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Flashcards in Immunodeficiency Diseases Deck (17)

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


Genetic diagnosis of immunodeficiency




Therapies for immunodeficiencies

Gamma globulin - fraction of blood that contais Igs; pooled from 2,000 - 10,000 donors; contains Abs to many different antigens

Bone marrow transplantation - requires good match (sibling) - removed from pelvic bones

Antibiotics - supportive


Gene therapy