L13 Immune defence Flashcards
what are the pathogens were exposed to
bacteria
viruses
parasites
fungi
what is involved in innate immunity
complement
macrophages/neutrophils
eosinophils
mast cells
what is the role of complement
opsonisation
cellular recruitment
lysis
what is the role of macrophages/neutrophils
phagocytosis
intracellular digestion
what is the role of eosinophils
extracellular digestion
what is the role of mast cells
inflammation
what is involved in adaptive immunity
B cells
T cells
what is the role of B cells
immunoglobulin production
antibody mediated/humoral
what is the role of T cells
helper T cells
cytotoxic T cells
(cell mediated)
what are the three pathways
classical
lectin
alternative
which pathways are antibody independent
lectin
alternative
which pathways are antibody dependent
classical
what do the three pathways do
activate C3 and generation of C5 convertase
what does C5 convertase do
lytic attack pathway
what happens in the classic pathway
antibody bind to specific antigen on pathogen surface
what happens in the lectin pathway
mannose binding lectin binds to pathogen surface
what happens in the alternative pathway
pathogen surface makes local environment conductive to complement activation
what happens when complement activated
C3b covalently bound to surface compounds of pathogen
what happens when C3b binds to pathogen
death of pathogen by:
recruitment of inflammatory cells
opsonise pathogen
perforation of pathogen membrane
what are the physiological complement activation consequences
lysis of bacteria
chemotaxis of phagocyte
opsonisation of bacteria
what happens in macrophage killing
bacteria bind to endocytic receptors of macrophages
engulfment and degradation
bacterial components binding to signalling receptors of macrophages induce inflammatory cytokines
what happens in neutrophil killing
neutrophil expresses receptors for many bacterial constituents neutrophils engulf and digest bacteria they bind to
where is macrophage killing
intracellular
where is neutrophil killing
intracellular
what are the macrophage and neutrophil bactericidal agents
acidification toxic oxygen derived products toxic nitrogen oxides antimicrobial peptides enzymes competitors
what pH is macrophage and neutrophils acidification
3.5-4
what are they toxic oxygen derived products of macrophage and neutrophils
superoxide O2- hydrogen peroxide H2O2 singlet oxygen 1O2* hydroxyl radical OH* hypohalite OCI
what are the toxic nitrogen oxides of macrophage and neutrophils
nitric oxide NO
what are the antimicrobial peptides of macrophage and neutrophils
defensins
cationic proteins
what are the enzymes of macrophage and neutrophils
NAPDH dependent oxidases
lysozyme
acid hydrolases
what are the competitors of macrophage and neutrophils
lactoferrin (binds Fe) and vitamin V12 binding proteins
where is eosinophil killing
extracellular
what are the preformed and newly synthesised products of eosinophils
enzymes toxic protein cytokine chemokine lipid mediator
what are the preformed and newly synthesised proteins of eosinophils products
eosinophil peroxide
eosinophil collagenase
what do eosinophil peroxide do
toxic to target by catalysing halogenation
trigger histamine release by mast cells
what do eosinophil collagenase do
remodel connective tissue matrix
what are the preformed and newly synthesised toxic proteins of eosinophils products
major basic protein
eosinophil cationic protein
eosinophil derived neurotoxin
what are the biological effects of major basic protein for eosinophils
toxic to parasites and mammalian cells
triggers histamine release by amst cells
what are the biological effects of eosinophil cationic protein
toxic to parasite
neurotoxin
what are the biological effects of eosinophil derived neurotoxin
neurotoxin
what are the cytokines from eosinophils
IL3
IL5
GM-CSF
what do the eosinophil cytokines do
amplify eosinophil production by bone marrow
cause eosinophil activation
what are the eosinophil chemokines
CXCL8
what do the eosinophil and chemokines do
promote leukocyte influx
what are the lipid mediators of eosinophils
leukotrienes C4, D4 and E4
platelet activating factor
what do eosinophil leukotrienes C4, D4 and E4 do
cause smooth muscle contraction
increase vascular permeability
cause mucus secretion
what do eosinophil platelet activating factor do
chemotatic to leukocytes
amplify lipid mediator production
activate neutrophils, eosinophils and platelets
what are the products of a mast cell
enzyme toxic mediator cytokine chemokine lipid mediator
what are the mast cell enzymes
tryptase
chymase
cathepsin G
carboxypeptidase
what is the biological effect of mast cell enzymes
remodel connective tissue matrix
what are the toxic mediators of mast cells
histamine
herapin
what is the biological effect of mast cell toxic mediators
toxic to parasite
increase vascular permeability
cause smooth muscle contraction
what are the mast cell cytokines
TNF-alpha
IL4, IL13
IL3, IL5, GM-CSF
what are the mast cell TNF-alpha biological effects
promote inflammation
stimulate cytokine production
what are the mast cell IL4 and IL13 biological effects
stimulate and amplify Th2 cell response
what are the IL3, Il5 and GM-CSF
promote eosinophil production and activation
what are the mast cell chemokines
CCL3
what is the biological effect of mast cell chemokines
chemotatic for monocytes, macrophafes and neutrophils
what are the mast cell lipid mediators
leukotrienes C4, D4 and E4
platelet activating factor
what is the biological effect of mast cell leukotrienes
smooth muscle contraction
increase vascular permeability
mucus secretion
what is the biological effect of mast cell platelet activating factor
chemotactic for leukocytes
amplify lipid mediator production
activate neutrophils, eosinophils and platelets
what are the two adaptive immunities
cell mediated
humoral
what happens to bacterial toxins
neutralisation
ingestion by macrophage
what happens to bacteria in extracellular space
opsonisation
ingestion by parasite
what happens to bacteria in plasma
complement activation
lysis and ingestion
what happens in antibody dependent cell mediated cytotoxicity
antibody binds antigens on target cell surface
Fc receptors on NK recognise bound antibody
crosslinking Fc receptors signal NK to kill - apopotosis
what is ADCC
antibody dependent cell mediated cytotoxicity
what is involved in cell mediated immunity
CD4 TH1 cell and macrophage
cytokines
activated macrophage
what is involved in humoral immunity
CD4 TH2 and B cell
cytokines
plasma cell and antibodies
what does cytotoxic T cell recognise
complex of viral peptide with MHCI and kills infected cell
what are the cytotoxic effector moleucles
perforin
granzymes
granulysin
Fas ligand
what are the immune responses
extracellular infection
intracellular vesicular infection
intracellular cytosolic infection
what happens in extra cellular infection
Innate immune response activated
Complement activation and phagocytosis
At the same time info on the pathogen transported via lymphatic system to local lymphoid organ
Naïve B cells and T cells that are activated recirculate
B cells make antibodies
T cells activated and effector cells – help clear pathogen
what happens in intra cellular vesicle infection
Interferons and NK cells (innate immune response)
Info taken to local lymphoid tissue
Activation of Th1 and CD8 cytotoxic T cells
Recirculate and kill virally infected cells
what happens in intra cellular cytosolic infection
Phagocytes have already ingested the pathogen
Info on the pathogen taken to local lymphoid organ
Need cell mediated response (Th1)
Th1 activated and recirculate to infection site – make cytokine signals to activate macrophages to better intracellularly digest
