Dr. Mauricio Rodriguez-Lanetty PCB4233: Immunology Dr. Mauricio Rodriguez-Lanetty Email: rodmauri@fiu.edu 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

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

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

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

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

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

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

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

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

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

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

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

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?

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

Skin Neutrophils Blood vessel

How they kill the pathogens especially bacteria? 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

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)

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

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?

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]

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]