Chronic Inflammation I Flashcards
What are the 3 criteria for chronic inflammation?
- Inflammation
- Tissue destruction
- Attempts at repair coexist - evidenced via fibrosis or presence of fibroblasts
How does chronic inflammation develop?
Frequently begins insidiously as low grade, smoldering response without signs of acute inflammation (most common and disabling)
What are the causes of chronic inflammation?
- Persistent microbial infections
- Immune-related inflammatory diseases
- Prolonged exposure to potentially toxic agents
What occurs with persistent microbial infections of chronic inflammation?
Occurs usually with organisms with low pathogenicity
Often evoke delayed hypersensitivity
Hard to eradicate
May be granulomatous reaction
What are examples of immune-related inflammatory diseases that cause chronic inflammation?
Autoimmune diseases - RA, MS
Unregulated immune responses (IBD)
Allergic diseases against common environmental antigens
What occurs with prolonged exposure to potentially toxic agents and leads to chronic inflammation?
Exogenous (non-biodegradable silica) and endogenous (increased plasma lipid components –> atherosclerosis)
What are the 3 morphology criteria for chronic inflammation?
- Infiltration with mononuclear cells - macrophages, lymphocytes, and plasma cells
- Tissue destruction - induced by persistent stimulus or by inflammatory cells
- Attempts at healing - CT replacement of damaged tissue; new vessel proliferation (angiogenesis) and fibrosis
What will you see morphologically with chronic pancreatitis?
Extensive fibrosis
Chronic inflammatory cells
Residual ductal structures
Residual islet
No acinar tissue remaining
What will you see with chronic inflammation in the lung?
Collection of chronic inflammatory cells, destruction of alveolar spaces and fibrosis
What can we interpret about tissue if we see a plasma cell?
Chronic inflammation!
What are the role of macrophages?
Key cell in chronic and granulomatous inflammation
Derive from circulating blood monocytes
Monocytes emigrate to site of injury in 24-48 hours after onset of acute inflammation
Act as filters and sentinels for lymphocytes stimulation
Where are macrophages located?
Numerous in liver (Kupffer cells)
Spleen
LN’s and lungs (pulmonary or alveolar macrophages)
CNS (microglia)
Bone (osteoclasts)
What are features of activated macrophages?
Increased size
Increased number of lysosome
Increased amount of lysosomal enzymes
Increased ability to kill organisms
How do macrophages mature and how do they appear?
Monocytes can transform into macrophages and become activated
Activated macrophages appear large and flat, similar to squamous cells
What is the maturation of macrophages?
Stem cell
Monoblast
Monocyte
Macrophage
What are the macrophage activation signals?
- Cytokines secreted by activated T cells and NK cells
- Bacterial endotoxins
- Microbial products
- Other inflammatory mediators
How do activated macrophages aid in inflammation and tissue injury?
Reactive oxygen and nitrogen species
Proteases
Cytokines and chemokines
Coagulation factors
AA metabolites
How do activated macrophages function in repair?
Growth factors (PDGF, FGF, TGFbeta)
Fibrogenic, cytokines
Angiogenic factors (FGF)
Remodeling collagenesis
What are the macrophage products?
Acid and neutral proteases, plasminogen activator
Complement components and coagulation factors
ROS and NO
AA metabolites
Cytokines (IL-1 and TNF)
Growth factors - proliferation of smooth muscle cells and fibroblasts
When does macrophage activation occur and what happens?
Within 48 hours, may be predominant cell type
Emigration governed by adhesion molecules and inflammatory mediators with chemotactic and activating properties
If short-lived acute inflammation, macrophages eventually….
Disappear
In chronic inflammation, macrophage accumulation persists, due to
Continuous recruitment
Local proliferation at site of inflammation
What is released when macrophages are activated?
TNF
IL-1
What does TNF and IL-1 activate after being released by activated macrophages?
Local effects - vascular endothelium, leukocytes, and fibroblasts
Systemic effects
What are the systemic effects after being activated by TNF and IL-1?
Fever
Leukocytes
Increased acute phase proteins
Decreased appetite
Increased sleep
All systemic manifestations of inflammation
What occurs in the vascular endothelium upon activation by TNF and IL-1?
Increased expression of leukocyte adhesion molecules
Production of IL-1 chemokines
Increased procoagulant and decreased anticoagulant activity
All lead to inflammation
What occurs with the leukocytes upon activation by TNF and IL-1?
Activation
Production of cytokines
Leads to inflammation
What occurs to the fibroblasts upon activation by TNF and IL-1?
Proliferation
Increased collagen synthesis
What are the roles of lymphocytes in chronic inflammation?
Can be mobilized in setting of specific immune stimulus (infections), as well as non-immune inflammation (trauma)
What is the reciprocal relationship that occurs during chronic inflammation?
T cells and macrophages
Macrophages initially activate T cells (or vice versa)
How do macrophages and lymphocytes interact in chronic inflammation?
Activated macrophages present to T-cells (IL-12) which leads to the T cells activating
Activated T cells release TNF, IL-17, chemokines which lead to the recruitment of neutrophils and macrophages
This then leads to the activation of more macrophages
Activated macrophages then released TNF and IL-1 which stimulate inflammation
What are plasma cells and their function?
Terminal product of B cell activation
Produce antibodies against persistent antigens in inflammatory site or against altered tissue components
Where are eosinophils seen and what does their recruitment depend on?
Most often seen around parasitic infections or as part of immune reactions mediated by IgE (typically associated with allergies)
Recruitment depends on chemokine eotaxin
What do the granules of eosinophils contain?
Major basic protein (MBP)
MBP is toxic to parasites, but leads to epithelial cells lysis
Contributes to tissue damage in immune reactions such as allergies
What are the roles of mast cell in inflammation?
Participates in both acute and chronic inflammatory reactions
Armed with IgE to certain antigens - will release histamine and PG
Central role in anaphylactic reactions and helpful in parasitic infections since it may produce cytokines such as TNF that contribute to fibrosis
Can neutrophils be found in chronic inflammation? What is that due to?
Even in apparent chronic inflammation, numerous neutrophils may be found:
Due to persistent microbes or due to mediators elaborated by macrophages, necrotic cells, and T cells
What is it called when neutrophils are found in chronic inflammation due to persistent microbes or due to mediators by macrophages, necrotic cells, or T cells?
Chronic active inflammation
Acute and Chronic Inflammation
What are the results of chronic inflammation?
Continued tissue damage/destruction
Ongoing tissue destruction can activate inflammatory cascade, leading to co-existence of both acute and chronic inflammation
What can fuel chronic inflammation?
Can be fueled by lifestyle factors which promote production of inflammatory mediators
Some include:
Smoking
Excessive alcohol intake
Physical and emotional stress
Obesity
Lack of exercise
Diet
