The effectors of innate immunity (W11) Flashcards
what is complement
set of soluble proteins in blood called C1, -> C9
triggered enzyme cascade
3 types of complement activation pathways
classical
mannose-binding lectin
alternative
3 types of complement effector pathways
anaphylatoxins (inflammation)
membrane attack complex (lysis)
opsonisation
classic pathway of complement activation?
only occurs when there are antibodies present specific to a foreign antigen
antibodies bind to complement component Clq activating subsequent complement components
alternative pathway of complement activation?
complete component C3 spontaneously activates and binds to nearby membranes
host cell control proteins deactivate C3 but bacterial cells do not
mannose-binding lectin pathway of complement activation?
activation through mannose-binding lectin binding to mannose or similar carbs on bacteria
mannose is not present on host cells
what occurs in complete lysis
Membrane Attack Complex (MAC) forms in membrane of bacteria
C6-C9 form pore for water to enter and ions to exit cell
bacteria swells and bursts
complement-mediated anaphylatoxins?
soluble complement components (anaphylatoxins) are released on complement activation, causing blood vessels to become leaky (oedema) allowing infiltration of plasma proteins, recruitment of immune cells, activation of mast cells
opsonisation?
complement opsonin binds to bacteria
phagocytes bind to complement through complement receptors
encourages phagocytosis
complement cascade?
C1 complex of 2 antibodies bound to target cell antigen
activates C2 & C4 and cleaves them in half, C2b &C4b form C3 convertase
(above is classical, below is alternative)
C3 convertase hydrolyses C3 splitting it into C3b & C3a
C3b activates C5 into C5a & C5b
membrane attack complex (pore) formed by C5b, C6-C9
C3a & C5a (anaphylatoxins) acting on endothelial cells
types of phagocytes
neutrophils
macrophages
dendritic cells
neutrophils features
rapid recruit to scene
good at killing
short lived
main part of pus
limited to circulation
macrophages features
good at killing when activated
involved in tissue healing, clearing dead cells, metabolism
reside in tissue (supplemented by monocytes
produce cytokines needed to pull in neutrophils
dendritic cells function
reside in tissues
rare
pick up antigens in tissue and take to T cells
process of neutrophils getting from circulation to site of inflammation?
extravastation
process of extravastation?
blood vessel endothelium altered by inflammatory cytokines
neutrophil rolls along endothelium then firmly adheres and exits between cells (diapedesis)
neutrophils then follow chemokine gradient to site of inflammation
phagocytosis?
phagocyte engulfs pathogen forming phagosome
lysosome containing toxic products fuses with phagosome to create a phagolysosome
more lysosomes fuse and pump in H+ ions, proteases, oxygen radicals, nitric oxide, pre-forming proteins
neutrophils also make HOCl (bleach)
antigen definition
molecule that is recognised by the adaptive immune system
how does antigen-specificity come about
adaptive immune cells randomly generate unique receptors that recognise specific antigens
when do dendritic cells mature and what occurs
when they sense danger.
improve antigen presentation and upregulate chemokine receptors
migrate to lymphatics (following naturally present chemokine gradients) and into lymph node where the antigen is presented to T cells
adaptive leukocytes and recognition of antigens? (signal 1)
B cell receptor - recognises soluble antigen in normal form
T cell receptor - antigen must be cut into peptides by dendritic cells and ‘presented’ with MHC molecules on the dendrites surface to be recognised
how is signal 2 passed on between dendrite and T cell
costimulation!
CD28 (most important costimulatory molecule receptor) on T cell binds with B7 (ligand) on dendritic cell
how does negative selection occur
when T cells are produced in the thymus they are presented with all the bodies ‘self’ antigens, and if a T cell recognises any it is given the signal to die, therefore the remaining T cells only recognise ‘non self’ antigens.
what occurs to T cells in the lymph nodes if they recognise ‘self’ antigens? when does this occur?
anergy (permanent stasis) or death
This occurs when there is a small signal one and absence of signal 2
what is signal 3?
production of cytokines (specific to pathogen type) from the dendritic cell (or other innate immune cells) which then act on the T cell and drives differentiation (when also activated with signal 1 and 2) towards particular effector cell type. This allows specialisation of the adaptive immune response - develop T cells better at killing bacteria, fungi, etc
