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Questions and Answers
Wiskott-Aldrich Syndrome is an X linked disorder caused by a mutation in the ______ gene.
Wiskott-Aldrich Syndrome is an X linked disorder caused by a mutation in the ______ gene.
WAS
In Leukocyte Adhesion Deficiency, the most common type is a defect in ______.
In Leukocyte Adhesion Deficiency, the most common type is a defect in ______.
CD18
Chronic Granulomatous Disease results from a loss of function of ______ oxidase.
Chronic Granulomatous Disease results from a loss of function of ______ oxidase.
NADPH
Children with Chediak-Higashi Syndrome may experience severe neuro impairment due to ______ dysfunction.
Children with Chediak-Higashi Syndrome may experience severe neuro impairment due to ______ dysfunction.
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A classic presenting infection associated with delayed umbilical cord separation in Leukocyte Adhesion Deficiency is ______.
A classic presenting infection associated with delayed umbilical cord separation in Leukocyte Adhesion Deficiency is ______.
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Patients with Chronic Granulomatous Disease are susceptible to infections from catalase ______ bacteria.
Patients with Chronic Granulomatous Disease are susceptible to infections from catalase ______ bacteria.
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Elevated levels of ______ and IgA are commonly found in patients with Wiskott-Aldrich Syndrome.
Elevated levels of ______ and IgA are commonly found in patients with Wiskott-Aldrich Syndrome.
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The Nitroblue tetrazolium test is used to assess the presence of ______ oxidase in neutrophils.
The Nitroblue tetrazolium test is used to assess the presence of ______ oxidase in neutrophils.
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The absence of the WAS protein in Wiskott-Aldrich Syndrome affects T-cell reaction to ______ cells.
The absence of the WAS protein in Wiskott-Aldrich Syndrome affects T-cell reaction to ______ cells.
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Chediak-Higashi Syndrome is characterized by ______ infections, particularly with Staph and Strep bacteria.
Chediak-Higashi Syndrome is characterized by ______ infections, particularly with Staph and Strep bacteria.
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Chronic mucocutaneous candidiasis is often associated with ______ dysfunction.
Chronic mucocutaneous candidiasis is often associated with ______ dysfunction.
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Severe Combined Immunodeficiency (SCID) usually involves a primary T cell ______.
Severe Combined Immunodeficiency (SCID) usually involves a primary T cell ______.
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ADA deficiency leads to excess ______, which inhibits DNA synthesis.
ADA deficiency leads to excess ______, which inhibits DNA synthesis.
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Ataxia Telangiectasia is caused by a defect in the ______ gene.
Ataxia Telangiectasia is caused by a defect in the ______ gene.
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In Hyper-IgM Syndrome, B cells are unable to switch from making IgM to ______.
In Hyper-IgM Syndrome, B cells are unable to switch from making IgM to ______.
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The classic case of SCID includes infants with recurrent ______.
The classic case of SCID includes infants with recurrent ______.
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Neutrophils are crucial for ______ defense against infections.
Neutrophils are crucial for ______ defense against infections.
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Ataxia Telangiectasia presents with ataxia in the ______ year of life.
Ataxia Telangiectasia presents with ataxia in the ______ year of life.
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Classic symptoms of chronic skin candidiasis include ______.
Classic symptoms of chronic skin candidiasis include ______.
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Patients with Hyper-IgM Syndrome are more prone to ______ infections.
Patients with Hyper-IgM Syndrome are more prone to ______ infections.
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Loss of T-cells, B-cells, Granulocytes, and Complement can lead to immune ______.
Loss of T-cells, B-cells, Granulocytes, and Complement can lead to immune ______.
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X-linked Agammaglobulinemia is associated with a failure of B cell precursors to become ______.
X-linked Agammaglobulinemia is associated with a failure of B cell precursors to become ______.
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In X-linked Agammaglobulinemia, symptoms typically begin around ______ months of age.
In X-linked Agammaglobulinemia, symptoms typically begin around ______ months of age.
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Selective IgA Deficiency is a very common syndrome with an incidence of about 1 in ______.
Selective IgA Deficiency is a very common syndrome with an incidence of about 1 in ______.
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Common Variable Immunodeficiency (CVID) is characterized by defective B cell ______.
Common Variable Immunodeficiency (CVID) is characterized by defective B cell ______.
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Thymic Aplasia is also known as ______ Syndrome.
Thymic Aplasia is also known as ______ Syndrome.
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A classic triad of DiGeorge Syndrome includes loss of thymus, loss of parathyroid glands, and congenital ______ defects.
A classic triad of DiGeorge Syndrome includes loss of thymus, loss of parathyroid glands, and congenital ______ defects.
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In Hyper-IgE Syndrome, there is a failure to produce ______ which affects the attraction of neutrophils.
In Hyper-IgE Syndrome, there is a failure to produce ______ which affects the attraction of neutrophils.
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Chronic mucocutaneous candidiasis results from a defect in autoimmune regulator (AIRE) ______.
Chronic mucocutaneous candidiasis results from a defect in autoimmune regulator (AIRE) ______.
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Patients with X-linked Agammaglobulinemia often experience recurrent respiratory bacterial infections due to loss of ______ by antibodies.
Patients with X-linked Agammaglobulinemia often experience recurrent respiratory bacterial infections due to loss of ______ by antibodies.
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Common Variable Immunodeficiency is often sporadic, meaning it usually occurs without a family ______.
Common Variable Immunodeficiency is often sporadic, meaning it usually occurs without a family ______.
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Symptoms of Selective IgA Deficiency can include recurrent sinus and pulmonary ______.
Symptoms of Selective IgA Deficiency can include recurrent sinus and pulmonary ______.
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Patients with Hyper-IgE Syndrome might show facial deformities, such as a broad ______ bridge.
Patients with Hyper-IgE Syndrome might show facial deformities, such as a broad ______ bridge.
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The treatment for X-linked Agammaglobulinemia typically involves intravenous ______ (IVIG).
The treatment for X-linked Agammaglobulinemia typically involves intravenous ______ (IVIG).
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A hallmark finding in DiGeorge Syndrome includes a low ______ count due to thymic dysgenesis.
A hallmark finding in DiGeorge Syndrome includes a low ______ count due to thymic dysgenesis.
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Study Notes
Immune Deficiency Syndromes
- Immune deficiencies encompass a range of conditions, impacting the body's ability to fight infections.
- These deficiencies can be acquired (e.g., HIV, chemotherapy) or genetic/congenital.
- A common manifestation is recurrent infections, frequently presenting in infancy.
- Several specific immune deficiency syndromes are discussed, each with unique characteristics, including X-linked agammaglobulinemia (Bruton's), Selective IgA deficiency, Common Variable Immunodeficiency (CVID), Thymic Aplasia (DiGeorge Syndrome), Hyper-IgE Syndrome, Chronic mucocutaneous candidiasis, SCID, and more.
X-linked Agammaglobulinemia (Bruton's)
- Inherited in an X-linked manner.
- B cell precursors fail to develop into mature B cells.
- Light chains are absent, impacting antibody production. A defect in the Bruton tyrosine kinase (BTK) gene underlies this condition.
- Symptoms usually appear around 6 months of age due to the waning of maternal antibodies.
- Recurrent respiratory bacterial infections, enteroviruses (echo, polio, coxsackie), and Giardia are common infections.
- Key diagnostic findings include absence of mature B cells (CD19, CD20, BCR) in peripheral blood and underdeveloped germinal centers of lymph nodes. Antibodies of all classes are absent. Treatment involves IVIG therapy.
Selective IgA Deficiency
- A relatively common condition (~1 in 600).
- The exact mechanism is unknown, but defective IgA B-cells play a role.
- Most affected individuals are asymptomatic.
- Symptoms may include recurrent sinus, pulmonary, or other infections, and recurrent diarrheal illness (from Giardia).
- Blood transfusions may trigger anaphylaxis due to IgA in blood products, which triggers antibody production in affected individuals.
- IgA-deficient patients often have additional autoimmune disorders like SLE and RA (20–30%).
- Diagnosis is based on a serum IgA level below 7 mg/dL, with normal IgG and IgM levels. Treatment typically involves prophylactic antibiotics and IVIG. A false positive result of the $\beta$-HCG test is a frequent finding, due to heterophile antibodies produced in the deficiency.
Common Variable Immunodeficiency (CVID)
- A condition where B-cell maturation is defective leading to an absence of antibodies.
- Many genetic causes exist, though a specific genetic mutation is frequently not established.
- Patients often present in their late teens or twenties.
- Features include normal B cell counts, but absence of antibodies, as well as recurrent respiratory infections, enteric infections (e.g., Giardiasis), and enteroviruses. The condition may be accompanied by autoimmune disorders like RA or lymphoma.
- Treatment involves IVIG therapy
Thymic Aplasia (DiGeorge Syndrome)
- Caused by a deletion on chromosome 22q11, not familial.
- Characterized by the incomplete development of the thymus and other affected structures, leading to a lack of T cells.
- Presents with a triad of symptoms:
- Loss of thymus (and thus T-cells), leading to recurrent infections
- Loss of parathyroid glands, resulting in hypocalcemia and tetanic seizures.
- Congenital heart defects (conotruncal)
- Other common manifestations include abnormal aortic arch, truncus arteriosus, tetralogy of Fallot, and ASDs/VSDs.
- Key findings include absence of the thymus shadow on chest X-ray in infants. and severely underdeveloped T-cell structures in lymph nodes and spleen. Treatment may include thymic transplantation or hematopoietic cell transplantation.
Hyper-IgE Syndrome (Job's Syndrome)
- A rare syndrome characterized by immune dysregulation, skin and bone issues.
- Patients commonly have defective CD4+ Th17 cells (and thus IL-17). This leads to a loss of attraction of neutrophils, and STAT3 signalling pathway defects.
- A characteristic feature is increased IgE levels. This leads to recurrent infections without fever, a rash, and skin abscesses (staph skin lesions that lack warmth/redness).
- Associated abnormalities often include craniofacial abnormalities (broad nasal bridge) and retained primary teeth.
- Diagnosis based on elevated IgE and low IFN-$\gamma$ levels.
Chronic Mucocutaneous Candidiasis
- Characterized by a defect in the AIRE gene, which regulates immune function in the thymus.
- AIRE function #1 is associated with the Dectin-1 receptor response to Candida antigens, which, absent or faulty, lead to recurrent candidal infections.
- AIRE function #2, defective, promotes defective self-antigen presentation to T-cells (negative selection) and a lack of, or faulty, autoimmune T cells. This can be accompanied by endocrine dysfunction (parathyroid and/or adrenal).
- T-cell dysfunction is characterized by a deficiency in Th1 cytokines (IL-2 and IFN-γ) and increased IL-10, suggesting a cell-mediated defect. This often results in recurrent thrush, and skin/mucous membrane infections.
SCID (Severe Combined Immunodeficiency)
- A severe immunodeficiency affecting both cell-mediated and humoral immunity.
- Typically arises from a primary T-cell problem, with B-cell and antibody deficiencies often a secondary issue.
- Involves loss of T-cell/B-cell areas in lymphoid tissue, and the absence of thymic shadow.
- Affected individuals are highly susceptible to infections (viral, fungal, bacterial and also thrush, diaper rash and failure to thrive, in babies). They often die without a bone marrow transplant.
- Most common forms are X-linked (boys) with a mutation in the γ subunit of the cytokine receptor gene IL2RG, though adenosine deaminase (ADA) deficiency is another cause.
- In newborn screening, maternal T-cells can falsely increase T cell counts. The presence of TRECS (T cell receptor excision circles) and the absence of a thymic shadow are additional diagnostic clues.
Ataxia Telangiectasia
- A genetic disorder caused by a defect in the ATM gene on chromosome 11.
- This mutation results in an inability to repair DNA, specifically double-stranded breaks, often due to ionizing radiation, leading to hypersensitivity.
- Characterized by a complex mix of symptoms and findings that include nervous system issues (ataxia), skin issues (telangiectasias), and an increased susceptibility to infections and malignancies (e.g., lymphomas). The condition typically begins with gait and balance problems.
- Symptoms typically appear in childhood. Cerebellar atrophy, the presence of telangiectasias (dilated capillaries/blood vessels), and low levels of several immunoglobulins (especially IgA and IgG) are common features. Increased AFP is often observed.
Hyper-IgM Syndrome
- A disorder characterized by defective class switching of B cells, specifically, a failure of B-cell (CD40) to interact properly with T-cells (CD40L). This usually stems from a T-cell dysfunction.
- 70% of cases involved defective CD40L (gene), and is typically X-linked.
- Diagnostic indicator is an elevated IgM level coupled with the absence of other immunoglobulins. Characterized by recurrent bacterial infections, in infancy. The infections are commonly caused by encapsulated bacteria like S. pneumo and H. Flu, and also opportunistic infections like Pneumocystis, Cryptosporidium, and Histoplasmosis are possible.
Wiskott-Aldrich Syndrome (WAS)
- An X-linked immunodeficiency disorder due to a WASP gene defect. The WAS protein is needed for cytoskeleton maintenance in cells, particularly T cells.
- This inability to form "immunological synapses" means T cells don't interact correctly with antigen-presenting cells.
- Clinical symptoms frequently include eczema, thrombocytopenia (low platelets), and recurrent infections. Symptoms often become worse with age.
- Treatment usually involves bone marrow transplantation.
Leukocyte Adhesion Deficiency (LAD)
- A genetic autosomal recessive disorder, specifically affecting the CD18 protein, which is part of integrins (adhesion molecules), preventing proper migration of neutrophils (and other immune cells) into infected areas.
- A critical feature is the delayed shedding of the umbilical cord, and often presenting omphalitis infection (stump infection).
- Significant clinical manifestations include recurrent bacterial infections, and high WBC counts (neutrophilia) during episodes of infection and inflammation.
Chediak-Higashi Syndrome
- A rare disorder involving a defect in the lysosomal trafficking regulator (LYST) protein. The failure of lysosomes (organelles containing enzymes) to fuse properly with phagosomes (vesicles containing engulfed material) negatively impacts the ability of white blood cells to perform their killing functions.
- Presenting features include recurrent bacterial infections, including frequent episodes with staphylococci and streptococci infections. Oculocutaneous albinism (including fair skin, light coloured hair and light colored eyes) is a common indicator of the disease. Children who survive are frequently wheelchair bound due to neuro impairment.
Chronic Granulomatous Disease (CGD)
- A disorder in which phagocytes cannot produce the reactive oxygen species H2O2 as an antimicrobial defense. This stems from a defective NADPH oxidase. Catalase-negative bacteria (such as Staph aureus, Pseudomonas, Serratia, Nocardia) will already produce H2O2, while those positive for catalase can be destroyed because the host lacks H2O2 for their destruction. Defects in NADPH results in recurrent bacterial infections.
- A diagnostic test for CGD is the Nitroblue tetrazolium test, which assesses the presence and activity of NADPH oxidase production.
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Test your knowledge on immune deficiency syndromes, including both congenital and acquired conditions. This quiz explores various specific syndromes like X-linked agammaglobulinemia and others, helping to understand their characteristics and symptoms. Perfect for students and healthcare professionals alike!
