Week 2: Chronic Inflammation Flashcards
What are the four general features of chronic inflammation? How is chronic inflammation disease characterized?
Inflammation is not a disease, but a response to insult or injury. It involves the steps of:
Insidious onset
Prolonged duration
Tissue destruction
Ongoing healing and fibrosis
What are common etiologies of chronic inflammation?
Viral infections and other persistent infections
Toxic substances
Hypersensitivity diseases like asthma, autoimmune disorders, inflammatory bowel disease
What are the “five R’s” that make up the general steps to inflammation pathways?
Recognition
Recruitment
Removal
Regulation
Repair
___________ play a role in both innate and adaptive immunity
Macrophages
Innate = general phagocytosis
Adaptive = APC for B cells/T cells
What immune cells are generally associated with acute and chronic inflammation?
Acute = neutrophil
Chronic = lymphocytes (B/T cells)
What is the technical term for scarring? What is being deposited?
Fibrosis, which is the deposition of collagen
What are some main forms of toxic substances that cause chronic inflammation?
Prolonged exposure to toxic substances like silicone, asbestos, or endogenous particles
What is this an example of?
This is the skin of a patient with rheumatoid arthritis, an hypersensitivity disease.
What are the main differences in chronic and acute inflammation?
Cells involved:
acute = neutrophils (early), macrophages (late)
chronic = macrophages, lymphocytes, plasma cells
Tissue changes:
acute = vascular changes
chonic = tissue destruction
Long vs. short term:
acute = edema
chronic = fibrosis
What are the main roles of macrophages?
Activated by various stimuli (sometimes lymphocytes)
Microbial removal
Initiation of repair
What signals stimulate inflammation in macrophages? Which stimulate tissue repair and anti-inflammatory effects?
Inflammation = microbes, IFN-gamma
Repair/anti-inflammatory effects = IL-13, IL-4
Describe the recruitment and roles of lymphocytes
Lymphocytes are mobilized by cell-mediated and antibody-mediated immune reactions
They respond to signaling by activated macrophages, which display antigens for lymphocytes (APCs)
Lymphocytes also produce cytokines that produce T-cell responses
Describe the recruitment and roles of plasma cells
Plasma cells develop from activated B cells, and produce antibodies against altered tissue components or against a persistent antigen. They act as the humoral mediators of leukocyte immunity.
What are mast cells and what roles do they play in the inflammatory process?
Mast cells are cytokine-producing granulocytes that play roles in both acute and chronic inflammation
Acute = anaphylactic reactions
Chronic = cytokine production that may contribute to fibrosis
What are eosinophils and what roles do they play in inflammation?
Eosinophils are granulocytes that play a role in parasitic infections and immune reactions mediated by IgE.
They respond to eotaxin, a cytokine responsible for recruitment of eosinophils to a site of infection
They also include major basic protein, a nerve toxin that helps kill parasites.
What causes tissue damage in chronic inflammation?
Toxins or injurious stimuli
Products secreted by macrophages
T-lymphocytes
Fibroblasts
What is granulomatous inflammation?
A subtype of chronic inflammatory reaction
Tuberculosis is an example. It occurs when a nodule of specialized macrophages form a giant cell and can recruit other inflammatory cells, including TDTH cells
There are epitheloid (very large) and spindled (thinned out) forms.
What are the two main forms of granulomatous inflammation, and how does each occur?
Foreign body type granulomas - initiated by inert foreign bodies like sutures, asbestos slivers, or splinters
Immune granulomas - poorly degradeable or particulate agents, T-lymphocytes and macrophages induce transformation of macrophages
Involves IL-2, TNF and interferons
What is caseating granulomatous inflammation?
A type of inflammation associated with mycobacterial infection–for example, tuberculosis, a prototype of this kind of inflammation
Activated macrophage accumulates to attempt to destroy the infective agent. We observe central necrosis (caseous) in the middle of the granuloma (pink area)
What is non-caseating granulomatous inflammation?
This is a granuloma that forms without central necrosis, and is associated with syphilis, cat-scratch disease, and sarcoidosis
What are the systemic, general effects of inflammation?
Systemic inflammatory response syndrome (acute phase response)
Reaction to cytokine production
Fever, leukocytosis and acute phase proteins
What is involved in the acute phase response of inflammation?
“ACute End For Luke”
Acute phase reactions: fever, sleep, decreased appetite, neutrophilia, hemodynamic shock
Endothelial effects: increased leukocyte adherence, procoagulant activity, decreased anticoagulant activity, increased IL-1,6,8 production, PDGF production
Fibroblast effects: increased proliferation and collagen synthesis, increased collagenase and protease, increased PGE synthesis
Leukocyte effects: increased cytokine secretion (IL-1,6)
What steps of the acute phase response leads to fever?
“P-IL for Thursday Night Fever”
Pyrogens
IL-1 and TNF
Conversion of AA to prostaglandins
Action on the hypothalamus to reset the temperature set point
Can relieve with NSAIDS
What helps us assess leukocytosis, and what are the two major elements involved?
Neutrophilia is an increase in neutrophils, and lymphocytosis is an increase in lymphocytes.
You can assess these values with a CBC (complete blood count) of:
Hemoglobin
Hematocrit
WBC count
Platelet count
What are the acute phase proteins that are relevant to the immune response? What do we look for in this process and what might it mean?
Crack For SAAle En Montana
Proteins:
C-reactive protein
Fibrinogen
Serum amyloid A protein
Look for:
Erythrocyte sedimentation rate
Might mean:
Markers for inflammatory disorders
What are the symptoms of the acute phase response?
The People aRe Chilly And Mad
Tachycardia
Peripheral vasoconstriction
Rigors
Chills
Anorexia
Malaise
What is the difference between regeneration and repair?
Regeneration occurs when there is intact tissue framework (superficial wounds, parenchyma damage), and allows normal tissue to reform
Repair occurs when the tissue framework is damaged (deep wounds, parenchyma and mesenchyma damage), and creates scar formation
What occurs with persistent tissue damage?
Fibrosis (NOT the same as scarring)
Chronic inflammatory diseases like:
Cirrhosis
Chronic pancreatitis
Pulmonary fibrosis
What are the major components (5) of wound healing?
Inflammation
Angiogenesis
Fibroblastic proliferation
Collagen deposition (scarring) from angiogenesis and the formation of granulation tissue
Tissue remodeling (maturation and wound contraction)
What is angiogenesis?
Neovascularization where pre-existing vessels give rise to new vessels. It involves many growth factors (VEGF) and ECM (Notch) proteins direct endothelial cell growth.
How does deposition of connective tissue occur?
Fibroblasts migrate and proliferate at the site of the wound due to growth factors and cytokines. They secrete collagen and other ECM factors.
Vessel and fibroblast proliferation are components of granulation tissue.
What are the major components of granulation tissue?
New vessel formation and fibroblastic proliferation
What are the two main forms of cutaneous wound healing?
Primary intention - uncomplicated, clean incision, little scar formation
Secondary intention - large, deep wounds with excessive granulation tissue and scarring, wound contracture
Main steps to either: Inflammation, Proliferation, Maturation (remodeling and contraction)
What systemic and local factors influence healing?
Systemic:
Nutrition and metabolism, blood supply, hormones
Local:
Infection, mechanical stretching, foreign bodies, size of wound, location of wound
What is fibrosis?
Abnormal deposition of collagen in internal organs that occurs with chronic disease.
Ongoing inflammation and stimulation of fibroblasts
