Ostuni 1 Flashcards
granulocytes leukocytes
basophils
eosinophils
neutrophils
agranulocytes leukocytes
lymphocytes
monocytes
what are the cells involved in innate immunity?
granulocytes and monocytes
who mediates adaptive immunity?
T cells
what is innate immunity?
a branch of the immune system that has an instantaneous immune reaction as soon as the pathogen enters in contact with the body
what do the receptors of monocytes and granulocytes recognize in a pathogen?
broad common structure conserved in pathogens, not specific ligands.
What are the molecules recognized by the innate immune receptors?
PAMPs
pathogen associated molecular patterns
-conserved across classes of pathogens
-structures that microbes can’t modify
-they are essential for the physiology of the microbes
LPS, lipopolysaccharide
-a component of the cell wall of bacteria
-a type of PAMP
-made of sugar and lipids
-recognized by receptors of innate immune system
->we can sense what’s is pathogenic and what’s not based on the presence of this PAMP
what is the name of the receptors expressed by innate immune cells to recognize PAMPs?
PRRs
pattern recognition receptors
what is the common structure of toll like receptors?
they all have a transmembrane domain and an intracellular domain.
1. recognition of the PAMPs
2. dimerization
3. intracellular signaling cascade as the following consequence
what’s the TOLL like receptor (PRR) that recognizes LPS (PAMP)?
Toll-like receptor 4
what are the transcription factors that get activated following the activation of toll like receptors? what do these transcription factors do?
NFKB and AP1
they go to the nucleus, activate the expression of genes that encode for molecules that are necessary to fight the infections (such as cytokines)
interferon pathway
-activated by the receptors located in the endosomes and responsible to recognize bacterial DNA and RNA patterns.
-this pathway stimulates the production of transcription factors of the IRF family
-these transcription factors stimulate the production of another type of cytokines important to respond to viruses and bacteria
when are DAMPs released?
after damage (injuries, burns) the cells go necrosis and release these DAMPs
HMGB1
type of DAMP that is recognized by Toll like receptor 4 (the one that recognizes LPS-PAMP)
NB: the receptors that recognize PAMP also recognize DAMP
why do the receptors that recognize PAMP (PRR) also recognize DAMP?
because an infection comes potentially after an injury.
when we have an injury, DAMP activate an immune response that is fundamental to prepare for the potential infection that comes afterwards.
after a damage or an infection, what are the first cells that get recruited from the blood and go to the infection/damage site?
neutrophils
the rolling phase of neutrophils is mediated by which molecules?
selectins
the adhesion phase of neutrophils is mediated by?
integrins
what do cytokines cause during an inflammatory response?
-vasodilation
-increased permeability of endothelial cells
wha generates the cytoskeletal rearrangement in neutrophils?
the interaction between the pathogen and the phagocytic receptors in the membrane of neutrophils.
what’s the name of the place in which the pathogen is entrapped inside the neutrophil?
phagosome
how is the killing of the pathogen happening once the bacteria is entrapped into the phagosome?
the granules in the neutrophil are filled with cytotoxic substances and enzymes that are released inside the phagosome
–>the pathogen is killed
Oxygen dependent microbial killing
NADPH oxidase is present in the membrane of phagosome and partially reduces oxygen species to generate an hostile environment for the pathogen.
ROS are actively generated in the immune system because they can interact and deteriorate bacterial structures.
NETs
-neutrophils extracellular traps
-generated when the infection is so severe that the phagocytosis of one single pathogen at a time is not sufficient or the pathogens are way too big
-neutrophils die, release their cytoplasm and their DNA outside the cell.
-They release also their granules content (full of cytotoxic enzymes)
-the DNA is a DAMP and will generate the recruitment of other cells to fight the infection
-the enzymes in the granules are very toxic and can damage the surrounding tissues other than killing the pathogens
->the NETs have to be highly regulated
what is the shape of the nuclei in a mature neutrophil?
multi lobed connected by thin layers of chromatin with very highly compact DNA.
once they are mature, due to this structure of the DNA, neutrophils can express very few genes and they have a decreased plasticity.
G-CSF
granulocytes colony stimulating factor.
-stimulates the differentiation of hematopoietic stem cells into neutrophils
-G-CSF increase when an inflammation reaction is happening and the same inflammatory factors that are released at the site of infection act on the bone marrow.
the level of GCSF increase and more neutrophils are produced to fight the infection
neutropoiesis
neutrophils get produced in the bone marrow
mature in the bone marrow
and then they are released in the blood.
how long do neutrophils live in circulation?
they are very short lived.
they are constantly replaced in a way that the ones that are alive will function and won’t activate in wrong situations
what is the shape of the nucleus of monocytes
U shaped nucleus
can monocytes perform neptosis?
no they can’t
macrophages can be of 2 origins
-embryonic origin, from EMP precursors->they were in the tissues during the developing of the organs in the embryo and they remain there in the adult life
-from monocyte differentiation: monocytes get recruited at the site of infection, they finish up the inflammation reaction and then they differentiate into macrophages
in which organ macrophages are 100% embryonic derivative?
in the brain
in which organ macrophages are 100% monocytes derived?
in the intestine
