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Question 1

In general, antibody deficiencies result in an increased susceptibility to what kinds of infections?

Answer 1

extracellular bacterial and fungal, especially encapsulated bugs that are resistant to phagocytosis

Question 2

What are some examples of inherited antibodies deficiencies?

Answer 2

X-linked agammaglobulinemiapre-B cell receptor deficiencyX-linked hyper IgM syndromeselective IgA deficiencyselective IgG deficiency

Question 3

What is the preferred treatment for inherited antibody deficiency?

Answer 3

Monthly passive immunization (IVIg) as a replacement therapy.

Question 4

What is X-linked agammaglobulinemia caused by?

Answer 4

is a condition that results from a mutation that renders Bruton’s tyrosine kinase non-functional. Btk is required for B cell development, and a defect in this gene results in an inability of B cells to survive bone marrow development.This results in a patient having very low B cell counts, leaving them without a humoral immune system

Question 5

Patients with X-linked agammaglobulinemia are susceptible to which kinds of infections?

Answer 5

extracellular bacterial pathogens as well as many viruses because they lack the ability to neutralize virions

Question 6

X-linked agammaglobulinemia is associated with what main clinical presentation?

Answer 6

underdeveloped tonsils in young children

Question 7

What is Pre-B cell receptor deficiency caused by?

Answer 7

A genetic defect in the surrogate light chain (lambda 5 gene) that results in apoptotic death of B cells during the early stages of B cell development.lambda 5 is a component of the surrogate light chain that pairs with the mu heavy chain during somatic recombination of light chain genes Patients are susceptible to both extracellular bacteria and many viruses.

Question 8

What are the possible causes of X-linked hyper IgM syndrome?

Answer 8

1) A defect in CD40 ligand (or CD40) production results in an inability of helper T cells to activate B cells and macrophages. Almost all of the antibodies that will be produced by a person with this condition will be IgM, and the patient’s IgM levels will probably be higher than in an immunocompetent person.2) In contrast, a person with AID deficiency would be unable to class-switch, but these patients are able to have fully activated B cells. The IgM levels in these patients will be higher that those with a CD40 ligand deficiency.Better to have the AID deficiency because effector T cells would still be able to supply the second signals of activation to B cells.

Question 9

A person that can activate B cells will have germinal centers in their secondary lymphoid tissues.Those that cannot activate B cells, for whatever reason, will not have any germinal centers in their secondary lymph nodes.

Answer 9

A person that can activate B cells will have germinal centers in their secondary lymphoid tissues.Those that cannot activate B cells, for whatever reason, will not have any germinal centers in their secondary lymph nodes.

Question 10

What is Selective IgA deficiency caused by?

Answer 10

one of (if not the) most common genetic immunodeficiency. The genetic mutation(s) are unknown, and most people with this problem never are diagnose unless they are exposed to PARASITE pathogens

Question 11

What are some major problems with those who have selective IgA deficiency?

Answer 11

these patients are at risk for developing anaphylactic reactions following blood transfusions. Because they do not make any IgA, there are not tolerant to the IgA that is transplanted in during a transfusion.It is also important for you to know that patients with selective IgA deficiency have an increased chance of developing immediate type hypersensitivities, such as asthma, as well as autoimmune diseases that include systemic lupus erythematosus and rheumatoid arthritis.

Question 12

In adults, what are the relative percentages of IgG subtypes in circulation?

Answer 12

IgG1- 60-70%IgG2- 20-30%IgG3- 5-8%IgG4- 1-3%

Question 13

Notes on Selective IgG deficiency.

Answer 13

genetic cause is unknown; likely heterogeneousdeficiency of each IgG subtype is possible:IgG1 deficiency (most important) is very rare; susceptibility to many bacterial and viral pathogens IgG2 deficiency is most common in kids; susceptibility to encapsulated bacteria IgG3 deficiency s most common in adultsIgG4 deficiency is of unknown significance

Question 14

What is common variable immunodeficiency?

Answer 14

a group of around 150 primary immunodeficiencies that have common features that typically include reduced levels of antibodies, but different etiologies (many of which remain undefined). Causes are genetic, but diagnosis typically does not occur until 2nd or 3rd decade of patient’s life

Question 15

What are the clinical manifestations of common variable immunodeficiency?

Answer 15

recurring infections mainly with bacterial and/or viral pathogens involving the ears, eye, sinuses, nose, bronchi, lungs, skin, GI tract, joints, bones, CNS, parotid glands

Question 16

What other symptom is common with common variable immunodeficiency?

Answer 16

hypogammaglobulinemia is typical, but not as dramatic as observed in X-linked agammaglobulinemia

Question 17

What is Ataxia telangiectasia caused by?

Answer 17

caused by an inherited defect in the ATM gene (encodes a DNA repair enzyme).Causes B and T cell deficiency in some patients (but not as bad as SCID) and patients have low lymphocyte numbers (especially T cells) in the blood and very low levels of either IgA or IgE (most typically IgA)

Question 18

Patients with Ataxia telangiectasia typically have the following clinical triad:

Answer 18

(1) Ataxia (cerebellar defects)(2) Spider angiomas(3) Either IgA (most commonly) or IgE deficiency•• elevated alpha-fetoprotein levels are also common

Question 19

What are some of the consequences of genetic IL-12 deficiency?

Answer 19

Any deficiency that results in defective IL-12 signaling leaves a patient with the ability to make only small amounts of IFN-gamma. This in turn results in very diminished ability to produce TH1-type CD4 effector cells and the inability to fully activate macrophages. Mutation in either chain of the IL-12 heterodimer or the IL-12 receptor can cause this condition.

Question 20

The most common susceptibility observed in patients with IL-12 deficiency is to ____.

Answer 20

disseminated mycobacterial infections.

Question 21

What is Job’s syndrome?

Answer 21

a genetic deficiency of STAT-3 function that results in reduced production of IFN-gamma by TH1 T cells and neutrophils that fail to respond to chemotactic signals (for some undefined reason)These patients make immune responses that are highly polarized toward a TH2 phenotype. One of the end results of this is high concentrations of IgE in the blood.

Question 22

What are the main clinical manifestation of Job’s syndrome?

Answer 22

Patients suffer from eczema and recurrent abscesses with Staph aureus (primarily). These patients also have characteristic facial features that include a broad nose, frontal bossing (which is an unusually prominent forehead with a very prominent brow ridge), deep set eyes, and retention of primary teeth.Common mnemonic: FATED- coarse of leonine Facies, cold staph Abscesses, retained primary Teeth, increased IgE, and Dermatologic problems (eczema)

Question 23

What is Chronic Mucocutaneous Candidiasis?

Answer 23

a condition (or panel of conditions) that results from undefined T cell dysfunction leaves patients susceptible to recurrent or persistent superficial infections of the skin, mucous membranes, and nails with Candida organisms, usually Candida albicans (yeast only)

Question 24

What does TAP-1 or TAP-2 deficiency (aka bare lymphocyte syndrome (MHC class I)) result in?

Answer 24

results in very low numbers of CD8+ T cells in the repertoire because MHC class I is unstable if peptides are not loaded into their binding groove. The end result is that very few CD8+ T cells receive positive selection in the thymus, so there are very few CD8+ T cells in the repertoire, and really no ability to generate an effector CD8+ T cell response.A CD8 alpha chain defect results in essentially the same phenotype as a TAP transporter deficiency for the same reasons. Patients with these conditions are highly susceptible to viral and some intracellular bacterial infections.

Question 25

Perforin deficiency would result in what?

Answer 25

it is possible to have a non-sense mutation of perforin. Because perforin is a critical effector molecule of CTLs and NK cells, people that have this mutation are highly susceptible to viral and some intracellular bacterial infections.Patients still have normal numbers of CD8 T cells, but they cannot induce apoptosis in target cells

Question 26

Genetic defects that prevent CD4+ T cell effector functions result in ____.

Answer 26

SCID because B cell responses require effector T cell function.

Question 27

What is Bare lymphocyte syndrome (classic MHC class II version)?

Answer 27

people that lack expression of MHC class II molecules are unable to mount acquired CD4+ T cells responses or acquired B cell responses. causes SCID

Question 28

What is Wiskott-Aldrich syndrome (WAS)?

Answer 28

caused by a defect in cytoskeletal reorganization. T cells reorganize their cytoskeleton so that they can deliver their effector molecules directly onto their target cell. This goes for both CD4+ and CD8+ T cells. The defect in WAS causes a crosstalk deficiency that prevents proper cytokine signaling from effector T cells to B cells and macrophages.Causes SCID

Question 29

What is Adenosine deaminase (ADA) or Purine nucleotide phosphorylase?

Answer 29

deficiencies both result in accumulation of toxic nucleotide catabolites that kills almost all lymphocytes during their development. So, these two deficiencies result in patients that have no B cells or T cells. Causes SCIDThink Azathioprine

Question 30

What is Common gamma chain deficiency?

Answer 30

gamma/c is a component of several important cytokine receptors, and a deficiency of this protein prevents signaling through each of those receptors. This receptor chain interacts with Jak3. Because several of the cytokine receptors are critical for B and T cell development (IL-2 [T cell growth factor], IL-7 [B cell growth factor], etc), this deficiency results in SCID. These patients have no functional B cells and no effector T cells.Janus kinase 3 (Jak3) deficiency is essentially identical to common gamma chain deficiency.

Question 31

CD3 deficiency: this deficiency results in a patient having no CD4+ or CD8+ T cells; no T cell function = SCID. Deficiency can result from nonfunctional CD3 delta, epsilon, or zeta chain

Answer 31

CD3 deficiency: this deficiency results in a patient having no CD4+ or CD8+ T cells; no T cell function = SCID. Deficiency can result from nonfunctional CD3 delta, epsilon, or zeta chain

Question 32

Thymic aplasia

Answer 32

For whatever reason results in a SCID phenotype because there is no development of a T cell repertoire in the absence of the thymus.

Question 33

What is DiGeorge Syndrome caused by genetically?

Answer 33

incidence 1/4000. Results from small deletion in chromosome 22 (q11.2)Complete DiGeorge Syndrome is simply DiGeorge Syndrome that includes a total absence of a thymus or a non-functional thymus.

Question 34

What is DiGeorge Syndrome characterized by? Treatment?

Answer 34

congenital heart disease (40%), palatal abnormalities (505), learning disabilities (90%), mild difference in facial featurespatients have high susceptibility to bacterial, fungal, and viral infections, including opportunistic pathogens. Treatment of athymia: Thymic transplant (there is no treatment for any of the other maladies associated with DiGeorge Syndrome).

Question 35

What is Zap-70 deficiency caused by?

Answer 35

Zap-70 is a tyrosine kinase that associates with ITAMs during T cell receptor signaling, and it is required for transduction of signals through the TCR.Because these patients have no T cell function, the result is a SCID phenotype.

Question 36

What is Zap-70 deficiency characterized by?

Answer 36

Patients that have this deficiency have a near total absence of CD8+ T cells, but normal numbers of non-functional CD4+ T cells. It is not known why these patients have normal CD4 levels, but I assume it has something to do with thymic selection. It could be that thymocytes that are destined to become CD8+ T cells can only survive positive selection if their TCR signaling is functional, whereas CD4+ T cells do not require signaling through the TCR to be positively selected.

Question 37

Treatment options for Zap-70 deficiency?

Answer 37

The only effective treatment is bone marrow transplant

Question 38

What is Omenn Syndrome caused by?

Answer 38

an immunodeficiency that results in SCID, but also in autoimmune disease. It results from mis-sense mutations that result in RAG-genes that are only partially active. These patients have no B cells, and low numbers of T cells that are oligoclonal and autoreactive (their specificity appears to be mostly directed at self determinants).

Question 39

Patients with Omenn syndrome are susceptible to what kinds of infections?

Answer 39

These patients are susceptible to all types of infections, and they also suffer from autoimmune disease that is manifested in the skin and the intestinal tract.

Question 40

Symptoms of Omenn syndrome?

Answer 40

Erthyroderma, desquamation, alopecia, chronic diarrhea, lymphadenopathy, and hepatosplenomegalyThis disorder causes failure to thrive as well.

Question 41

Treatment for Omenn Syndrome?

Answer 41

Only effective treatment is a bone marrow transplant.

Question 42

What is Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) caused by?

Answer 42

a genetic deficiency of the gene that encodes the autoimmune regulator (AIRE) that is expressed in the thymic medulla.The purpose of this transcription factor is to drive expression of many host proteins that can be used as a source of self peptides for display on MHC class I and MHC class II during negative selection of T cells.

Question 43

Clinical presentation of APECED?

Answer 43

polyglandular problems including hypoparathyroidism, hypogonadism (with sex gland failure), adrenal insufficiency, type I (insulin-dependent) diabetes, latent hypothyroidism, alopecia totals, keratoconjunctivitis, tooth enamel hypoplasia, candidiasis (yeast infections), juvenile-onset pernicious anemia, GI problems (diarrhea and malabsorption)

Question 44

What is Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked Syndrome (IPEX) caused by?

Answer 44

genetic deficiency of FoxP3 expression by Tregs. This results in early onset (typically 1st year of life) autoimmunity manifested in a variety of tissues.

Question 45

Clinical presentation of IPEX?

Answer 45

clinical triad of:1) watery diarrhea, 2) eczematous dermatitis, and 3) endocrinopathy (type 1 diabetes). Also typical to display Coomb’s positive anemia, autoimmune thrombocytopenia, autoimmune neutropenia, and tubular nephropathy

Question 46

Treatment of IPEX?

Answer 46

immunosuppression and/or bone marrow transplant

Question 47

What is Autoimmune Lymphoproliferative Syndrome (ALPS)?

Answer 47

a condition that is characterized by lymphadenopathy and splenomegaly. It results from a mutation that results in no expression of functional Fas, Fas-ligand, or caspase 10. Without any of these molecules, immune cells fail to undergo apoptotic death following an immune response, resulting in overpopulation of secondary lymphoid tissues.

Question 48

Clinical presentation of ALPS:

Answer 48

Autoimmune hemolytic anemia and neutropenia, thrombocytopenia, lymphadenopathy, splenomegaly, and a large number of double-negative (CD4-/CD8-) T cells.

Question 49

Treatment of ALPS?

Answer 49

Treatment: immunosuppression and IVIg