cytokines and chemokines Flashcards
what are cytokines
small proteins around 25kDa that act as intracellular signalling molecules
what are chemokines
chemotactic cytokines which act to specifically attract leukocytes to target location
what is in the group of soluble pattern recognition molecules
- lysozyme
- clotting factors
- complement
- beta defensins
- CRP
what are beta defensins
cationic anti-microbial peptides (2-6 kDa)
- derived by proteolytic cleavage of larger molecules
where are alpha defensins found
neutrophil granules and paneth cells (intestine)
where are beta defensins found
epithelial cells - gut, respiratory and female reproductive tract, organ gingiva and lung airways
- skin
- kidneys
where are θ-defensins found
primates, mutated/inactivated in humans
what are beta defeinsins packaged into
lamellar bodies - lipid rich secretory organelles to produce protective surface
what do beta defensins do
- associated with resistance of epithelial surfaces to microbial colonisation
- change interacts with bacterial LPS and lipoteichoic acid (LTA
- this replaces Ca2+ and Mg2+, destabilises membrane and pore formation
what are the secondary functions of beta defensins
- chemoattractant - monocytes, T cells, dendritic cells and mast cells
- induces mast cell degranulation
- improves macrophage phagocytosis
what is C reactive protein (CRP)
- hepatic protein with an annular ring structure
- severe inflammation - 1000x in 24h
- blood test for inflammation
what does C-reactive protein (CRP) do
- binds phosphocholine of bacterial and fungal cell wall LPS
- opsonisation activates CP of complement by binding C1q
where is C- reactive protein synthesised
synthesised by liver, macrophage, neutrophils following stimulation by IL-6
what do cytokines normally signal by
autocrine and paracrine
what is pleiotropic
activate cells, induce differentiation, inhale microbial activity - functions of cytokines
what are the families of cytokines
- interleukins
- interferons
- colony- stimulating factors
- tumour necrosis factors
what initiates the signalling pathway of cytokines
PAMP/ DAMP binding to PRR on macrophages or dendritic cells
what does the cytokine signalling pathway do
produces specific pattern of cytokine / chemokine expression for the type and site of infection
what are type 1 interferons induced by
viral infections
what do type 1 interferons do
- secreted into extracellular fluid
- binds receptors on unaffected neighbouring cels - interferon alpha receptor (IFNAR)
what proteins make type I interferons
IFN alpha and IFN beta
what makes type 2 interferons
- natural killer cells
- CD4+ and CD8+ T cells
what is the function of type 2 interferons
- activates macrophages
- induces MHC class 2 expression
- directly inhibits viral replication
what are the effects of IFNy
- promotes activity of NK cells
- primes macrophages against secondary infections
- increases antigen-presenting capabilities of macrophages
- induces expression of viral suppression genes
- improves phagocytic activity of macrophages
- upregulates expression of adhesion molecules of blood vessel endothelial cells
