BMS314 Lecture Notes - Lecture 18: World Population, Caseous Necrosis, Endothelium
Definition of Chronic Inflammation
Inflammation of prolonged duration in which
• Active inflammation
• Tissue destruction
• Attempts of repair
Occur simultaneously
Circumstances of Chronic Inflammation
1. May arise from unresolved acute inflammation that becomes chronic (failed removal of source
of inflammation)
2. Often begins insidiously as a smouldering process with no recognizable acute phase
• e.g. The liver has a high functional reserve capacity, therefore tissue destruction is
difficult to recognise until it has progressed.
3. Always incited by the persistent presence of:
• An irritant (endogenous or exogenous)
• e.g. silica/other foreign body
• Micro-organism
• e.g. myobacteria, fungi, parasites, viruses, OIA
• Injured tissue
• An immune response
• e.g. hypersensitivity and autoimmune diseases
4. Arises in a variety of circumstances - varied
5. May be sterile or infected
• Infectious agent may be long gone, left with the attack of the immune system
Hallmarks of Chronic Inflammation
1. Cellular Process - Cellular infiltrate comprised of any of
• Macrophages
• Lymphocytes
• Plasma cells (lesion > 2 weeks old)
• +/- neutrophils / eosinophils
• (acute inflammation was very vascular)
2. The infiltrate destroys and replaces tissues
3. Attempts at healing result in proliferation of tissue stroma and abundant fibrosis
Chronic inflammation similar to neoplasia
Gross Pathology of Chronic Lesions
• Areas of swelling/thickening/nodularity
• Fibrosis --> areas appear pale and firm
• Cellular infiltration and proliferation --> areas appear pale (due to lack of vascularity), variable
texture (firm +/- soft)
• Concurrent tissue loss --> organ appears irregular +/- shrunken
• Significant change in the architecture/appearance of organs
Abnormalities - Chronic
Little white dots
Pale
Smaller than what it should be
(showing all the signs of a chronic inflammation reaction)
Abnormalities - Acute
Red
Swollen
Shiny (fluid oozing out)
(showing all the signs of an acute inflammation reaction
Cellular Features of Chronic Inflammation
Histiocytes (Bone Marrow)
= Antigen presenting cell's (APC's):
Macrophages and Dendritic Cells
• Macrophages (=APC's)
• Derived from blood monocytes, migrate into areas of tissue injury (24-48hrs)
• The major phagocytic cells (IC destruction)
• Long lived (months) unlike neutrophils ; mitotic
• Important in
• Induction and Effector phase of adaptive immune response
• M1 and M2 types of macrophage
M1 = activated by endotoxin + TLF
• ROS, NO, IL-1, IL-12
• Increased inflammation and destruction of pathogens
M2 = activated by IL-4, IL-13; tissue repair
•
• Monocyte
• Dendritic Cells (=APC's)
• = Histiocytes present in all organs
• Derived from Monocytes (under the influence of cytokines and chemical
mediators --> IL-4, GM-CSF, others)
Stimulated monocytes --> Dendritic cells (DC's)
• DC's: numerous surface receptors (for capturing infectious agents)
TLR's, lectins, +/- Fc, C3b
• Present Antigen to T lymphocytes
--> acquired/adaptive immune response
• Produce IL-1, TNF-a, IL-12
Pro-inflammatory cytokines (to control tissue destruction)
• Produce IL-10
Anti-Inflammatory (calm it down to prevent the immune response causing
tissue destruction)
• Growth factors for fibrosis (tissue repair)
FGF, TGF-Beta
Lymphocytes and Immune Reponse
1. Innate (NK)
2. Humoral (B)
3. Cell Mediated Immunity (T)
Lymphocytes
• T lymphocytes: antigen-specific helper, cytotoxic and suppressor subtypes
• B lymphocytes produce antibodies specific to an antigen
• B lymphocytes that produce specific antibodies appear morphologically different
• = plasma cells
• Plasma cells are associated with --> Chronic inflammation
Natural Killer cells
= Type of lymphocyte (large granular lymphocyte)
~10% of circulating lymphocytes
Innate immune response
Fibroblasts
• Main cell type in connective tissue
• Stable cells
Document Summary
Inflammation of prolonged duration in which: active inflammation, tissue destruction, attempts of repair. Injured tissue: an immune response, e. g. hypersensitivity and autoimmune diseases, arises in a variety of circumstances - varied, may be sterile or infected. Infectious agent may be long gone, left with the attack of the immune system. Hallmarks of chronic inflammation: cellular process - cellular infiltrate comprised of any of, macrophages. Lymphocytes: plasma cells (lesion > 2 weeks old, +/- neutrophils / eosinophils (acute inflammation was very vascular, the infiltrate destroys and replaces tissues, attempts at healing result in proliferation of tissue stroma and abundant fibrosis. Gross pathology of chronic lesions: areas of swelling/thickening/nodularity. Fibrosis --> areas appear pale and firm: cellular infiltration and proliferation --> areas appear pale (due to lack of vascularity), variable texture (firm +/- soft, concurrent tissue loss --> organ appears irregular +/- shrunken. Smaller than what it should be (showing all the signs of a chronic inflammation reaction)
