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Pathology – Innate Immunity
innate immunity
Epithelial interfaces
Epithelial surfaces serve as the primary entry points for infections into the body. A continuous epithelial layer establishes a physical barrier to infection. The acidic pH of the skin and the presence of fatty acids in sebum suppress microbial proliferation.
The gastrointestinal system contains gastric acid, pancreatic enzymes, mucosal IgA, and normal colonic flora that function to inhibit the onset of infection. The respiratory tract produces mucus to capture organisms, while cilia facilitate their passage to the throat for swallowing. Continuous urination along the urinary system inhibits microbial adherence to the urothelium.
Phagocytes
Organisms penetrating epithelial surfaces meet tissue macrophages that identify infections and recruit neutrophils to the location
Macrophages and neutrophils are phagocytic cells that engulf bacteria through phagocytosis, forming a phagosome
The phagosome then merges with cytoplasmic lysosomes, which harbor enzymes and reactive oxygen species that eliminate the bacterium. Phagocytes identify species by pattern recognition receptors, such as mannose receptors, Toll-like receptors, and Nod-like receptors.
Acute-phase proteins
Cytokines generated by phagocytes prompt the liver to swiftly manufacture and discharge acute phase proteins. Mannose-binding lectin identifies microbial surface sugars and undergoes a conformational alteration, enabling it to attach to the protein MASP, thereby forming a complex that activates the complement system.
C-reactive protein attaches to the phosphorylcholine components of microbial lipopolysaccharides, facilitating their phagocytosis by macrophages.
Complement
• A assemblage of circulating proteins that aid the immune system in eliminating pathogens.
• Can be initiated by antibodies attached to a microbe (traditional pathway), automatically activated by bacteria devoid of a regulatory protein found on host cells (alternative pathway), or by mannose-binding protein (lectin pathway). A sequential cascade results in the formation of C3 convertase, an enzyme that cleaves many C3 molecules into C3b.
• Microbes coated with C3b are eliminated through phagocytosis or the membrane assault complex, a polymer of terminal complement components that creates pores in the microbial cell membrane.
• The complement system is stringently regulated to avert unregulated activation. Decay-accelerating factor impedes the binding of C3b to cellular surfaces, while membrane cofactor protein degrades C3b.
innate immunity
Epithelial interfaces
Epithelial surfaces serve as the primary entry points for infections into the body. A continuous epithelial layer establishes a physical barrier to infection. The acidic pH of the skin and the presence of fatty acids in sebum suppress microbial proliferation.
The gastrointestinal system contains gastric acid, pancreatic enzymes, mucosal IgA, and normal colonic flora that function to inhibit the onset of infection. The respiratory tract produces mucus to capture organisms, while cilia facilitate their passage to the throat for swallowing. Continuous urination along the urinary system inhibits microbial adherence to the urothelium.
Phagocytes
Organisms penetrating epithelial surfaces meet tissue macrophages that identify infections and recruit neutrophils to the location
Macrophages and neutrophils are phagocytic cells that engulf bacteria through phagocytosis, forming a phagosome
The phagosome then merges with cytoplasmic lysosomes, which harbor enzymes and reactive oxygen species that eliminate the bacterium. Phagocytes identify species by pattern recognition receptors, such as mannose receptors, Toll-like receptors, and Nod-like receptors.
Acute-phase proteins
Cytokines generated by phagocytes prompt the liver to swiftly manufacture and discharge acute phase proteins. Mannose-binding lectin identifies microbial surface sugars and undergoes a conformational alteration, enabling it to attach to the protein MASP, thereby forming a complex that activates the complement system.
C-reactive protein attaches to the phosphorylcholine components of microbial lipopolysaccharides, facilitating their phagocytosis by macrophages.
Complement
• A assemblage of circulating proteins that aid the immune system in eliminating pathogens.
• Can be initiated by antibodies attached to a microbe (traditional pathway), automatically activated by bacteria devoid of a regulatory protein found on host cells (alternative pathway), or by mannose-binding protein (lectin pathway). A sequential cascade results in the formation of C3 convertase, an enzyme that cleaves many C3 molecules into C3b.
• Microbes coated with C3b are eliminated through phagocytosis or the membrane assault complex, a polymer of terminal complement components that creates pores in the microbial cell membrane.
• The complement system is stringently regulated to avert unregulated activation. Decay-accelerating factor impedes the binding of C3b to cellular surfaces, while membrane cofactor protein degrades C3b.
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Pathology - Inflammation and Healing
Acute inflammation
• A swift, non-specific reaction to cellular damage
. • Coordinated by cytokines generated from damaged cells, such as histamine, serotonin, prostaglandins, leukotrienes, and platelet-activating factor. Cytokines stimulate endothelial cells, resulting in the development of an acute inflammatory exudate including fluid, fibrin, and neutrophils. Severe acute inflammation may result in a localized accumulation of pus within a necrotic cavity (abscess). Acute inflammation may resolve, heal with fibrosis, or advance to chronic inflammation.
Chronic inflammation is a sustained type of inflammation characterized by concurrent tissue damage and attempts at healing.
• May originate from acute inflammation or manifest from the onset.
• Defined by the presence of chronic inflammatory cells, specifically macrophages, lymphocytes, and plasma cells.
• More prone to healing with permanent scarring rather than resolution.
Granulomatous inflammation is a distinct form of chronic inflammation marked by the presence of activated macrophages referred to as epithelioid histiocytes. Collections of epithelioid macrophages are referred to as granulomas. Granulomatous inflammation is linked to foreign substances, chronic infections (such as mycobacteria), and conditions of indeterminate etiology (for instance, sarcoidosis).
Restoration
• The procedure of substituting necrotic and impaired tissue with viable tissue
. • May transpire via regeneration or repair. Regeneration (resolution) substitutes injured cells with identical cell types and represents the optimal outcome. This can only happen if the connective tissue framework is intact and if the tissue possesses regenerative capabilities. Repair initiates with the development of granulation tissue, subsequently transformed into a collagen-dense scar. While the structural integrity is preserved, the functionality of the damaged tissue is compromised.
Acute inflammation
• A swift, non-specific reaction to cellular damage
. • Coordinated by cytokines generated from damaged cells, such as histamine, serotonin, prostaglandins, leukotrienes, and platelet-activating factor. Cytokines stimulate endothelial cells, resulting in the development of an acute inflammatory exudate including fluid, fibrin, and neutrophils. Severe acute inflammation may result in a localized accumulation of pus within a necrotic cavity (abscess). Acute inflammation may resolve, heal with fibrosis, or advance to chronic inflammation.
Chronic inflammation is a sustained type of inflammation characterized by concurrent tissue damage and attempts at healing.
• May originate from acute inflammation or manifest from the onset.
• Defined by the presence of chronic inflammatory cells, specifically macrophages, lymphocytes, and plasma cells.
• More prone to healing with permanent scarring rather than resolution.
Granulomatous inflammation is a distinct form of chronic inflammation marked by the presence of activated macrophages referred to as epithelioid histiocytes. Collections of epithelioid macrophages are referred to as granulomas. Granulomatous inflammation is linked to foreign substances, chronic infections (such as mycobacteria), and conditions of indeterminate etiology (for instance, sarcoidosis).
Restoration
• The procedure of substituting necrotic and impaired tissue with viable tissue
. • May transpire via regeneration or repair. Regeneration (resolution) substitutes injured cells with identical cell types and represents the optimal outcome. This can only happen if the connective tissue framework is intact and if the tissue possesses regenerative capabilities. Repair initiates with the development of granulation tissue, subsequently transformed into a collagen-dense scar. While the structural integrity is preserved, the functionality of the damaged tissue is compromised.
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Pathology - Cellular death
Necrosis is an inadequately regulated kind of cell death characterized by the loss of membrane integrity, resulting in the spilling of cellular contents and an inflammatory reaction.
• Coagulative necrosis is the predominant type, marked by the absence of cell nuclei while maintaining the overall structural integrity. The necrotic tissue appears macroscopically pale and firm.
Liquefactive necrosis results in the total destruction of cellular architecture, transforming it into a mushy, semi-solid mass. This is commonly observed in the brain subsequent to cerebral infarction.
Caseous necrosis is a form of necrosis characterized by dead tissue that macroscopically resembles cream cheese. It can manifest in several diseases, but is predominantly linked to tuberculosis.
• Gangrene denotes necrotic tissues altered by air exposure, leading to desiccation (dry gangrene) or infection (wet gangrene). In cases of critical limb ischaemia, toes that experience blood deprivation typically exhibit dry gangrene.
Apoptosis is a regulated process of cellular demise when no intracellular components are expelled from the dying cell, hence preventing any inflammatory response. Apoptosis can occur naturally, such as in the elimination of cells during embryogenesis and those with DNA damage, or pathologically. Apoptosis can be initiated via two primary mechanisms: the activation of surface death receptors, such as Fas or TNF-α (extrinsic pathway), or through cellular damage (intrinsic pathway). The final outcome is the activation of protease enzymes known as caspases, which deconstruct the cell's cytoplasm and nucleus.
Apoptotic cells undergo shrinkage and fragmentation into apoptotic bodies, each maintaining an unbroken cell membrane. • Apoptotic entities are promptly eliminated by neighboring cells. • Dysregulated apoptosis is believed to play a crucial role in various significant disease mechanisms, especially carcinogenesis.
Necrosis is an inadequately regulated kind of cell death characterized by the loss of membrane integrity, resulting in the spilling of cellular contents and an inflammatory reaction.
• Coagulative necrosis is the predominant type, marked by the absence of cell nuclei while maintaining the overall structural integrity. The necrotic tissue appears macroscopically pale and firm.
Liquefactive necrosis results in the total destruction of cellular architecture, transforming it into a mushy, semi-solid mass. This is commonly observed in the brain subsequent to cerebral infarction.
Caseous necrosis is a form of necrosis characterized by dead tissue that macroscopically resembles cream cheese. It can manifest in several diseases, but is predominantly linked to tuberculosis.
• Gangrene denotes necrotic tissues altered by air exposure, leading to desiccation (dry gangrene) or infection (wet gangrene). In cases of critical limb ischaemia, toes that experience blood deprivation typically exhibit dry gangrene.
Apoptosis is a regulated process of cellular demise when no intracellular components are expelled from the dying cell, hence preventing any inflammatory response. Apoptosis can occur naturally, such as in the elimination of cells during embryogenesis and those with DNA damage, or pathologically. Apoptosis can be initiated via two primary mechanisms: the activation of surface death receptors, such as Fas or TNF-α (extrinsic pathway), or through cellular damage (intrinsic pathway). The final outcome is the activation of protease enzymes known as caspases, which deconstruct the cell's cytoplasm and nucleus.
Apoptotic cells undergo shrinkage and fragmentation into apoptotic bodies, each maintaining an unbroken cell membrane. • Apoptotic entities are promptly eliminated by neighboring cells. • Dysregulated apoptosis is believed to play a crucial role in various significant disease mechanisms, especially carcinogenesis.
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Pathology - Cellular modifications
Atrophy
• A decrease in the dimensions of a tissue or organ.
• Can result from a decrease in cell quantity by death or a loss in cell volume through shrinkage.
• Atrophy can manifest as a natural physiological phenomenon, such as thymic atrophy throughout puberty and ovarian atrophy during menopause. Pathological atrophy examples encompass muscle atrophy resulting from denervation and cerebral atrophy caused by cerebrovascular illness.
Hypertrophy
An augmentation in the dimensions of individual cells.
• As a result of an augmentation of cellular proteins and organelles.
• Observed in organs with terminally differentiated cells that are incapable of proliferation, such as cardiac and skeletal muscle. Examples of physiological hypertrophy encompass the myometrium of the uterus during pregnancy and the musculature of a bodybuilder. Pathological hypertrophy examples encompass left ventricular hypertrophy resulting from hypertension or aortic stenosis.
Hyperplasia
• An augmentation in cellular quantity. Examples of physiological hyperplasia encompass the endometrium and breast lobules in reaction to cyclical estrogen stimulation. Pathological hyperplasia examples include benign prostatic hyperplasia and parathyroid hyperplasia.
Metaplasia
A transformation in which one cellular type is replaced by another. • Considered to arise from progenitor cells differentiating into a novel cell type rather than through direct morphogenesis from one cell type to another. • Predominantly observed in epithelial cells, frequently as a reaction to chronic injury. • Metaplasia is designated based on the newly formed cell type; for instance, a transition from non-squamous to squamous epithelium is referred to as squamous metaplasia. Common locations of squamous metaplasia encompass the endocervix, forming the transformation zone associated with cervical neoplasia, and the bronchi of smokers. Common locations of glandular metaplasia encompass the lower esophagus in certain individuals with reflux illness, resulting in a discernible Barrett's esophagus.
Metaplasia serves as an indicator of chronic epithelial injury that may, in certain instances, progress to epithelial dysplasia and ultimately cancer.
Atrophy
• A decrease in the dimensions of a tissue or organ.
• Can result from a decrease in cell quantity by death or a loss in cell volume through shrinkage.
• Atrophy can manifest as a natural physiological phenomenon, such as thymic atrophy throughout puberty and ovarian atrophy during menopause. Pathological atrophy examples encompass muscle atrophy resulting from denervation and cerebral atrophy caused by cerebrovascular illness.
Hypertrophy
An augmentation in the dimensions of individual cells.
• As a result of an augmentation of cellular proteins and organelles.
• Observed in organs with terminally differentiated cells that are incapable of proliferation, such as cardiac and skeletal muscle. Examples of physiological hypertrophy encompass the myometrium of the uterus during pregnancy and the musculature of a bodybuilder. Pathological hypertrophy examples encompass left ventricular hypertrophy resulting from hypertension or aortic stenosis.
Hyperplasia
• An augmentation in cellular quantity. Examples of physiological hyperplasia encompass the endometrium and breast lobules in reaction to cyclical estrogen stimulation. Pathological hyperplasia examples include benign prostatic hyperplasia and parathyroid hyperplasia.
Metaplasia
A transformation in which one cellular type is replaced by another. • Considered to arise from progenitor cells differentiating into a novel cell type rather than through direct morphogenesis from one cell type to another. • Predominantly observed in epithelial cells, frequently as a reaction to chronic injury. • Metaplasia is designated based on the newly formed cell type; for instance, a transition from non-squamous to squamous epithelium is referred to as squamous metaplasia. Common locations of squamous metaplasia encompass the endocervix, forming the transformation zone associated with cervical neoplasia, and the bronchi of smokers. Common locations of glandular metaplasia encompass the lower esophagus in certain individuals with reflux illness, resulting in a discernible Barrett's esophagus.
Metaplasia serves as an indicator of chronic epithelial injury that may, in certain instances, progress to epithelial dysplasia and ultimately cancer.
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Terminology of pathology
Nomenclature of diseases
Aetiology denotes the fundamental cause of an illness. Diseases with an unclear aetiology are termed idiopathic, cryptogenic, or essential.
Pathogenesis denotes the mechanism via which the etiological agent induces the signs of a disease.
Incidence denotes the quantity of newly diagnosed instances of an illness within a specified timeframe.
Prevalence denotes the aggregate number of disease cases within a community at a specific point in time.
Prognosis refers to the anticipated progression of an illness.
Morbidity refers to the degree to which a patient's overall health is impacted by a condition. •
Mortality indicates the probability of mortality due to a specific disease
.Acute and chronic denote the temporal progression of a disease occurrence. Acute diseases manifest abruptly.
Chronic illnesses typically exhibit a gradual onset and are more prone to a protracted duration.
A syndrome denotes a collection of symptoms and clinical indications that, when present concurrently, indicate a certain underlying cause(s).
Classification of diseases
Genetic disorders are hereditary conditions resulting from a faulty gene, such as cystic fibrosis.
Infectious disorders arise from the invasion of the body by pathogenic microorganisms, such as malaria.
Inflammatory disorders result from excessive activity of inflammatory cells in an organ, such as rheumatoid arthritis.
Neoplastic illness arises from the unregulated proliferation of cells, such as breast cancer.
• Vascular diseases occur as a result of blood vessel disorders, such as ischemic heart disease.
• Metabolic disorders stem from abnormalities in metabolic processes, such as diabetes mellitus.
Degenerative diseases arise from the destruction and/or loss of specialized cells, such as the loss of neurons from the cerebral cortex in Alzheimer's disease. Iatrogenic disease arises from the consequences of medical treatment, such as osteoporosis resulting from prolonged glucocorticoid therapy
. • Congenital disorders are present at birth, while those that arise postnatally are termed acquired diseases.
Nomenclature of diseases
Aetiology denotes the fundamental cause of an illness. Diseases with an unclear aetiology are termed idiopathic, cryptogenic, or essential.
Pathogenesis denotes the mechanism via which the etiological agent induces the signs of a disease.
Incidence denotes the quantity of newly diagnosed instances of an illness within a specified timeframe.
Prevalence denotes the aggregate number of disease cases within a community at a specific point in time.
Prognosis refers to the anticipated progression of an illness.
Morbidity refers to the degree to which a patient's overall health is impacted by a condition. •
Mortality indicates the probability of mortality due to a specific disease
.Acute and chronic denote the temporal progression of a disease occurrence. Acute diseases manifest abruptly.
Chronic illnesses typically exhibit a gradual onset and are more prone to a protracted duration.
A syndrome denotes a collection of symptoms and clinical indications that, when present concurrently, indicate a certain underlying cause(s).
Classification of diseases
Genetic disorders are hereditary conditions resulting from a faulty gene, such as cystic fibrosis.
Infectious disorders arise from the invasion of the body by pathogenic microorganisms, such as malaria.
Inflammatory disorders result from excessive activity of inflammatory cells in an organ, such as rheumatoid arthritis.
Neoplastic illness arises from the unregulated proliferation of cells, such as breast cancer.
• Vascular diseases occur as a result of blood vessel disorders, such as ischemic heart disease.
• Metabolic disorders stem from abnormalities in metabolic processes, such as diabetes mellitus.
Degenerative diseases arise from the destruction and/or loss of specialized cells, such as the loss of neurons from the cerebral cortex in Alzheimer's disease. Iatrogenic disease arises from the consequences of medical treatment, such as osteoporosis resulting from prolonged glucocorticoid therapy
. • Congenital disorders are present at birth, while those that arise postnatally are termed acquired diseases.
