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Questions and Answers
What primarily characterizes chronic inflammation?
What primarily characterizes chronic inflammation?
Which of the following is a common cause of chronic inflammation?
Which of the following is a common cause of chronic inflammation?
What type of cells are primarily associated with chronic inflammation?
What type of cells are primarily associated with chronic inflammation?
Which of the following diseases is linked to chronic inflammation due to prolonged exposure to toxic agents?
Which of the following diseases is linked to chronic inflammation due to prolonged exposure to toxic agents?
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What is a common outcome of chronic inflammation?
What is a common outcome of chronic inflammation?
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Which cells are primarily involved in chronic inflammation?
Which cells are primarily involved in chronic inflammation?
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What are the primary actions of macrophages in chronic inflammation?
What are the primary actions of macrophages in chronic inflammation?
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What type of macrophages is involved in the inflammatory response?
What type of macrophages is involved in the inflammatory response?
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What triggers the activation of macrophages?
What triggers the activation of macrophages?
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What is the role of dendritic cells in the immune response?
What is the role of dendritic cells in the immune response?
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What type of granuloma is typically found in sarcoidosis?
What type of granuloma is typically found in sarcoidosis?
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Which cells interact to activate CD4 T helper cells in type IV delayed hypersensitivity?
Which cells interact to activate CD4 T helper cells in type IV delayed hypersensitivity?
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What is a common manifestation of fibrinous inflammation?
What is a common manifestation of fibrinous inflammation?
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What is typically associated with suppurative inflammation?
What is typically associated with suppurative inflammation?
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Which condition is characterized by Schaumann bodies?
Which condition is characterized by Schaumann bodies?
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What is the primary function of coagulase produced by Staphylococcus aureus?
What is the primary function of coagulase produced by Staphylococcus aureus?
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Which characteristic distinguishes acute ulcers from chronic ulcers?
Which characteristic distinguishes acute ulcers from chronic ulcers?
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What is a sinus in the context of chronic inflammation?
What is a sinus in the context of chronic inflammation?
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What composition primarily makes up an abscess?
What composition primarily makes up an abscess?
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What defines a fistula in medical terms?
What defines a fistula in medical terms?
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What is the primary function of T-helper cells?
What is the primary function of T-helper cells?
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Which type of cell is rich in rough endoplasmic reticulum and responsible for antibody production?
Which type of cell is rich in rough endoplasmic reticulum and responsible for antibody production?
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What is the main characteristic of giant cells in granulomatous inflammation?
What is the main characteristic of giant cells in granulomatous inflammation?
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Which condition is NOT associated with granulomatous inflammation?
Which condition is NOT associated with granulomatous inflammation?
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What type of hypersensitivity is associated with tuberculosis?
What type of hypersensitivity is associated with tuberculosis?
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Which immune cell type is primarily responsible for the destruction of parasites?
Which immune cell type is primarily responsible for the destruction of parasites?
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What is a defining feature of epithelioid macrophages found in granulomatous inflammation?
What is a defining feature of epithelioid macrophages found in granulomatous inflammation?
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Which of the following is NOT a specific infectious cause of granulomatous inflammation?
Which of the following is NOT a specific infectious cause of granulomatous inflammation?
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Which of the following is a typical systemic effect of chronic inflammation?
Which of the following is a typical systemic effect of chronic inflammation?
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What is one potential outcome of prolonged chronic inflammation?
What is one potential outcome of prolonged chronic inflammation?
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What microscopic feature is commonly associated with chronic inflammation?
What microscopic feature is commonly associated with chronic inflammation?
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Which of the following best describes the initiation of chronic inflammation?
Which of the following best describes the initiation of chronic inflammation?
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Which persistent infection is commonly associated with the onset of chronic inflammation?
Which persistent infection is commonly associated with the onset of chronic inflammation?
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What is a key characteristic of sarcoidosis?
What is a key characteristic of sarcoidosis?
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Which cytokines are primarily produced by T cells during type IV delayed hypersensitivity?
Which cytokines are primarily produced by T cells during type IV delayed hypersensitivity?
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Which statement best describes fibrous inflammation?
Which statement best describes fibrous inflammation?
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What defines the morphological pattern of serous inflammation?
What defines the morphological pattern of serous inflammation?
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Which of the following is NOT a potential location for fibrinous inflammation?
Which of the following is NOT a potential location for fibrinous inflammation?
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What is the primary role of activated macrophages during chronic inflammation?
What is the primary role of activated macrophages during chronic inflammation?
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Which type of cell is primarily responsible for initiating immune responses by stimulating naive T cells?
Which type of cell is primarily responsible for initiating immune responses by stimulating naive T cells?
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Which of the following features is NOT associated with macrophages in chronic inflammation?
Which of the following features is NOT associated with macrophages in chronic inflammation?
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What is a consequence of macrophage activation during chronic inflammation?
What is a consequence of macrophage activation during chronic inflammation?
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What leads to the transformation of monocytes into macrophages during inflammation?
What leads to the transformation of monocytes into macrophages during inflammation?
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What is the primary component that distinguishes chronic ulcers from acute ulcers?
What is the primary component that distinguishes chronic ulcers from acute ulcers?
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What is the defining characteristic of a fistula?
What is the defining characteristic of a fistula?
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Which of the following best describes an abscess?
Which of the following best describes an abscess?
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What distinguishes a sinus from other types of lesions?
What distinguishes a sinus from other types of lesions?
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What type of ulcer is often deep and always associated with scarring?
What type of ulcer is often deep and always associated with scarring?
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What substance is typically associated with the immune response in granulomatous inflammation?
What substance is typically associated with the immune response in granulomatous inflammation?
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Which type of T lymphocyte is primarily associated with cytotoxic activity?
Which type of T lymphocyte is primarily associated with cytotoxic activity?
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What histological feature is indicative of tuberculosis?
What histological feature is indicative of tuberculosis?
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Which type of granulomatous inflammation is triggered by the presence of foreign bodies?
Which type of granulomatous inflammation is triggered by the presence of foreign bodies?
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What is the role of macrophages in the context of granulomatous inflammation?
What is the role of macrophages in the context of granulomatous inflammation?
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Which of the following best describes the nature of substances triggering granulomatous inflammation?
Which of the following best describes the nature of substances triggering granulomatous inflammation?
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In granulomatous inflammation, what type of hypersensitivity is primarily involved?
In granulomatous inflammation, what type of hypersensitivity is primarily involved?
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Which of the following conditions is associated with the formation of Langhans giant cells?
Which of the following conditions is associated with the formation of Langhans giant cells?
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What distinguishes chronic inflammation from acute inflammation?
What distinguishes chronic inflammation from acute inflammation?
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Which of the following is NOT a known cause of chronic inflammation?
Which of the following is NOT a known cause of chronic inflammation?
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Which microscopic feature is characteristic of chronic inflammation?
Which microscopic feature is characteristic of chronic inflammation?
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Granuloma formation is associated with which of the following conditions?
Granuloma formation is associated with which of the following conditions?
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What is a typical systemic effect of chronic inflammation?
What is a typical systemic effect of chronic inflammation?
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What is a major function of activated macrophages during chronic inflammation?
What is a major function of activated macrophages during chronic inflammation?
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In the context of chronic inflammation, what outcome is primarily associated with the activity of macrophages?
In the context of chronic inflammation, what outcome is primarily associated with the activity of macrophages?
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What role do dendritic cells play in the immune response linked to chronic inflammation?
What role do dendritic cells play in the immune response linked to chronic inflammation?
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Which of the following components is NOT typically released by macrophages during chronic inflammation?
Which of the following components is NOT typically released by macrophages during chronic inflammation?
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Which characteristic distinguishes M1 macrophages from M2 macrophages in the context of chronic inflammation?
Which characteristic distinguishes M1 macrophages from M2 macrophages in the context of chronic inflammation?
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What mechanism does coagulase perform in the body?
What mechanism does coagulase perform in the body?
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Which of the following correctly differentiates between acute and chronic ulcers?
Which of the following correctly differentiates between acute and chronic ulcers?
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What is a defining feature of a fistula?
What is a defining feature of a fistula?
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Which statement describes the content found within an abscess?
Which statement describes the content found within an abscess?
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Which characteristic is true of a sinus in relation to chronic inflammation?
Which characteristic is true of a sinus in relation to chronic inflammation?
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Which of the following describes the primary characteristic of serous inflammation?
Which of the following describes the primary characteristic of serous inflammation?
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What type of granulomas are associated with sarcoidosis?
What type of granulomas are associated with sarcoidosis?
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In type IV delayed hypersensitivity, which cells primarily present antigens to activate CD4 T helper cells?
In type IV delayed hypersensitivity, which cells primarily present antigens to activate CD4 T helper cells?
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Which of the following best describes a hallmark of fibrinous inflammation?
Which of the following best describes a hallmark of fibrinous inflammation?
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What is a common infectious organism associated with suppurative inflammation?
What is a common infectious organism associated with suppurative inflammation?
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What type of T lymphocyte interacts primarily with MHC class II molecules?
What type of T lymphocyte interacts primarily with MHC class II molecules?
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What is a defining histological feature of the granulomas seen in tuberculosis?
What is a defining histological feature of the granulomas seen in tuberculosis?
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Which of the following is NOT a known infectious cause of granulomatous inflammation?
Which of the following is NOT a known infectious cause of granulomatous inflammation?
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What component is produced by eosinophils to damage parasites?
What component is produced by eosinophils to damage parasites?
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Which of the following best describes the cells that form epithelioid macrophages?
Which of the following best describes the cells that form epithelioid macrophages?
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What role do T lymphocytes play in relation to macrophage activation?
What role do T lymphocytes play in relation to macrophage activation?
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Which factor primarily leads to the formation of giant cells in granulomatosus inflammation?
Which factor primarily leads to the formation of giant cells in granulomatosus inflammation?
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Which of the following is considered a chronic inflammatory response to a foreign body?
Which of the following is considered a chronic inflammatory response to a foreign body?
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Study Notes
Chronic Inflammation
- A prolonged inflammatory response marked by tissue damage and attempted repair, contrasting with acute inflammation's rapid onset.
- Characterized by a balance between persistent stimulus-induced damage and repair efforts seeking to eliminate the damaging agent.
- Involves lymphocytes and macrophages as primary inflammatory cells.
- Progresses insidiously - a gradual, subtle onset.
Causes of Chronic Inflammation
-
Following acute inflammation:
- Progression of acute inflammation, e.g., acute osteomyelitis evolving into chronic osteomyelitis due to abscess formation.
- Presence of indigestible materials, e.g., implanted wood or surgical sutures within a wound.
- Recurrent episodes of acute inflammation, e.g., chronic cholecystitis.
-
Chronic inflammation ab initio:
- Persistent infections caused by organisms like Mycobacterium tuberculosis, Treponema pallidum, or fungi.
- Prolonged exposure to toxic agents, e.g., pneumoconiosis (inhalation of silica, asbestos, or carbon dust).
- Autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE).
- Diseases of unknown etiology, e.g., inflammatory bowel disease.
Microscopic Features of Chronic Inflammation
- Presence of mononuclear cells, primarily macrophages, lymphocytes, and plasma cells.
- Fibrosis, the formation of fibrous connective tissue as a wound-healing response.
Macrophages
- Primary effector cells in chronic inflammation.
- Extravasation of monocytes from the bloodstream facilitated by adhesion molecules and chemical mediators.
- Differentiate into larger macrophages within the inflamed tissue.
Roles of Macrophages
- Activated by cytokines and bacterial endotoxins.
- Phagocytosis and antigen presentation - essential for initiating an immune response.
- Release of various inflammatory mediators, leading to:
- Tissue destruction (e.g., proteases, arachidonic acid metabolites, toxic oxygen metabolites, nitric oxide, coagulation factors, neutrophil chemotactic factors).
- Vascular proliferation (angiogenesis) and fibrosis (e.g., growth factors, cytokines, remodeling collagenase and metalloproteinase).
M1 and M2 Macrophages
- Represent two distinct activation states of macrophages, each with specific functions and roles in inflammation.
Dendritic Cells
- Originate from bone marrow progenitors.
- Circulate in blood as immature precursors, differentiating into various types when settling in specific tissues.
- Act as professional antigen-presenting cells, initiating an immune response by stimulating naïve T cells.
T-Lymphocytes
- Originate in the bone marrow and mature in the thymus.
- Possess T cell receptors (TCR) for antigen recognition.
- Two major types:
- CD4 helper cells: Recognize antigens presented by MHC class II molecules.
- CD8 cytotoxic cells: Recognize antigens presented by MHC class I molecules.
- Require activation by antigen/MHC complexes.
- Release lymphokines (signaling molecules) to modulate macrophage activation and recruitment.
T-Helper Cells
- Play a critical role in orchestrating the immune response, primarily through cytokine production.
B-Lymphocytes
- Originate in the bone marrow.
- Differentiate into memory B cells and plasma cells.
- Plasma cells produce antibodies.
Natural Killer (NK) Cells
- Innate lymphoid cells that lack antigen-specific receptors.
- Contribute to immune defense by killing infected or cancerous cells.
Mast Cells/Basophils
- Least common leukocytes in the blood.
- Migrate to tissues and differentiate into mast cells.
- Participate in allergic reactions and inflammation.
Eosinophils
- Abundant in allergic inflammatory reactions.
- Effective killers of parasites.
- Possess phagocytic activity.
- Release major basic protein (MBP), a toxic compound for parasites that can also contribute to tissue damage.
Granulomatous Inflammation
- A specific form of chronic inflammation characterized by aggregates of macrophages.
- Macrophages assume an epithelium-like appearance, termed epithelioid macrophages, surrounded by a rim of lymphocytes.
- Giant cells, formed by the fusion of macrophages, are also present.
- Occurs in response to persistent, poorly digestible irritants or substances provoking a cell-mediated immune response.
- Aims to contain or eliminate the damaging agent.
Causes of Granulomatous Inflammation
-
Infections (specific types):
- Bacteria: Mycobacterium tuberculosis, Mycobacterium leprae, causative agent of cat scratch disease.
- Spirochaetes: Treponema pallidum (syphilis).
- Fungi: Histoplasma capsulatum (histoplasmosis), Blastomyces dermatitidis (blastomycosis).
- Parasites: Schistosoma species (schistosomiasis), Toxoplasma gondii (toxoplasmosis), Leishmania species (leishmaniasis).
-
Foreign bodies:
- Exogenous: Splinters, sutures, graft materials.
- Endogenous: Keratin, hair shafts in pilonidal sinus.
-
Response to tumors.
-
Metal/dust:
- Berylliosis.
- Silicosis.
-
Unknown etiology:
- Sarcoidosis.
- Crohn's disease.
Granulomatous Inflammation - Infectious Causes
Bacteria: M. tuberculosis, M. leprae, cat scratch disease. Spirochaetes: T. pallidum. Fungi: H. capsulatum, B. dermatitidis. Parasites: Schistosoma species, T. gondii, Leishmania species.
Tuberculosis
- Type IV hypersensitivity reaction.
- Microscopic features in lungs and lymph nodes:
- Caseating granuloma with central necrosis.
- Epithelioid macrophages and Langhans giant cells.
- T-helper cells within the granuloma.
- Occasional plasma cells.
- Peripheral rim of suppressor T cells and fibroblasts.
- Detection methods:
- Ziehl-Neelsen stain.
- Culture.
- Fluorescent staining with auramine.
- Polymerase chain reaction (PCR).
Sarcoidosis
- Granulomatous condition of unknown etiology.
- Predominant in young adults and more prevalent in Black individuals.
- Can affect various tissues.
- Non-caseating, "naked" granulomas without central necrosis.
- Characteristic findings:
- Schaumann bodies: Concentric calcifications (calcium oxalate crystals).
- Asteroid bodies: Star-shaped inclusions within giant cells.
Type IV Delayed Hypersensitivity
- Involves interactions between CD4 T helper cells and macrophages.
- Macrophages present antigens via MHC II to CD4 helper cells, activating them.
- Activated T cells release cytokines like IL-2 and IFN-γ, contributing to the response in:
- Tuberculosis.
- Fungal infections.
- Sarcoidosis.
Hypersensitivity Reactions
- Immune responses that are exaggerated or harmful to the host.
Morphologic Patterns in Acute and Chronic Inflammation
-
Serous inflammation: Accumulation of thin fluid derived from blood serum or mesothelial lining.
- Effusion:
- Peritoneal.
- Pleural.
- Pericardial.
- Skin blisters:
- Viral infections.
- Burns.
- Effusion:
-
Fibrinous inflammation: Accumulation of fluid and fibrin due to increased vessel permeability.
- Common in serosal linings (pericardium, peritoneum, pleura).
- May resolve via fibrinolysis.
-
Suppurative inflammation (purulent inflammation): Localized proliferation of pus-forming organisms.
- Associated with bacteria like Staphylococcus aureus, containing coagulase that traps bacteria and neutrophils in fibrin, localizing the infection.
- Cellulitis: Spreading bacterial infection of subcutaneous tissue, often occurring after skin trauma.
Abscess
- Localized collection of pus containing:
- Dead and degenerate leukocytes, primarily neutrophils.
- Dead and degenerate host tissue cells.
- Edema fluid.
- Dead microorganisms.
Ulcer
- Local defect in an epithelial surface caused by shedding of dead epithelial cells.
- Found in skin and mucosal surfaces, e.g., peptic ulcer.
- Distinguished from erosions by the extent of tissue loss.
Ulcer Types
-
Acute ulcers: Loss of the full thickness of epithelium.
- May or may not be associated with scarring at the base.
-
Chronic ulcers: Typically deep penetrating.
- Always associated with scarring at the base.
Sinus
- Tract lined by granulation tissue that connects a chronically inflamed cavity to a body surface.
- Example: Sinuses associated with osteomyelitis, pilonidal sinus.
Fistula
- Track open at both ends, establishing abnormal communication between two surfaces.
- Example: Gastrointestinal fistula in Crohn's disease.
Chronic Inflammation
- Prolonged inflammation lasting weeks or months.
-
Causes:
- Persistent damaging stimulus or recurrent episodes of acute inflammation.
- Indigestible material (surgical sutures or wood), recurrent acute episodes (chronic cholecystitis).
- Examples of persistent infections include Mycobacterium tuberculosis, Treponema pallidum, and fungi.
- Prolonged exposure to toxic agents like silica, asbestos, or carbon dust can cause pneumoconiosis.
- Autoimmune diseases such as rheumatoid arthritis and SLE can also lead to chronic inflammation.
- Diseases of unknown aetiology like inflammatory bowel disease.
-
Features:
- Dominated by mononuclear cells including macrophages, lymphocytes, and plasma cells.
- Characterized by fibrosis (scarring) due to the deposition of collagen and other extracellular matrix components.
Macrophages
- Key effector cells in chronic inflammation.
- Derived from monocytes that extravasate from the blood.
-
Role:
- Activated by cytokines and bacterial endotoxins.
- Phagocytosis of debris and microorganisms.
- Professional antigen-presenting cells, initiating immune responses.
- Release inflammatory mediators that contribute to tissue destruction, vascular proliferation (angiogenesis), and fibrosis.
M1 and M2 Macrophages
- M1 macrophages: Pro-inflammatory, release pro-inflammatory cytokines, involved in tissue destruction and immune defense.
- M2 macrophages: Anti-inflammatory, release anti-inflammatory cytokines, promote tissue repair and resolution of inflammation.
Dendritic cells
- Derived from bone marrow progenitors.
- Circulate in the blood and settle in tissues, where they differentiate.
- Professional antigen-presenting cells, initiating immune responses by stimulating naive T cells.
- Different types exist based on location, such as Langerhans cells in the skin.
T-Lymphocytes
- Produced in the bone marrow and mature in the thymus.
- Essential for adaptive immune responses.
-
Types:
- CD4 helper cells: Recognize antigens presented by MHC class II molecules on antigen-presenting cells, releasing cytokines to regulate other immune cells.
- CD8 cytotoxic cells: Recognize antigens presented by MHC class I molecules on infected or cancerous cells, eliminating them.
- Activation of T cells requires binding to the antigen/MHC complex.
- Release lymphokines, which play a critical role in immune regulation.
T-helper cells
- TH1 cells: Promote cell-mediated immunity by activating macrophages and cytotoxic T cells, important in eliminating intracellular pathogens like Mycobacterium tuberculosis.
- TH2 cells: Promote humoral immunity by stimulating B cells to produce antibodies, essential for combating extracellular pathogens.
B-lymphocytes
- Produced in the bone marrow.
- Differentiate into either memory B cells or plasma cells.
- Plasma cells produce antibodies that target specific antigens.
Natural Killer (NK) Cells
- Part of the innate immune system.
- Kill virus-infected cells and tumor cells without prior sensitization.
- Release cytotoxic granules containing perforin and granzyme, which induce apoptosis in target cells.
Mast cells/Basophils
- Basophils are the least common leukocytes in blood and migrate into tissue to become mast cells.
- Release histamine and other inflammatory mediators involved in allergic reactions and parasitic infections.
Eosinophils
- Important in allergic reactions and parasitic infections.
- Effective killers of parasites through cytotoxic granule release.
- Phagocytic and release major basic protein (MBP), which is toxic to parasites and contributes to tissue damage.
Granulomatous Inflammation
- Specific form of chronic inflammation characterized by the formation of granulomas.
- Granuloma: A cluster of macrophages, epithelioid macrophages, and giant cells surrounded by a rim of lymphocytes.
- Caused by poorly digestible agents that trigger a cell-mediated immune response.
- Aimed at controlling or removing the damaging agent.
-
Causes:
-
Infections:
- Bacteria: Tuberculosis, leprosy, cat scratch disease.
- Spirochaetes: Syphilis.
- Fungi: Histoplasmosis, blastomycosis.
- Parasites: Schistosomiasis, toxoplasmosis, leishmaniasis.
-
Foreign bodies:
- Exogenous: splinters, sutures, graft materials.
- Endogenous: keratin, hair shafts (pilonidal sinus).
- Response to tumors.
-
Metal/dust:
- Berylliosis
- Silicosis
-
Unknown aetiology:
- Sarcoidosis
- Crohn's disease.
-
Infections:
Granulomatous Inflammation-Infectious Causes
- Bacteria: Tuberculosis, Leprosy, Cat Scratch Disease.
- Spirochaetes: Syphilis.
- Fungi: Histoplasmosis, Blastomycosis.
- Parasites: Schistosomiasis, Toxoplasmosis, Leishmaniasis.
Tuberculosis
- Caused by Mycobacterium tuberculosis.
- Type IV hypersensitivity reaction.
-
Histological features:
- Caseating granuloma with central necrosis.
- Epithelioid macrophages and Langhans giant cells.
- T-helper cells within the granuloma.
- Occasional plasma cells.
- Peripheral rim of suppressor T cells and fibroblasts.
- Diagnostic methods: - Ziehl-Neelsen (ZN) stain for acid-fast bacilli. - Culture for Mycobacterium tuberculosis. - Fluorescent staining with auramine. - Polymerase chain reaction (PCR) for detection of M. tuberculosis DNA.
Sarcoidosis
- Granulomatous condition of unknown aetiology.
- Affects young adults, with higher prevalence in blacks than whites.
- Can affect any tissue.
-
Histological features:
- Non-caseating 'naked' granulomas.
- Schaumann bodies (concentric calcification).
- Asteroid bodies (stellate inclusions).
Type IV Delayed Hypersensitivity
- Immune response mediated by CD4 T-helper cells and macrophages.
- Macrophages present antigens to CD4 helper cells via MHC II, activating them.
- Activated T cells release cytokines like IL-2 and IFN-γ, leading to macrophage activation and inflammation.
-
Examples:
- Tuberculosis
- Fungal infections
- Sarcoidosis
Morphological Patterns in Acute and Chronic Inflammation
-
Serous inflammation: Accumulation of thin fluid derived from blood serum or secretion of mesothelial lining.
- Effusion (pericardial, pleural, peritoneal)
- Skin blisters (viral infection, burn)
-
Fibrinous inflammation: Accumulation of fluid and fibrin due to increased vascular permeability.
- Common locations: Pericardium, peritoneum, pleura.
- Fibrinolysis (resolution) can remove fibrinous exudates.
-
Suppurative (purulent) inflammation: Localized bacterial proliferation and pus formation.
- Characterized by pus, consisting of dead neutrophils, microorganisms, and debris.
- Examples: skin Abscesses (S.aureus).
-
Ulcers: Local defects in epithelial surfaces.
- Caused by shedding of dead epithelial cells.
- Distinguishing feature from erosions: extent of tissue loss.
- Sinus: Tract lined by granulation tissue leading from a chronically inflamed cavity to a surface.
- Fistula: Track open at both ends, creating abnormal communication between two surfaces.
Chronic Inflammation
- Chronic inflammation is a prolonged inflammatory response, unlike acute inflammation which is a rapid response.
- It is characterized by a balance between tissue damage caused by a persistent stimulus and the body's attempts to repair the damage.
- Chronic inflammation is often preceded by acute inflammation.
Causes of Chronic Inflammation
- Persistent infection: This can be caused by bacteria (e.g., Mycobacterium tuberculosis, Treponema pallidum), fungi, or other organisms.
- Prolonged exposure to toxic agents: Examples include pneumoconiosis caused by silica, asbestos, or carbon dust, and toxic agents found in cigarette smoke.
- Autoimmune diseases: These are conditions where the immune system attacks the body's own tissues, like rheumatoid arthritis and systemic lupus erythematosus (SLE).
- Diseases of unknown aetiology: These include conditions like inflammatory bowel diseases (IBD).
Microscopic Features of Chronic Inflammation
- Mononuclear cells: Macrophages, lymphocytes, and plasma cells are the predominant inflammatory cells in chronic inflammation.
- Fibrosis: The process of scar tissue formation occurs as the body tries to repair damaged tissue.
Macrophages
- Macrophages are the main effector cells in chronic inflammation.
- They arrive at the site of inflammation by migrating from the blood (extravasation of monocytes) and differentiate into larger macrophages.
Role of Macrophages
- Activated by cytokines and bacterial endotoxins.
- Phagocytose and remove debris.
- Antigen-presenting cells that stimulate the immune response.
- Release inflammatory mediators that can cause tissue destruction (proteases, AA metabolites, reactive oxygen species, nitric oxide, clotting factors, neutrophil chemotactic factors) or tissue repair (growth factors, cytokines, collagenases, metalloproteinases).
Dendritic Cells
- Dendritic cells are professional antigen-presenting cells that initiate the immune response by activating T cells.
- They are found in various tissues, including the skin (Langerhans cells).
T-Lymphocytes
- Produced in the bone marrow and mature in the thymus where they develop unique T cell receptors (TCR).
- CD4 helper cells: Interact with MHC Class II molecules on antigen-presenting cells.
- CD8 cytotoxic cells: Interact with MHC Class I molecules on infected cells.
- Activated by binding to specific antigens presented by MHC molecules.
- T cells release lymphokines, which regulate the immune response.
T-Helper Cells
- There are two main types of helper T cells:
- TH1 cells: Promote cell-mediated immunity and activate macrophages.
- TH2 cells: Promote humoral immunity and activate B cells to produce antibodies.
B-Lymphocytes
- B cells differentiate into plasma cells, which produce antibodies.
- Generate memory cells that provide long-term immunity.
Natural Killer (NK) Cells
- NK cells are part of the innate immune system that kill infected or cancerous cells without prior sensitization.
Mast Cells/Basophils
- Mast cells are found in tissues and are involved in allergic and inflammatory reactions.
- Basophils are present in circulation and become mast cells when they migrate into tissues.
Eosinophils
- Eosinophils are important in allergic reactions and parasitic infections.
- They release toxic substances like major basic protein (MBP) that damage parasites and contribute to tissue damage.
Granulomatous Inflammation
- A specific type of chronic inflammation characterized by the formation of granulomas.
- Granulomas are aggregates of macrophages forming epithelioid macrophages surrounded by lymphocytes.
- Giant cells (fused macrophages with multiple nuclei) are often present.
- Granulomas are usually formed in response to poorly digestible agents that induce cell-mediated immune responses.
Granulomatous Inflammation - Causes
- Infections: Mycobacterium tuberculosis, leprosy, syphilis, fungal infections (histoplasmosis, blastomycosis), parasites (schistosomiasis, toxoplasmosis, leishmaniasis).
- Foreign body reactions: Exogenous (splinters, sutures) or endogenous (keratin, hair).
- Tumors: Response to the presence of cancer cells.
- Metal/dust: Berylliosis, silicosis.
- Unknown aetiology: Sarcoidosis, Crohn's disease.
Tuberculosis (TB)
- Caused by Mycobacterium tuberculosis.
- Type IV hypersensitivity reaction.
- Histological features: Caseating granuloma with central necrosis, epithelioid macrophages and Langhans giant cells, T helper cells, plasma cells, fibroblasts, and suppressor T cells.
- Diagnosis: Ziehl-Neelsen (ZN) staining, culture, fluorescent staining with auramine, PCR.
Sarcoidosis
- Granulomatous condition of unknown cause, affecting young adults, with higher prevalence in black individuals.
- May involve any tissue.
- Non-caseating granulomas.
- Schaumann bodies: Concentric calcifications (calcium oxalate crystals).
- Asteroid bodies: Star-shaped structures.
Type IV Delayed Hypersensitivity
- Involves interactions between CD4 helper T cells and macrophages.
- Macrophages activate CD4 T cells by presenting antigens via MHC class II molecules.
- Activated T cells release cytokines (IL-2 and IFN-γ) that amplify the immune response.
- Important in the pathogenesis of TB, fungal infections, and sarcoidosis.
Morphologic Patterns in Acute and Chronic Inflammation
- Serous inflammation: Accumulation of thin fluid derived from serum or mesothelial secretions.
- Fibrinous inflammation: Accumulation of fluid and fibrin due to increased vascular permeability.
- Suppurative inflammation: Localized proliferation of pus-forming organisms (e.g., Staphylococcus aureus).
- Ulcers: Local defects in epithelial surfaces caused by shedding of dead cells.
- Sinus: Tract lined by granulation tissue connecting a chronically inflamed cavity to a surface.
- Fistula: Abnormal communication between two surfaces created by a tract open at both ends.
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Description
Explore the concepts surrounding chronic inflammation, including its characteristics, causes, and contrasting features with acute inflammation. Understand the roles of lymphocytes and macrophages as well as various stimuli that can lead to chronic inflammatory conditions.
