7 – Innate Immunity IV (Signaling & Cell migration) Flashcards
4 effects of PRR signaling:
-Cytokine production
-Chemokine production
-Increases expression of costimulatory responses
-Enhance migration to regional secondary lymphoid organ
pro-inflammatory cytokines:
IL-1, IL-6, IL-18, TNF-α, IL-12
potent antiviral cytokines:
Type I IFN (IFN-α, IFN-β)
Chemokines do what?
lead migration of cells to site of infection
2 families of chemokines:
CC chemokines
CXC chemokines
costimulatory molecuels:
B7.1 (CD80), B7.2 (CD86)
which signal is costimulatory molecule for T cell activation
2nd signal
how to enhance migration to regional secondary lymphoid organ
Upregulation of specific adhesion molecules
Type I IFN has … effect
antiviral
chain of reaction with type I IFN secretion
-after type I IFN being secreted by PRR signaling
-it can bind to receptors on surrounding cells
-this triggers more intracellular signaling
-more transcription of genes
( has an effect on viral life cycle)
what triggers Migration & targets…
-PRR signaling triggers migration & targeting of DCs to lymphoid tissue
-Secondary lymphoid tissue –lymph nodes
Chemokine receptors – example of
G-protein-coupled receptors
what is G-protein-coupled receptors
transduce signals via interaction with GTP/GDP binding G protein
Chemokines direct…
leukocyte migration -> chemotaxis
Chemotaxis is…., can change in cell’s …..
-Signaling thru chemokine receptors help cell move to different areas
-Change in cell adhesiveness
-Change in cell cytoskeleton
-Induce movement of leukocytes up a chemokine concentration gradient
Many receptors can bind to…
more than one chemokine
Several chemokines can bind to
more than 1 receptor
inflammatory responses: steps-
- breach of epithelial layer
- bacteria enters body
- PAMP binding ot its PRR
- cytokines & chemokines released
- inflammation
what happens to cells when there is inflammation?
all recruited to site of infection
what happens to blood essels when there is inflamamtion?
vasodilation, so cells can actually pass through
4 hallmarks of inflammation:
haet, redness, swelling, pain
Monocytes recruited to site of infection via..
adhesion molecules
how does monocytes migrate into site of infection?
- monocytes recruited to site of infection
- adhesion molecules binds the monocyte
- chemokines binds to its receptor
- chemokines lewad to intracellular signaling
- changes conformation of adhesion molecules
- anchors monocytes
- migrate to tissue/sote of infection
Different families of adhesion molecules
Selectins
Integrins
Immunoglobulin superfamily
Different tissue distribution
Some adhesion molecules are expressed at…, or….
baseline OR expressed when infection occurs
leokocytes … endothelium, how does it happen?
roll along
weak adhesion momlecule interaction (weak binding)
Recruitment of leukocytes
-Monocytes (precursor of macrophages), neutrophils & other leukocytes recruited to site of infection
(lead to increase of adhesion molecules)
-Heat, redness, swelling (edema), pain
Severe/chronic inflammation causes
arthritis/loss of function
To clear infection, we only need
acute inflammation only
Migration steps
1.Rolling adhesion
2.Tight bunding (anchoring)
3.Diapedesis
4.Migration
what is Diapedesis
PROCESS:
-Cell crosses from lumen of vessel, between endothelial cells and into surrounding tissue
-Cell crosses to site of infection
Migration in direction of…
In direction of higher chemokine concentrations
