Immunology Flashcards
what happens when cells re-encounter an allergen?
allergen binds to IgE coated mast cells & basophils
degranulation
release of vasoactive mediators (histamine, tryptase)
increased expression of pro-inflammatory cytokines & luekotrienes
name vasoactive mediators
histamine
tryptase
which 2 cells express receptors that bind to the Fc region of IgE antibodies on their surface?
mast cells
basophils
what happens in type 2a hypersensitivity?
destruction of antigen-positive cells via phagocytosis, opsonins (C3b)
what happens in type 2b hypersensitivity?
stimulation of cell surface antigens,
complement mediated inflammation, C3a, C5a, MAC
what activates macrophages to superkillers?
TH1
what does TH2 do in autoimmunity?
IgE class switching
mast cell activation
what is VDJ?
variable diverse joining
the random recombination of segmented genes to form unique VDJ sequence (for variable region of B cell)
what is IPEX syndrome?
an X linked monogenic disorder
what is IPEX caused by?
mutations in FOXP3 gene
causes failure of peripheral tolerance mechanisms due to absent regulatory (Treg) cells
what can act as a superantigen? what is the process?
bacterial toxins
can non-specifically activate all T-lymphocytes, including auto-reactive T & B cells
Trigger T cell activation
what is an epitope?
the part of an antigen that is recognised by the immune system and generates an immune response
explain tissue injury and antigen sequestration?
previously sequestered (hidden) self-antigens can become exposed and cause an autoimmune reaction during infection/trauma
e.g. eyes, testes
what stimulates immature tissue-resident dendritic cells to increase expression of co-stimulatory molecules?
TNF alpha
what are possible defects in neutrophil cell cycle?
neutrophil development
trans-endothelial migration
neutrophil killing
what is the mutation and its effect in SCN type 1?
(severe congenital neutropenia)
mutations in ELANE gene on chromosomes that encode for neutrophil elastase
accumulation of precursors in bone marrow i.e. neutrophils cannot mature
autosomal dominant
what do you give to treat SCN type 1?
recombinant G0CSE
give recombinant cytokine, allows mature neutrophil production@ cannot mature properly if not enough ELANE precursor
what is there an insufficiency of when there is defects in trans-endothelial migration?
ICAM-1
(an adhesion molecule)
insufficient adhesion molecules for neutrophils to move through
what are the characteristics of leukocyte adhesion deficiency?
autosomal recessive
genetic defect in CD18 integrin gene
failure of neutrophil activation and migration
what happens in granulomatous disease (CGD) ?
deficiency in intracellular killing mechanism: no respiratory burst
deficiency in p47phox gene- a component of NADPH oxidase complex
granuloma formation-starve of nutrients
cannot generate oxygen/ nitrogen free radicals
what are treatments for PIDS?
immunoglobulin replacement therapy
aggressive infection management- oral/IV antibiotics & antifungals
definitive therapy- hematopoietic stem cell transplantation, gene therapy
what is SCID?
severe combined immunodeficiency
it is failure of production of lymphocytes
i.e. T cells, B cells, NK cells
what causes X-linked (the commonest form) of SCID?
mutation of a component of the IL-2 receptor
what does the mutation in X-linked SCID cause?
(mutation is of component of IL-2 receptor)
inability to respond to cytokines
failure of T cell & NK cell development, immature B cell production
very low or absent T cells
normal/ increased B cells
poor developed lymphoid tissue & thymus
what kind of infections lack functional T-cell compartments?
recurrent viral
recurrent bacterial
recurrent fungal
what causes recurrent viral infection?
no CD8 cells
so no cytotoxic cells
no elimination of infection reservoir
what causes recurrent bacterial infections?
CD4+T FH cells,
(co)stimulation of B cells, antibody production negatively affected
what causes recurrent fungal infections?
faulty effector CD4+TH cells & antibodies
which are essential for defence against fungi
what are possible pathways of SCID?
cytokine receptor deficiency
signalling molecule deficiency
metabolic defects
defective receptor arrangement
treatments for SCID?
stem cell transplant from HLA identical sibling
stem cell transplant from other sibling/ parent/ from matched unrelated donor
IV Ig replacement
to avoid: no live attenuated vaccines
what is Burton’s X-Linked hypogammaglobulinemia?
no circulating B cells
no plasma cells
no circulating antibody after first 6 months
BTK gene is essential for B cell development- not working
what is a defence against intracellular mycobacteria?
IL-12 IFNgamma network
