Immunodeficiency

Question 1

What immune cell deficiency presents with recurrent fungal, viral, or protozoal infections?

Answer 1

T-cell deficiency

Question 2

X-linked hypogammaglobulinemia (Bruton agammaglobulinemia) has low levels of all immunoglobulins due to what underlying deficiency?

Answer 2

Deficiency of B-cell tyrosine kinase receptors, leading to failure of differentiation of pre-B cells to mature B cells

Question 3

How does Bruton agammaglobulinemia manifest clinically?

Answer 3

Recurrent bacterial infections

Question 4

Who typically gets Bruton agammaglobulinemia and why?

Answer 4

Young boys due to the X-linked recessive inheritance

Question 5

How is Bruton agammaglobulinemia treated?

Answer 5

Treat with pooled immunoglobulin (Ig)
Mnemonic: Bruton He X-iBITS: He=boys, X-linked, Bacterial infections, Immunoglobulins are low, Tyrosine kinase gene, six months=start symptoms

Question 6

At what age do most congential B cell immunodeficiencies manifest?

Answer 6

About 6 months as levels of maternal IgG acquired transplacentally during the fetal period begin to fall

Question 7

What immune cell deficiency presents with recurrent infections with encapsulated bacteria such as Staphylococcus and Haemophilus influenzae?

Answer 7

B cell deficiency

Question 8

What is the most common selective immunoglobulin deficiency and how do patients present?

Answer 8

Selective IgA deficiency causes recurrent sinus and lung infections (recall IgA is typically present in mucous)

Question 9

What can occur when patients with selective IgA deficiency receive a blood transfusion?

Answer 9

Anaphylactiv reaction if the patients have anti-IgA antibodies that react against IgA in the donor serum

Question 10

What embryologic process is defective in DiGeorge syndrome?

Answer 10

Development of third and fourth pharyngeal arches, and subseqent aplasia of thymus (third arch) and parathyroids (third arch: inferior parathyroids, fourth arch: superior parathyroid)

Question 11

What immune deficiency is part of DiGeorge syndrome and how is it treated?

Answer 11

Deficit of T cells due to thymic aplasia results in fungal, viral, and protozoal infections (eg, Pneumocystis pneumonia [PCP] and Candida albicans ) Treat with fetal thymic transplant

Question 12

What elyctrolyte disturbance is seen in DiGeorge syndrome?

Answer 12

Hypocalcemia (and tetany) due to failure of parathyroid development
Mnemonic: DiGeorge syndrome affects TWO arches (3 and 4), TWO organs (thymus and parathyroid), and has TWO defects (defective T cells and hypocalcemia)

Question 13

What are the clinical and laboratory manifestations of hyper IgM syndrome?

Answer 13

Clinical: recurrent pyogenic bacterial infections early in life
Lab: see high IgM but low IgG, IgA, IgE

Question 14

What is the underlying genetic defect in hyper IgM syndrome?

Answer 14

A mutation in CD40 ligand gene leads to a defective CD40 L on T cell surfaces. Without the proper CD40L-CD40 signaling, B cells cannot switch isotypes from IgM to other classes

Mnemonic: Hyper IgM Alphabet: A….HIJK_MMMMMMM…Z (No L=CD40Ligand and a lot of IgM)

Question 15

To what infections are patients with IL12 receptor deficiency predisposed?

Answer 15

Disseminated myobacterial infections because IL-12 is involved in development of cell mediated Th1 response against myobacteria

Question 16

What types of immune cells are defective in SCID and how is it inherited?

Answer 16

B and T cells. Most cases (75%) are X-linked

Question 17

How does SCID clinically manifest and how is it treated?

Answer 17

Patients are predisposed to recurrent bacterial, viral, fungal, and protozoal infections. Treat with bone marrow transplant

Question 18

What defects can lead to SCID?

Answer 18

Most common, 50%, is the lack of the common gamma chain of the IL-2, IL-4, IL-7, and IL-15 receptors (needed for T cell development); the next most common, about 16% is an adenosine deaminase (ADA) deficiency required for the purine salvage pathway

Question 19

How is Wiskott-Aldrich syndrome inherited and how does it present?

Answer 19

X-linked recessive; presents with pyogenic infections, eczema and bleeding due to thrombocytopenia

Question 20

What is the major defect in Wiskott Aldrich syndrome and how is it treated?

Answer 20

Lack of an IgM response to bacterial capsules; treat with bone marrow transplant
Mnemonic:
Turn the W in Wiskott upside down: W–> IgM
X-PECT infections with Wiskott Aldrich: Xlinked, Pyogenic infections, Capsular response impaired, thrombocytopenia

Question 21

What cancer are patients with Wiskott-Aldrich syndrome prone to develop?

Answer 21

Non-Hodgkin lymphoma

Question 22

How does ataxia-telangiectasia present?

Answer 22

Patients have recurrent infections at a young age in addition to uncoordinated gait (ataxia) and skin lesions consisting of small, dilated terminal vessels (telangiectasias)

Question 23

How is ataxia telangiectasia inherited and what is the genetic defect?

Answer 23

Autosomal recessive mutation in DNA repair enzymes

Question 24

What immunoglobulin deficiency is often seen with ataxia telangiectasia?

Answer 24

IgA deficiency

Question 25

What is the genetic defect in chronic granulomatous disease (CGD) and how is it inherited?

Answer 25

Lack of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; usually X-linked recessive

Question 26

What is the function of NADPH oxidase and in what cell is it found?

Answer 26

NADPH oxidase helps generate H2O2 used in respiratory bursts of neutrophils

Question 27

What are the principal sources of infection in chronic CGD and the most common cause of death?

Answer 27

Fungal and bacterial infections; pneumonia due to Aspergillus fumigatus is the most common cause of death from chronic CGD

Question 28

What bacteria typically infect patients with CGD?

Answer 28

Catalase positive bacteria (staphylococcus aureus and Escherichia coli) that use catalase to degrade their endogenous H2O2, which is then utilized by neutrophils. The bacteria provide the bullet!

Question 29

Chediak-Higashi syndrome is due to a microtubule dysfunction, and presents with recurrent pyogenic infections. What are the two abnormalities seen in the immune cells of these patients?

Answer 29

Failure of lysosome/phagosome fusion–>large granular inclusions of abnormal lysosomes
Abnormal neutrophil chemotaxis

Question 30

What are the features of Job syndrome (hyper IgE syndrome)?

Answer 30

High IgE, recurrent cold staphylococcal abcesses, eczema, and skeletal abnormalities

Question 31

What is the underlying deficiency in Job syndrome?

Answer 31

Lack of interferon gamma production by Th1 cells (inflammatory cells)

Question 32

What is a cold abscess?

Answer 32

Low interferon gamma favors the development of Th2 cells that are anti-inflammatory (and the source of Il-4 that induces B cell production of IgE). Therefore, staphylococcus abscesses cannot trigger the hot or inflammatory response

Mnemonic: GEt an EASy Job (Gamma IFN, IgE, Eczema, Abcesses, Skeletal abnormalities)

Question 33

What is leukocyte adhesion deficiency syndrome? How does it present?

Answer 33

Autosomal recessive defect of lymphocyte function associated 1 (LFA1), an adhesion protein on leukocytes, leads to severe pyogenic infections

Question 34

Common variable immunodeficiency presents with recurrent pyogenic infections. What is the underlying cause of this disorder?

Answer 34

Hypogammaglobulinemia due to a block in B cell differentiation to plasma cells

Question 35

What immune cells are most affected in HIV/AIDS and what types of immunity are compromised?

Answer 35

HIV targets CD4+ helper T cells which results in dysfunction of both humoral and cell mediated immunities

Question 36

What are some examples of bacterial infections that are common in AIDS patients?

Answer 36

Mycobacterium tuberculosis, Mycobacterium avium complex, stereptococcus pneumoniae (most common case of pneumonia in AIDS patients, not PCP), Salmonella, etc

Question 37

What are some examples of fungal infections that are common in AIDS patients?

Answer 37

Cryptococcus, Candida, Histoplasma, Mucor, Pneumocytis jiroveci (formerly pneumocytis carnii), Coccidioides, Blastomyces, etc

Question 38

What are some examples of protozoal infections that are common in AIDS patients?

Answer 38

Cryposporidium, Toxoplasma, etc

Question 39

AIDS patients are at increased risk for what malignancies?

Answer 39

Kaposi sarcoma, Anal carcinoma, Non-Hodgkins lymphoma, and Cervical cancer (KANCer)