Exam 1 Path (Inflammation and tissue repair) Flashcards
(42 cards)
What are the 5 Rs of the inflammatory response?
- Recognition of the injurious agent
- Recruitment of leukocytes
- Removal of agent
- Regulation (control) of the response
- Resolution (repair)
What is the first cell type to come in during inflammation?
-Neutrophils
What are the vascular reactions that occur with acute inflammation?
- Arteriolar vasodilation with engorgement of downstream capillaries (redness and warmth) (may follow initial vasoconstriction)
- Increase in vascular permeability (protein-rich fluid exits vascular compartment into surrounding tissue spaces and causes swelling)-exudate
- Viscosity increase results in stasis with leukocytes settling out and accumulating on endothelial surfaces (margination)
What are the sequence of events that occur in acute inflammatory response?
1) Margination and rolling of the cells
2) Adhesion onto the endothelium
3) Transmigration
4) Migration in interstitial tissues (chemotaxis)
Explain acute inflammation
- Relatively short duration (minutes to days)
- neutrophil accumulation
- fluid and plasma protein exudation
- process is designed to deliver leukocytes and plasma proteins to the sites of injury (clear invading microbes)
- stimulated by infection, tissue necrosis, foreign bodies
explain chronic inflammation
- longer duration (days to years)
- lymphocytes, macrophages
- vascular proliferation ans car tissue accumulation
What cells recruit white blood cells?
Capillary cell walls
What are the mechanisms of permeability?
Endothelial recontraction:
–occurs mainly in venules
–induced by histamine, NO, other mediators
–rapid and short lived (minutes)
Direct endothelial injury (due to trauma, microbes, leukocytes)
–occurs in arterioles, capillaries, venues
–caused by burns, some microbial toxins
–rapid: may be long-lived (hours to days)
Increased transcytosis:
–occurs in venues
–induced by VEGF
Leukocyte mediated vascular injury:
–occurs in venues, pulmonary capillaries
–associated with late stages of inflammation
–long lived (hours)
What are some examples of inflammatory signals that activated endothelium which increases the number and activity of surface adhesion molecules
- Selectins (relatively loose and transient (rolling))
- CD34 (rolling) (help WBC stick)
- Ig superfamily adhesion molecules (ICAM, VCAM) interact with interns on leukocyte surface (firm adhesion) (really stick so it can get through capillary wall)
After edema what is the first cell you see and last cell you see?
- Neutrophils
- Monocytes/Macrophages
What are some mechanisms of leukocytes at the site of injury?
- Phagocytosis and elaboration of degradative enzymes
- Neutrophils predominate in first 6 to 24 hours, replaces by monocytes at 24 to 48 hours
What are the three distinct steps of phagocytosis?
1) recognition and attachment to antigen
2) Engulfment
3) Killing/degradation of ingested material
What are some leukocyte-induced tissue injury?
1) Collateral damage to native tissue
- TB and associated lung injury
- long term issues
2) Inappropriate targeting of the immune response
- autoimmune conditions
3) excessive reaction by host tissue to harmless antigens
- allergies
What are some outcomes of acute inflammation?
1) Resolution
- short-lived, no residual tissue injury
- normal histology and function restored
2) Scarring (fibrosis)
- significant tissue destruction or inability to regenerate
- unable to restore normal histology
- collagen deposition
3) Progression to chronic inflammation
- if injury persists through acute inflammatory response
What are some of the morphology that occurs with the inflammatory response?
1) Serous-accumulation of serous fluid
- blister, sunburn
2) Fibrinous-fibrin deposits in extracellular space
- pericarditis
3) Supporative-production of pus/purulent exudate
- abscess, zit
4) Ulcer
What is the job of the chemical mediators of inflammation?
- Direct the vascular and cellular events of the acute inflammatory response
- Tight regulation is important!
What is the job of vasoactive amines as chemical mediators?
1) Affect vasculature by inducing contraction and dilation and altering vascular permeability (affected by drugs) Histamine -Mast cells -Basophils -Platelets Serotonin (platelets) -released during platelet aggregation -effector similar to histamine
What is the job of Arachidonic acid metabolites as chemical mediators?
Derived from metabolism of arachidonic acid (AA)
- AA metabolites also referred to as eicosanoids
- Part of lipid bilayer
- Metabolized via two major pathways
1) Cyclooxyrgenase acts on AA to produce - Prostaglandins–>vasodialation, inhibit platelets, increased vascular permeability
- ->these can also cause vasoconstriction and promote platelets
2) Lipoxygenase acts on AA to produce Leukotrienes - ->vasoconstriction, bronchospasm, increased vascular permeability
Why would you want to inhibit AA?
- because it is responsible signals that produce
1) vasconstircition
2) Increased vascular permeability
3) Vasodilaiton
4) Inhibit neutrophil adhesion and chemotaxis
Explain Platelet activating factor (PAF) in chemical mediated inflammation
- Bioactive phospholipid derived mediator form a variety of cell types
- multiple inflammatory effects through a G-protein couple receptor
- 100 to 10,000 more potent than histamine
- no drugs that affect PAF yet
What are the actions of cytokines in chemical mediated inflammation?
-pull in inflammatory cells
5 classes
1) Regulate lymphocyte function (IL-20
2) Innate immunity (TNF and IL-1)
3) Inflammatory cell activation (IFN-y and IL-12)
4) Chemokines -promote chemotaxis
5) Stimulate hematopoiesis (IL-3, GM-CSF)
What are lysosomal components and oxygen free radicals chemical mediators of inflammation?
- Forms hydrogen peroxide and bleach to kill bacteria
- Designed to kill microbes
- Likely responsible for tissue destruction associated with inflammation, including endothelial cell damage and parenchymal cell damage
- Held in check by system of antiproteases and antioxidants
What is the job Nitrous Oxide as a chemical mediator of inflammation?
- produced by endothelial cells and macrophages
- potent vasodilator
- NO-derived free radicals are microcidal
- may modulate (reduce) the effects of inflammation
What is the job of plasma proteins as a chemical mediator of inflammation?
-Kinin system (repercussions similar to histamine
-clotting system
-fibrinolytic system
(LINKED BY THE ACTIVATION OF HANGMAN FACTOR)
Complement system
-20 proteins
-innate and adoptive immunity functions
-attaches on to cell and kills it
-Activation: Vascular phenomenon, leukocyte adhesion/chemotaxis and activation, phagocytosis, Cell lysis (membrane attack complex)
-C3 and C5 are the most important inflammatory mediators
