Primary Immunodeficiencies Flashcards
how do mutant genes contribute to infection?
can provide the immune evasion needed by microbes to establish infection
how do mutant genes contribute to immunodeficiency
inadequate immune responses due to these genes result in an immunodeficient state and susceptibility to colonization and infection by microbes
what are primary immunodeficiency diseases?
inherited defects in genes for components of the immune system
what are secondary immunodeficiency diseases?
not due to defective genes, but diseases that develop as a consequence of environmental factors
what environmental factors could contribute to secondary immunodeficiency diseases?
drug abuse, malnutrition, chronic disease, medication, age
what are 3 warning signs of primary immunodeficiency?
- four or more new ear infections within one year
- two or more pneumonias within one year
- persistent thrush in mouth or fungal infection on skin
what 4 clinical features are suggestive of specific types of primary immunodeficiencies?
- recurrent bacterial infections
- recurrent viral infections
- recurrent/chronic infections of soft tissues
- angioedema, autoimmunity, recurrent pyogenic and neisserial infections
what primary immunodeficiency is indicated by recurrent bacterial infections
defect in antibody mediated (humoral) immunity.
what results if there is deficiency in antibody mediated immunity?
recurrent bacterial infections involving encapsulated bacteria (strep pneumo, h influenzae, etc) or chronic enteroviral gasterenteritis and giardiasis
what primary immunodeficiency is indicated by recurrent viral infections?
defect in cell mediated immunity
what results if there is a deficiency in cell mediated immunity?
recurrent viral or mycotic infections like fungal pneumo, mucocutaneous candidiasis, PJP
what primary immunodeficiency is indicated by recurrent/chronic infections of soft tissues?
defect in phagocytic function (mostly neutrophils, maybe T cells)
what results if there is a defect in phagocytic function?
poor wound healing, soft tissue abscesses and granulomas of liver, lung, spleen, chronic gingivitis, periodontal disease, mucosal ulcerations
what primary immunodeficiency is indicated by angioedema, autoimmunity, recurrent pyogenic and neisserial infections?
defects in complement system
what causes angioedema and autoimmunity?
defects in regulatory proteins of complement
what causes recurrent pyogenic infections and autoimmunity?
defects in early components C1-4 of complement
what causes recurrent neisserial infections and autoimmunity?
defects in late components oC5-9 of complement
what causes humoral immunodeficiencies?
antibody synthesis is predominantly impaired
when do pt develop symptoms of humoral immunodeficiencies?
do not develop symptoms until over 1yo because of the disappearance of maternal IgG
symptoms of humoral immunodeficiencies?
recurrent sinopulmonary infections with encapsulated bacterial pathogens like strep pneumo and h influenzae
pathogenesis of X linked (infantile) agamaglobulinemia? (XLA)
mutation in Bruton’s tyrosine kinase (BTK), which leads to lack of synthesis or production of nonfunctional protein –> lack of B cells in the blood and tissues (and plasma cells)
what does Bruton’s tyrosine kinase do?
triggers light chain rearrangement and BCR formation from pro-B cell to pre-B cell
(B cell differentiation, maturation, BCR signaling)
what impact does BTK have on B cells?
B cell maturation arrests early in development and there is normal levels of pro-B cells in bone marrow (just don’t have pre-B, immature or mature) HOWEVER lack of B cells (and plasma cells) in blood and tissues
what impact does XLA have on Ig?
there are severe deficiencies in IgM, IgA, IgE, IgG (no plasma cells to release)