Immunodeficiency Flashcards
1
Q
describe X-linked agammaglobulinemia
A
- B cells in the bone marrow fail to mature beyond the pre-B cell stage, resulting in a marked decrease or absence of mature B-lymphocytes and serum immunogloublins
- disease is caused by mutations in the gene encoding a kinase called Bruton tyrosine kinase (BTK)
- recurrent pyogenic infections
2
Q
describe IgA and IgG subclass deficiency
A
- results from failure in terminal differentiation of B cells
- IgA deficiency is most common
- risk of anaphylactic shock during blood transfusion due to reaction against donor IgA
- patients tend to develop immune complex disease
- susceptible to pyogenic infections
3
Q
describe X-linked hyper-IgM syndrome
A
- characterized by defective B cell heavy-chain isotype (class) switching so that IgM is the major serum antibody and by severe deficiency of cell-mediated immunity against intracellular microbes
- caused by mutations in CD40L (on T cells)
- susceptible to pyogenic infections
4
Q
describe common variable immunodeficiency (CVID)
A
- characterized by poor antibody responses to infections and reduced serum levels of IgG, IgA and IgM
- underlying causes of CVID include defects in various genes invovled in B cell maturation and activation
- recurrent pyogenic infection
- may follow viral infection
5
Q
describe hypogamaglobulinemia of infancy
A
-
due to delay in IgG synthesis approx. up to 36 months
- in normal infants, synthesis begins at 3 months
- all other immunoglobulins are normally expressed
- deficiency in various functions of Th cells has been linked to dminished IgG class switch
- normal B-lymphocytes
6
Q
describe DiGeorge’s syndrome
A
- results from incomplete development of the thymus and a failure of T-cell maturation
- T cells are completely absent or presence of few abnormal T cells
- B cell, plasma cells and serum Ig levels are detected but in subnormal levels
- most common are intracellular infxns such as viruses and yeast infxns such as Candida albicans and Pneumocystis carinii but pts should be able to cope with most common bacterial infxns
- should never be immunized with live attenuated viral vaccines
7
Q
describe ataxia-telangiectasia
A
- associated with a lack of coordination of movement (ataxia) and dilation of small blood vessels of the facial area (telangiectasia)
- T-cells and their functions are reduced to various degrees
- B-cell numbers and IgM concentrations are normal to low
8
Q
describe Wiskott-Aldrich syndrome
A
- X-linked disease caused by a mutation in a gene that encodes a protein responsible for actin cytoskeleton rearrangement; because of the proteins absence, platelets and leukocytes do not develop normally, are small and fail to migrate normally
- associated with normal T-cell numbers with reduced functions, which get progressively worse
- IgM concentrations are reduced but IgG levels are normal
- both IgA and IgE are elevated
- boys with this syndrome develop severe eczema
9
Q
describe bare leukocyte syndrome
A
- caused by failure to express class II MHC molecules, as a result of mutations in the transcription factors that normally induce class II MHC expression
- some individuals have a defect in their TAP gene and can’t express class I MHC and are also deficient in CD8 T cells
- profound decrease in CD4 T cells, because of defective maturation of these cells in the thymus and defective activation in peripheral lymphoid organs
10
Q
describe cyclic neutropenia
A
- marked by low numbers of circulating neutrophil approx. every 3 weeks
- the neutropenia lasts about a week during which the patients are susceptible to infection; the defect appears to be due to poor regulation of neutrophil production
11
Q
describe leukocyte adhesion deficiency
A
- leukocytes lack the complement receptor CR3 due to a defect in CD11 or CD18 peptides and consequently cannot respond to C3b opsonin
12
Q
describe X-linked SCID
A
- due to a defect in gamma-chain causing impaired signalling through IL-2 as well as IL-4, -7, -11 and -15
- all involved in lymphocyte proliferation/differentiation
- when the gamma chain is not functional, immature lymphocytes, especially pro-T cells, cannot proliferate
13
Q
describe autosomal SCID
A
- caused by mutations in the ADA gene, which is involved in the breakdown of adenosine
- deficiency of ADA leads to the accumulation of toxic purine metabolites in cells that are actively synthesizing DNA, namely, proliferating cells
- lymphocytes are particularly susceptible to injury because these cells undergo tremendous proliferation during their maturation
- ADA def. results in a block in T cell maturation more than in B cell maturation
14
Q
describe the effects of corticosteroids
A
- cause changes in circulating leukocytes
- depletion of CD4 cells
- decreased in circulating eosinophils and basophils
- inhibition of T cell activation and B cell maturation
- inhibits cytokine production
15
Q
describe the effects of methotrexate
A
- structural analogue of folic acid
- blocks folic acid dependent synthetic pathways essential for DNA synthesis
- prolonged use for treatment reduces immunoglobulin synthesis