INFLAMMATION – COMPLETE NOTES (FROM INTRODUCTION TO GRANULOMATOUS
INFLAMMATION)
INTRODUCTION
Inflammation is a protective response of vascularized tissues to harmful stimuli such as infections,
toxins, and tissue necrosis. Its major aims are to eliminate the initial cause of injury, remove necrotic
cells, and initiate tissue repair. Inflammation can be classified into acute and chronic inflammation.
COMPONENTS OF INFLAMMATION
1. Vascular Component: changes in blood vessels including vasodilation and increased vascular
permeability.
2. Cellular Component: migration of leukocytes, mainly neutrophils (in acute inflammation) and
macrophages, lymphocytes, and plasma cells (in chronic inflammation).
PATTERNS OF INFLAMMATION
1. Acute inflammation – rapid onset, short duration, dominated by neutrophils.
2. Chronic inflammation – prolonged duration, dominated by macrophages, lymphocytes, fibroblasts,
with simultaneous inflammation, destruction, and repair.
CARDINAL SIGNS OF ACUTE INFLAMMATION
- Rubor (redness)
- Tumor (swelling)
- Calor (heat)
- Dolor (pain)
- Functio laesa (loss of function)
VASCULAR CHANGES IN ACUTE INFLAMMATION
1. Vasodilation – leads to increased blood flow.
2. Increased vascular permeability – causes protein-rich exudate to escape.
3. Stasis – slowing of blood flow allowing leukocytes to marginate.
ROLE OF LYMPHATICS IN INFLAMMATION
Lymphatic vessels drain edema fluid, leukocytes, and debris from inflamed sites. Lymph nodes act as
filters and sites of immune activation.
CELLULAR EVENTS IN ACUTE INFLAMMATION
1. Margination and Rolling – mediated by selectins.
2. Adhesion – mediated by integrins.
3. Transmigration (diapedesis) – through endothelial gaps.
4. Chemotaxis – movement toward chemotactic agents such as C5a, LTB4, and bacterial products.
5. Phagocytosis – recognition, engulfment, and killing of microbes via ROS, RNS, and lysosomal
enzymes.
MEDIATORS OF INFLAMMATION
A. Vascular Mediators
- Histamine: vasodilation, increased permeability.
- Serotonin: vasoconstriction.
- Bradykinin: vasodilation, pain.
- Prostaglandins: vasodilation, fever, pain.
- Leukotrienes: increased permeability, chemotaxis.
B. Cellular Mediators
- Cytokines (IL-1, TNF): fever, leukocyte recruitment.
- Chemokines: leukocyte migration.
- Complement fragments (C3a, C5a): anaphylatoxins, chemotaxis.
MORPHOLOGICAL PATTERNS OF ACUTE INFLAMMATION
1. Serous inflammation – watery exudate.
2. Fibrinous inflammation – fibrin-rich exudate.
3. Purulent (suppurative) inflammation – pus formation, abscess.
4. Ulcers – necrosis on epithelial surfaces.
INTRODUCTION TO CHRONIC INFLAMMATION
Chronic inflammation is a prolonged inflammatory response lasting weeks to years, characterized by
simultaneous inflammation, tissue destruction, and repair. It arises:
1. Following acute inflammation.
2. As a response to persistent stimuli.
3. De novo as low-grade inflammation.
CAUSES OF CHRONIC INFLAMMATION
1. Persistent infections (e.g., Mycobacterium tuberculosis, viruses).
2. Immune-mediated diseases (autoimmune diseases, IBD).
3. Prolonged exposure to toxic substances (silica, lipids).
MORPHOLOGY OF CHRONIC INFLAMMATION
- Infiltration by mononuclear cells: macrophages, lymphocytes, plasma cells.
- Tissue destruction due to persistent injury.
- Healing by connective tissue (fibrosis and angiogenesis).
CELLS OF CHRONIC INFLAMMATION
1. MACROPHAGES
Derived from monocytes; central to chronic inflammation.
Functions:
- Phagocytosis.
- Antigen presentation.
- Cytokine production.
- Tissue repair and fibrosis.
PATHWAYS OF MACROPHAGE ACTIVATION
A. Classical (M1) Activation – induced by IFN-γ, endotoxin.
Functions: microbicidal activity, ROS, RNS, inflammation.
B. Alternative (M2) Activation – induced by IL-4, IL-13.
Functions: tissue repair, growth factor secretion, collagen synthesis.
2. LYMPHOCYTES
Interact bidirectionally with macrophages.
CD4+ T-cell Subsets:
- TH1: produce IFN-γ → activate macrophages (M1).
- TH2: produce IL-4, IL-5, IL-13 → activate macrophages (M2), recruit eosinophils.
- TH17: recruit neutrophils and monocytes.
B lymphocytes differentiate into plasma cells that produce antibodies.
3. EOSINOPHILS
Prominent in IgE-mediated reactions and parasitic infections.
Recruited by eotaxin.
Contain major basic protein (MBP) toxic to parasites and host tissues.
4. MAST CELLS
Found in connective tissues; involved in acute and chronic inflammation.
Express high-affinity IgE receptors.
IgE + antigen crosslinking → degranulation → release of histamine and AA metabolites.
Responsible for anaphylaxis and allergic reactions.
GRANULOMATOUS INFLAMMATION
A distinctive form of chronic inflammation characterized by granulomas—aggregates of epithelioid
macrophages surrounded by lymphocytes.
FEATURES:
- Activated macrophages become epithelioid cells.
- Can form multinucleated giant cells.
- TH1 cells release IFN-γ → macrophage activation.
- May show central necrosis (caseous necrosis in TB).
CAUSES:
- Infections: TB, leprosy, syphilis, fungi, schistosomiasis.
- Immune diseases: sarcoidosis, Crohn disease.
- Foreign bodies.
TYPES OF GRANULOMAS
1. Foreign Body Granulomas – caused by inert materials (sutures, talc); minimal immune response.
2. Immune Granulomas – due to persistent antigens; TH1-mediated; prototype = tuberculosis with
caseous necrosis.