2-4. The inflammatory response: neutrophils and macrophages

What are the most common pathways of infection?

inhalation, ingestion, open wounds

__________ cells can recognize invaders and generate signals to attract/ activate defensive cells to site of invasion

sentinel

what are the 3 main types of defensive cells?

dendritic cells, mast cells, macrophages

T/F: an inflammatory/ immune response can be due to cellular damage, a pathogen, or both

t

DAMPs

Damage-associated molecular patterns signaling tissue damage which is recognized as foreign

PAMPs

pathogen associated molecular patterns

uniques components of microorganisms ESSENTIAL FOR SURVIVAL

T/F: PAMPS are found on normal host tissue

FALSE

What transmembrane proteins mediate PAMP recognition? where are they found

toll like receptors

dendritic cells, macrophages, mast cells, + eosinophil and mucosal epithelial cells

What is the major regulator of inflammatory gene transcription that regulates expression of chemokines, cytokines, etc?

nuclear factor kappa B

What is the hallmark of acute inflammation?

VASODILATION

What is the primary effector cells when TLRs release cytokines to attract phagoytic cells?

neutrophil

Explain what causes the production of cytokines?

sentinel cells recognize pathogen via PAMP/ TLR -> activate NFkB -> proinflammatory genes -> produce cytokines

What cell is a source of all cytokines?

macrophages

which cytokines active endothelial cells?

TNFa and IL-1

Which cytokine stimulates liver to produce acute phase proteins? what does this cause?

IL-6- however both TNFa and IL-1 also

sickness behavior

What is the main intended action of cytokines?

attract leukocytes to site of infection to suppress the inflammatory response

what are the effects of cytokines on the hypothalamus?

loss of appetite

why is it important that one of the effects of cytokines on the liver is iron sequestration?

bacteria needs iron to grow, so depriving it of iron will kill it

The liver produces many acute phase proteins in response to proinflammatory cytokines.

Explain the role of: Seroid Amyloid A

leukocyte chemotaxis, induction of enzymes that degrade cellular matrix

The liver produces many acute phase proteins in response to proinflammatory cytokines.

Explain the role of: fibrinogen

hemostasis

The liver produces many acute phase proteins in response to proinflammatory cytokines.

Explain the role of: C reactive protein

assist in complement binding to antigenic or damaged cells

The liver produces many acute phase proteins in response to proinflammatory cytokines.

Explain the role of: Ceruloplasmin

oxidize iron, facilitate ferritin, inhibit microbe iron uptake

The liver produces many acute phase proteins in response to proinflammatory cytokines.

Explain the role of: AGP

role unclear

Acute phase proteins have different protein fractions in serum electrophoresis. Which fractions are features of inflammation? which is where antibodies are found?

alpha 1 and 2, beta

gamma

what are the 5 cardinal signs of inflammation

redness, heat, swelling, pain, loss of function

Inflammation centers on the vascular response of small blood vessels in the area of infection. what are the three main changes that occur?

arterioles dilate

capillaries become more permeable = transudate

leukocytes migrate through venule walls = exudate

T/F: transient vasoconstriction occurs before vasodilation

T, it has no role in inflammatory response but does activate platelets which is important in hemorrhage

What mediates the leukocyte adhesion cascade? what is the importance of this?

cytokines

ensure the appropriate WBC enter the correct vessel

Explain the process of the leukocyte adhesion cascade

1. cytokines are released from sentinel cell and act on vascular endothelium and leukocyte

2. Margination: which moves leukocyte toward endothelium

3. Rolling: in which glycoproteins bind to selectin ligands

3. Integrin activation by chemokines - transfers integrin to high affinity state

4. stable adhesion

5. migration through endothelium

what is the major blood leukocyte that kills most invading organisms?

neutrophil

what cells cleans up the mess left behind by neutrophils?

macrophages

T/F: neutrophils have surface receptors that must correctly be triggered to perform an action

true

what is the purpose of a neutrophil net?

directs neutrophil granules and contents toward inflammatory stimulus

what must rupture in order for the neutrophil net to be released?

nuclear envelope then plasma membrane

- need to be able to break down CT

respiratory burst

process in which antimicrobial compounds/ radicals are produced that can neutralize or eliminate pathogens

What must be present for respiratory burst to occur in neutrophils?

oxygen

what are the key steps of respiratory burst?

1. NADPH oxidation -> superoxide production

2. superoxide -> hydrogen peroxide

3. hydrogen peroxide -> ROS, ClO-

4. neutralization of ROS

List 4 primary neutrophil granules and their function

defensins- bactericidal

myeloperoxidase - respiratory burst

neutral and acid hydrolases - degrade bacteria

lysozyme - destroy bacterial cell walls

list 3 secondary neutrophil granules and their functions

lactoferrin - binds iron

collagenase - degrades CT

lysozyme - destroys bacterial cell walls

Why is it notable that elastase and cathepsin G (neutrophil granules) activate TNF alpha?

to stimulate macrophages

what do macrophages arise from?

myeloid stem cell -> monocyte in blood -> macrophage in circulation

T/F: same as neutrophils the correct receptor must be triggered for macrophages to perform a specific action

true

What are the 4 steps of phagocytosis?

chemotaxis

adherence

ingestion

digestion

what triggers phagocytosis?

binding of pathogen to receptors on surface on phagocyte

T/F: only one receptor is required to be triggered in order to both initiate and complete the phagocytic response

false

___________ is the main mechanism by which macrophages recognize pathogens

opsonization

explain opsonization

process by which molecules such as antibodies (called opsonins) bind to the surface of a pathogen and make it more susceptible to destruction

(PAMPs/DAMPs) cause a macrophage to release pro-inflammatory cytokines

PAMPs

DAMPs cause release of anti-inflammatory

How do macrophages and neutrophils crosstalk? why is this important?

cytokine networks

function for cellular activation and deactivation

in what species is the site of clearance of particles from the blood is the lung?

calf, sheep, cat

in what species is the site of clearance of particles from the blood is the liver/ spleen?

dog, rabbit, guinea pig, rat, mouse