Chapter 2.5- Pathology Of Inflammation Flashcards
What are the four cardinal signs of inflammation?
- Rubor
- Rubmor
- Calor
- Dolor
What cells are primarily associated with acute inflammation?
Neutrophils
What are the components of acute inflammation?
- Alterations in vascular caliber (vasodilation)
- Structural changes in microvasculature (edema)
- Emigration of leukocytes from microcirculation
What can stimulate inflammation?
Infections
Tissue necrosis
Foreign bodies
Immune reactions
What is the function of toll-like receptors?
Recognize ligands on Bacteria
Binding triggers the production of inflammatory mediators
What elicits inflammation?
Molecules realized from
necrotic cells
Hypoxia (HIF-1alpha)
What changes do blood vessels undergo in response to inflammation?
- Increased hydrostatic pressure (decreased colloid)
- Increased permeability- exudation (high protein concentration to interstitium)
- Pus
- Vasodilation
- Stasis- fluid loss and increased vessel diameter
What is vasodilation induced by?
Histamine
NO
What increases vessel permeability?
Endothelial contraction
Endothelial injury
Transcytosis
What are the two kinds of lymphatic inflammation?
Lymphangitis- channels
Lymphadenitis- nodes
What are the phases of leukocyte extravasation?
- Margination- vasoconstriction
- Rolling- via selectins
- Adhesion- via integrins
- Migration- across vessel wall (PECAM-1)
- Chemotaxis- migration to injury
What molecules mediate rolling and adhesion?
Rolling- L, E and P selectins, TNF and IL-1
Adhesion- integrins, TNF, IL-1 and V and I-CAM-1
How does diapedesis occur?
Chemokines stimulate leukocyte migration
Cells pierce the BM (collagenases)
Migration along the chemotactic gradient
Adherence to ECM (integrins and CD44)
What molecules are involved with diapedesis?
PECAM-1 and CD31
What are the two types of genetic deficiencies in adhesion molecules?
Type I- defect in LFA-1 and Mac-1 integrins
Type II- absence of ligand for E and P selectins
What is chemotaxis?
Morphological changes that move leukocytes along a chemical gradient
How does chemotaxis occur?
Chemokines bind to GPCRs and induce actin polymerization and myosin localization
Filopodia extend
What receptors due leukocytes express to recognize external stimuli?
- TLRs- microbial products
- GPCRs- recognize components of bacterial cell walls
- Opsonin- proteins coating microbes
- Cytokine- bind those produced in response to microbes (INF-gamma)
What are the characteristics of mediators?
Active
One mediator can stimulate the release of others
Vary in range of targets
Short lived
What are types of cell derived mediators and their characteristics?
- Histamine- mast cells, released upon degranulation, vasodilation and increased permeability, allergic reactions and anaphylaxis
- Serotonin- plts, vasodilation and increases vessel permeability
- Prostaglandins- mast cells, macrophages, endothelial cells, pain and fever, vascular reaction
- Leukotrienes- mast cells and leukocytes, chemoattractants, vasoconstriction and increased permeability, bronchospasm (asthma)
- PAF- leukocytes and mast cells, vasodilation and increased permeability, leukocyte adhesion, chemotaxis, oxidative burst
- ROS- leukocytes, smooth muscle relaxation, microbicidal
- Chemokines- leukocytes and activated macrophages, chemotaxis, leukocyte activation
- Cytokines- activated macrophages, endothelial activation, chemical mediator synthesis, IL-1 production, fever, pain
What are the two forms of vascular reaction induced by prostaglandins and which are they produced by?
Prostacyclin- vasodilation, plt aggregation inhibition
Thromboxane- vasoconstriction, plt aggregation promotion
What is the function of complement?
Innate and adaptive immunity for pathogen defence
Proteins are involved with increasing vascular permeability, chemotaxis, opsonization
What are the different complement pathways?
- Classical- Ab binding
- Alternative- surface molecules
- Lectin- plasma mannose binding lectin binds microbes and activates the pathway directly
What is common among all the complement pathways?
C3 convertase is produced
C3b attaches and forms MAC
Which complement proteins stimulate histamine release?
C3a, C5a, C4a
What complement proteins act as opsonins?
C3b and iC3b
What are the phases of phagocytosis?
- Recognition and attachment
- Engulfment (phagocytosis vacuole)
- Killing and degradation (respiratory burst)
What are neutrophil extracellular traps?
Viscous meshwork of nuclear chromatin that can trap microbes
Antimicrobial peptides and enzymes
How is inflammation terminated?
Stimulus removed
Mediators and neutrophils have short half lives
Stop signals
What kinda of stop signals terminate inflammation?
Switch in amino acid metabolite produced
Liberation of anti-inflammatory cytokines
Production of anti-inflammatory mediators
Neural impulses can inhibit TNF production
How can leukocytes injure normal cells?
ROS
NOS
Enzymes
What types of inflammation are seen in acute?
Serous- thin fluid
Fibrinous- fibrin is formed and deposited, scarring
Suppurative- large amounts of pus from pyogenic bacteria (abscesses=localized collections)
Ulcer- sloughing of necrotic tissue (inflammation and necrosis on surface)
What are the outcomes of acute inflammation?
Complete resolution
Healing/fibrosis
Chronic inflammation
What can cause excessive inflammation?
Allergies
Autoimmune disorders
Atherosclerosis
Alzheimer’s disease
How do leukocyte induced injuries occur?
When materials that can’t be easily ingested are encountered granular contents are released
Cells may rupture
Enzymes may be released into the extracellular space
What are the inherited defects in leukocyte function?
- Adhesion- defects of integrin and selectin ligands
- Phagolysosome function (Chediak-Higashi)- defect of phagosome and lysosome fusion, defective degranulation, giant granules
- Microbicidal activity (granulomatous disease)- defects in phagocyte oxidase
What is the most common cause of acquired defects in leukocyte function?
Marrow suppression
What are causes of chronic inflammation?
Persistent infections
Immune mediated inflammatory diseases
Prolonged exposure to toxic agents
What cell type predominates in chronic inflammation?
Mononuclear cells
Macrophages specifically
What is associated with chronic inflammation?
Angiogenesis
Fibrosis
What activates macrophages?
Microbial products
Cytokines (T lymphs and NK cells)
Mediators
What cells are responsible for most tissue damage in chronic inflammation?
Macrophages
How do lymphs participate in chronic inflammation?
Cells migrate (adhesion molecules and chemokines)
Activated by Ags displayed by macrophages
Produce cytokines that recruit monocytes
What cells are associated with lymphoid organogenesis?
Plasma cells
What types of inflammatory reactions do eosinophils mediate?
Parasitic infections
IgE
What do eosinophil granules contain?
Major basic protein
What inflammatory reactions do mast cells mediate?
Hypersensitivity (allergies)
IgE
What do mast cell granules contain?
Histamine
Prostaglandins
What is granulomatous inflammation?
Pattern of chronic inflammation
Microscopic aggregation of macrophages surrounded by lymphs
Attempt to contain a difficult to remove agent
What types of granulomatous reactions are there?
- Foreign body- objects big enough to avoid engulfment
2. Immune- agents capable of inducing a cell mediated response
What is the prototype of the granulomatous reaction?
Tuberculosis
What is a naked granuloma?
No surrounding lymphs
