Overview of Innate Immunity

What are the first lines of defense against pathogens?

Physical barriers such as skin, oral mucosal, respiratory epithelium, intestine, cornea and conjungtiva

Barriers can be ____, ____, or ____.

mechanical, chemical, microbiological (normal microbiota)

After anatomic barriers, the next layer of protection is?

Complement/antimicrobial proteins →preformed soluble effectors. These are preformed and available all the time ciruclating in body

Preformed soluble effectors include?

Complement, Defensins

How does the complement system defeat pathogens?

A multiprotein proteolytic cascade

Assembles a pore of multiple complement protein 9 (C9) on the bacterial surface

Causes osmotic lysis of the pathogen

How do Defensins defeat pathogens?

Similar to complement, but is an individual protein. Assembles a pore on bacterial surface, causes osmotic lysis

How are Defensins and C9 able to create pores?

They are able to associate with bacterial membranes because they are cationic (positively charged and lipid membranes are negatively charged), and amphipathic (have hydrophobic and hydrophilic sides)

Complement and Defensins are specific or not specific?

No specificity

What is the 3rd layer of host protection (after preformed soluble effectors?)

Innate immune cells (macrophages, neutrophils, eosinophils, basophils, mast cells, natural killer (NK) cells)

Identify this immune cell

Neutrophil

Identify this immune cell

Eosinophil

Identify this immune cell

Basophil

Identify this immune cell

Mast Cell

Identify this immune cell

Monocyte

Identify this immune cell

Macrophage

What role do macrophages have in the innate immune response?

The initiators/ the first recognizers

How do macrophages respond to pathogens?

Express innate immune receptors (pattern recognition receptors) to detect microbes, phagocytoses them, presents the microbe antigen on its surface and secretes inflammatory cytokines thus initiating inflammation

What inflammatory cytokines do macrophages secrete?

Tumor Necrosing Factor (TNF), Interleukin 1 (IL1), Interleukin 6 (IL6)

Macrophages can also respond to environmental cues to do what?

They can undergo polarization to differentiae into multiple functional states such as tissue repair

Immune cell direct communication

Direct cell to cell binding and signaling such as T cell binding to APC, cytotoxic T cells, regulatory T cell inhibition

Immune cell indirect communication

Indirect communication through soluble effectors (cytokines) that bind to receptors (specific receptors for specific cytokines). Binding to receptor triggers a signal cascade to activate cell transcription

Autocrine

Cell secretes a cytokine that stimulates itself

Paracrine

Cell secretes a cytokine that stimulates nearby cells

What is the role of neutrophils in the innate immune system?

They are the eliminators, the first responders

How do neutrophils eliminate pathogens?

Highly phagocytic, contain granules containing preformed mediators that kill pathogens

How are neutrophils stimulated?

They are very plentiful circulating in the blood. TNF, IL-1, IL-6 stimulate the bone marrow to release more neutrophils.

What are the 4 steps of neutrophil recruitment?

1. Rolling

2. Firm adhesion

3. Transmigration

4. Chemotaxis

What molecule is responsible for the recruitment signaling to neutrophils to a site?

Interleukin 8 (IL-8), a chemokine

What immune cell connects the innate immune system to the adaptive immune system?

Dendritic Cells

A naive T cell can only be activated by what?

a professional APC (dendritic cell)

Compare and Contrast Immature and Mature Dendritic Cells

Immature: Highly endocytic (eats a lot), in tissues, poor T cell interactions, poor antigen presentation (low surface MHC II, low costimulatory molecules)

Mature: Poorly endocytic (not eating anymore), moves to lymph nodes, strong T cell interactions, highly antigen presenting (high surface MHC II, high costimulatory molecules)