Primary immunodeficiency

Question 1

What embryonic structures are maldeveloped in DiGeorge Syndrome?

Answer 1

3rd and 4th pharyngeal pouches

Question 2

What deletion causes DiGeorge syndrome?

Answer 2

22q11 microdeletion

Question 3

What are the clinical signs of DiGeorge syndrome?

Answer 3

CATCH 22

• Cardiac defects
• Abnormal facies
• Thymic aplasia
• Cleft palate
• Hypocalcemia - lack of parathyroid glands

Question 4

T cell deficiency will leave a patient vulnerable to what kind of infections?

Answer 4

• Fungal

- Viral

Question 5

What are the 3 eitiologies behind SCID (severe combined immunodeficiency)

Answer 5

• Cytokine receptor defects
• Adenosine deaminase deficiency
• MHC class II deficiency

Leads to defective cell-mediated and humoral immunity

Question 6

What is adenosine deaminase?

- Why is this essential to lymphocytes

Answer 6

Enzyme necessary for deamination of adenosine and deoxyadenosine
- Build up of adenosine and deoxyadeonsine is toxic to lymphocytes

Question 7

What vaccines should be avoided in SCID and X-linked agammaglobulinemia patients?

Answer 7

Live vaccines

- e.g polio

Question 8

What is the treatment of SCID?

Answer 8

• Sterile isolation (bubble boy)

- Stem cell transplant

Question 9

What is X-link agammaglobulinemia due to?

What enzyme is defective?

Answer 9

• Mutated Bruton tyrosine kinase
• Disordered B-cell maturation
• Naive B cells cannot mature to plasma cells -> no immunoglobulins

Question 10

Where is the bruton tyrosine kinase (BTK) enzyme found?

Answer 10

X chromosome

• X-linked agammaglobulinemia

Question 11

When does X-linked agammaglobulinemia present?

Answer 11

6 months after life

Question 12

What infections become recurrent in X-linked agammaglobulinemia?

Answer 12

• Bacterial

- Enterovirus and Giardia (found on mucosa of GI tract - no IgA to protect)

Question 13

What is common variable immunodeficiency (CVID) due to?

Answer 13

Low immunoglobulin due to B-cell or helper T-cell defects

Question 14

What diseases are those with CVID at risk of?

Answer 14

• Bacterial, enterovirus and Giardia - usually late childhood
• Increased risk for autoimmune disease and lymphoma

Question 15

What is the most common Ig deficiency?

Answer 15

IgA deficiency

- At risk for mucosal infections - especially viral

Question 16

What GI disease has a high propensity of patients with IgA deficiency?

Answer 16

Celiac

Question 17

What is Hyper-IgM syndrome due to (mutation)?

- Describe the eitiology

Answer 17

• Mutated CD40L or CD40 receptor
• 2nd signal cannot be delivered to helper T cells during B-cell activation
• Cytokines necessary for Ig class switching not produced
• Low IgA, IgG and IgE result in recurrent pyogenic infections, esopecialy at mucosal sites

Question 18

What is the triad behind Wiskott-Aldrich Syndrome?

Answer 18

• Thrombocytopenia
• Eczema
• Recurrent infections (defective humoral and cellular immunity)

Question 19

How is Wiskott-Aldrich Syndrome inherited?

Answer 19

X-linked

- WAS protein (WASP)

Question 20

What infections are those with C5-C9 deficiency at risk of?

Answer 20

Neisseria (meningitis)

Question 21

What will those with C1 inhibitor deficiency develop, what characteristic sign?

Answer 21

• Hereditary angioedema
• Characterised by edema of skin - periorbital edema
• Mucosal surfaces edema