108 Questions
In hypersensitivity reactions, which type involves IgE?
Type I
Which type of hypersensitivity reaction is characterized by T cell-mediated damage?
Type IV
What type of hypersensitivity reaction is associated with Th2 cytokine release?
Type IVb
Which of the following is an example of a Type IVc hypersensitivity reaction?
SJS/TEN
What is a characteristic of Type IVd hypersensitivity reactions?
Th17-mediated neutrophilic inflammation
In a Type III hypersensitivity reaction, which type of antibodies are involved?
IgG, IgM
What is the primary mechanism of Type I hypersensitivity reactions?
Mast-cell mediated – acute recruitment of basophils, eosinophils
Which disease is likely to be a combination of type IVa and type IIa hypersensitivity reactions?
Type 1 diabetes
What is the primary mechanism of Type IIa hypersensitivity reactions?
Antibody-mediated cytotoxic reactions
Which of the following diseases is likely to involve type IVc hypersensitivity reactions?
Multiple Sclerosis
What is the primary mechanism of Type IIb hypersensitivity reactions?
Antibody-mediated ligand-receptor interactions
What is a common feature of many hypersensitivity reactions?
Involvement of multiple types of hypersensitivity
What is the main characteristic of hypersensitivity reactions?
An excessive and/or pathogenic immune response to either foreign or self antigens
What is the other name for Type I hypersensitivity?
Immediate hypersensitivity
How many types of hypersensitivity reactions were classified in 1963?
4
What type of hypersensitivity reaction is characterized by T-cell mediated reactions?
Type IV
What is the primary mediator of Type I hypersensitivity reactions?
IgE
What type of hypersensitivity reaction is characterized by immune-complex reactions?
Type III
Which type of hypersensitivity reaction involves the activation of mast cells with IgE and Th2 cytokines?
Type I
What is the result of the binding of antibodies to a cell component or a matrix component in Type II hypersensitivity?
All of the above
What is the characteristic time course of symptoms for Type I hypersensitivity reactions?
Rapid - minutes to < 2 days
What is the primary mechanism of tissue damage in Type III hypersensitivity?
Formation of antigen-antibody complexes
Which type of hypersensitivity reaction is characterized by the activation of T cells and the recruitment of eosinophils and basophils?
Type IV
What is the typical outcome of the late-phase response in Type I hypersensitivity?
Airway obstruction
Which type of hypersensitivity reaction involves the binding of antibodies to self-antigens?
Type II
What is the primary role of eosinophils in the late-phase response of Type I hypersensitivity?
Releasing proteolytic enzymes
Which type of hypersensitivity reaction is characterized by the formation of immune complexes?
Type III
What is the typical time course of the late-phase response in Type I hypersensitivity?
2-12 hours
What is the typical outcome of the deposition of immune complexes in areas of high pressure or filtration?
Fibrinoid necrosis of blood vessels
What is the role of Th cells in Type IV Hypersensitivity Reactions?
They play a major role in the pathogenesis
What is the typical time frame for the development of Type IV Hypersensitivity Reactions?
Months to years
What is the characteristic histopathological feature of Type III Hypersensitivity Reactions?
Fibrinoid necrosis of assorted blood vessels
What is the role of complement in Type III Hypersensitivity Reactions?
It plays a large role in the tissue damage
What is the characteristic feature of the immune complexes that form in Type III Hypersensitivity Reactions?
They are insoluble and stimulate robust inflammation
What type of hypersensitivity reaction is characterized by granuloma formation and a Th1 response?
Type IVa Hypersensitivity Reaction
What is the typical outcome of vasculitis in Type III Hypersensitivity Reactions?
The vessel is occluded
What is a common characteristic of chronic inflammation?
It lasts weeks, months, or years
What is a risk factor for a wide range of diseases?
Visceral obesity
What is a characteristic of granulomatous inflammation?
It is a type of chronic inflammation
What is a difference between chronic and acute inflammation?
Chronic inflammation lasts longer
What is a common underlying cause of chronic inflammation?
All of the above
What is a consequence of visceral obesity?
Increased risk of diabetes
What is a characteristic of wound healing?
It involves both inflammation and tissue repair
What is a type of disease that can have a chronic inflammatory component?
All of the above
What is the main purpose of granuloma formation?
To wall off an inflammatory stimulus
What type of immune response is elicited in immune granulomas?
Cell-mediated immune response
What is characteristic of the macrophages in a granuloma?
They resemble epithelial cells
What is a giant cell in the context of a granuloma?
A fusion of multiple macrophages
What is a characteristic of chronic inflammation in the context of granulomas?
Chronic inflammation with formation of granulomas
What is a common cause of granuloma formation?
Both infectious and autoimmune causes
What is the role of T-cells in immune granulomas?
They recognize and respond to antigens
What is the result of the activation of macrophages in immune granulomas?
Further antigen presentation and inflammation
What is a potential consequence of excessive lipid build-up in adipocytes?
Increased production of IL-6 and TNF-alpha
Which type of cells predominate in chronic inflammatory responses?
Macrophages and lymphocytes
What is a consequence of chronic inflammation in the lungs?
Impaired gas exchange and restricted lung movement
What is an example of an endogenous toxin that can cause chronic inflammation?
Oxidized lipids
What is a characteristic of autoimmune diseases?
They result from an inappropriate immune response over a long period of time
What is a consequence of chronic inflammation in tissues?
Replacement of damaged cells with fibrotic tissue
What is a characteristic of allergic diseases?
They result from an excessive immune response to exogenous allergens
What is a potential consequence of chronic inflammation in adipocytes?
Insulin resistance and type II diabetes
What is the primary function of platelets during the hemostasis phase of healing?
To form a blood clot and stop bleeding
What type of cells are particularly implicated in chronic inflammation?
Cytotoxic T-cells
What is the term for the redundant, inflamed synovium that forms in joints during chronic inflammation?
Pannus
What is the term for the process of blood extravasation into a tissue, followed by platelet activation and blood coagulation?
Hemostasis
What type of cells can form lymphatic nodule-appearing regions in areas of chronic inflammation?
Plasma cells, macrophages, and lymphocytes
What is the primary difference between healing and scarring?
Healing results in the restoration of normal tissue function, while scarring results in the formation of non-functional tissue
What is the typical outcome of frustrated phagocytosis?
Production of free radicals and proteases
What is a characteristic feature of caseating granulomas?
Necrotic core of caseous cellular debris
What is the primary site of granuloma formation in tuberculosis?
Lungs
What is the typical outcome of chronic inflammation?
Formation of granulomas
What is the typical spread of tuberculosis in the body?
Virtually any organ in the body
What is the term for the necrotic core of cellular debris in caseating granulomas?
Caseous
Which of the following can lead to the production of IL-6 and TNF-alpha by the adipocyte?
Excessive lipid build-up
What type of cells predominate in chronic inflammation?
Macrophages and lymphocytes
What is a consequence of chronic inflammation in the respiratory system?
Thickening of the respiratory membrane and development of granulomas
What is a common underlying cause of chronic inflammation?
Prolonged exposure to toxins
What is a characteristic of chronic inflammation?
Persistent inflammation with tissue damage and repair
What is a consequence of visceral obesity?
Increased risk of chronic inflammation
What is a characteristic of granulomatous inflammation?
Formation of granulomas
What is the main purpose of granuloma formation?
To contain and isolate foreign substances or microorganisms
What is the primary function of classically-activated macrophages?
To recruit other leukocytes and damage pathogens
What is the role of alternatively-activated macrophages in tissue repair?
To promote angiogenesis and fibrosis
What is the role of macrophages in chronic inflammation?
To recruit other leukocytes and damage pathogens
What is the primary function of Langerhans cells?
To present antigens to T-cells
What is the role of free radicals in macrophage function?
To destroy bacteria and remove cellular debris
What is the role of cytokines in macrophage function?
To recruit other leukocytes and damage pathogens
What is the role of macrophages in the resolution of inflammation?
To suppress inflammation and resolve tissue damage
What is the primary function of dendritic cells?
To present antigens to T-cells
What is the primary function of platelets during the hemostasis phase of wound healing?
To form a blood clot and stop bleeding
Which type of cells are particularly implicated in chronic inflammation and are recruited to sites of chronic inflammation by macrophages?
Cytotoxic T-cells
What is the term for the redundant, inflamed synovium that forms in joints during chronic inflammation?
Pannus
During the process of wound healing, what is the term for the formation of new blood vessels through the proliferation of endothelial cells?
Angiogenesis
What is the term for the structure that forms when plasma cells, macrophages, and lymphocytes aggregate in an area of chronic inflammation?
Tertiary lymphoid organ
During the process of wound healing, what is the primary function of vasodilation?
To allow for the delivery of oxygen and nutrients to the wound site
What is the main characteristic of the necrotic core in a caseating granuloma?
It is composed of a cheesy, amorphous material with no distinct cellular structures.
What is the result of frustrated phagocytosis in foreign-body granulomas?
Production of free radicals and proteases that can damage extracellular matrix and viable cells.
What is the primary location of granulomas in tuberculosis?
Lung tissue
What type of granuloma is characterized by a necrotic core surrounded by epitheloid macrophages and lymphocytes?
Caseating granuloma
What is the role of macrophages in granuloma formation?
To surround and isolate the foreign body or antigen.
What is the characteristic feature of chronic inflammation in the context of granulomas?
The formation of granulomas around a foreign body or antigen.
What is the primary function of giant cells in a granuloma?
To perform the 'walling-off' function of a granuloma
What is the characteristic of the adaptive immune system involved in immune granulomas?
It involves a cell-mediated immune response
What is the net result of chronic inflammation in the context of granulomas?
Replacement of normal tissue by fibrosis
What is the role of IFN-gamma in immune granulomas?
It contributes to the activation of macrophages
What is the characteristic of macrophages in a granuloma?
They resemble epithelial cells
What is the type of hypersensitivity reaction characterized by granuloma formation and a Th1 response?
Type IV hypersensitivity
What is the role of T-cells in immune granulomas?
They produce IL-2 and IFN-gamma
What is the characteristic of the inflammatory stimulus in immune granulomas?
It is difficult to eradicate or it elicits a Th1 +/- Th17 response
Study Notes
Hypersensitivity Reactions - Overview
- Hypersensitivity reactions are excessive and/or pathogenic immune responses to foreign or self-antigens.
- Classified into four types: I, II, III, and IV.
Hypersensitivity Reactions - Classification
- Type I (IgE-mediated hypersensitivity):
- Immediate hypersensitivity reaction
- Involves mast cells, basophils, and eosinophils
- Examples: anaphylaxis, angioedema, urticaria (hives), asthma, allergic rhinitis
- Type II (antibody-mediated cytotoxic reactions):
- Antibodies bind to cell surface or matrix components
- Examples: immune destruction of RBCs or platelets, rheumatic fever
- Type III (immune-complex reactions):
- Immune complexes deposit in tissues, leading to inflammation
- Examples: lupus, vasculitis, renal glomerular disorders
- Type IV (delayed-type hypersensitivity):
- T-cell-mediated reactions
- Examples: granulomatous disease, T1DM, MS
- Subtypes: IVa, IVb, IVc, and IVd
Type I Hypersensitivity - Pathogenesis
- Two phases: immediate and late-phase responses
- Immediate response: mast cell degranulation, edema, and smooth muscle contraction
- Late-phase response: recruitment of basophils and eosinophils, leading to tissue damage
Type II Hypersensitivity
- Antibodies bind to cell surface or matrix components
- Activation of complement, antibody-dependent cell-mediated cytotoxicity, and inflammation
- Examples: Graves' disease, myasthenia gravis
Type III Hypersensitivity
- Immune complexes deposit in tissues, leading to inflammation and tissue damage
- Examples: vasculitis, lupus, renal glomerular disorders
Type IV Hypersensitivity
- Extremely variable, depending on the disease
- Examples: granuloma formation (IVa), eosinophilic inflammation (IVb), cytotoxic T-cell activation (IVc), and Th17-mediated inflammation (IVd)
Organizing Hypersensitivity Reactions
- Are antibodies involved? (IgE, IgG, IgM)
- Are T-cells thought to be the major pathologic players?
- Is there a particular Th subtype involved? (Th1, Th2, Th17)
- Time course of symptoms: rapid (minutes to <2 days), subacute (days to weeks), or chronic (months to years)
Chronic Inflammation
- Chronic inflammation lasts for weeks, months, or years, characterized by the coexistence of inflammation, tissue injury, and tissue repair.
- Chronic inflammation can result from the inability to resolve acute inflammation, autoimmune disease, or continuous damage to an organ or tissue.
Chronic Inflammation and Obesity
- Visceral obesity is a risk factor for various diseases, including diabetes, atherosclerosis, metabolic syndrome, and cancer.
- Excessive lipid buildup in adipocytes can stress them, leading to the production of reactive oxygen species (ROS).
- Free fatty acids at high concentrations can bind to pattern recognition receptors (PAMP-R) within adipocytes, leading to the production of pro-inflammatory cytokines IL-6 and TNF-alpha, which contribute to insulin resistance and eventually type II diabetes.
Causes of Chronic Inflammation
- Persistent infections can lead to chronic inflammation, characterized by the predominance of macrophages and lymphocytes, replacement of parenchymal cells with fibrotic tissue, and impaired tissue function.
- Immune-mediated inflammatory diseases, such as autoimmune and allergic diseases, can also cause chronic inflammation.
- Prolonged exposure to toxins, either exogenous (e.g., silica) or endogenous (e.g., VEGF, NO), can also contribute to chronic inflammation.
Chronic Inflammation and Lymphocytes
- Cytotoxic T-cells are particularly implicated in chronic inflammation, recruited to sites of inflammation by macrophages that continue to respond to the inflammatory stimulus.
- Plasma cells may be recruited to inflamed areas, forming lymphatic nodule-appearing regions known as tertiary lymphoid organs, prominent in some autoimmune diseases (e.g., rheumatoid arthritis).
Healing and Scarring
- The healing process involves phases, including hemostasis, inflammation, proliferation, and remodeling.
- Chronic inflammation can lead to the replacement of normal tissue with fibrosis, resulting in scarring.
Granuloma Formation
- Granulomas are an attempt by lymphocytes and macrophages to "wall off" an inflammatory stimulus, characterized by a microscopic aggregation of macrophages transformed into epithelium-like cells, surrounded by lymphocytes and occasionally plasma cells.
- Granuloma-causing conditions include tuberculosis, leprosy, syphilis, sarcoidosis, and Crohn's disease.
- Immune granulomas involve the adaptive immune system, with a cell-mediated immune response (Type IV hypersensitivity) elicited in response to an inflammatory stimulus.
Tuberculosis
- Tuberculosis was once the leading cause of death, characterized by the formation of large, widely-disseminated granulomas that destroy lung tissue and lead to pleural effusions.
- The pathological hallmark of tuberculosis is the caseating granuloma, characterized by epitheloid macrophages and lymphocytes surrounding a necrotic core of caseous cellular debris.
Chronic Inflammation
- Excessive lipid buildup can stress adipocytes, leading to the production of IL-6 and TNF-alpha, which can cause insulin resistance and eventually type II diabetes.
- Chronic inflammation can lead to the replacement of parenchyma with fibrotic tissue, which can impair gas exchange and restrict lung movement.
Causes of Chronic Inflammation
- Persistent infections can lead to chronic inflammation, characterized by the predominance of macrophages and lymphocytes.
- Immune-mediated inflammatory diseases, such as autoimmune and allergic diseases, can cause chronic inflammation.
- Prolonged exposure to toxins, both exogenous and endogenous, can lead to chronic inflammation.
The Role of Macrophages in Chronic Inflammation
- Macrophages play a crucial role in chronic inflammation, with two main functions:
- Pro-inflammatory macrophage functions: destroying bacteria, producing free radicals, secreting cytokines and growth factors, and recruiting other leukocytes.
- Macrophage functions of particular interest in chronic inflammation: destroying bacteria, secreting cytokines and growth factors, and contributing to fibrosis and angiogenesis.
Macrophage Responses in Chronic Inflammation
- Macrophage responses can evolve as inflammation and damage continue in a tissue.
- Two main types of macrophage activation:
- Classically-activated macrophages: recruit other leukocytes, damage pathogens, and often damage bystander host cells.
- Alternatively-activated macrophages: promote angiogenesis, fibrosis, and tissue repair.
Repair and Macrophages
- Angiogenesis is a critical step in tissue repair, involving vasodilation, pericyte separation, endothelial migration, and proliferation of endothelial cells.
- Fibrosis and chronic inflammation are closely linked, with macrophages playing a key role in promoting fibrosis.
Chronic Inflammation and Lymphocytes
- Cytotoxic T-cells are particularly implicated in chronic inflammation, recruited to sites of inflammation by macrophages that continue to respond to the inflammatory stimulus.
- Plasma cells may be recruited to inflamed areas, forming lymphatic nodule-appearing regions in an area of chronic inflammation.
Granulomas and Chronic Inflammation
- A granuloma is an attempt by lymphocytes and macrophages to "wall off" an inflammatory stimulus.
- Granuloma-causing conditions include tuberculosis, leprosy, syphilis, sarcoidosis, and Crohn's disease.
- Immune granulomas involve the adaptive immune system, with a cell-mediated immune response elicited.
Chronic Inflammation and Healing
- The steps of healing include hemostasis, inflammation, proliferation, and remodeling.
- Chronic inflammation can lead to scarring, with the formation of fibrotic tissue replacing normal tissue.
- Granulomas can form in response to chronic inflammation, with macrophages and lymphocytes aggregating to "wall off" the inflammatory stimulus.
Classification of hypersensitivity reactions including type I, II, III, and IV. Understanding the time course, pathophysiologic mechanism, and representative disorders.
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