Inflammation - Key Terms Flashcards
Goals of Inflammation
- Eliminate initial cause of injury
- Remove dead cells
- Begin process of tissue repair
Innate immunity
The defense system a person is born with
Components of innate immunity
- Physical barriers
- Enzymes (lysozymes)
- Complement proteins
- C-reactive protein
- Toll-like receptors
- Cells releasing inflammatory mediators
- Antimicrobial peptides
- Phagocytes
Benefit of inflammation
- Interact with acquired immune system
- Prevent further tissue damage
- Prevent spread of infection by dilution of pathogens
- Prepare area for healing
Complement proteins
Destroy bacteria
WBCS
Prevent inflammatory response from spreading to healthy tissues, eat pathogens
Plasma protein system
Clotting
Granulomatous response
Inflammation contains the infection/damaged site by walling it off
Vascular events in inflammation
- Arterioles temporarily constrict
- Brief vasoconstriction followed by vasodilation (this lasts)
What do damaged cells release
Prostaglandins and leukotrienes that cause vasodilation
What does vasodilation help with during the vascular events
- Slows blood velocity
- Increases blood flow to increase tissue perfusion
- Causes redness and warmth at site
What are plasma protein systems known as
Cascades
Complement system
Normally circulate in inactive form and cause
1. Increased vascular permeability and vasodilation
2. Chemotaxis
3. Opsonization
4. Cell killing
How is complement protein system triggered?
- Activated by IgC or IgM antigen-antibody complexes.
- Lectin pathway - can opsonin for phagocytosis or activate next part of cascade
- Alternative pathway activated as part of innate immune system
Coagulation/clotting system is activated by
Extrinsic and intrinsic pathway
Thrombin
Enzyme that proteolytically activates fibrinogen
Thrombin is a part of what system
Clotting
What does the clotting system do
Stops bleeding, localizes microorganisms, provides a meshwork for repair and healing.
Prevents spread of infection by bacteria remaining at localized site
Factor XII
Activates plasma proteins, promotes formation of bradykinin and kallikrien.
Kinin System
Activates and assists inflammatory cells
Bradykinin
Most important product of kinin system, like histamine
What does bradykinin cause
Vascular permeability, vasodilation, smooth muscle contraction in lungs, and pain
Kinins
Potent vasodilators, regulators of inflammatory process, and involved in pain sensation and growth
What does the endothelium do during inflammation
Represses receptors that help leukocytes leave the vessel
Retract to allow fluid to pass into tissues
What is the most important activator of inflammatory response
Mast cell
Mast cell
Initiates inflammation by releasing biochemical mediators
Histamine
Major vasoactive amine released from mast cells
What does histamine do
Dilation of capillaries and retraction of endothelial cells lining capillaries to increase vascular permeability Causes bronchoconstriction
Chemotactic factors
Attract neutrophils and eosinophils to inflammation site
Neutrophil chemotactic factor
Attracts neutrophils
Eosinophil chemotactic factor
Attracts eosinophils
What do mast cells release after granules are released
Leukotrienes, prostaglandins, platelet-activating factor
Leukotrienes
Slower and more prolonged responses than histamine in later stages
Prostaglandins
Similar effects to leukotrienes and also induce pain
Platelet-activating factor
Similar effect to leukotrienes and platelet activation - causes blood clotting
Chemotaxis
Movement of an organism in response to a chemical stimulant
Causes WBCs to move
Leukocyte
White blood cell
Phagocytosis
Lysozyme fuse with phagosome and digest it
Granulocytes
Neutrophils, eosinophils, basophils/mast cells
Monocytes
Monocytes, macrophages, dendritic cells
Lymphocytes
T cells, B cells, Natural killer cells
Neutrophils
Most common type of WBC
First responders to injury/inflammation
Live about 5 days
Actively phagocytose bacteria
When do monocytes become macrophages
When they enter the site 24 hours after neutrophils and replace them
Dendritic cells
Antigen-presenting cells found in tissue that contacts the external environment
Natural killer cells
Large, granular lymphocytes activated by T-cell released cytokines
Contain perforin and granzyme
Perforin and granzyme
Activate cell apoptosis via cell membrane receptors
Platelets
Interact with the coagulation cascade to stop bleeding and release a number of mediators that promote and control inflammation
Primary cell types that produce mediators during acute inflammation
Macrophages, dendritic cells, mast cells
Mediators produced in response to specific stimuli
Short-lived and stimulate the release of other mediators which amplifies the inflammatory response
Serotonin
Stored in platelets and neuroendocrine cells in the GI tract - cause vasconstriction
Eicosanoids
Lipid mediators
Cytokines
Cells of the innate immune system secrete many biochemical mediators that are responsible for activating other cells.
Small proteins that are pro-inflammatory or anti-inflammatory
What are examples of cytokines
Interleukins, chemokines, interferons
Interleukins
Most important proinflammatory cytokines are interleukin 1, 6, and tumor necrosis factor-alpha
Interleukins are primarily produced by
Macrophages and lymphocytes
IL-6
Stimulates growth and differentiation of blood cells in the bone marrow, induces hepatocytes from the liver to produce acute phase proteins
Chemokines
Group of signaling proteins that act as chemoattractants to recruit leukocytes to areas of damaged tissue
Interferons
Produced by cells that are infected by viruses
Tumor necrosis factor-alpha
Secreted by macrophages in response to PAMP and toll-like receptor recognition.
Induces fever by acting as an endogenous pyrogen.
Serous exudate
Fluid accumulation as a result of tissue injury that does not contain many cells. Watery plasma leaks into IF - blister which indicates early infection
Exudative
Contains proteins
Fibrinous inflammation
Result of large vascular leak that allows fluid with large proteins to leak out into surrounding tissue
Causes thick clotting
Purulent inflammation
Forms pus, which contains many neutrophils, cellular debris, and edema fluid.
Usually walled-off lesions with an abscess/necrotic center
Suppuration
Formation of pus that may occur if the pathogen is difficult to eliminate or severe
Pyogenic bacteria
Commonly causes pus formation
Ulceration
Results from very severe inflammation and is a local defect caused by necrosis of cells and sloughing of necrotic tissue
Pattern Recognition Receptors (PRR)
Help to identify pathogen-associated molecular patterns, leading to production and release of cytokines and other chemicals that mediate the response of the cells causing inflammation
Anti-inflammatory pathways
Hypothalamic-pituitary-adrenal pathway
Sympathetic nervous system
Parasympathetic nervous system
HPA anti-inflammatory pathway controls release of
Glucocorticoids - Cortisol
Interleukin-10 inhibits production of proinflammatory cytokines by macrophages
Sympathetic nervous system (anti-inflammatory pathway)
Releases NE and epi to downregulate production of pro-inflammatory cytokines and upregulate the production of anti-inflammatory cytokines
Promotes recruitment of leukocytes
Increases blood and lymph flow
Parasympathetic nervous system
Inhibits pro-inflammatory cytokine production in the spleen and decreases neutrophil activation
Principal systemic effects of inflammation are
Fever and increases in levels of circulating leukocytes and plasma proteins.
Acute-phase response (definition)
Systemic effects caused by chemical mediators in inflammatory response
Acute-phase response
Fever, increase in serum proteins, leukocytosis, release interleukins and tumor necrosis factor
Systemic inflammatory response syndrome (SIRS)
Severe systemic response to inflammation
Cause is infection: sepsis
Septic shock
Bacterial or fungal - vasodilation - peripheral pooling - decreased BP
Gut barrier failure
Decrease perfusion of the gut, normal flora bacteria and toxins escape into tissue fluid, inflammatory response, vasodilation, shock
Multiple organ dysfunction syndrome
Progressive dysfunction of two or more organ systems from uncontrolled inflammatory response to severe illness or injury
Acute inflammation is characterized by
Brisk onset of relatively short duration
Prominent systemic signs and local responses
Chronic inflammation is characterized by
High levels of lymphocytes, macrophages, monocytes
Impaired or excessive inflammation is characterized by
Overexpression of leukocyte adhesion molecules
Production of excessive pro-inflammatory cytokines
Damage to tissues
Risks for developing chronic inflammation
Poor blood supply, malnutrition, abnormal neutrophil function, prolonged use of anti-inflammatory medications
Granuloma
Body walls off and isolates infection to protect against tissue damage
Epitheliod cell formation
Chronic inflammation is associated with
Tissue destruction
Replacement of damaged tissue with fibrous tissue via angiogenesis
Alzheimer disease
Beta-amyloid peptide plaques and neurofibrillary tangles in the brain
Asthma
Chronic airway inflammation, dysfunction of the airways, tissue remodeling
Atherosclerosis
Believed to be chronic inflammatory response of leukocytes to low-density lipoproteins particles in arterial walls
What does atherosclerosis involve
- Involve both innate and acquired immunity systems
- Leukocytes involved mostly monocytes and macrophages
- Begins in childhood
T2D mechanisms that contribute
Excess levels of glucose and free fatty acids from overnutrition
Adipose tissue growth exceeding vascular supply
Inflammaging
Chronic, low grade inflammation associated with aging
Potential causes of inflammaging
Damaged cells that accumulate with age
Gut’s inability to adequately respond to harmful substances produced by microbiota
Obesity
Adipose tissue secretes hormones, cytokines, chemokines, growth factors, complementary proteins
Adipose tissue implicated in development and progression of many chronic inflammatory disorders
Three phases of wound healing
Hemostasis, inflammatory phase, proliferative/reconstruction phase, remodeling/maturation
Factors that affect wound healing
Nutrition, circulation, age
Hypovolemia (dysfunctional wound healing)
Can’t deliver WBCs to injury site
Hemorrhage (dysfunctional wound healing)
Large clots and increased exudate are mechanical barriers to O2 diffusion, slows repair
Fibrous Adhesion
If fibrin not reabsorbed, it forms adhesions and binds organs together
Hypoproteinemia
Impairs fibroblast proliferation
Anti-inflammatory steroids
Block macrophages from getting to injury and releasing cytokines
Dehiscence
Wound pulls apart at the suture line
Impaired (excessive) contraction
Contracture: occurs with burns, decreases ROM
