Acquired Immunodeficiencies

Question 1

• Cellular Abnormality: Non-functional Bruton’s Tyrosine Kinase (BTK)
• Result: Inability of B cells to survive bone marrow development
• Susceptibility: EC Bacteria and some viruses
• Symptom: Underdeveloped tonsils
• Only B cell function is effected

Answer 1

X-Linked Agammaglobulinemia (XLA)

Question 2

• Cellular Abnormality: Defect in surrogate light chain from Lambda-5 gene
• Result: Inability of developing B cells to produce a pre-B cell receptor. All B cells undergo apoptosis
• Susceptibility: EC bacteria and viruses

Answer 2

Pre-B Cell Receptor (Lambda-5) Deficiency

Question 3

• Cellular Abnormality: Defect in CD40 ligand
• Result: Inability of helper T cells to activate B cells and macrophages. Almost all antibodies will be IgM, and will be in lower levels than normal
• Susceptibility:
• Symptom:
• Cannot activate effector T cells

Answer 3

X- linked hyper IgM Syndrome

Question 4

• Cellular Abnormality: AID deficiency
• Result: Unable to class-switch
• Susceptibility:
• Symptom:
• Have fully activated B cells
• IgM levels are higher levels than with patients with CD40 deficiency
• Still able to produce and activate effector T cells that can supply second signals of activation to B and T cells

Answer 4

X-linked hyper IgM Syndrome

Question 5

A person that can activate macrophages will have ________ in their secondary lymphoid tissues

Answer 5

Germinal Centers

Question 6

• Cellular Abnormality:
• Result: At risk for developing anaphylactic reactions following blood transfusions. Not tolerant to the IgA in a blood transfusion.
• Susceptibility:
• Symptom:
• Most common genetic immunodeficiency

Answer 6

Selective IgA Deficiency

Question 7

• IgG1 deficiency: susceptibility to many bacterial and viral pathogens
• IgG2 deficiency: Most common in kids; susceptible to encapsulated bacteria
• IgG3: common in adults

Answer 7

Selective IgG Deficiency

Question 8

• Most common primary immunodeficiency disorder
• Recurrent bacterial and viral infections in ears, eyes, nose, sinuses, lungs, GI, skin, etc.
• Hypogammaglobulinemia is typical, but not as big as XLA

Answer 8

Common Variable Immunodeficiency Disease

Question 9

• Cellular Abnormality: inherited defect in ATM gene that encodes DNA repair enzyme
• Result: deficient in both B and T cells, but not SCID. Patient has low numbers of lymphocytes (especially T cells) and low levels of IgA and IgE
• Symptoms: Cerebellar defects (ataxia), Spider angiomas (telangiectasia), IgA (or IgE) deficiency
• Elevated alpha-fetoprotein levels

Answer 9

Ataxia Telangiectasia

Question 10

• Cellular Abnormality: genetic deficiency of IL-12 or IL-12R
• Result: inability to generate Th1 type responses. They make much less IFN-Gamma than normal. There is an inability to fully activate macrophages.
• Susceptibility: mycobacterial infections

Answer 10

IL-12 Signaling Deficiency

Question 11

• Cellular Abnormality: genetic deficiency of STAT-3
• Result: Reduced production of IFN-Gamma by Th1 T cells
• Patients make immune responses highly polarized to Th2 phenotype
• Results with high concentration of IgE in blood
• Neutrophils do not répond to chemotactic signals
• Symptoms: eczema, recurrent abscesses w/ S. Aureus, broad nose, frontal bossing, deep set eyes, retention of primary teeth

Answer 11

Job’s Syndrome (Hyper IgE Syndrome)

Question 12

• Result: undefined T cell dysfunction

- Susceptibility: Candida sp. (albicans)

Answer 12

Chronic Mucocutaneous Candidiasis

Question 13

• Low numbers of CD8 T cells
• Result: few CD8 T cells receive positive selection in the thymus
• Also synonymous CD8 alpha chain defect
• Susceptibility: highly susceptible to viral and some IC bacterial pathogens

Answer 13

Tap Deficiency (Bare Lymphocyte Syndrome)

Question 14

• Non sense mutation of perforin
• Perforin is a critical effector molecule of CTLs and NK cells
• Susceptibility: highly susceptible to viruses and IC bacteria

Answer 14

Perforin Deficiency

Question 15

• Classic MCH class II version
• Patient lacks expression of MHC class II molecules
• Unable to mount acquired CD4+ T cell response or acquired B cell response

Answer 15

Bare Lymphocyte Syndrome (SCID)

Question 16

• Caused by a defect in cytoskeletal reorganization
• Defect causes crosstalk deficiency that prevents proper cytokine signaling from effector T cells to B cells and macrophages

Answer 16

Wiskott-Aldrich Syndrome (SCID)

Question 17

• Deficiency resuls in accumulation of toxic nucleotide catabolites that kills all lymphocytes during their development
• Patients have no B or T cells

Answer 17

Adenosine Deaminase (ADA) or Purine Nucleotide Phosphorylase Deficiency (SCID)

Question 18

• Deficiency of the protein prevents signaling through each of the important cytokine receptors
• The receptor chain interacts with Jak3
• IL-2, IL-7 are critical cytokine receptors for T and B cell development, respectively
• Patients will have no B or T cells

Answer 18

Common Gamma Chain Deficiency

Question 19

Identical to Common Gamma Chain Deficiency

Answer 19

Janus Kinase 3 Deficiency (Jak3)

Question 20

• Patients have no CD4+ or CD8+ T cells
• No T cell function
• Deficiency results from nonfunctional CD3 delta, epsilon, or zeta chain

Answer 20

CD3 Deficiency

Question 21

• Results in a SCID phenotype

- No development of a T cell repertoire in the absence of the thymus

Answer 21

Thymic Aplasia

Question 22

• Small deletion in chromosome 22
• Highly susceptible to bacterial, fungal, and viral infections
• total absence of thymus or a non-functional thymus
• Treatment: thymic transplant

Answer 22

DiGeorge Syndrome

Question 23

• Genetic defect that prevents expression of functional ZAP-70
• ZAP-70 is a tyrosine kinase that associates with ITAMs
• Near total absence of CD8 T cells
• Normal numbers of non-functional CD4 T cells
• Treatment: bone marrow transplant

Answer 23

ZAP-70 Deficiency

Question 24

• Results in SCID, but also in autoimmune disease
• Mis-sense mutations that result in partially active RAG- genes
• No B cells
• Low numbers of T cells
• Susceptible to fungal, bacterial, and viral infections
• Treatment: bone marrow transplant

Answer 24

Omenn Syndrome

Question 25

• Genetic deficiency of a gene that encodes AIRE

- Symptoms: underproductions of hormones, baldness, malabsorption

Answer 25

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED)

Question 26

• Results from genetic deficiency of FoxP3 expressed by Tregs
• Symptoms: watery diarrhea, eczematous dermatitis, and endocrinopathy
• Treatment: immunosuppression/ bone marrow transplant

Answer 26

Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome (IPEX)

Question 27

• Characterized by lymphoadenopathy and splenomegaly
• Immune cells failing to undergo apoptotic death
• Causes overpopulation of secondary lymphoid tissues
• No expression of functional Fas Ligand, Fas, or caspase 10
• Treatment: Immunosuppresion and IVIg

Answer 27

Autoimmune Lymphoproliferative Syndrome (ALPS)