Primary Immunodeficiencies

Question 1

DiGeorge syndrome is due to what failure of development?

Answer 1

Failure of formation of the 3rd and 4th pharyngeal pouch

Question 2

What is the gene mutation with DiGeorge syndrome?

Answer 2

22q11 microdeletion

Question 3

What are the three classic findings of patients with DiGeorge syndrome?

Answer 3

Abnormalities of the face
Hypocalcemia
T-cell deficiency

Question 4

What is the pathophysiology behind the T cell deficiency seen in DiGeorge syndrome?

Answer 4

Lack of a thymus

Question 5

What is the pathophysiology behind the hypocalcemia seen in DiGeorge syndrome?

Answer 5

No parathyroids thus no PTH

Question 6

What two types of pathogens are pts with DiGeorge syndrome susceptible to?

Answer 6

Viruses
Fungi
(these are T cell mediated defenses)

Question 7

Which types of immunity are affected in SCID: humoral or cell mediated?

Answer 7

Both

Question 8

What are the three major etiologies of SCID?

Answer 8

1. Cytokine receptor defects
2. Adenosine deaminase deficiency
3. MHC class II deficiency

Question 9

Why does an adenosine deaminase deficiency result in SCID?

Answer 9

Inability to deaminate adenosine results in accumulation of toxic adenosine in lymphocytes

Question 10

Why does MHC class II deficiency result in SCID?

Answer 10

No CD4+ Th cell activation, thus no helper cells (T-helper cells are the conductors of the immune system)

Question 11

What is the treatment for SCID?

Answer 11

Stem cells transplant in bone marrow

Question 12

What is the pathophysiology behind X-linked agammaglobinemia?

Answer 12

Disordered B cell maturation, leading to a complete lack of immunoglobin

Question 13

What is the protein that is mutated in X-linked agammaglobinemia?

Answer 13

Bruton Tyrosine Kinase

Question 14

What are the three infections that pts with X-linked agammaglobinemia are susceptible to?

Answer 14

Bacterial
Enterovirus
Giardia

Question 15

What patients must avoid live vaccines? (2)

Answer 15

X-linked agammaglobinemia

SCID

Question 16

Why is it that pts with X-linked agammaglobinemia do not present with symptoms before 6 months of age?

Answer 16

Still have maternal antibodies

Question 17

What is the pathophysiology behind common variable deficiency?

Answer 17

Low immunoglobin d/t B cell or Th cell defects

Question 18

What are the three infections that CVID pts are susceptible to?

Answer 18

1. Bacterial
2. Giardia
3. Enterovirus

Question 19

What is the malignancy that CVID pts are susceptible to? Why?

Answer 19

B cell lymphoma d/t proliferation of B cells

Question 20

What is the pathophysiology behind IgA deficiency?

Answer 20

Low serum IgA, leading to an increased risk for mucosal infections

Question 21

What is the most common immunoglobin deficiency?

Answer 21

IgA deficiency

Question 22

Which GI disease is associated with IgA deficiency?

Answer 22

Celiac disease

Question 23

What type of infections are patients with IgA deficiencies susceptible to?

Answer 23

Mucosal infections, especially viral

Question 24

What is the mutation involved in hyper IgM syndrome?

Answer 24

Second cell signals to B cells (CD40 ligand) do not function, thus no class switching from IgM

Question 25

What are the two ways in which B cells are activated?

Answer 25

Antigen binds IgM on cell surface B cell internalizes antigen, and presents to CD4+ Th cells

Question 26

When CD4+ T cells are activated by B cells, what two cytokines do they produce to induce B cells to switch from IgM to other immunoglobin classes?

Answer 26

IL-4 | IL-5

Question 27

Why is there still adequate amounts of IgM in hyper IgM syndrome?

Answer 27

B cells can still be activated via IgM binding to antigens on cell surface receptor

Question 28

What are the three symptoms of Wiskott-Aldrich syndrome?

Answer 28

1. Thrombocytopenia 2. Eczema 3. Recurrent infx

Question 29

What is the mutation involved in Wiskott-Aldrich syndrome (what gene on what chromosome)?

Answer 29

Defect in the WASP gene on the X chromosome

Question 30

Deficiency if C5-C9 pose an increased risk with what infection in particular?

Answer 30

Neisseria (gonorrhea, meningitis etc)

Question 31

C1 inhibitor deficiency causes what physical symptoms?

Answer 31

Hereditary angioedema

Question 32

What is the pathophysiology behind C1 inhibitor deficiency?

Answer 32

Not inhibiting C1 will lead to chronic edema and inflammation d/t no inactivation of complement

Question 33

C1 inhibitor deficiency causes what physical symptoms?

Answer 33

Hereditary angioedema--periorbital edema especially