inflammation Flashcards
Definition of acute inflammation
well-organized cascade of vascular and cellular changes within living vascularized tissue
(zachary)
Aim of acute inflammation
LOCALIZATION of destructive effect in the site of entry
ELIMINATION of exo- and endogenous agents + necrotic tissues and cells.
Keeping INTEGRITY of organism, initiation of tissue REPAIR (growth factors)
4 signs of inflammation
Rubor (redness),
Tumor (swelling),
Calor (heat)
Dolor (pain)
Loss of function - 5th sign
3 phases of acute inflammation
Fluidic, cellular, reparative
Aim of fluidic phase of acute inflammation?
To dilute, isolate and trap the stimulus of damage, so limiting the extent of involvement adjacent normal cells and tissue
Why signs of inflammation occur?
Increased blood flow, vasodilation, fluid accumulation
What is the difference between acute and chronic inflammation?
Chronic:
- longer duration
- response is mainly by lymphocytes and macrophages, tissue necrosis
- tissue repair: healing, fibrosis and granulation tissue formation
(zachary)
How to distinguish vascular and cellular response during inflammation?
Vascular - what is going before WBCs actually fighting the agent
Cellular - actual fighting
How does acute inflammation starts (for example in case of bacteria infection)
- Tissue damage -› cell membrane damage -› arachidonic acid -› prostaglandins (by COX) and leukotriens (by lypooxygenase)
- Activation of mast cells
What do mast cells release in the case of inflammation?
Histamines, Leukotriens, Prostaglandins. They are preformed, so release is very quick!
Importance of arachidonic acid in inflammation?
Starting material for prostaglandins (COX) and leukotriens (lipooxygenase)
How do cytokines (PGs, leukotriens, histamines) act on endothelial cells and smooth muscle?
- stimulate contraction of endothelial cells (gaps between cells appear)
- stimulate endothelial cells to expose selectin proteins (adhesion of white blood cells)
- vasodilation of smooth muscle -› increase of blood flow
What is margination?
migration of white blood cells (WBCs) toward the endothelium during blood flow. -› Slowing down -› rolling -› adhesion -› diapedesis
What is diapedesis?
squeezing of WBCs out of the bloodstream into surrounding tissues through gaps between endothelial cells
What do macrophages secrete?
Interleukines and TNFs
How WBCs entering the tissue know where is site of injury?
Positive chemotaxis
oxidative burst
release of reactive oxygen species (free radicals) to degrade pathogen. Also can be harmful to the cell itself
What cells are antigen presenting cells?
macrophages, dendritic cells, B cells
What are the only cells that can have MHC-1 ?
Antigen presenting cells
Panniculitis - ?
Inflammation of adipose tissue
Two components of inflammatory response?
VASCULAR response and CELLULAR response
Parallel processes!
What are toll-like receptors (TLRs)?
TLRs are class of pattern recognition receptors (PRRs) that initiate innate immune response
What are interferons?
molecules secreted by cells invaded by viruses that stimulate other cells to help defend against viruses
What receptors “identify” inflammatory stimuli?
Toll-like receptors and other pattern recognition receptors (PRRs) of macrophages, dendritic cells, mast cells, B-lymphocytes, neutrophils
What patterns do pattern recognition receptors recognise?
Pathogen-associated molecular patterns (PAMPs)
Damage-associated molecular patterns (DAMPs) (non-index inflammatory response)
What are many DAMPs?
Nuclear or cytosolic proteins. Damage/death of cell -> release
Vascular response.
Vasodilation, increased blood flow
By what vasodilation is induced?
Histamine, serotonin (mast cells, basophils, platelets)
Prostaglandins, nitric oxide (mast cell, platelets)
Cytokines - ? ЧТО ЭТО ВООБЩЕ НАХУЙ ЗА ОПРЕДЕЛЕНИЕ
Category of small proteins that are important in cell signalling
Cytokines are produced by …?
Macrophages, b- and t-lymphocytes, mast cells, endothelial cells, fiibroblasts and stromal cells
Cytokines include … ?
Chemokines, interferons, interleukins, lymphokines and tumor necrosis factors but generally NOT HORMONES OR GROWTH FACTORS
What do cytokines do in inflammation?
They signal immune cells to travel to the site of infection, activate those cells and stimulate to produce more cytokines. This feedback loop is controlled by the body.
Vascular changed in acute inflammation
1) Haemostasis
2) Venula-hyperpermability
3) Micro vascular exsudation
Why haemostats happens?
Vasodilation + loss of fluid -> concentration of blood in vessels of microcirculation, increased viscosity, slower blood flow
For how long does haemostasis occur?
Few minutes (severe injury)
15-30 minutes with mild stimuli
Vascular leakage
Leads to escape of protein rich fluid (exudate) into the extravascular tissue (inflammatory edema)
Leads to increased interstitial hydrostatic pressure and endothelial dysfunction.
Types of endothelial permeability increase:
- Formation of ENDOTHELIAL GAPS in POSTCAPILLARY VENULES due to endothelial construction (histamine, leukotriens, 10-15 mins) most common
- DIRECT ENDOTHELIAL INJURY (everywhere, hours to day)
- LEUKOCYTE MEDIATED ENDOTHELIAL INJIRY (late response, hours)
Sequence of leukocyte extravasation:
1 - margination and adhesion to vascular lumen
2 -transmigration across endothelium (= leukocytadiapedesis)
3 - migration in the interstitium (chemotactic stimulus)
4 - leukocyte activation, phagocytosis
5 - IC degradation
What are the names of main adhesion molecules?
Selectin (weak adhesion)
integrin (strong connection)
Leukocyte adhesion deficiency - ?
Decreased expression of adhesion molecules on the surface of leukocytes -> leukocytes can’t cross vascular walls properly
What breeds are predisposed to LAD (leukocytes adhesion deficiency) ?
Holstein calves (bovine LAD, beta-2 integrin deficiency)
Irish setters (canine LAD)
Symptoms of bovine leukocyte adhesion deficiency
- gingivitis
- tooth loss
- ulcers (oral, enteric, cutaneous)
- abscesses without pus
- leukocytosis
- pneumonia
- death within few days after birth
Leukocytediapedesis - ?
= extravasation. Movement of leukocytes into interstitial-extravascular connective tissue
What cells predominate in the first 24 to 48 hours of acute inflammation?
Neutrophils
By what cells are neutrophils replaced later in acute inflammation?
Macrophages (extravasation takes longer than neutrophils)
Substances that cause chemotaxis are called … ?
Chemoattractants
Examples of chemoattractants
Exo: bacterial products
Endothelial: components of complement system, cytokines, arachidonuc acid metabolites
Sequence of phagocytosis:
- recognition and attachment
- engulfment, formation of phagocytosis vacuole
- degradation of ingested material
Types of intracellular degradation
Oxygen dependent (ROS) and independent (proteolytic enzymes)
What happens to neutrophils after they phagocyte the agent?
Undergo apoptosis and ingested by macrophages
Specificity of inflammation in dogs?
INCREASED ERYTHROCYTE-DIAPEDESIS. (RBCs extravasation) -> haemorrhagic appearance of the purulent inflammatory fluid.
