Immunology 2 Flashcards
what is primary immunodeficiency
congenital, resulting from genetic defects
deficiency causes disease
normally recessive inheritance
rarely dominant
a lot are X linked
how can primary immunodeficiency present in young children
allergies
autoimmunity
abnormal lymphocyte proliferation
cancer
describe B cell deficiency in primary immunodeficiency
absent or reduced follicles and germinal centres in lymphoid organs
reduced serum Ig levels
leads to pyogenic bacterial infections
describe T cell deficiency in primary immunodeficiency
may be reduced T cell zones in lymphoid organs
reduced DTH reactions to common antigens
defective T cell proliferative responses to mitogens in vitro
leads to viral and other intracellular microbial infections
- virus associated malignancies
describe innate immune deficiency in primary immunodeficiency
variable, depending on which component of innate immunity is defective
leads to variable; pyogenic bacterial infections
what is X-linked SCID
combined immunodeficiency (without syndromic features)
mutations in cytokine receptors
- il2ry chain (il2 receptor leads to stimulation of T cell proliferation)
cant make a working common gamma chain (cant make receptor)
T cells and NK cells fail, B cells normal but no help for efficient antibody repsonses
what is ADA-SCID
combined immunodeficiency (without syndromic features)
adenosine deaminase deficiency
depletes T, B and NK cells
basal expression in all cells, enhanced in thymocytes
describe therapy for ADA-SCID
bone marrow stem cells from suitable donor
manipulate immune system to make an autonomous bone marrow transplant
complicated, difficult, expensive and dangerous
list some examples of combined immunodeficiency (without syndromic features)
X-linked SCID
ADA-SCID
hyper IgM syndrome (CD40L deficiency)
describe hyper IgM syndrome
CD40L deficiency
high IgM, low others
molecular defect lies on CD40L molecules (T cells)
limited proliferation of B cells
what causes hyper IgM syndrome
fault in class switches - can’t produce IgG
- IgG is more effective than IgM in responding to bacterial infections
lit examples of combined immunodeficiency with syndromic features
FOXN1 deficiency
Bruton’s agammaglobulinemia
IgA deficiency
describe FOXN1 deficiency
athymic and alopecia
- no hair and thymic epithelium fails to develop - ineffective thymus - no T cells
B cells are normal but no help
describe Bruton’s agammaglobulinemia
X-linked, recessive
first describe immunodeficiency
mutation in Bruton’s tyrosine kinase gene
prevents B cell development
pro-B to pre-B stage
few follicles in lymph nodes
results in low serum antibody levels
describe IgA deficiency
most common
cytokines needed to mature lymphocyte into mature IgA plasma cell
how does IgA deficiency manifest
many asymptomatic
- only notice if diet changes sufficiently to alter gut microbiome)
children with mild deficiency will outgrow
what is the impact of a lack of antibodies
recurrent sepsis
bacterial infections often in airways
chronic gastroenteritis
failure to thrive
give examples of phagocyte defects
defects of neutrophil function
Mendelian susceptibility to mycobacterial disease (MSMD)
describe chronic granulomatous disease
no superoxide burst
multiple granulomas form as a result of a defective elimination of bacteria
when macrophage3 consumes bacteria, cannot kill it
- defects in the NADPH enzymes that generate the superoxide radicals involved in bacterial killing
nodule of persistent immune cells trying to kill bacteria
- eventually compromises gaseous exchange/ lung function
describe familial Mediterranean fever
inflammasome converts pro-il to il1 -> drive inflammation
in FMF, inflammasome regulators are mutated
inflammasome activated, increase il1 produced
describe therapy for FMF
identify the trigger and avoid that circumstance
inflammation can respond to anti il1 antibody
targets specific immune molecule
supresses symptoms
