Innate Immunity Flashcards
adaptive response
- soluble receptors: antibodies
- cell receptors- B/T cells
Innate response
- soluble: complement, pentraxins, collecting, fictions
- cell receptors: TLR, Nod-like etc
immunity requires
recognition and elimination- containment
most of the mechanisms against infectious agents
are provided by innate immune system
what recognise PAMPs
Pattern Recognition receptors
innate responses are
activated within hours of contact, but not signify increased by previous exposure
pathogens are capable of
-colonising the cytoplasm, intracellular vesicles, intersistital spaces, blood, lymph and epithelial surfaces
first critical barrier is
the skin- cuts, abrasions, burns expose body to bacterial, viral and fungal infections that can be fatal
main portals of entry for pathogens
-mucosal epithelia of gastrointestinal, respiratory and urogenital tracts
cells of the innate and adaptive immune system are derived from
pluripotent hematopoeitic stem cells
immune cell differentiation process
1) hematopoietic stem cells divide to produce a progenitor cell with the potential to give rise to all the hematopoietic lineages
2) generation of further progenitor cells committed to progressively narrower ranges of differentiated fates
both WBC and RBC are derived from
hematopoietic stem cells via committed progenitors which give rise to erythroid, myeloid and lymphoid lineages
THE ERYTHROID LINEAGE
gives rise to the erythrocytes and to megakaryocyes which shed fragments that form the platelets- that initiate blood clotting
THE MYELOID LINEAGE
gives rise to phagocytes and inflammatory cells of innate immunity
THE LYMPHOID LINEAGE
gives rise to the T and B cells of the adaptive immune system
activation of innate immune system
-invoked either directly by a pathogen, or by the adaptive immune response
indirect activation of the innate immune system
a lymphocytes o te adaptive immune system produces antibodies whose variable regions recognise a surface component of the bacterium. A non-variable region of the antibody is then recognised by a receptor of the phagocyte, which in turn is activated to engulf it.
- in this way bacteria that have masked the conserved component can be recognised and destroyed by the innate immune system
opsonin
a general term for soluble
components of the immune
system e.g. IgG1 that coat micro-organisms
and stimulate uptake by phagocytes
process of opsonisation
1) binding of soluble opsonins to particle
2) particle binding via phagocytic receptor
3) particle engulfment with actin polymerisation
4) interlization
5) fusion of phagosome with primary, secondary granules and lysosomes–> destruction
why are phagocytes important
1) when they sense PAMPs they release cytokines and chemokines that amplify response to infection (e.g. increasing permeability of blood vessels and recruiting additional cells - inflammatory response)
2) they activate the adaptive immune system e.g. dendritic
Ilya Mechnikov
discovered phenomenon of phagocytosis
1) observed mobile cells in larvae of starfish
2) introduced small thorns rom tangerine tree which had been prepared as a christmas tree for his children
3) next morning he found the thorns surrounded by the mobile cells
4) he knew that when inflammation occurred in animals, with a vascular blood system- leucocytes escaped from their blood vessels
5) occurred to him that leucocytes might take up and digest the bacteria that get into the body
three lineages of the Hematopoietic stem cell lineages
- myeloid
- lymphoid
- erythroid
myeloid cells are
innate
name 8 myeloid cells
- mast
- macrophage
- dendritic
- mast
- neutrophil
- eosinophil
- basophil
macrophages and their receptors
display an extensive array of receptors that recognise conserve components of micro-organism as well as scavenger receptors that recognise particles released by dead or damage tissue
macrophages also have receptors for
complement and antibodies
TLR2
response to peptidoglycan
TLR4
response to LPS
C-type lectin - DC-SIGN
mostly dendritic cells- pathogen recognition. ICAM adhesion
NK-like C-type lectin- Dectin -1
B-glucan receptor
SR-A - scavenger (collagenous)
phagocytosis of bacteria
CD36 (non-collagenous) CD36
phagocytosis of apoptotic cells
chemotaxis
neutrophils are attracted to bacterial chemical products like peptide fMLP
fluid matrices contain
antibacterial peptides and toxic proteins
antibacterial peptides and toxic proteins are..
constitutively secreted and further induced in response to cell wall components such as LPS
examples of antibacterial peptides found in the lungs and skin
B-defensins
examples of antibacterial peptides found in the Paneth cells of the intestinal tract
a-defensins
examples of antibacterial peptides found in the fluids bathing the cornea
Lysoszyme
what are cathelicidins
(another group of antimicrobial defensives) which are produced by activated neutrophils and epithelial cells
as well as their antimicrobial activity cathelicidins also …
trigger signalling through the formyl peptide receptor
the formyl peptide receptor
an innate immune recognition element- which aids in the recruitment of neutrophils to the inflammatory site
formyl-methionyl peptides are…
bacterial peptides
give an example of a formyl-methionyl peptide
Formyl-methionyl-leucyl-phenylalanine (fMLP)
fMLP
Formyl-methionyl-leucyl-phenylalanine
where are fMLP derived from
NH2-terminal extensions of newly synthesised
polypetides
FMLP is
is a potent polymorphonuclear leukocyte (PMN) chemotactic factor and is also a macrophage activator.
three roles of FMLP
(a) released by tissue bacteria,
(b) attract and activate circulating blood leukocytes by binding to specific G protein coupled receptors on these cells, and
(c) thereby direct the inflammatory response to sites of bacterial invasion.
