Immunodeficiency Diseases Flashcards
X-linked agammaglobulinemia
Aka Brutons’ agammaglobulinemia or XLA
A humoral deficiency
Characterized by:
Low levels or absence of gamma globulin in the blood
Reduced or absent B cells in the peripheral blood and lymphoid tissues
No germinal centers in lymph nodes
No plasma cells
Maturation, numbers and functions of T cells are usually normal
Failure of B cells to mature beyond the pre-B cell stage in the bone marrow because of mutations or deletions in the gene encoding B cell tyrosine kianse (Btk) encoded on X chromosome
Treatment: IV Ig, bone marrow transplant
Hyper-IgM syndrom
Deficiency of IgG, IgA, and IgE - elevated levels of Igm
Normal numbers of B cells
Autoantibodies to PMNs, platelets, and RBC
Failure to produce germinal centers; germinal centers are completely absent in lymph nodes
Defect is in gene ecodign CD40L (CD154) expressed on T cells, required for B cell responses to T-dependent antigens; X-linked
Can also be a defect in CD40 (on B cells and APC)
Class switching and memory B cells are not formed
Therapy: Ig replacement
Selective Ig deficiencies
Humoral deficiences
IgA deficiency - most common of all primary immunodeficiencies; symptoms range from unoticed to various problems including recurrent respiratory and g/u tract infections; other problems: intestinal malabsorption, allergic disease, autoimmune disorders; some pts can substitute IgM for IgA as a mucosal antibody
IgM deficiency - rare; autosomal recessive; severe infections, malignancies, autoimmune diseases
IgG deficiency - rare; may be unnoticed until adulthood; treatment is Ig administration
Combined variable immunodeficiency diseases (CVID)
Often shows up later in life
Decrease in numbers of plasma cells - therefore reduced serum levels of IgG, IgA, and often IgM - recurrent infections
Diagnosis is made by exclusion of other causes of Ab deficiency
Some cases are sporadic but some are familial - may be due to genuine B cell defects presumably at the stage where B cells become plasma cells - mutations in TACI, a member of the TNFR family have been identified
Severe combined immunodeficiency disease (SCID)
Defects in lymphoid development affecting T cells alone or w/ B cells and NK cells
Thymus does not develop; few circulating T cells
Defective T cell numbers and function - may extend to B cells and NK cells
Usually presents in infancy: failure to thrive, fungal or viral infections (skin, mouth, throat lesions), pneumonia, chronic diarrhea
Almost half of cases are due to deficiency of the common γ-chain of the IL-2 receptor - XSCID (boy in bubble) affects IL-7 signaling
Causes of SCID
There a bunch of forms that cause SCID
A particular one is ADA deficiency, so there is inability to produce appropriate nucleotides
ZAP-70 - T cell signal transduction
Relatively normal levels of Ig (IgM) and CD4+ lymphocytes but their CD4+ T cells are nonfunctional; can’t get class switching to other Ig subtype
Bair lymphocyte syndrome
Defects in MHC expression
MHC class II: impairment of MHC gene transcription, treatment is bone marrow transplant
MHC class I: mutation in TAP genes - necessary for Ag processing in CD8+ mediate immunity; treatment is antibiotics and IVIG
Wiskott-Aldrich syndrome
Triad of: recurrent infection (particularly sinopulmonary), thrombocytopenia, eczema
Treatments can include: anti-infective prophylaxis, Ig replacement, hematopoietic stem cell transplantation
Caused by a variety of mutations in the gene encoding the WAS protein
This protein is involved in relaying signals from the cell surface to the actin cytoskeleton → leads to poor immune cell function
X chromosome linked
DiGeorge syndrom
Congenital malformation that results in defective development of the thyroid and the parathyroid glands
Deficient T cell maturation
Absent parathyroid causes abnormal calcium homeostatsis and muscle twitching (tetany)
Abnormal development of the heart
Facial deformities
Peripheral T cells are absent or redued in number and do not respond to polyclonal T cell activators
B cells may be normal but antibody levels may be reduced in severely affected patients
Patients are susceptible to mycobacterial, viral and fungal infections
Failure to thrive
Chronic granulomatous disease (CGD)
X-linked (70%) and AR (30%) forms
Defect in pathway that produces hydrogen peroxide and reactive products that kill phagocytosed bacteria (missing or defective components of phagocyte oxidase system, including b558 (X-linked)) - also decrease in mononuclear cell ability to process and present antigen
Excessive inflammatory reactions leading to gingivitis, swollen lymph nodes, and granulomas - also intracellular bacterial and fungal infections
IFN-γ treatment has been successful - gene therapy is also promising
Nitroblue Tetrazolium Test (NBT)
Used to diagnose CGD
Used to measure phagocytic activity of polymorphonuclear lymphocytes by the amount of color change in the dye
Chediak-Higashi syndrome
Autosomal recessive
Recurrent bacterial infections, lack of skin and eye pigment
Phagocytes contain giant granules - cannot kill bacteria
Mutation in LYST - protein involved in the regulation of intracellular trafficking
Impaired targeting of proteins to secretory lysosomes, which makes them unable to kill bacteria
Hereditary angioneurotic edema
Rare but serious problem that is passed down through families
Causes swelling, particularly of the face and airways, and abdominal cramping
Caused by low levels or improper function of C1 inhibitor
What are initial screening tests for immunodeficiency?
Blood count - hemoglobin, WBC count, lymphocyte morphology, differential count, platelet estimation or count
Quantitative immunoglobulins
Antibody responses to previous vaccines
Isoagglutinin (anti-A and anti-B titers) - for IgM function
Total hemolyic complement - test classical complement pathway
Infection evaluation - erythrocyte sedimentation rate, appropriate cultures, appropriate roentgenograms
