Primary immunodeficiency Qs

What causes Chronic granulomatous disease (CGD)?

What B cell developmental outcome would a carrier female with normal X inactivated have?

In individuals with XLA, B cells are arrested at and fail to progress beyond which stage of development?

a. immature B cell stage

b. plasma-cell stage

c. pro-B cell stage

d. pre-B cell stage

Which of the following conditions is associated with immune-complex disease?

a. elevated bradykinin

b. oedema

c. anaemia

d. inflammation and tissue damage

e. C2a- angiodema

Which type(s) of gene defects are associated with primary immunodeficiency diseases?

a. dominant, recessive and X-linked

b. recessive an X-linked but not dominant

c. only recessive

d. only dominant

Which gene is responsible for X-linked agammaglobulinemia (XLA)?

a. BTK

b. RAG1

c. TAP

d. NOX1

Defects in the X-linked gene that encodes the common γ chain (γc) of a certain receptor are so severe that survival requires hematopoietic stem-cell transplantation. What is the name of this receptor?

a. cytokine receptor

b. IFNgamma receptor

c. CD3

d. Fc receptor

Inherited immunodeficiency diseases that manifest more frequently in males than in females are due to which type of defective allele?

a. dominant autosomal

b. recessive autosomal

c. recessive X-linked

What are individuals with X-linked agammaglobulinemia (XLA) unable to do?

a. kill bacteria in phagolysosomes

b. kill virus infected cells

c. produce antibodies

d. produce functional T cells

Women who are carriers of one nonfunctional copy of the BTK gene will have which one of the following?

a**.** mature B cells that have inactivated the same X chromosome

b. only half of the normal numbers of circulating B cells

c. sons who all lack mature B cells

d. XLA, because an insufficient amount of Bruton’s tyrosine kinase is made

HLA and KIR polymorphisms influence progression to AIDS. The scale shown in the accompanying figure represents relative hazard, which measures the speed of progression to AIDS, with 1.0 being faster than 0.

The HLA-B*27 and HLA-B*57 allotypes (represented by B27 and B57, respectively) share the Bw4 epitope, the ligand for the NK-cell receptor KIR3DL1 (3DL1). KIR3DL1 can be highly expressed (3DL1h) or weakly expressed (3DL1l). Combinations of Bw4+ HLA-B and KIR3DL1/S1 genes are associated with different rates of progression to AIDS.

People called elite controllers and viremic controllers are likely to benefit the most from the presence of which of the following?

a. Bw4+ HLA-B*57

b. Bw4+ HLA-B*57 and KIR3DL1h

c. Bw4+ HLA-B*27 and KIR3DL1h

d. a complete lack of Bw4 epitope on the HLA-B allotype

Interferon-γ (IFN-γ) is the main cytokine that activates macrophages. The IFN-γ receptor is a dimer of the IFNγR1 and IFNγR2 polypeptides, which associate with the JAK1 and JAK2 tyrosine kinases, respectively. Dominant and recessive mutations in the gene for IFNγR1 have been found in individuals suffering from persistent mycobacterial infections. Which of the following statements accurately describes the effect of mutations in the IFN-γ receptor?

a. Patients with two recessive defective IFNγR1 alleles express neither IFNγR1 nor IFNγR2 on the cell surface of monocytes and macrophages.

b. Mutations in the recessive IFNγR1 alleles prevent any cell surface expression of IFNγR1.

c. Individuals with one dominant defective IFNγR1 allele have more-severe disease than patients with two recessive IFNγR1 alleles.

d. Signaling through the IFN-γ receptor is not very important for the functions of macrophages.

When does the loss of an immune-system gene associated with an inherited immunodeficiency disease usually NOT pose a serious consequence?

a. if a compensatory function is provided by another member of the multigene family

b. if the loss or defect is in the receptor genes, such as the one for CCR5, which code for receptors exploited by pathogens like HIV

c. f the defect arises after a well-established circulating lymphocyte pool has been produced

d. If gene reversion converts the defective gene to the normal variant early in embryogenesis

When is the autoimmune disease hereditary angioedema (HAE) manifested?

a. when both C1INH alleles are nonfunctional

b. when C1INH is overexpressed

c. when one C1INH allele is nonfunctional, but the other is unaffected

Which function is affected by defects in the CHS1 gene that is present in individuals with Chédiak–Higashi syndrome (CHS)?

a. the respiratory burst

b. chemotaxis

c. opsonization

d. vesicle fusion

Which of the following is NOT observed in leukocyte adhesion deficiency?

a. impaired migration of monocytes and neutrophils to infected tissues

b. defective respiratory burst

c. defective uptake of opsonized bacteria

d. susceptibility to encapsulated bacteria

A deficiency of which one of the following causes a selective absence of CD8 T cells?

a. RAG proteins

b. SH2D1A protein

c. TAP transporters

d. purine nucleoside phosphorylase (PNP)

e. Wiskott–Aldrich syndrome protein (WASP)

Which of the following is true of the disease caused by adenosine deaminase (ADA) deficiency?

a. It is a recessive X-linked disorder that affects more males than females.

b. It results from the accumulation of nucleotide metabolites that are especially toxic to T cells.

c. It is characterized by the inability to deliver intracellular signals in T cells.

d. It interferes with cognate interactions between T cells and B cells.

Which one of the following statements accurately describes an immune condition associated with severe combined immune deficiency (SCID)?

a. Physical barriers of innate immunity are compromised.

b. All complement pathways are inhibited.

c. Neither antibody nor T-cell responses are made.

d. Both innate and adaptive immunity are ineffective.

Intravenous administration of which of the following can cure neutropenia in individuals with X-linked hyper-IgM syndrome?

a**.** granulocyte–macrophage colony-stimulating factor (GM-CSF)

b. antibiotics

c. immunoglobulin

d. CD40 ligand

Which pathogen poses the biggest threat to individuals with XLA?

a. an intestinal helminth

b. an opportunistic fungus

c. an extracellular protozoan parasite

d. an enveloped virus

e. a pyogenic bacterium

Which of the following syndromes is caused by a defective protein involved in cytoskeletal reorganization that is needed for cytokine delivery and the formation of conjugate pairs?

a. Wiskott–Aldrich syndrome (WAS)

b. Janus 3 kinase (JAK3) deficiency

c. Omenn syndrome

d. Chédiak–Higashi syndrome (CHS)

Which cells fail to develop in individuals with a homozygous defect in CIITA?

a. platelets

b. B cells

c. NK cells

d. CD4 T cells

e. CD8 T cells

Which of the following syndromes are associated with the inefficient killing of ingested pathogens?

Correct Answer(s)

a. myeloperoxidase deficiency (MPOD)

b. hereditary angioedema (HAE)

c. glucose-6-phosphate dehydrogenase (G6PD) deficiency

d. paroxysmal nocturnal hemoglobinuria (PNH)

e. chronic granulomatous disease (CGD)

f. Chédiak–Higashi syndrome (CHS)

g. leukocyte adhesion deficiency (LAD)

Select all the statements that are true regarding IFN-γ receptor deficiency.

a. IFNγR2 cannot function in the absence of IFNγR1.

b. Patients with two recessive defective IFNγR1 alleles express neither IFNγR1 nor IFNγR2 on the cell surfaces of monocytes and macrophages.

c. In IFN-γ receptor deficiency, macrophages infected with Mycobacterium tuberculosis cannot be activated in either innate or adaptive immune responses.

d. Dominant mutant forms of IFNγR1 are less abundant at the cell surface than normal forms.

e. Patients with two recessive defective IFNγR1 alleles exhibit more severe disease at an earlier age than patients with one dominant defective IFNγR1 allele.

Which of the following are observed in individuals who do not produce functional CD40 ligand?

a. an increased susceptibility to pyogenic bacterial infections

b. high levels of granulocyte–macrophage colony-stimulating factor (GM-CSF)

c. the absence of germinal centers in secondary lymphoid tissues

d. low amounts of all isotypes of antibody

e. a state called neutropenia

What do CR3, CR4, and LFA-1 have in common?

a. They are all leukocyte integrins.

b. They all contain CD18.

c. They are all complement receptors.

d. They are all serpins.

Which the following statements regarding an IL-12 receptor deficiency are correct?

a. Signaling through the IL-12 receptor of NK cells stimulates the production of IFN-γ.

b. Innate, but not adaptive, immune responses to intracellular bacteria are intact in patients with an IL-12 receptor deficiency.

c. Individuals with an IL-12 receptor deficiency are predisposed to infections caused by mycobacteria.

d. Signaling through the IL-12 receptor of naive CD4 T cells induces their differentiation into TH2 cells.

Which of the following are required for signaling by the IFN-γ receptor?

a. JAK1 and JAK2

b. STAT1

c. MyD88

d. NFκB

What will a normal male have as the correct B-cell development outcome?

What B-cell developmental outcome will a carrier female with defective X inactivated have?

What B cell developmental outcome would an XLA male have?

MHC class II deficiency is associated with which homozygous defect?

a. CIITA

b. either of RAG proteins

c. either of TAP peptide transporters

d. any of the components of RFX

Which of the following holds true if a woman carries one defective Bruton’s tyrosine kinase (BTK) allele?

a. She has no functional B cells and is therefore unable to produce antibodies.

b. She will produce IgM, but not IgG or IgA, antibodies.

c. If her husband has a normal form of BTK, then 50% of her daughters will not be able to produce antibodies.

d. Her B cells will exhibit nonrandom X-chromosome inactivation.

e. She requires monthly injections of gamma globulin to prevent bronchiectasis.

Mutations that lead to a nonfunctional NADPH oxidase system are associated with _____.

a. neutropenia

b. chronic granulomatous disease

c. immune-complex disease

d. opportunistic viral infections

e. Chédiak–Higashi syndrome

Which primary immunodeficiency results in recurrent respiratory/genitourinary infections?

What 3 main B cell markers are used for enumerate B cells by immunophenotyping?

What type of inheritance is Chediak-Higashi disease?

Proportion of CGD that is X-linked?

Proportion of autosomal recessive genes in CGD?

Nitroblue Tetrazolium Test in cells from a patient with X-linked chronic granulomatous disease

The mother of the patient is a carrier of the mutation and has what NBT result?

SCID suffer with

Defects in AIRE

Infections of those with defects in AIRE

Defects in Foxp3

Deletion of what causes digeorge syndome?

Deficiency in C1, C2, C4

Deficiency in C3

Deficiency in C5-C9

Deficiency in Factor D, properdin (factor P)

What deficiency has similar effects to deficiency in C3?

Deficiency in DAF, CD59

Deficiency in C1INH

Inheritance of hereditary angioedema

Characterizing the condition of HAE

Which condition involves the impairment of platelets and lymphocytes

CHS1

Leukocyte adhesion deficiency (LAD) defect in

Clinical effect of LAD

What 3 disorders have the same functional effect: Defective respiratory burst Phagocytes unable to kill pathogens?

What is deficient in Myeloperoxidase deficiency (MPOD)?

What is deficient in G6PD?

What in addition to chronic bacterial and fungal infections are CGD patients susceptible to?

In addition to chronic bacterial and fungal infections what else is effected in G6PD?

What is the clinical effect of MPOD?

What is deficient in Chédiak-Higashi syndrome?

What is the functional defect of a defect in Lysosomal trafficking regulator protein in CHS patients?

What is the clinical effect of CHS?

Twelve-year-old Morgan Boyd had a 7-month history of several episodes of sudden onset of swelling of her tongue, lips, and eyes. These recurrences lasted 1–3 days before subsiding without medical intervention. Her older brother, Stephen, had had a similar problem when he was 16 years old. The edema was not itchy and there was no urticaria. Morgan did not experience airway obstruction or abdominal discomfort during any of her episodes. She was not taking any medications and did not have any drug allergies. A diagnosis of hereditary angioedema (HAE) was made on the basis of (1) blood measurements of key complement components after remission and again during a subsequent attack of angioedema, and (2) C1INH quantitative and qualitative tests. Which of the following complement proteins would be well below normal range in Morgan in both of her blood tests?

a. C1q

b. C3

c. C4

d. C5

e. C9

Loss-of-function mutations in the common γ chain (γc) gene are particularly damaging to the immune system because _____. (Select all that apply.)

a. homozygotes and heterozygotes fail to make sufficient γc protein for lymphocyte activation

b. they can result in severe combined immune deficiency (SCID)

c. T-cell dependent and T-cell independent B-cell responses are inhibited

d. multiple cytokine receptors cannot signal

e. MHC class II genes are unable to be expressed

Type of SCID with B+, nk+

SCID T-/B+/NK-

SCID T-/B-/NK+

SCID T-/B-/NK-

SCID T-/B-/NK- and causes reticular dysgenesis

SCID T-/B-/NK+

CD3E, CD3DELTA, CD45, CORO1A (1%, 1%)

SCID T-/B+NK-

SCID T-/B+ /NK- X-linked

Digeorge gene

TBX1

DiGeorge FISH

t-/b+/nk+

Why is there a T cell deficiency in DiGeorge syndrome?

DiGeorge (Velocardiofacial) syndrome: Treatment total aplasia

DiGeorge (Velocardiofacial) syndrome: Treatment partial aplasia

Which of these is not a consequence of a lack of thymus?

1. No T cells

2. Sparsely populated lymphoid tissue (thymus-dependent areas)

3. Poorly developed lymphoid follicles

4. No cell-mediated immunity

5. Complete abnormal antibody response

6. Subnormal antibody response

Primary T cell deficiency: DiGeorge (Velocardiofacial) syndrome

Other features DiGeorge

Diagnosis of Primary T-cell deficiency

Patients with no T-cells or poor T-cell function are vulnerable

SCID treatment

RAG1/2-recombination activating gene 1/2 –important genes which control the recombination of the v,d, and j segments of the Ig and T cell receptor loci,.  Mutations of these genes prevent

Which genetic defect leads to defective cytokine signalling?

Which genetic defect leads to no TCR or Ig gene rearrangement → no mature lymphocytes?

What defect leads to a toxic metabolite in T and B cells?

What blocks differentiation of early myeloid and lymphoid precursosrs?

most important receptorfor lymphocyte differentiation

TRANSDUCES gamma chain signal