PCB4233: Immunology

Dr. Mauricio Rodriguez-LanettyEmail: 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

Blood vessel

SkinInteractions: consequences:

Blood vessel

SkinInteractions: consequences:

Macrophage

Blood vessel

SkinInteractions: consequences:

PRR-PAMP

Macrophage

Blood vessel

SkinInteractions: consequences:

PRR-PAMP 1) Phagocytosis of the pathogen

2) Cell signaling that trigger

expression of cytokines and chemokines

Blood vessel

SkinInteractions: 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

SkinInteractions: consequences:

PRR-PAMP 1) Phagocytosis of the pathogen

2) Cell signaling that trigger

expression of cytokines and chemokines

Cell membrane

CD14 TLR4

Toll-like receptor signaling pathway

Blood vessel

SkinInteractions: consequences:

PRR-PAMP 1) Phagocytosis of the pathogen

2) Cell signaling that trigger

expression of cytokines and chemokines

Cell membrane

Bacteria

LPS

CD14 TLR4

Blood vessel

SkinInteractions: consequences:

PRR-PAMP 1) Phagocytosis of the pathogen

2) Cell signaling that trigger

expression of cytokines and chemokines

Activation of transcription

factors (NF-kB)

Stimulation of gene expression

Cytokines (TNF-α, IL-1, CXCL8)

Inflammation, migration of leukocytes,

adaptive immunity

Cell membrane

Bacteria

LPS

CD14 TLR4

Blood vessel

SkinInteractions: consequences:

PRR-PAMP 1) Phagocytosis of the pathogen

2) Cell signaling that trigger

expression of cytokines and chemokines

Cytokines

Blood vessel

SkinInteractions: consequences:

PRR-PAMP 1) Phagocytosis of the pathogen

2) Cell signaling that trigger

expression of cytokines and chemokines

Cytokines

Cytokines – blood vessel

endothelia cells

Blood vessel

SkinInteractions: consequences:

PRR-PAMP 1) Phagocytosis of the pathogen

2) Cell signaling that trigger

expression of cytokines and chemokines

Cytokines

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

Blood vessel

SkinInteractions: consequences:

PRR-PAMP 1) Phagocytosis of the pathogen

2) Cell signaling that trigger

expression of cytokines and chemokines

Cytokines

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

Chemokines – Leukocytes

CXC8 or IL-8

Blood vessel

SkinInteractions: consequences:

PRR-PAMP 1) Phagocytosis of the pathogen

2) Cell signaling that trigger

expression of cytokines and chemokines

Cytokines

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

Chemokines – Leukocytes

CXC8 or IL-8

5) Induce chemotaxis6) Help in the adhesion of phagocyte during migration

Blood vessel

SkinInteractions: consequences:

PRR-PAMP 1) Phagocytosis of the pathogen

2) Cell signaling that trigger

expression of cytokines and chemokines

Cytokines

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

Chemokines – Leukocytes

CXC8 or IL-8

Blood vessel

Skin

Who are the first to migrate to the site of infection?

Blood vessel

Skin

Neutrophils

Do neutrophils look (morphological) similar to macrophages?

Blood vessel

Skin

Neutrophils

Blood vessel

Skin

Neutrophils

How they kill the pathogens especially bacteria?

The respiratory burst in macrophages and neutrophils is caused by a transient increase in oxygen consumption during the production of microbicidal oxygen metabolites

Once ingested: inside the phago-lysosome

This occur both in macrophages and neutrophils

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 important is this Respiratory burst to clear infections?

Blood vessel

Skin

Neutrophils

How they kill the pathogens especially bacteria?

Phagocytosis Respiratory burst (a production of a buch nasty reactive oxygen species that kill bacteria)

Blood vessel

Skin

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

Blood vessel

Skin

Neutrophils

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?

Blood vessel

Skin

•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-phagocyticKiller]

Blood vessel

Skin

•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-phagocyticKiller]

How they distinguish an infected from a healthy, uninfected cell?