1. Dr. Mauricio Rodriguez-Lanetty
PCB4233: Immunology
Dr. Mauricio Rodriguez-Lanetty
Phone:
Lecture 3

2. 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

3. Skin
Interactions:
consequences:
Blood vessel

4. Skin
Interactions:
consequences:
Macrophage
Blood vessel

5. Skin
Interactions:
consequences:
PRR-PAMP
Macrophage
Blood vessel

6. Interactions: consequences:
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
Blood vessel

7. A well known example of this!
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
A well known example of this!
Blood vessel

8. Toll-like receptor signaling pathway
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
Blood vessel
TLR4
CD14
Cell membrane
Toll-like receptor signaling pathway

9. Interactions: consequences:
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
Bacteria
Blood vessel
LPS
TLR4
CD14
Cell membrane

10. Interactions: consequences:
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
Bacteria
Blood vessel
LPS
TLR4
CD14
Cell membrane
Activation of
transcription
factors (NF-kB)
Stimulation of gene
expression
Cytokines
(TNF-α, IL-1, CXCL8)
Inflammation,
migration of
leukocytes,
adaptive immunity

11. Interactions: consequences:
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
Cytokines
Blood vessel

12. Interactions: consequences:
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
Cytokines
Blood vessel
Cytokines – blood vessel endothelia cells

13. Interactions: consequences:
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
Cytokines
Blood vessel
Cytokines – blood vessel endothelia cells
TNF-α
3) Activate endothelia cells. So more adhesion molecules are expressed, like selectins and ICAMS
4) Vasodilation and increase vascular permeability

14. Interactions: consequences:
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
Chemokines
Cytokines
Blood vessel
Cytokines – blood vessel endothelia cells
TNF-α
3) Activate endothelia cells. So more adhesion molecules are expressed, like selectins and ICAMS
4) Vasodilation and increase vascular permeability
Chemokines – Leukocytes
CXC8 or IL-8

15. Interactions: consequences:
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
Chemokines
Cytokines
Blood vessel
Cytokines – blood vessel endothelia cells
TNF-α
3) Activate endothelia cells. So more adhesion molecules are expressed, like selectins and ICAMS
4) Vasodilation and increase vascular permeability
Chemokines – Leukocytes
CXC8 or IL-8
5) Induce chemotaxis
6) Help in the adhesion of phagocyte during migration

16. Interactions: consequences:
Skin
Interactions:
consequences:
PRR-PAMP
1) Phagocytosis of the pathogen
2) Cell signaling that trigger expression of cytokines and chemokines
Chemokines
Cytokines
Blood vessel
Cytokines – blood vessel endothelia cells
TNF-α
3) Activate endothelia cells. So more adhesion molecules are expressed, like selectins and ICAMS
4) Vasodilation and increase vascular permeability
Chemokines – Leukocytes
CXC8 or IL-8

17. Who are the first to migrate to the site of infection?
Skin
Blood vessel
Who are the first to migrate to the site of infection?

18. Do neutrophils look (morphological) similar to macrophages?
Skin
Neutrophils
Blood vessel
Do neutrophils look (morphological) similar to macrophages?

19. Skin
Neutrophils
Blood vessel

20. How they kill the pathogens especially bacteria?
Skin
Neutrophils
Blood vessel
How they kill the pathogens especially bacteria?

22. 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

23. 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

24. How they kill the pathogens especially bacteria?
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)

25. Interferon (another cytokine) induced by viral infection:
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

26. So, do all leukocytes kill through phagocytosis?
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?

27. NK (natural killer) Cells [Non-phagocytic Killer] Skin Blood vessel
Natural killer cells are non-phagocytic 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
NK (natural killer)
Cells
[Non-phagocytic
Killer]

28. How they distinguish an infected from a healthy, uninfected cell?
Skin
How they distinguish an infected from a healthy, uninfected cell?
Blood vessel
Natural killer cells are non-phagocytic 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
NK (natural killer)
Cells
[Non-phagocytic
Killer]