Chp. 2 Primary Immunodeficiency

Question 1

What syndrome is due to maldevelopment of the 3rd and 4th pharyngeal pouches?

Answer 1

DiGeorge Syndrome

Question 2

DiGeorge Syndrome is due to failure of which structure(s)?

Answer 2

3rd and 4th pharyngeal pouches

Question 3

What is the 3rd pharyngeal pouch responsible for?

Answer 3

Dorsal Wing: Inferior PTH glands
Ventral Wing: Thymus

Both structures supplied by CN 9

Question 4

What is the 4th pharyngeal pouch responsible for?

Answer 4

Superior PTH gland
Parafollicular C cells
Cartilage and Laryngeal Muscles

Question 5

What exact chromosomal deletion is responsible for the failure of the 3 and 4 pharyngeal pouch development?

Answer 5

It is due to 22q11 micro deletion. This means that the deletion is on chromosome 22 on the long arm at spot 11; there are 30-40 genes missing.

Question 6

What do patients with DiGeorge present with?

Answer 6

DiGeorge presents with T-cell deficiency due to a lack of a thymus

Hypocalcemia due to lack of parathyroid glands

Abnormalities of the great vessels (Tetrology of Fallot)

Facial and Ear deformities

Question 7

In SCID, what kind of immunity is defective?

Answer 7

Both Humoral AND Cell Mediated Immunity

Question 8

What are the three etiologies (or 3 different ways a patient can get) of SCID?

Answer 8

1. Cytokine Receptor Defects
2. Adenosine Deaminase Deficiency
3. MHC II Deficiency

Question 9

What kind of infections would be seen in SCID patients?

Answer 9

These patients are susceptible to fungal, viral, bacterial, protozoal; opportunistic infections and live vaccines (body can’t tolerate live vaccine)

Question 10

What is treatment for SCID patients?

Answer 10

Sterile Isolation (Bubble Baby)
Stem Cell Transplantation

Question 11

How does cytokine receptor defects lead to SCID?

Answer 11

Because cytokine signaling is necessary for proliferation and maturation of B cells

Question 12

How does ADA Deficiency lead to SCID?

Answer 12

ADA is necessary for the deamination of adenosine and deoxyadenosine. Deamination is a step in breaking down these molecules. W/o this enzyme, these 2 molecules can’t be broken down and instead will accumulate inside the lymphocyte. Not good bc these molecules are CYTOTOXIC TO LYMPHOCYTES

Question 13

How does MHC II Deficiency lead to SCID?

Answer 13

W/o MHC II, CD4+ T cells cannot recognize Ag. If they never recognize Ag, they can never become activated. Thus many parts of the immune system will never become activated!!!

Question 14

What is the disorder that is characterized by a complete lack of immunoglobulin?

Answer 14

X-Linked Agammaglobulinemia and is due to disordered B-cell maturation.

Specifically, the Pre and Pro B cells cannot mature. Basically, naive cells cannot become Plasma cells, and its plasma cells that secrete Abs.

Question 15

What enzyme is deficient in X-Linked Agammaglobulinemia?

Answer 15

Bruton’s Tyrosine Kinase. BTK is necessary for a naive B cell to mature into a plasma cell.

Question 16

When does BTK present?

Answer 16

Presents after first 6 mod of life with RECURRENT BACTERIAL, ENTEROVIRUS, AND GIARDIA LAMBLIA INFECTIONS.

Bacterial, esp extracellular encapsulated
Enterovirus ie polio and cocksackie virus

After first 6 mos of life bc this is when maternal Abs start to wear off. Maternal Abs are present during the first 6 mos of life.

Question 17

When lacking Ab production, what three types of infection will always be seen?

Answer 17

Bacterial
Bacteria need to be “tagged” by an opsonin to aid in phagocytosis. There are two opsonins - C3b and IgG. If no IgG can be made, then a majority of opsonization is gone, and phagocytic activity will de decreased.

Enterovirus
Enteroviral infections target the mucosal GI tract. IgA protects mucosal linings. If no IgA can be made, then the GI tract will constantly be attacked bc its nothing but mucosa down there

Giardia Lamblia
These infections for the same reasons as enterovirus

Question 18

What must be avoided in X-Linked Agammaglobulinemia?

Answer 18

Live Vaccines

Question 19

What disease is due to LOW immunoglobulin due to either a B cell or Helper T cell DEFECT (not deficiency)?

Answer 19

Common Variable Immunodeficiency. There is a low amount of Ab production. Usually asymptomatic. Presents late in childhood

Question 20

What types of infection would be expected in CVID?

Answer 20

Bacterial, Enterovirus, Giardia Lamblia because there is decreased Ab production. Usually late in childhood.

Question 21

What are CVID patients at risk for developing?

Answer 21

Autoimmune disease and Lymphomas

Question 22

Describe IgA syndrome

Answer 22

Low SERUM and MUCOSAL IgA.

THIS IS THE MOST COMMON Ab DEFICIENCY!!

Question 23

What are IgA deficient patients most at risk for developing?

Answer 23

Mucosal Infections, especially viral ones. However most patients are asymptomatic.

Just a heads up: Celiac Disease is due to a IgA deficiency

Question 24

What primary immunodeficiency is characterized by elevated IgM?

Answer 24

Hyper IgM syndrome

Question 25

What is responsible for the development of Hyper IgM syndrome?

Answer 25

It is due to a mutated CD40L on CD4+ helper OR defective CD40 receptor on the B cell.

The binding of CD40L to its receptor is the second signal needed for B cell activation. Once the B cell is activated, CD4+ will release IL-4 and IL-5 needed for CLASS TYPE SWITCHING.

Without that second signal, the B cell is stuck as an IgM bc it can’t class switch

Question 26

What Abs are in low number (obvious) and what kind of infections are thus seen?

Answer 26

Low IgA, E, G and result in pyogenic infections due to poor opsonization, especially at mucosal sites.

IgA–>mucosal infections
IgG–>pus infections bc IgG is an opsonin

Question 27

What is a pyogenic infection?

Answer 27

It is an infection that has severe localized inflammation usually with pus formation and is due to infection with the pyogenic bacteria such as:

Staph, Strep, E. Coli…just any that cause a pus forming infection. pyogenic just means pus forming.

Question 28

What is Wiskott Aldrich Syndrome

Answer 28

This is a disease where you will see:

Thrombocytopenia
No platelets so bleeding could be a problem…AS A MATTER OF FACT, BLEEDING IS A MAJOR CAUSE OF DEATH!!

Eczema

Recurrent infections due to defective cellular and humoral immunity

Question 29

What is Wiskott Aldrich Syndrome due to? What is the mode of inheritance?

Answer 29

Mutation in the WASP gene, X-Linked

Question 30

What are the two complement deficiencies?

Answer 30

Deficiency in C5-C9 (any one of these)
or
Deficiency in C1 INHIBITOR, not C1 itself…so too much C1

Question 31

What do patients with a C5-C9 deficiency have an increased risk for?

Answer 31

These people are at increased risk for NEISSERIA INFECTIONS! It is bc C5-C9 make the MAC complex and even tho Neisseria can escape phagocytosis, they are vulnerable to MAC.

Question 32

A C1 Inhibitor deficiency results in what disorder?

Answer 32

It results in hereditary ANGIOEDEMA on mucosal surfaces but ESPECIALLY PERIORBITAL AREA!!!

When C1 Inhibitor is deficient, too much C1. C1 activates complement, and with too much C1, complement is overactive. This mimics hyper acute inflammation, so you get the swelling.