3 - innate immunity Flashcards
examples of potentially pathogenic microorganisms
viruses
fungi
parasites
bacteria
1st defensive barrier of body
skin
breaking of skin - cuts
exposes body tissues to bacteria and fungal infections
main portals of entry to the body
mucosal epithelia of …
1 - GI tract
2- respiratory tract
3 - urogenital tract
why does immune system find parasites hard to remove
too big
tries to surround and encapsulate them
PAMPs
Pathogen associated molecular patterns
recognised by an array of PRRs
conserved or specific
where are innate immune cells found
sitting under skin of lung surfaces
features of innate immune cells
always there
no prior activation required
encoded in germline
under constant surveillance
where are immune cells derived from
pluripotent haematopoietic stem cell
HSC differentiation
divides to replace itself and produce a progenitor cell with potential to form all 3 lineages
myeloid lineage
produces phagocytic cells and inflammatory cells
innate
protect epithelial surfaces
mast cells role
sentinel role
differentiate and sit in tissues waiting to be activated
basophils/eosinophils role
circulating cells
recruited from blood stream to infected tissue when signal is received
killing mechanism of baso/eosino/mast cells
attack pathogens too large to be internalised
- degranulate when signal received on outside of cell
- release toxic contents creating hostile environment or directly kills pathogen
granulocyte granules
contain toxic components
e.g. histamines (important for allergies)
proteases
mechnikov 1898
discovery of phagocytosis
observational study of sticking thorns into cells
realised that migratory cells surround site of damage in animals with a vascular system
front line effector cells
macrophages and neutrophils
role of macrophages
sentinel
surveillance
send chemical signals to recruit more neutrophils (more effective)
phagocytic cells
dendritic cells
similar to macrophages
however..
dont fully destroy pathogens
action of DCs
break up pathogen and present fragments on cell surface to cells of adaptive immunity
ANTIGEN PRESENTATION
monocytes
type of WBC/leukocyte
differentiate into dendritic cells and macrophages
granulocytes
leukocytes (neutrophils)
basophils
mast cells
eosinophils
natural killer (NK) cells
specialised cytotoxic T lymphocyte
innate
types of macrophage receptors
scavenger receptors
complement receptors
receptors for conserved components of pathogens
Fc receptors
from Ig superfamily
found on surface of immune cells
recognise antibody (produced by adaptive immunity) binding to outside of pathogen
2 methods of innate activation
direct
indirect
direct activation of innate immunity
PAMP recgnised on pathogen by PRR on immune cell
indirect activation of innate immunity
if rececptors cannot grasp pathogen e.g. pathogen has slime capsule
delay
adaptive immunity activated
antibodies produced which opsonise pathogen
recognised by Fc receptor - phagocytosed
define opsonin
soluble component of immune system
coats microorganisms and stimulates their uptake by phagocytosis
‘ruffling’
motile cells migrate to cell membrane
actin polymerisation takes place
recognised by Fc receptors
dragged into phagosome
phagocytic cell roles
1 - release cytokines and chemokines
2 - activate adaptive immune response
chemokine
chemotactic cytokine
lays trails for migration of cells to site of infection
example of chemokine
e.g. IL-8/CXCL-8
cytokines
signalling molecules
increase permeability of blood vessels
allows cells to move out towards site of infection
inflammatory response can occur
cytokine receptors
JAK/STAT
STAT molecules are phosphorylised and dimerise
STAT dimer translocates to nucleus and initiates transcription
transendothelial migration
neutrophil rolls along epithelium of blood vessel
squeezes through loosened tight junction into adjacent connective tissue
migrates along concentration gradient of chemokine towards site of infection
why are selectins important
interactions with selectins are low affinity
constantly made and broken allowing rolling along surface of epithelium of blood vessel
what do fluid matrices e.g. tears contain
and why are they important in immunity
antibacterial peptides
toxic proteins
upregulated when pathogen component recognised
important for recruiting neutrophils to inflammatory sites
examples of antibacterial peptides and where are they found
B-defensins - lungs/skin
a- defensins - paneth cells of intestinal tract
lysozyme - fluid bathing cornea (potent)
cathelicidins
cathelicidins
produced by activated neutrophils and epthelial cells
signal thorugh formyl peptide receptors (GPCR)
aids neutrophil recruitment when bound
fMLP - formyl-methionyl peptide
bacterial peptide (chemotactic)
chemoattractant –> activates neutrophil recruitment
cleaved by peptidase and released into extracellular space
binds to receptor on outside of neutrophils
