L5 - Acute Inflammation Pt.1
What is exudate?
-"pus" -plasma proteins + PMNs -neutrophils are the most abundant and ready to go
What is chemotaxis?
-PMN follows concentration gradient of: bacterial polysaccharides and inflammatory molecules -Neutrophil follows gradient of increasing cytokines
What are some cells under the lymphoid lineage?
-T cell -B cell -NK cells
What is inflammation?
-a response of vascularized tissues that delivers leukocytes (WBCs) and molecules of host defense from the circulation to the sites of infection and/or cell damage in order to eliminate the offending agents -inflammation is usually a beneficial host response to invaders and necrotic tissue but it can cause collateral damage
What occurs during vasodilatation?
-arteriole side dilates, driven by chemical mediators (histamine) -this disturbs the laminar flow (more turbulence) -increases hydrostatic pressure (squeezing fluid through blood vessel wall)
What do mast cells do during cell injury?
-big supplier of histamine and leukotrienes -"sentinels" stationed in tissue like histiocytes -major responder to allergens, trauma and anaphylactic substances -come from bone marrow
What are some cells under the myeloid lineage?
-erythroid/megakaryocytic cell -granulocytic cell -monocytic cell
What occurs during increase in vascular peremeability?
-happening at the same time as vasodilatation -causes increased vascular permeability on the post-capillary side -endothelial cells are contracting and letting fluid and cells out -happens quickly but is short-lived (bee sting) -sometimes happens slow -> UV injury (sunburn)
What is the difference between a macrophage and a hisitocyte?
-histiocyte is a tissue resident cell; it arrives at the tissue and stays there for its entire life -macrophages are derived from monocytes and come in way later than histiocytes -they are interchangeable because cant tell if the cell was a resident or came in later
What is the role of Arachidonic Acid (AA) in cell injury during an acute inflammatory response?
-if phospholipids on cell membrane are injured -> phospholipase is activated -activation of phospholipase -> formation of AA -AA is eventually converted into prostaglandins and leukotrienes
What causes acute inflammation?
-infection -trauma -chemical agents -necrosis -foreign bodies -immune reactions
What is pavementing?
-integrin on PMNs bind ICAM (intra-cellular adhesion molecule) -stops PMN movement completely on endothelial cell
What is diapedesis?
-interaction of CD31 on both PMN and endothelium -same marker is working to squeeze neutrophil out -other WBC can go through this process but markers may be different
What are some characteristics of the innate immune system?
-is always "active" (but can become more active) and responds quickly (within minutes) -has no memory -is less specific to a threat vs. adaptive immunity -cells: NK cells, macrophages, complement system
What do platelets do during cell injury?
-main job: forming thrombus (L-8) -also involved in acute inflammation (recruited) -made from megakaryocytes in bone marrow -on aggregation, release serotonin (most comes from platelets) and platelet activating factor -drives vasodilatation and vascular permeability
What immune system cells are also involved in acute inflammation?
-monocytes: can migrate to tissue and differentiate into macrophage, professional phagocytes -macrophage/histiocyte
What is margination?
-occurs when there is a disruption of laminar flow (dilated blood vessel) -allows neutrophil to get closer to the wall -movement is slower
What is chronic inflammation?
-prolonged and can involve simultaneous tissue destruction and repair -it can follow after acute inflammation
What are some characteristics of the adaptive immune system?
-responds slow (requires several days before becoming effective) -highly specific -has memory -cells: helper T cells, cytotoxic T cells, antibodies (produced by B cells)
What is rolling?
-selectin ligand (SLIG) on neutrophil binds selection on endothelium -PMN slows down and rolls -PMN still able to move, just rolling along the surface of endothelium -has not stopped, just allowing other interactions to take place
What are the primary cells driving vasodilatation?
1. Histamine!!! (fast and potent) 2. Nitric Oxide 3. Prostaglandins
What are the primary cells driving an increase in vascular permeability?
1. Histamine!!! (most important, again) 2. Serotonin 3. Leukotrienes
During a chronic inflammatory response, what are the key cells present?
1. lymphocytes and plasma cells (antibody factory) are most common 2. macrophages are also very common 3. neutrophils are rarely present (only a few)
What are the different ways WBCs can move into the blood?
1. margination 2. rolling 3. pavementing 4. diapedesis 5. chemotaxis
What are the two possible lineages for a multipotent hematopoietic stem cell?
1. myeloid 2. lymphoid
During an acute inflammatory response, what is the timeline of the cells that arrive at the site?
1. neutrophils are first responders (early on site) 2. macrophages join later in the process (were monocytes in the blood) 3. lymphocytes only very few in acute inflammation
What are the goals of acute inflammation? (5 Rs)
1. recognition (of threat/dead tissue) 2. recruitment (of WBC, plasma proteins to site) 3. removal (of inflammatory stimulus using the above WBC, plasma proteins) 4. regulation (termination of the response when it is done) 5. repair (of any damaged tissue)
What are the 5 signs of inflammation?
1. redness (rubor) 2. heat (calor) 3. swelling (mass, tumor) 4. pain (dolor) 5. loss of function (functio laesa)
How do WBCs get from the blood to the injury site?
1. vasodilatation 2. increased vascular permeability 3. migration of WBCs from vessel to the battle
What is the enzyme that produces leukotrienes from arachidonic acids?
5-lipoxygenase
Just as PAMPs are used to recognize pathogens, which protein is used to recognize the products of cellular damage (necrosis or apoptosis)?
Damage Associated Molecular Patterns (DAMP) -recognize products of cell damage
What do leukotrienes cause?
Increased vascular permeability
All cells involved in immunity originate from?
Multipotent Hematopoietic Stem Cell -self-renewing stem cells in the bone marrow and fetal liver
What inhibits cyclooxygenase (COX)?
NSAIDS *reduces amt of vasodilation *reduces cytokines that cause pain
What immune system cells are primarily involved in acute inflammation?
PMN (polymorphonuclear neutrophil) -professional phagocyte -releases bleach
On the invaders surface, what do the PRRs recognize as a "common pattern"?
Pathogen Associated Molecular Patterns (PAMP) -a protein or carbohydrate unique to pathogens (not in humans) -PAMPs must be conserved/important pieces of an invader (not easily altered)
What are the key cells that help recognition work in acute inflammation?
Sentinel cells: -macrophages -dendritic cell -mast cell
What is an important group of PRRs?
Toll-like Receptors (TLR) *GERMAN SCHOOL IS COOL!
Why does rubor occur?
arterioles are dilated during vasodilatation (causing redness)
Why does calor occur?
arterioles are dilated during vasodilatation (gets heat on arteriole side)
What inhibits the activity of phospholipase?
corticosteroids
What is the enzyme that produces prostaglandins from arachidonic acids?
cyclooxygenase
Why does tumor occur?
during increased vascular permeability fluid is leaked out which causes a mass/swelling
Why does loss of function occur?
it depends on the injury
Why does dolor occur?
prostacyclin (and other prostaglandins) and other cytokines cause pain *key cells in vasodilatation
What is acute inflammation?
rapid (minutes/hours), usually self-limited response driven by the innate immune system
What instigates the recruitment process in acute inflammation?
sentinel cells release cytokines that recruit more inflammatory cells from the blood to the battle
How do these sentinel cells recognize common patterns on invader surfaces (or evidence of damage)?
using Pattern Recognition Receptor (PRR)
What do prostaglandins cause?
vasodilation, increased vascular permeability, pain, fever
