PRIMARY IMMUNODEFICIENCY

Question 1

What is DiGEORGE Syndrome? What is the genetic etiology?

Answer 1

Dvlm failure of 3rd and 4th pharyngeal pouches

22q11 microdeletion

Question 2

What are the lab findings of DiGEORGE SYNDROME?

Answer 2

HYPOCALCEMIA - Lack of Parathyroids

DECREASED T-cell count: Lack of Thymus (More susceptible to viral and fungal infections)

Question 3

What other structural abnormalities do you see with DiGeorge Syndrome other than lack of thymus/parathyroids?

Answer 3

SUPERIOR aspect of heart + great vessels + face

Question 4

What are 3 possible causes of SCID (Defective HUMORAL + T-cell mediated immunity)?

Answer 4

1) ADA DEFICIENCY - Lack of ADA -> Buildup of ADENOSINE and DEOXYADENOSINE that are toxic to lymphocytes
2) COMPLEMENT RECEPTOR DEFECTS
3) MHC CLASS II DEFICIENCY

Question 5

Which infections are SCID pts most susceptible to?

Answer 5

1) Increased susceptibility to FUNGAL/VIRAL infections - Defective T-cell function
2) Increased susc to PROTOZOAL/BACTERIAL infections - Defective B-cell function
3) Increased susc to OPPORTUNISTIC infections (almost like AIDS) - Defective CD4+ required for both B-cell and T-cell function

Question 6

What is the short-term Tx of SCID? What is the long-term Tx of SCID?

Answer 6

SHORT TERM: Sterile isolation (bubble baby)

LONG TERM: Stem cell Tx of donor intact HSC that can become B cells and T cells

Question 7

What is the etiology of X-LINKED AGAMMAGLOBULINEMIA? What is the pathology?

Answer 7

X-linked mutation of BRUTON TYR KINASE

Defective B-cell maturation into plasma B cells -> Lack Igs in the blood

Question 8

What infections (3) are X-linked AGAMMAGLOBULINEMIA pts susceptible to?

Answer 8

1. BACTERIAL - Lack IgG -> Can NOT opsonize bacteria
2. ENTEROVIRUS (Polio, Coxsackie) - Lack IgA
3. GIARDIA LAMBLIA - Lack IgA

Question 9

When do recurrent infections present themselves in a X-LINKED AGAMMAGLOBULINEMIA pt?

Answer 9

After 6mo of life - First 6mo, dependent on mother’s Igs

Question 10

What is the pathology of CVID?

Answer 10

Low Igs due to either:

1) B-cell defect
2) Th cell defect

Question 11

What infections are CVID pts most susceptible to? When do they tend to present? How is that different from X-linked agammaglobulinemia?

Answer 11

1-3) Low Igs (like X-linked agammaglobulinemia) - BACTERIAL, ENTEROVIRUS, GIARDIA

ASYMPTOMATIC until late childhood (unlike X-linked agammaglobulinemia - presents 6mo after birth)

Question 12

What two other conditions are CVID pts more susceptible to acquiring?

Answer 12

AUTOIMMUNE DISEASE

LYMPHOMA

Question 13

What is the most common Ig Deficiency? What infections are they most susceptible to?

Answer 13

IgA DEFICIENCY

MUCOSAL, viral infections

Question 14

What are the two possible etiologies of HYPER IgM SYNDROME?

Answer 14

1. Mutation in CD40L (CD4+Th2 cell)

2. Mutation in CD40R (B cell - APC)

Question 15

What is the pathology of HYPER-IgM SYNDROME?

Answer 15

No second signal of CD4+ Th2 cell - No IL-4, IL-5 produced 
NO IL-4: No class switching to IgG, IgE
NO IL-5: No class switching to IgA 
Elevated pre-class switching IgM

Question 16

What infections are HYPER-IgM SYNDROME most susceptible to?

Answer 16

Low IgE, Low IgA - Mucosal, viral infections
Low IgG - Low opsonization of bacteria, Pyogenic infections
BACTERIAL + ENTEROVIRUS + GIARDIA

Question 17

What is the etiology of WISKOTT-ALDRICH SYNDROME?

Answer 17

X-linked mutation in WASP gene (Cytoskeleton re-arrangement)

Question 18

What is the clinical triad of WISKOTT-ALDRICH SYNDROME?

Answer 18

THROMBOCYTOPENIA - Petechiae, increased bleeding
ECZEMA
RECURRENT INFECTIONS - Defective humoral and cellular immunity

Question 19

What is a major cause of death in WISKOTT ALDRICH SYNDROME pts?

Answer 19

Bleeding

Question 20

Which infection is C5-C9 COMPLEMENT DEFICIENT pts most susceptible to?

Answer 20

NEISSERIA infection - N. gonorrhoeae + N. meningitidis

Question 21

Explain the pathophysiology of C1 INHIBITOR DEFICIENCY.

Answer 21

Deficiency in C1 inhibitor -> HIGH C1 -> HIGH activation of CLASSICAL COMPLEMENT PATHWAY -> Extreme vasodilation + Increased capillary permeability

Question 22

What is the classic presentation of C1 INHIBITOR DEFICIENCY?

Answer 22

HEREDITARY ANGIOEDEMA: Edema of skin (PERIORBITAL**) + Skin
Puffy eyes/face of baby/lips
(Also puffy larynx, extremities)

Question 23

**UW: Pt is a celiac disease pt with a recurrent history of pneumonia. Receives blood transfusion with O- RBC, and during the transfusion develops facial swelling, generalized hives (URTICARIA), and SB. What is the diagnosis? Why?

Answer 23

IgA Deficiency
Has Anaphylaxis during transfusion because of the IgE Ab directed against IgA

IgE = anti-IgA (from the RBC transufsions) -> Fatal anaphylaxis

Question 24

**UW: NODULAR LYMPHOID HYPERPLASIA OF THE INTESTINE is commonly seen in which immunodeficiency?

Answer 24

CVID (Low Igs)