Imm 9 - Immunodeficiencies

Question 1

What are two B cell deficiencies?

Answer 1

Bruton agammaglobulinemia. Selective immunoglobulin deficiencies.

Question 2

What are 4 T cell deficiencies?

Answer 2

Thymic aplaisa (DiGeorge syndrome). Chronic mucocutaneous candidiasis. Hyper IgM syndrome. IL-12 receptor deficiency.

Question 3

What are three combined B and T cell deficiencies?

Answer 3

Severe combined immunodeficiency. Wiskott-Aldrich syndrome. Ataxia-telangiectasia.

Question 4

What are 4 phagocyte disorders?

Answer 4

Chronic granulomatous disease. Chediak-Higashi disease. Hyperimmunoglobulin E (Job Syndrome). Leukocyte adhesion deficiency syndrome.

Question 5

What is Bruton agammaglobulinemia?

Answer 5

X-linked (Boys) disorder causing B cell deficiency caused by defective tyrosine kinase gene that causes low levels of all immunoglobulins. This results in recurrent bacterial infections after 6 months of age.

Question 6

What is the most common immunoglobulin deficiency?

Answer 6

Selective IgA deficiency.

Question 7

What is Selective IgA deficiency?

Answer 7

Appear healthy but causes lots of sinus and lung infections (1/600 European descent). Associated w/ atopy, asthma. Possible anaphylaxis to blood transfusions and blood products.

Question 8

What is Thymic aplasia (DiGeorge)?

Answer 8

The third and fourth pouches fail to develop, causing no thymus (leading to no mature T cells), and no parathyroids (causing tetany from low Ca2+). Associated w/ congenital defects in heart/great vessels. Predisposed to recurrent viral, fungal, protozoal infections. 90% have a chromosome 22q11 deletion (detect w/ FISH).

Question 9

What PE can be done to check for hypocalcemia?

Answer 9

Chvostek sign: Tapping patient’s cheek will cause facial muscle spasm. Trousseau sign: Tighten BP cuff on arm and will cause carpopedal spasm.

Question 10

What is mucocutaneous candidiasis?

Answer 10

T cell dysfunction vs C.albicans. Tx is ketoconazole.

Question 11

What is Hyper-IgM syndrome?

Answer 11

Lots of IgM but decrease in all other immunoglobulins. There are 3 ways that can be inherited: X-linked (no CD40 ligand on T cell), AR (B cells do not have CD40), NEMO deficiency.

Question 12

What does IL-12 receptor deficiency lead to?

Answer 12

Increased mycobaterial infections.

Question 13

What is Severe Combined Immunodeficiency (SCID)?

Answer 13

Defect in early stem cell differentiation causing B and T cell deficiency. Can be caused by at least 7 different gene defects (Adenosine deaminase deficiency is the most important). This leaves NK cells as last defense. No thymic shadow on newborn CXR.

Question 14

What is the triad of Severe Combined Immunodeficiency (SCID)?

Answer 14

Triad of Severe infection, chronic diarrhea, and Failure to thrive. The severe infection portion includes chronic mucocutaneous candidiasis, fatal or recurrent RSV, VZV, HSV, measles, flu, parainfluenza, and Pneumocystis jirovecii pneumonia (PCP).

Question 15

What 2 disease would not be able to see thymic shadow on newborn CXR?

Answer 15

Severe combined immunodeficiency (SCID). DiGeorge.

Question 16

What is Wiskott-Aldrich syndrome?

Answer 16

An X-linked disease that causes B and T cell immunodeficiencies. There is no IgM vs capsular polysaccharides of bacteria, causing low IgM and high IgA.

Question 17

What are the symptoms of Wiskott-Aldrich syndrome?

Answer 17

[WAITER] Wiskot, Aldrich, Immunodeficiency, Thrombocytopenia and purpura, Eczema (on the trunk), Recurrent pyogenic infections.

Question 18

What are the X-linked immunodeficiencies?

Answer 18

[WACH] Wiskott-aldrich. brunton Agammaglobulinemia. (+/-) Chronic granulomatous disease. (+/-) Hyper-IgM syndrome.

Question 19

What is Ataxia-Telangiectasia?

Answer 19

A combined immunodeficiency, there is IgA deficiency and low levels of T cells. Causes radiation sensitivity (try to avoid x-rays) due to defective DNA repair. (+/-) increased AFP in children above 8 months. Average age of death is 25 y.o.

Question 20

What are the symptoms of Ataxia-Telangiectasia?

Answer 20

Cerebellar ataxia and poor smooth pursuit of moving target w/ eyes. Telangiectasias of face in children above 5 y.o. Increased risk of lymphomas and leukemias.

Question 21

What is Chronic Granulomatous disease (GCD)?

Answer 21

A phagocyte disorder, the lack of NADPH oxidase activity causing impotent phagocytes. Patients are susceptible to organisms w/ catalase (S.aureus, E.coli, Klebsiella spp., Asperillus spp., Candida spp.)

Question 22

How do we diagnose Chronic Granulomatous Disease?

Answer 22

A negative nitroblue tetrazolium (NBT) dye (No yellow to blue-black oxidation): NBT is added to sample of patients blood, where normally the phagocytes ingest the dye and the oxygen free radicals will oxidize it from yellow to blue-black color.

Question 23

What is the treatment for Chronic Granulomatous disease?

Answer 23

Prophylactic TMP-SMX. IFN-gamma is also helpful.

Question 24

What is Chediak-Higashi disease?

Answer 24

A phagocyte disorder, it is caused by defective LYST gene (lysosomal transport gene, important in getting enzymes into the lysosomes), causing defective phagocyte lysosome. They engulf things but cannot do anything with it, causing giant cytoplasmic granules in PMNs, which are diagnostic.

Question 25

What are the symptoms of Chediak-Higashi disease?

Answer 25

Triad: partial albanism, Recurrent respiratory tract and skin infections, Neurologic disorders.

Question 26

What is Hyperimmunoglobulin E syndrome?

Answer 26

AKA Job syndrome, a phagocyte disorder where deficiency in IFN gamma leads to impaired neutrophil chemotaxis. This causes High levels of IgE and eosinophils. Also common to have retained primary teeth resulting in 2 rows of teeth.

Question 27

What are the symptoms of Hyperimmunoglobulin E syndrome?

Answer 27

Eczema. Recurrent cold S.aureus abscesses (think of biblical Job w/ boils). Coarse facial features (broad nose, prominent forehead {frontal bossing}, deep set eyes, and doughy skin.

Question 28

What is Leukocyte Adhesion Deficiency Syndrome?

Answer 28

There are Abnormal integrins causing inability of phagocytes to exit circulation. One of the classic presentations is delayed separation of umbilical cord.

Question 29

RFF: Eczema, recurrent cold abscesses, high serum IgE.

Answer 29

Hyperimmunoglobulin E (Job syndrome).

Question 30

RFF: Large lysosomal vesicles in phagocytes.

Answer 30

Chediak-Higashi disease.