What is the goal of inflammation?
a protective response to dilute, isolate, and/or get rid of injurious stimulus, and the consequences of the injury
what can be a major consequence of inflammation?
it can be inappropriately triggered or poorly controlled leading to tissue injury
What is acute inflammation?
- rapid onset
- short duration (hrs to a few days)
- characterized by edema and emigration of White blood cells
What is chronic infammation?
- back-up plan
- long duration
- characterized by lymphocytes, macrophages, proliferation of vessels, fibrosis, and tissue destruction
What are the 4 events of acute inflammation?
- stimuli for acute inflammation
- vascular changes
- cellular reaction: white blood cells extravasation and phagocytosis
- termination of acute inflammatory response
what is Dolor?
pain due to stimulation of nerolan pathways by bradykinin, prostaglandins, histamine and serotonin
What are the 3 major components of acute inflammation?
- increased blood flow
- leakage of plasma proteins= edema
- white blood cell emigration
What are the stimuli for acute inflammation?
- foreign bodies or environmental elements
- tissue necrosis
- immune reactions
What types of infections stimulate inflammation?
bacterial, viral, fungal, parasitic, and microbial toxins
What are some examples of foreign bodies and environmental elements?
UV light, radiation, trauma, thermal injury, chemicals
How does tissue necrosis cause inflammation?
necrotic cells release uric acid, ATP, DNA which induce inflammation
What is hypoxia-induced factor-1a?
released by cells deprived of O2 activating the transcription of many mediators involved in inflammation
How is inflammation induced by immune reactions?
- hypersensitivity reactions
- cytokines for t cells
What are the 4 components of the innate immune system?
- physical barriers and microenvironments
- molecular products from mucosal epithelia
- preformed and synthesized chemical mediators from tissue effector cells
- effector molecules in the blood like plasma proteases and in certain nerve fibers
What are the physical barriers and microenvironments that make up the innate immune system?
skin, mucosa, pH, mucociliary escalator, salivia, mucous secretions, peristalsis
What are some molecular products for mucosal epithelia that make up the innate immune system?
lactoferrin, antimicrobial peptides, surfactant protiens
What are the effector molecules in blood and nerve fibers that make up the innate immune system?
blood: complement, kinin, clotting fibers
nerves: sensory fibers, C-reactive fibers that release substance-P
What do the severity and clinical signs of acute inflammatory response depend on?
- the route of exposure
- the physical and biological characteristics of the stimulus
Once the TLR recognizes the PAMPs, what happens?
triggers release of chemokines and cytokines to activate cells
What are the chemical mediators of acute inflammation?
vasoactive amines, plasma proteases, lipid mediators, PAF, cytokines, chemokines and NO
In acute inflammation, how is vascular flow and caliber changed?
vasodilation, increased permeability of the microvasculature, loss of fluid, and leukocyte accumulation along the vascular endothelium
What is vasodilation?
- early manifestation
- constriction of arterioles for a few seconds, then opening of new capillary beds in the area to increase blood flow
What occurs with you increase the permeability of the microvasculature?
there is an outpouring of protein-rich fluid into extravascular tissues (edema)
What is a consequence of the loss of fluid to the extravasculature space?
inc. conc of RBCs in small vessels, increased viscosity of blood, dilation of vessels, and slow blood flow
What are some ways the vascular permeability is increased?
- retraction of the endothelial cells
- direct endothelial cell injury
- delayed prolonged leakage
- leukocyte-mediated endothelial injury
- increased transcytosis
- leakage from new blood vessels
What is the most common mechanism of increasing vascular permeability?
retraction of the endothelial cells
What triggers the contraction of endothelial cells?
histamine, bradykinin, NO, leukotrienes, and neuropeptide substance-P
What does direct endothelial injury result in?
endothelial cell necrosis or platelet adhesion and thrombosis
What is delayed prolong leakage of the endothelium caused by?
mild to moderate injury:
- thermal, UV, radiaton, or certain bacterial toxins
Where does leukocyte-mediated endothelial injury normally occur?
venules, pulmonary capillaries, and glomerular capillaries
How does leukocyte-mediated endothelial injury normally occur?
by WBCs adhering to the endothelium for prolonged periods of time
What is a visiculovacular organelle?
channel in the cytoplasm of endothelial cells that is made up of vesicles and vacuoles in which transcytosis takes place
What is VEGF?
- vascular endothelial grwoth factor
- inc. vascular leakage by increasing the size of vesiculovacuolar channels
What is extravasation?
sequenced events of white blood cells from the vessel lumen to the interstitial tissue
What are the effector cells of the acute inflammatory response?
- vascular endothelial cells
- mast cells
- macrophages/ monocytes
What is the function of vascular endothelial cells?
- regulate hemostasis/coagulation, vascular pressure, angiogenesis during wound healing, carcinogenesis, leukocyte homing, and inflammation
what are the main functions of neutrophils?
- kill or limit the growth of microbes
- to kill tumor cells
- to eliminate foreign materials via phagocytosis
what do neutrophil granules contain?
myeloperoxidase, defensins, cathelicidins, lactoferrin, elastases, and gelatinase
What is the function of defensin and cathelicidin when released by neutrophils?
degrade by forming pores in microbial membranes
What is the function of gelatinase and myeloperoxidase when they are release by neutrophils together?
kill extracellular microbes and degrades the ECM
What types of pathological processes are eosinophils normally seen?
- helminthic infections and allergic diseases
What are the steps of extravasation?
- margination (cell accumulation)
Whate mediators stimulate the distribution of P-selectin on endothelial cells?
histamine, thrombin, and PAF
What molecules are important in white blood cells to get rid of bacterial infections?
What is leukocyte adhesion deficiency?
- mutation in B2 integrins
- results in neutrophilia with impared transmigration bc they cannot adhere to the endothelium
- severe gingivitis, tooth loss, ulcers, abscesses lacking pus, pneumonia
What is phagocytosis?
release of enzymes by neutrophils and macrophages to eliminate injurious agents
What are the steps in phagocytosis?
- recognition and attachment to antigen
- engulfment in vacuole
- killing or degradation of ingested material