Inflammatory Response - Neutrophils and Macrophages

innate immunity

molecules and cells that distinguish host from infectious agents by recognizing conserved motifs

adaptive immunity

cells with exquisitely specific receptors for a potentially unlimited number of targets

sentinel cells

if antigens make it into the body, what recognizes the invaders and generates signals to attract and activate defensive cells

dendritic cells, mast cells, macrophages, eosinophils, neutrophils, lymphocytes

give some examples of sentinel cells (the first three listed are the MAIN THREE)

true; the body sees damages cells as foreign

true/false: the inflammatory/immune response can be set off both by foreign substances and by cellular damage

damage associated molecular patterns

what does DAMP stand for?

Pathogen Associated Molecular Patterns

What does PAMP stand for?

Toll-like receptors

What allows the host cell to recognize DAMPs or PAMPs?

intracellularly (the TLRs are transmembrane proteins)

When the toll like receptors bind to PAMPs, they initiate a signal WHERE?

Nuclear factor - Kappa B (NF-kB)

the binding of TLRs to PAMPs initiates a signal pathway that culminates in _______________.

inflammatory gene transcription

NF-kB is a major regulator of what?

sentinel cells

TLRs are found on the surface of what type of cells?

vasodilation

______________ is the hallmark of the acute inflammatory response

cytokines

sentinel cells release ______ in order to cause vascular changes and attract and activate phagocytic cells

neutrophils

What are the first cells to arrive after cytokines have been released? These cells also deal with the majority of invading organisms.

macrophages, dendritic cells, mast cells

what are the three most important sentinel cells

true

true/false: macrophages are scattered through most of the body but may have different names based on location

Pro-inflammatory cytokines;

TNF-alpha, IL-1, IL-6

What specific substance is produced to call other macrophages to the area and give some examples.

NF-kB, pro-inflammatory genes, Cytokines

BIG PICTURE:

Sentinel cells circulate and recognize pathogens via PAMP/TLR interactions. They then send intracellular signals to activate __________ which leads to the regulation of ______- ________________ and production of ______________________.

tumor necrosis factor alpha

What does TNF-a stand for?

endothelial cells, vasodilation

both TNF-a and IL-1 activate ________________ in order to cause __________________

IL-1, IL-6, chemokines

What 3 cytokines (that we were given) do macrophages and endothelial cells both produce?

causes bone marrow to release more macrophages

AND

causes the liver to produce acute phase protein

What does interleukin-6 (IL-6) actually DO?

regulate cell movement

what do CHEMOkines actually do?

lamellipodia

Cytokines trigger the formation of _________ on leukocytes.

Beta integrins

cytokines increase the expression of adhesion molecules (specifically _________) on leukocytes

IL-1B, IL-6, TNF-a

what inflammatory mediators come from macrophages and activate leukocytes and endothelial cells + systemic reactions

redness, heat, swelling, pain, loss of function

what are the five cardinal signs of inflammation?

redness and heat

what signs of inflammation are caused by increased blood flow to the site

swelling

what sign of inflammation is caused by accumulation of fluid and cells?

pain

what sign of inflammation is caused by stimulation of sensory neurons by inflammatory mediators

loss of function

what sign of inflammation is caused by tissue damage

loss of appetite, fever, anorexia, sleepiness, depression

when cytokines act on the hypothalamus, what reactions occur?

increased synthesis of acute-phase proteins, iron sequestration

when cytokines act on the liver, what reactions occur?

increased white cell production, neutrophilia

when cytokines act on the hypothalamus, what reactions occur?

liver

what organ produces increased amounts of acute phase proteins in response to the proinflammatory cytokines

acute phase proteins

the liver produces increased amounts of ________ in response to proinflammatory cytokines

proinflammatory cytokines

the liver produces increased amounts of acute phase proteins in response to what?

a1, a2, B

what are the three specific protein fractions that are features of inflammation?

y fraction

which fraction of the serum protein electrophoresis are the antibodies found in?

serum protein electrophoresis

what is this?

right side

which of these charts is showing a sample with inflammation?

arterioles dilate,

capillaries become more permeable,

leukocytes leave vessels

inflammation consists of what three changes in the vessels around the area of infection?

false; vasoconstriction happens first BRIEFLY to stop potential hemorrhage

True/false: Vasodilation is the hallmark of acute inflammation because it is the first step that happens

cytokines

What directs which type of WBCs get to squeeze through the interstitial space and where the WBC go.

high affinity state integrins

during the initial stages of the leukocyte adhesion cascade, the WBC rolls along the edges of a vessel and binds to the surface epithelium in a fast-on/fast-off sequence. What actually brings the WBC to a stop?

toll-like receptors, cytokines (TNF, IL-1), vasodilation

________ are activated on macrophages and cause them to release ________ which act on the blood vessel's epithelium to cause ____________

vasodilation causes turbulence which pushes them to the outside

normally, WBCs hang out in the center of the blood vessel. What pushes them to the outside during inflammatory response?

suppurative bronchopneumonia

what example of leukocyte adhesion cascades were we given where cytokines increase blood flow to the lungs, resulting in leukocytes entering alveolar spaces?

leukocyte adhesion cascade

generally speaking, what mechanism enables the leukocytes to move from circulation to the site of inflammation?

neutrophil

what is the major blood leukocyte in most animals?

neutrophil

which WBCs are the first cells to arrive at the site of inflammation?

Macrophages

which cells follow the neutrophils to inflammatory sites

true

true/false: in order for a neutrophil to perform a specific action, the correct receptor must first be triggered

neutrophil net

Activated neutrophils only get one shot, so they release ________ to direct neutrophil granules towards the inflammatory stimulus

MPO, elastase, cathespin G

what are some things that are released from a neutrophil in the neutrophil net?

nuclear envelope ruptures

what is the first step when releasing the neutrophil net?

proteolytic breakup of chromatin

What is the second step of the release of a neutrophil net

plasma membrane ruptures, releasing the net

what is the third and final step of the release of a neutrophil neT?

respiratory burst

in addition to casting the neutrophil net, neutrophils ungergo ________ by which numerous antimicrobial compounds and radicals are produced that can neutralize or eliminate pathogens

oxygen

respiratory burst MUST occur in the presence of what?

NADPH oxidation and superoxide production

what is the first step of respiratory burst

hydrogen peroxide

superoxide radicals are very intense radicals that can become what? (this is the second step of respiratory burst)`

further conversion of hydrogen peroxide into other ROS

what is the third step of respiratory burst

simultaneous neutralization of ROS

what is the fourth step of respiratory burst

defensins, myeloperoxidase, neutral and acid hydrolase, lysozyme

what are in the primary granules in neutrophils

lactoferrin, collagenase, lysozyme

what are in secondary granules in neutrophils?

bactericidal

what do defensins do?

spurs respiratory burst

what does myeloperoxidase do?

degrades bacteria

what do neutral and acid hydrolases do?

destroys bacterial cell walls

what does lysozyme do?

binds iron

what does lactoferrin do?

degrades connective tissue

what does collagenase do?

TNF-a

what potent macrophage stimulator does Elastase Cathepsin G trigger when it's released from the neutrophil

myeloid stem cells

what do macrophages arise from?

monocytes

what do macrophages mature into in the blood stream?

true

true/false: just like literally everything else in this class, macrophages have specific receptors that must be triggered to enable that they perform the correct functions

Interleukins 1, 6, 12, 18, 23, and Tumor necrosis factor a

what are the important cytokines produced by macrophages? (6 of them)

stimulates T cell growth and acute phase responses, triggers inflammation, cytotoxic

what does tumor necrotic factor a do?

costimulator of Th2 cells, stimulates acute-phase responses

what does IL-1 do?

promotes B cell differentiation, stimulates acute-phase responses

What does IL-6 do?

costimulator of Th1 cells

what does IL-12 do?

promotes IFN-y production by Th1 cells

what does IL-18 do?

stabilizes Th17 cells

what does IL-23 do?

macrophages

when neutrophils degrade, they also damage tissue and someones gotta clean that up. Who?

macrophages

what is the most efficient phagocytic cell?

neutrophils, monocytes, dendritic cells

what are some phagocytic cells besides macrophages?

chemotaxis, adherence, ingestion, digestion

what are the four steps of phagocytosis?

chemotaxis

__________: migration to the offending agent via chemotactic agent

adherence

_______: mediated by cell surface receptors, step 2 of phagocytosis

ingestion

________: when the macrophage engulfs the particle

digestion

_________: breakdown of particle effectively neutralizing or killing the agent

binding of a pathogen to phagocyte surface

what triggers phagocytosis?

true

true/false: because it is a powerful reaction, more than one receptor is needed to trigger phagocytosis

opsonization

______________ is a process by which molecules bind to the surface of a pathogen making it more susceptible to phagocytosis

opsonins

the molecules that bind to pathogens in order to complete opsonization are called _________

crosstalk

interactions between different signal transduction pathways or between different types of cells (neutrophils and macrophages) to coordinate movement and battle strategies

dog, rabbit, guinea pig, rat, mouse

what species clear particles in the blood primarily in the liver and spleen

calf sheep and cat

what species clear particles from the blood primarily in the lungs?

when toll like receptors bind to damage or pathogens (DAMP/PAMP)

what is the point of no return that will set in motion the inflammatory response?