Immunodeficiency States Flashcards
Deficient humoral immunity results in increased susceptibility to infections by _________?
pyogenic bacteria
Defects in cellular immunity lead to infections with _______ and _________ ?
viruses, intracellular microbes
Immunodeficiencies may lead to increased susceptibility to cancers caused by __________?
oncogenic viruses
Immunodeficiency may result from defects in (4)?
Lymphocyte maturation, Lymphocyte activation, effector mechanisms of innate immunity, effector mechanism of adaptive immunity
Inherited abnormalities affecting innate immunity generally affect (2)?
complement pathway or phagocytes
How are B Lymphocyte deficiencies diagnosed?
Reduced level of Serum Ig, defective antibody response to vaccination, reduced # of b cells in tissues, plasma absent in tissues
How are T Lymphocyte deficiencies diagnosed?
reduced # of peripheral blood T cells, low response to TY cell activators, deficient cutaneous DTH rxn’s to ubiquitous microbial antigens
What is CGD and a defect in what type of immunity causes it?
Chronic Granulomatous Disease, Innate immunity
CGD is cause by mutations in components of _____?
phagocyte oxidase system enzyme complex
The most common x-linked form of CGD is a mutation in ___________?
α subunit of cytochrome b558
X-linked form of CGD results in defective production of ____?
Superoxide Anion
(CGD) Superoxide anion is a ________?
reactive oxygen species (ros) that constitutes a major microbicidal mechanism of phagocytes.
(CGD) Defective production of ______ results in the failure to kill phagocytized microbes.
ROS
CGD is characterized by _______ infections with _________ producing intracellular bacterial and fungal microbes, usually from early childhood.
recurrent, catalase
T/F Aggressive antibiotic therapy for CGD usually promotes a complete recovery of the individual.
False. Disease is often fatal, even with antibiotics.
(CGD) FN-γ stimulates the production of________ by normal _______.
superoxide (10% is effective), PMN’s
What is LAD-1?
Leukocyte Adhesion Deficiency - Type 1
LAD-1 is a rare autosomal _________ disorder characterized by recurrent bacterial and fungal infections and impaired wound healing.
recessive
(LAD1) The molecular basis for this defect is absent or deficient expression of the ________, due to various mutations in the ______ gene.
β2 integrins, CD18
(LAD1) The β2 integrins are proteins which participate in the adhesion of _________ to other cells, notably _________ cells and the binding of _____ to APCs.
Leukocytes, endothelial, T-cells
(LAD1) Blood PMN counts are usually significantly ________ even when no infection is present because of the inability of the cells to adhere to vascular endothelium and migrate into the ________ compartment.
elevated, intravascular
All cytotoxic lymphocyte functions are considerably impaired because of a lack of the adhesion protein _______ .
LFA-1
LAD-2 is ?
Leukocyte adhesion deficiency type II
LAD-2 results from the absence of sialyl Lewis X, the tetrasaccharide carbohydrate ligand on _______ that is required for binding to ___________ on cytokine-activated endothelium.
neutrophils, “e” and “p” selectin
LAD-2 defect is caused by a mutation in a ______ _______ gene.
fucose transporter
(LAD2). Result is defective _______ of PMN’s to endothelium and defective
_________ of leukocytes to sites of infection
binding, recruitment
Typical infections of LAD-2 (4)?
Pneumonia, Periodontis, otitis media, localized cellulitis
The chediak-higashi syndrome is a rare autosomal recessive disorder characterized by recurrent infections by pyogenic bacteria, partial oculocutaneous albinism, and infiltration of various organs by _________________ .
non-neoplastic lymphocytes
What are some other defects of chediak-higashi syndrome (3)?
Nerve defects, early death of neutrophils, reduced chemotaxis of neutrophils
What are 4 diseases associated with defects in innate immunity?
Chronic Granulomatous Disease, LAD-1, LAD-2, Chediak-Higashi Syndrome
What are SCID’s?
Severe Combined Immunodeficiencies
T/F. SCID’s result from impaired progression at various check points during T cell development only if there are defects in B cell maturation?
False. Progression with or without B-cell maturation.
Disorders that effect both ________ and cell-________ immunity are called severe combined immunodeficiencies.
humoral, cell-mediated
X-Linked SCID is Mutation in cytokine receptor common ___ chain
γ (gamma)
X-Linked SCID is due to mutations in the gene encoding the common γ chain shared by receptors for the interleukins _____________.
IL-2, IL-4, IL-7, IL-9 and IL-15
X-linked SCID condition is characterized by impaired maturation of ___ cells and ___ cells and greatly reduced numbers of mature T cells and NK.
T, NK
(X Linked SCID). The number of B cells is either ________ or _________.
normal, increased
(X linked SCID). The disease is the result of the inability of the lymphopoietic cytokine _____ whose receptor uses the ______ chain for signaling, to stimulate the growth of immature thymocytes.
IL-7, γc (gamma c)
(SCID) The _______ immunodeficiency in this disease is due to the lack of _____ help in antibody production.
humoral, T cell
(SCID). 50% patients show an autosomal recessive pattern of inheritance and many of these cases are due to a deficiency of the enzyme ____________.
adenosine deaminase (ADA).
DA functions in the salvage pathway of purine synthesis and catalyzes the irreversible deamination of adenosine and 2’- deoxyadenosine to ________.
inosine
(SCID) . Deficiency of ADA leads to ______ byproducts which directly or indirectly lead to apoptosis of ____________ and __________.
toxic, thymocytes and circulating lymphocytes
ADA deficiency can be cured by _____- identical or _______ T cell depleted bone marrow transplantation.
HLA, haploidentical
SCID has been linked to defects in _____ recombination.
V (D) J
A mutation in which two genes account for a large number of autosomal recessive forms of SCID?
RAG-1 and RAG-2
T/F. In children with RAG mutations, B and T cells are absent?
True.
SCID is fatal unless corrected by _________?
bone marrow transplant
What disease is caused by defective thymic development?
DiGeorge’s Syndrome
DiGeorge’s Syndrome is a ___________ deficiency due to a congenital malformation that results in defective development of the thymus and the parathyroid glands as well as other structure that develop from the 3rd and4th pharyngealpouchesduringfetallife.
selective T cell
Abnormal calcium homeostasis and muscle twitching (tetany) associated with DiGeorge Syndrome is cause by an absence of __________.
parathyroid glands
Abnormal development of the great vessels and facial deformities are Hallmark features of this disease?
DiGeorge’s Syndrome
This deficiency is characterized by the absence of gamma globulin (IgG) in blood and is one of the most common congenital immunodeficiencies.
X-Linked Agammaglobulinemia (XLA) (Bruton’s)
What is the last stage of B-Lymphocyte maturation of individual affected with Bruton’s Agammablobulinemia?
Pre-B cell stage
Mutations occur in a gene coding__________ which is involved in transducing signals from the pre-B cell receptor that are required for survival and differentiation of pre-B cells.
Bruton tyrosine kinase (Btk)
Boys with XLA remain well during the first ____ months , thereafter, they acquire extracellular bacteria infections but generally handle _____ infection reasonably well.
6-9 months, viral
This defect affects ~1 in 700 Caucasians and is thus the most common primary immunodeficiency known.
SELECTIVE IgA DEFICIENCY
This antibody deficiency defect displays either autosomal dominant or recessive patterns of inheritance.
SELECTIVE IgA DEFICIENCY
____ deficiency is characterized by low serum ____ with normal or elevated levels of IgM and IgG
IgA
T/F. With Selective IgA Deficiency, the α heavy chain genes and the expression of membrane- associated IgA are normal.
True. Only affects serum levels.
A group of heterogeneous disorders defined by reduced levels of serum Ig, impaired antibody responses to infection or vaccines and increased incidence of infections.
Common Variable Immunodeficiency
A high incidence of malignant tumors are associated with this disorder.
Common Variable Immunodeficiency
What is suggested when mature B cells are are present in lymphoid tissue, but plasma cells are absent?
Block in B cell differentiation to Ab-producing cells
Common variable syndrome is also known as ___________ because of generally later stage of onset of infections.
“acquired” hypogammglobukinemia
What is a rare disorder highlighted by defective switching of B cells to the IgG or IgA isotopes?
Hyper IgM Syndrome
Hyper IgM Syndrome defect s caused by mutations in the gene encoding the T cell effector molecule_______ ligand.
CD40
What is the treatment of choice for Hyper IgM Syndrome?
HLA-identical sibling bone marrow transplant at an early age
What are the major antibody deficiencies (4)?
X-Linked Agammaglobuoinemia, Selective IgA Deficiency, Common Variable Immunodeficiency, Hype IgM Syndrome
