Transcript Lecture 3 - IMaGeS Lab

PCB4233: Immunology
Dr. Mauricio Rodriguez-Lanetty
Email: [email protected]
Phone: 305-3484922
Lecture 3
On January 18th, the lectures will be uploaded to
Blackboard Learn
On January 21st, a question-based guide covering the
first four lectures will be provided
Skin
Interactions:
consequences:
Blood vessel
Skin
Interactions:
consequences:
Macrophage
Blood vessel
Skin
Interactions:
consequences:
PRR-PAMP
Macrophage
Blood vessel
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis
of the pathogen
Blood vessel
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
Skin
Interactions:
consequences:
PRR-PAMP
A well known
example of
this!
1) Phagocytosis
of the pathogen
Blood vessel
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis
of the pathogen
Blood vessel
CD14
TLR4
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
Cell membrane
Toll-like receptor signaling pathway
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis
of the pathogen
Bacteria
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
Blood vessel
LPS
CD14
TLR4
Cell membrane
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis
of the pathogen
Bacteria
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
Blood vessel
LPS
CD14
TLR4
Cell membrane
Activation of
transcription
factors (NF-kB)
Stimulation of gene
expression
Cytokines
(TNF-α, IL-1, CXCL8)
Inflammation,
migration of
leukocytes,
adaptive immunity
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis
of the pathogen
Cytokines
Blood vessel
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis
of the pathogen
Cytokines
Blood vessel
Cytokines –
blood vessel
endothelia cells
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis
of the pathogen
Cytokines
Blood vessel
Cytokines –
blood vessel
endothelia cells
TNF-α
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
3) Activate
endothelia cells.
So more adhesion
molecules are
expressed, like
selectins and
ICAMS
4) Vasodilation
and increase
vascular
permeability
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis
of the pathogen
Chemokines
Cytokines
Blood vessel
Cytokines –
blood vessel
endothelia cells
Chemokines –
Leukocytes
CXC8 or IL-8
TNF-α
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
3) Activate
endothelia cells.
So more adhesion
molecules are
expressed, like
selectins and
ICAMS
4) Vasodilation
and increase
vascular
permeability
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis
of the pathogen
Chemokines
Cytokines
Blood vessel
Cytokines –
blood vessel
endothelia cells
Chemokines –
Leukocytes
CXC8 or IL-8
TNF-α
5) Induce chemotaxis
6) Help in the adhesion of
phagocyte during migration
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
3) Activate
endothelia cells.
So more adhesion
molecules are
expressed, like
selectins and
ICAMS
4) Vasodilation
and increase
vascular
permeability
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis
of the pathogen
Chemokines
Cytokines
Blood vessel
Cytokines –
blood vessel
endothelia cells
Chemokines –
Leukocytes
CXC8 or IL-8
TNF-α
2) Cell signaling
that trigger
expression of
cytokines and
chemokines
3) Activate
endothelia cells.
So more adhesion
molecules are
expressed, like
selectins and
ICAMS
4) Vasodilation
and increase
vascular
permeability
Skin
Blood vessel
Who are the first to migrate to the site of infection?
Skin
Neutrophils
Blood vessel
Do neutrophils look (morphological) similar
to macrophages?
Skin
Neutrophils
Blood vessel
Skin
Neutrophils
Blood vessel
How they kill the pathogens
especially bacteria?
Once ingested: inside the phago-lysosome
The respiratory burst in
macrophages and neutrophils is
caused by a transient increase in
oxygen consumption during the
production of microbicidal oxygen
metabolites
This occur both in macrophages
and neutrophils
How important is this Respiratory burst to clear infections?
Chronic Granulomatous Disease:
a genetic deficiency of NADPH
oxidase, so the phagocytes do not
produce toxic oxygen species.
People with this disease are susceptible
to bacterial and fungal infections
Skin
Neutrophils
Blood vessel
How they kill the pathogens
especially bacteria?
Phagocytosis
Respiratory burst (a production of a buch nasty reactive
oxygen species that kill bacteria)
Skin
Blood vessel
Interferon (another cytokine) induced by
viral infection:
Interferon induce a state of resistance to
viral replication in all cells
IFN-α and IFN-β induce the expression of
proteins that help to inhibit viral replication
Autocrine and paracrine effect
Activate dentritic cells and macrophage
Skin
Neutrophils
Blood vessel
How they kill the pathogens
especially bacteria?
Phagocytosis
Respiratory burst (a production of a buch nasty reactive
oxygen species that kill bacteria)
So, do all leukocytes kill through phagocytosis?
Skin
Blood vessel
NK (natural killer)
Cells
[Non-phagocytic
Killer]
•Natural killer cells are nonphagocytic and granular
lymphocytes that kill abnormal
(e.g., infected or malignant)
host cells
•They account for 5-10% of all
lymphocytes in circulation
•The lineage of origin is
different to macrophages, mast
cells and the other granulocytes
Skin
How they distinguish
an infected from a
healthy, uninfected
cell?
Blood vessel
NK (natural killer)
Cells
[Non-phagocytic
Killer]
•Natural killer cells are nonphagocytic and granular
lymphocytes that kill abnormal
(e.g., infected or malignant)
host cells
•They account for 5-10% of all
lymphocytes in circulation
•The lineage of origin is
different to macrophages, mast
cells and the other granulocytes