Ppt 2 the innate immunity Flashcards
What do Natural Killer cells secrete?
Interferon gamma (IFN-y)
What does IFN-y (interferon gamma) do?
Activates Macrophages
What does IL-1 do?
IL-1 will recruit neutrophils and induce inflammation
What 2 cells are responsible for starting inflammation?
macrophages and dendritic cells
What is the PAMP’s of the Innate immunity? How are they?
it is defining how theinnate immuny has all receptors that are the same
How are the PAMP’s of the Adaptive immune system?
they are specific for each antigen
Where are the PRR’s of the innate immune system made?
in the germline
Where are the PRR’s of the adaptive immune system made?
by genes
how do the PRR’s of the adaptive immune system achieve diversity in order to recognize different antigens?
through somatic recombination
Are all the PRR’s of the innate immunity the same? (are they clonal or non-clonal?)
yes they are non-clonal
Are all the receptors the same for the adaptive immune system?
no; they are clonal
How do phagocytes recognize bacteria to phagocytose?
they have receptors for:- bacterial endotoxins in gram negative bacteria- bacterial terminal mannose residues
how do phagocytes recognize viruses?
receptors for double stranded RNA
who will respond to unmethylated CpG oligonucleotides?
phagocytes
will the innate immunity vary from microbe to microbe?
no, it always responds the same way
will the adaptive response vary?
yes, it has a receptor for each type of microbe
What receptors does the innate immunity have on its surface?
toll like receptors
what receptors does the innate immunity have on its cytoplasm?
viral RNA and bacterial peptide
What signaling pathway do toll-like receptors activate?
NF-KB
Activation of NF-KB by toll-like receptors will cause what?
expression of:- cytokines- endothelial adhesion molecules- IRF-3
What does IRF-3 do?
activates release of Type 1 Interferons (INF alpha/beta) to stop viral replication
What does the epithelium do in the innate immunity?
it acts as a barrierhas anti-microbial substanceshas intra-epithelial lymphocytes
What is the “Carpet-Wormhole model of action of Defensins”?
you use defensins that introduce into the microbial membrane, changing its conformation and leading to formation of pores that cause rupture.
What 2 chains do intra-epithelial lymphocytes express?what are these similar to?
y (gamma) and deltathe t cell receptor: alpha and beta
What are the most abundant phagocytesfound insites of inflammation and are recruited through the blood?
1) Neutrophils2) Monocytes
What is the most abundant blood leukocyte?
Neutrophils
What stimulates the production of neutrophils? Where do they get made?
CSF cytokine (Colony Stimulating Factor) and stimulates their production in the Bone Marrow
what is the first cell to respond to any infection?
neutrophils
what is another name for neutrophil?
polymorphonuclear leukocyte
what do neutrophilsdo to microbes?
they phagocytose them and enter the extra-vascular tissue
What do monocytes do?
they ingest microbes
mononuclear phagocytesthat are in the blood are called?
monocytes
mononuclear phagocytes in the tissues are called?
macrophages
when you have accumulation of leukocytes in a site and there is vascular dilation and leakage of proteins, what is this called?
inflammation
how do neutrophils and monocytes reach the site of infection?
by binding to endothelial adhesion molecules
What is Leukocyte Adhesion Deficiency? (LAD)
can’t express adhesion molecules (integrins and selectins)and leukocytes can’t enter sites of infection.
what is a selectin?
adhesion molecule that integrates extrinsic signals to the cytoskeleton
what is PECAM-1?
needed for leukocytes to enter through the endothelial cells
What is the sequence of events in the migration of blood leukocytes to the site of infection?
- macrophages and dendritic cells encounter antigen and produce IL-1 and TNF causing inflamation as well as chemokines
- IL-1 and TNF make the endothelial cells express selectins and integrins
- Neutrophils and monocytes adhere to these selectins
- once they cross they get activated by the cytokines
Selectins cause cells to…
roll and adhere weakly
Integrins cause cells to…
adhere firmly
What is an example of a endothelial selectin?
e-selectin
What receptors can we find in neutrophils and macrophages? whith what signal does this receptor work at the same time?
toll-like receptors which works with IFN-y
INF-y and toll-like receptors will activate who?
macrophages
What are the 5 typesphagocyte receptors?
1) Antibodies for receptor2) Toll-like receptors3) phagocyte activating receptors4) Phagocytosis receptor5) Product of complement activation receptor
what do toll-like receptors do?
allowmacrophages and neutrophils to recognize microbes in blood and tissues
what are two receptors involved in activating phagocytes?
- toll-like receptors
- N-formyl methionine
- receptors for cytokines (especially for INF-y)
What are the 2 receptors on phagocytes that get activated for phagocytosis to occur?
- mannose receptor
* scavenger
What is a receptor on phagocytes that is for binding complement products of complement?
CR1 receptor
What is a receptor on phagocytes used to bind antibodies?
Fc receptor
What happens to a microbe that is coated with C3B?
a phagocyte will ingest it
what is opsonization?
coating a microbe so that a phagocyte will ingest it
How are microbes killed after being ingested by the phagocyte?
they are put on a phagosome that will fuse with a lysosome. Inside the lysosome it will eventually get killed by using toxic substances
What 3 substances can be used to kill a ingested microbe inside a phagolysosome?
- NADPH oxidase–> reactive oxygen
- iNOS–>use arginine to make nitrogen
- Lysosomal Proteases
What cells do Natural Killers recognize? what happens to these cells?
stressed out cellsinfected cells- These get killed
how do NK cells help out macrophages?
by secreting IFN-y that activates macrophages
What do NK cells have in their cytoplasm?
they contain toxic granules that will induce apoptosis to their target
What cytokine causes natural killer cells to secreteIFN-y?
IL-12
who secretes IL-12?
macrophages
once a natural killer cell secretes IFN-y in response to IL-12, the macrophage gets activated..what will the activated macrophage do?
it will kill the microbe
What do Natural killer cells lack in their surface?
receptors
what keeps NK cell from killing healthy cell expressing normal amounts of MHC 1?
normal cells expressing ITIM’s
When will NK cells attack a host cell? (what needs to be expressed and what has to change?)
when the infected cell lowers the expression of MHC 1 and the inhibitory receptro is not being engaged –> ITAM’s will be expressed
What receptor for antibodies will cause Natural Killer cells to attack a cell?What antibody must be present?
FcyRIIIAIgG
When NK cells recognize a microbe coated with IgG and the FcyRIIIA receptor is engaged to kill the microbe, What is this mechanism called?
ADCC
MHC 1 is expressed in what cells?
all nucleated cells
All complement pathways lead to the production of what?
C3b
Is C3b part of the early or late component of complement?
early
What does C3b do?
initiate the late component of complement
how does the late component of complement end?
with formation of C9 and the production of a MAC complex which creates pores in the membrane of microbes
What 2 pathways of complement are used by the innate immunity?
Alternate pathwayMannose binding lectin pathway
what pathway of complement is used by the adaptive immune system?
the classical pathway
What is an example of an ITIM?
KIR receptor which binds to HLA-B and HLA-C
how is the alternative pathway engaged?
by directly binding to microbe
how is the classical pathway of complement engaged?
by binding a microbe with antibodies (IgG)
how is the mannose binding lecting pathway of complement engaged?
by using mannose binding lectin binding it to microbe
what does C3a do?
induces inflammation
What is the most powerful anaphylotoxin?
C5a
What are the 3 cytokines essential for the recruitment of neutrophils and monocytes to a site of infection?
- TNF
- IL-1
- chemokines
what does high concentration of TNF do?
promote thrombus formation and lower BP
what is septic shock?
when bacteria propagate throughout the whole body causing low BP, metabolic problems and clot formation inside blood vessels
What is C-reactive protein?
enhances the activation of the alternative pathway of complementcoats microbes in order for the to be ingested
what is the acute phase response?
it is when we get infected, there is increase in mannose binding lectin, c-reactive protein and surfactant protein as a protective response
3 ways bacteria can evade the innate immunity:
- resistance to phagocytosis
- resistance to reactive oxygen species
- resistance to complement
In order to activate T/B cells from the innate immunity what 2 signals must be given?
- signal 1 = the antigen
* signal 2 = costimulator
what is an example of a costimulator signal? what is its receptor on T cells?
signal = B7receptor = CD28
What 2 things will a macrophage secrete to activate a T cell?
1) IL-122) B7
when complement gets activated by microbes, what is made that gets stuck to the microbe?
C3d
What cellrecognizes C3d stuck to a microbes surface? What is its receptor?What will it cause?
B cells using CR2, leads to B cell activation
