Immunodeficiencies Flashcards
What are the common neutrophil disorders?
Chronic granulomatous disease, Chediak-Higashi Syndrome, Leukocyte Adhesion Deficiency
What are the common complement disorders?
Hereditary Angioedema, Complement Cascade Deficiencies
What are the primary combined antibody and cellular immunodeficiencies (B & T cells)?
Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome, Ataxia-telangiectasia
Severe combined immunodeficiency (SCID) is the most severe immunodeficiency. What is the pathophysiology?
Dysfunction of both cellular and humoral immune function due to multiple possible defects
What is the clinical presentation of severe combined immunodeficiency disorder?
Small thymus, no lymphocytes in the thymus or lymph tissue, underdeveloped lymph nodes, infancy, opportunistic infections
What is the treatment for severe combined immunodeficiency disorder?
Stem cell transplant
What triad is often present with Wiskott-Aldrich Syndrome?
Atopic dermatitis, thrombocytopenia, susceptibility to encapsulated and opportunistic infections
Wiskott-Aldrich Syndrome is an X-linked disorder. What is the pathophysiology?
Gene mutation that affects binding to adaptor molecules and cytoskeletal components in hemopoietic cells that prevents normal development of platelets and leukocytes
When does Wiscott-Aldrich syndrome generally present?
During infancy - a baby that bleeds excessively after circumcision, bloody diarrhea, eosinophilia and increased IgE
What triad is present with ataxia-telangiectasia?
Cerebellar ataxia, oculocutaneous telangiectasia (bloodshot eyes due to vasodilation), immunodeficiency
ATM kinase defects are present in what immunodeficiency disorder?
Ataxia-telangiectasia
Ataxia-telangiectasia is a progressive disorder. When does it typically present?
Around 1yr (soon after walking)
A patient presents with cardiac abnormalities, abnormal facial features, cleft palate, and thymic hypoplasia. What is the diagnosis and cause of the disorder?
DiGeorge Syndrome due to deletion on chromosome 22
From what embryonic structure do the thymus and inferior parathyroids develop?
Third pharyngeal pouch
DiGeorge syndrome causes a defect of what immune cells?
T cells - B cells are OK but do not receive signaling from T cells so poorer antibody funcitoning
MHC I deficiency affects what immune cells?
CD8+ T Cells - failure to transport molecules to the ER
MHC II deficiency affects what immune cells?
CD4+ T cells - failure of MHC II expression
True/False. MHC II is expressed on all nucleated cells.
False. MHC II is only expressed on APCs. MHC I is expressed on all nucleated cells
MHC II Deficiency results in no effective CD4+ T cells. What is the clinical presentation?
Severe Combined Immunodeficiency - MHC II deficiency is much more severe than MHC I deficiency
IL-12 cytokine receptor deficiency causes a loss of what T cell response?
Th1 response to intracellular and viral pathogens
What is the clinical presentation of Hyper-IgE (Job) Syndrome?
Recurrent skin and respiratory infections, dermatitis, staph infections
A male infant presents with recurrent bacterial infections. WBC reveals normal T cell levels, but no mature B cells and low IgG. What is the likely diagnosis?
X-Linked Agammaglobulinemia
This immunodeficiency of B cells presents in teenage years with deficiency of all classes of Ig antibodies.
Common Variable Immunodeficiency - B cells are unable to differentiate into plasma cells
This B cell disorder presents with normal or high levels of IgM, but deficiency of all other Ig classes.
Hyper IgM Syndrome
What is the pathophysiology of Hyper IgM Syndrome?
Deficiency of CD40L on activated T cells needed for class switching
Patients with IgA deficiency are often asymptomatic. What infections may recurrently present in these patients?
Sinopulmonary diseases, allergies, celiac disease
What is the clinical presentation of transient hypogammaglobulinemia?
Gradual decline in maternal IgG during the first 6mo of life. IgG remains low for first year of life and then gradually increases
This complement disorder is due to an autosomal dominant deficiency of C1-inhibitor.
Hereditary Angioedema
What test is used to screen for complement cascade deficiencies?
CH50 or CH100
Recurrent infections with encapsulated bacteria and N. meningitidis is often indicative of this immunodeficiency.
Complement cascade deficiencies
What is the pathophysiology of chronic granulomatous disease?
Abnormal neutrophil function due to a deficiency of the NADPH oxidase and failure to generate ROS
Patients with chronic granulomatous disease are most susceptible to what bacterial infections?
Catalase-positive bacteria and fungi (staph, aspergillus, candida)
What is the clinical presentation of Chediak-Higashi Syndrome?
Oculocutaneous albinism, recurrent and serious staph and strep infections
What is Chediak-Higashi Syndrome?
An inherited defect in lysosomal trafficking that causes giant granules in neutrophils and impairs phagocytosis
What is the clinical hallmark of leukocyte adhesion deficiency?
Infections with NO PUS
What is the pathophysiology of leukocyte adhesion deficiency type 1?
Absence of CD18, a subunit of integrin, that prevents neutrophils from exiting circulation and entering tissues
In LAD Type 2, sialyl-lewis X is absent and prevents leukocyte rolling
Delayed separation of the umbilical stump may be indicative of this immunodeficiency.
Leukocyte Adhesion Deficiency
Recurrent infections with encapsulated bacteria often point to what type of immunodeficiency?
Defect in antibody-mediated immunity
Recurrent viral infections often point to what type of immunodeficiency?
T cell immunodeficiencies
