Exam 1 (Lecture 5) - Early Detection and Response to Microbial Invasion

Question 1

Define sentinel cell. List 3 sentinel cells and provide a brief description of each.

Answer 1

Cells that recognize and respond to invading molecules; located throughout the body with highest numbers within tissues.

1) Dentritic cell = phagocytic cell with long projections
2) Mast cell = located in the skin; mucosal lamina propria, and along blood vessels
3) Macrophage = phagocytic cell

Question 2

Briefly explain where pattern recognition receptors (PRRs) are found, their function, and what they bind to.

Answer 2

1) Associated with sentinel cells
2) Located on surface of cell, in cytoplasm, and within vesicles
3) Recognize PAMPs and DAMPs to activate innate immune system

Question 3

Define PAMPs and DAMPs and give an example of each and how they influence the immune response.

Answer 3

1) PAMP (Pathogen Associated Molecular Pattern) = structures produced by microorganisms that are recognized by and stimulate the innate immune system.
- Ex: Lipopolysaccharide = released by gram-negative bacteria when they die (aka endotoxin)

2) DAMP (Damage Associated Molecular Pattern) = endogenous molecules that are produced by or released from damaged and dying cells that bind to pattern recognition receptors and stimulate innate immune response.
- Ex: extracellular ATP

Question 4

Describe the early response of a macrophage after something has bound to its pattern recognition receptors.

Answer 4

Early inflammatory response is initiated (tells the nucleus) and proinflammatory cytokines are produced and released.

Question 5

Define inflammasome.

Answer 5

Multi protein complexes that from in cytosol in response to PAMPs and DAMPs and generate active forms of inflammatory cytokines.

Question 6

Describe proinflammatory cytokines, including what cytokines are major proinflammatory cytokines, what induces their production, what cells make them, and what major effects they have on an animal when they are in low concentration, medium concentration, and high concentration.

Answer 6

1) Major proinflammatory cytokines: IL1, IL6, TNF

2) Production induced by binding of PAMPs and DAMPs to PRRs on or within sentinel cells

3) At low concentrations = induce local inflammation, upregulation of endothelial adhesion molecules, and increased vascular permeability.

At medium concentrations = induce local inflammation and systemic effects

At high concentrations = induce systemic and pathological effects: systemic vasodilation, increased vascular permeability, and upregulation of endothelial adhesion molecules leading to reduced blood pressure and cardiac output, vascular injury, thrombosis, etc.

Question 7

Describe the acute phase protein response, including the inciting cause, where the majority of the proteins are made, the timing of the response, and its purpose.

Answer 7

1) Innate defense component secreted early (24-48 hours) and works to control infection while the adaptive immune response develops response

2) Secreted by liver under the influence of proinflammatory cytokines; non-antigen specific

Question 8

List 3 major acute phase proteins and provide one way they contribute to the body’s defense against pathogens.

Answer 8

1) C reactive protein (CRP) = pentamer that opsonizes and activates complement

2) Serum amyloid P (SAP) = activates complement

3) Serum amyloid A (SAA) = chemoattactant for neutrophils, monocytes, and T cells

Question 9

List the 3 general types of macrophage activation and the important molecules and functions associated with each. Distinguish M1 and M2 macrophages with inducing cytokines and functions.

Answer 9

1) Innate activation
- Activated through PRRs by PAMPs and DAMPs
- Enhances lysosomal enzyme production, phagocytosis, membrane receptors for IgG and complement, and protease
secretion

2) Classic Activation (by IFN)
- M1 macrophage (angry macrophage)
- interferon gamma secreted by T Helper cells and NK cells active it
- Increased size, movement, and membrane activity
- Phagocytize and kill microbes with lysosomal enzymes, nitric oxide production, and reactive oxygen species production
- Can kill pathogens not typically killed by macrophages because of the activation with interferon gamma

3) Alternative Activation (by IFN)
- M2 macrophage
- Activated by IL4, IL10, and IL13 from various T cells
- Function for tissue repair and promotion of healing later in response; deceased microbial killing; increased MHCII
expression
- DO NOT produce nitric oxide; they are anti-inflammatory and responsible for healing.