Transcript Steps of Phagocytosis

Phagocytosis
= basic tool of innate immune respons


phagocyting cells
steps of phagocytosis
Phagocyting Cells



neutrophile granulocytes
destroying of extracellular bacteria,
short lived cells, pus forming cells
Monocytes / macrophages
destroying of self cells and intratracellular
micoroorganism, long lived cells
presentation of antigen to T cells
dendritic cells presentation of antigen to T
cells
The granulocytes
often take the first stand during an infection.
They attack any invaders in large numbers,
and "eat" until they die.
The pus in an infected wound consists chiefly
of dead granulocytes.
The macrophages ("big eaters")
- start out as white blood cells called
monocytes. Monocytes that leave the blood
stream turn into macrophages.
- are slower to respond to invaders than the
granulocytes, but they are larger, live longer,
and have far greater capacities.
- play a key part in alerting the rest of the
immune system (adaptive immunity)
The dendritic cells
are "eater" cells and devour intruders, like the
granulocytes and the macrophages.
And like the macrophages, the dendritic cells help
with the activation of the rest of the immune
system.
They are also capable of filtering body fluids to clear
them of foreign organisms and particles.
Localised Forms of Macrophages
Steps of Phagocytosis





migration to the site of inflammation
recognition of the antigen
ingestion
destroying of the pathogen
presentation of the antigen
Migration to The Site of Inflammation
Neutrophils and monocytes:
in circulation 7 %
in bone marrow 93%
ratio is changed in inflammation
Migration to The Site of Inflammation
rolling along the vessel wall
 contact between phagocyte and
endothelial cell = adhesion
 passing through the vessel wall
(diapedesis, extravasation)
 migration in tissue = chemotaxis

Adhesion molecules (AM)
a4/b1/VCAM-1 PSGL1/P-selectin L-selectin
rolling
CD18/ICAM-1
a4/b1/VCAM-1
adhesion
diapedesis
Contact of Phagocyte and Endothelium Adhesion Molecules
endothelium
phagocytes
selectins + sacharid structrures of neutrophil
(sialyl Lewis antigen) = rolling
ICAM-1 + β 2 integrins (CD 11/CD 18)
of neutrophils
VCAM-1 + β 1 integrins of monocytes
The Adhesion
The Moving in Tissue = Chemotaxis
Receptors for chemotactic factors:
 IL-8
 C3a, C5a
 leucotrien B4
 platelet activating factor (PAF)
 bacterial proteins (fMLP)
Diapedesis and Chemotaxis
Immune Recognition
PAMPs
pathogen associated molecular patterns
 DAMPs
damage associated molecular patterns


PRRs
pattern recognition receptors of
phagocytes
PAMPs
pathogen associated molecular patterns






conserved in evolution
shared by a large group of infectious agents
clearly distinguishable from self pattern
Gram-negative
Gram-positive
Yeast
lipopolysacharide
lipoteichoic acid
cell wall mannans
PRRs (pattern recognition receptors)
of phagocytes



lectins = proteins able to bind carbohydrates
mannose and galactose receptor
toll-like receptors
TLR1 – TLR10
CD14 scavenger receptors for lipopolysacharides
OPSONISATION
= making tasty for the eater, „ spice“
receptors of phagocytes for

antibodies (binding Fc fragment)

complement C3
Diapedesis and Chemotaxis
The Ingestion




The adherence: PRR and PAMP
Pseudopods around the particle:
interaction of receptors and activating an
actin and myosin contractile system
Plasma membrane is completly around:
the vacuole = phagosome
phagosome + lysosom = phagolysosom
Steps of Phagocytosis
Microbicidal Mechanisms
oxygen independent:
antimicrobial proteins (defensins)
enzyms (cathepsin, lysozym, lactoferrin)
 oxygen dependent:
catalyzed by NADPH oxidase:
NADPH + O2 = NADP + superoxide anion O2-,
reactive oxygen radicals
 myeloperoxidase, halogenating system


nitric oxide
Presentation of The Antigen




fragments of an antigen bind to MHC
molecules on the surface of phagocyting cell
= antigen presenting cell (APC)
APC presents the antigens fragments
to T cells
T cells help B cells to produce specific
antibodies, activate specific cytotoxic T cells
cooperation between innate and adaptive
immunity
Presentation of Antigen

http://www.youtube.com/watch?v=suCKm97y
vyk

http://www.youtube.com/watch?v=I9zSe0qm
XGw.