia
Eczema
Recurrent Infections (from defective cellular & humoral immmunity)

Question 17

Complement Deficiencies

Answer 17

Deficiency in C5 - C9 → Increased risk for Neisseria infection

C1 Inhibitor Deficiency → Increased C1 activation → Increased complement activation → Vasodilation & increased vascular permeability → Hereditary angioedema: Edema of skin, (ESPECIALLY PERIORBITAL) and mucosal surfaces