Inflammation and the immune system

Vocabulary flashcards related to inflammation and the immune system.

Acute Inflammation

A rapid and localized response that aims to eliminate the initial cause of cell injury and initiate the repair process.

Benefits of Acute Inflammation

1. Immune Response: Acute inflammation activates immune cells, such as neutrophils and macrophages, to combat pathogens and clear debris.

2. Tissue Repair: Inflammation triggers the release of growth factors and cytokines that promote tissue repair and regeneration.

3. Barrier Function: Inflammation helps isolate and contain pathogens, preventing their spread to other tissues.

Adaptive Immunity: Acute inflammation also primes the adaptive immune response for specific pathogen recognition and memory formation

Chronic Inflammation

A prolonged, systemic inflammatory response that persists over a longer period, potentially causing tissue damage.

Consequences of Chronic Inflammation

1. Tissue Damage: Chronic inflammation can lead to progressive tissue damage and fibrosis, impairing organ function.

2. Autoimmune Diseases: Persistent inflammation may trigger autoimmune reactions, where the immune system attacks healthy tissues.

3. Metabolic Effects: Chronic inflammation contributes to insulin resistance, dyslipidemia, and cardiovascular risk factors.

4. Cancer Risk: Prolonged inflammation is associated with DNA damage, cell mutations, and an increased risk of cancer development.

key component of immune system - blood

1. White Blood Cells (leukocytes): These are the primary cells of the immune system and are categorized into different types, such as neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Each type of white blood cell plays a specific role in the immune response.

Lymph Nodes - part of the lymphatic system

Small bean-shaped structures that filter lymph fluid and trap pathogens.

Tonsils and Adenoids - part of the lymphatic system

Tissues at the back of the throat that help prevent infections entering the body.

Spleen - part of the lymphatic system

Acts as a blood filter, removing old or damaged red blood cells and helping to fight infections.

Peyer's Patches - part of the lymphatic system

Found in the intestines and are part of the gut-associated lymphoid tissue, helping to protect against pathogens in the digestive tract.

Thymus - solid organ - part of the immune system

Located behind the breastbone, it plays a crucial role in the development and maturation of T-lymphocytes (T cells).

appendix - solid organ - part of immune system

1. While traditionally thought of as a vestigial organ, recent studies suggest the appendix may play a role in immune function and maintaining gut health.

Bone Marrow - part of the immune system

Spongy tissue found in the center of bones and is responsible for producing all blood cells, including white blood cells, red blood cells, and platelets.

Roles of immunity - protection against pathogens

Cells, such as T cells, B cells, macrophages, and dendritic cells, that work together to recognize and target specific pathogens.

1. The immune system is equipped with various specialized cells, such as T cells, B cells, macrophages, and dendritic cells, that work together to recognize and target specific pathogens. T cells identify infected cells and destroy them, while B cells produce antibodies that can neutralize pathogens. This immune response involves complex signaling pathways and interactions that lead to the elimination of the invading microorganisms.

role of immune system - isolate and remove foreign substances

1. the immune system has sophisticated mechanisms to detect and handle a wide range of foreign substances. Dendritic cells, for instance, act as sentinels, capturing and presenting foreign antigens to other immune cells for recognition and response. This process helps the immune system differentiate between harmless and harmful substances, facilitating their removal or neutralization.

role of immune system - Immune Surveillance

1. Immune surveillance involves a dynamic process where immune cells constantly survey the body for abnormal or mutated cells, including potential cancer cells. Natural killer (NK) cells, a type of lymphocyte, play a crucial role in detecting and eliminating these aberrant cells before they develop into full-blown tumors. Additionally, cytotoxic T cells can recognize and destroy cancerous cells, contributing to the body's defense against cancer development and progression.

Natural killer (NK) cells

A type of lymphocyte, play a crucial role in detecting and eliminating aberrant cells before they develop into full-blown tumors.

Skin - natural barrier

The outermost layer of the skin acts as a physical barrier, preventing the entry of bacteria, viruses, and other pathogens.

Mucous Membranes - natural barrier

Line various entry points to the body, such as the respiratory tract, gastrointestinal tract, and urogenital tract; produce mucus that traps pathogens and prevents them from entering the body.

Ciliary Activity - natural barrier

Tiny hair-like structures in the respiratory tract that help sweep mucus and trapped pathogens out of the airways.

Cells and secretory molecules - natural barrier

(characteristic of innate immune response)

Specialized cells in various tissues release molecules that create an inhospitable environment for pathogens. For example, the acidic pH of the stomach and urine can kill or inhibit the growth of certain pathogens.

Inflammatory Response (characteristic of innate immune response)

A key component of the innate immune response and is triggered in response to tissue damage, infection, or other threats.

Inflammation is a key component of the innate immune response and is triggered in response to tissue damage, infection, or other threats. During inflammation, blood vessels dilate, allowing immune cells to reach the site of infection or injury quickly. This response helps contain and eliminate pathogens, remove damaged cells, and promote tissue repair.

Innate and Adaptive Immunity Interaction

(characteristic of innate immune response)

While the innate immune system provides immediate, generalized defense against a wide range of threats, it also plays a crucial role in priming and shaping the adaptive immune response. Innate immune cells present antigens to adaptive immune cells, activating them and guiding their specific responses to pathogens.

Inflammatory response state 1

Recognition and Triggering Stage

Specialized immune cells recognize danger signals, such as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), through pattern recognition receptors (PRRs).

1. Recognition and Triggering Stage:

   • At the onset of inflammation, specialized immune cells recognize danger signals, such as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), through pattern recognition receptors (PRRs). This recognition initiates a cascade of events leading to the release of pro-inflammatory mediators like histamines, prostaglandins, and cytokines.

   • The initial vascular changes, including vasodilation and increased vascular permeability, are critical for promoting the influx of immune cells like neutrophils and monocytes to the affected site. These cells play pivotal roles in the elimination of pathogens and damaged cells through phagocytosis and the activation of the adaptive immune response.

Inflammatory response Stage 2

Inflammatory Mediator Release

1. Inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), interleukins, and chemokines, are released by immune cells and contribute to the amplification and propagation of the inflammatory response. These mediators orchestrate the recruitment and activation of additional immune cells, enhancing the body's defense mechanisms.

2. The balance between pro-inflammatory and anti-inflammatory mediators is crucial for ensuring an effective but controlled immune response, preventing excessive tissue damage while still combating the threat.

Inflammatory response stage 3

Immune Cell Activation and Phagocytosis

1. Phagocytic cells, notably neutrophils and macrophages, play key roles in engulfing and destroying pathogens, cellular debris, and foreign particles through phagocytosis. This process not only eliminates the immediate threat but also generates signaling molecules that regulate the immune response and facilitate tissue repair.

2. Concurrently, the activation of adaptive immune cells, particularly T cells and B cells, occurs, leading to a tailored and specific response against the invading pathogens, forming immunological memory for future encounters.

Inflammatory response stage 4

Resolution and Tissue Repair

1. With the threat neutralized and the immune response under control, the resolution phase begins. Anti-inflammatory mediators, including transforming growth factor-beta (TGF-β) and interleukin-10, dampen the inflammatory cascade, promoting the clearance of immune cells and the initiation of tissue repair processes.

2. Tissue repair involves the regeneration of damaged structures through the proliferation of fibroblasts, deposition of collagen, and angiogenesis. This regenerative phase aims to restore normal tissue architecture and function while minimizing scar formation.

Vascular response to inflammation

Promoting the influx of immune cells like neutrophils and monocytes to the affected site.

1. The vascular response in inflammation is characterized by rapid and dynamic changes in blood vessels that help facilitate immune cell recruitment to the site of injury or infection. Key aspects of the vascular response include:

   • Vasodilation: This process involves the relaxation of blood vessel walls, leading to an increase in blood flow to the affected area. Vasodilation is triggered by mediators like histamine and prostaglandins, creating redness and heat characteristic of inflammation.

   • Increased Vascular Permeability: The permeability of blood vessels is enhanced, allowing immune cells and plasma proteins to extravasate or move out of the bloodstream and into the tissues. This increased permeability is crucial for the delivery of immune cells to the site of infection.

   • Formation of Edema: The leakage of fluid from blood vessels due to increased permeability results in the accumulation of fluid in the tissues, causing swelling. Edema helps dilute toxins and provides a fluid environment for immune cells to work effectively.

Cell Mediated response to inflammation

Released by immune cells and contribute to the amplification and propagation of the inflammatory response.

1. Immune cells, particularly neutrophils, monocytes, and macrophages, play central roles in the cell-mediated response to inflammation. These cells are responsible for:

   • Phagocytosis: Engulfing and destroying pathogens, cellular debris, and foreign particles through phagocytosis.

   • Cytokine Production: Releasing signaling molecules such as cytokines and chemokines that regulate inflammation, immune cell recruitment, and the coordination of the immune response.

   • Tissue Repair: Initiating tissue repair processes by secreting growth factors that promote cell proliferation, collagen synthesis, and angiogenesis.

Plasma protein response to inflammation

1. Plasma proteins, including acute-phase proteins, complement proteins, and clotting factors, actively participate in the inflammatory response by:

   • Enhancing Immune Function: Some plasma proteins act as opsonins, marking pathogens for phagocytosis by immune cells. Complement proteins also contribute to the elimination of pathogens through direct lysis and the recruitment of inflammatory cells.

   • Regulating Inflammation: Acute-phase proteins modulate the inflammatory response by promoting or inhibiting immune cell activities and tissue repair processes.

   • Supporting Tissue Repair: Certain plasma proteins are involved in the coagulation cascade, forming blood clots to limit bleeding and provide a scaffold for tissue repair.

Mast cells in the lung and GI tract - role in inflammation

1. Mast cells are tissue-resident immune cells found in the lungs and GI tract that play a pivotal role in the inflammatory response:

   • Activation: Mast cells can be triggered by various stimuli, including heat, chemicals, and immune activation, leading to degranulation.

   • Degranulation: Mast cells release preformed mediators like histamine, proteases, and cytokines upon activation. They also synthesize and release new inflammatory mediators, amplifying the immune response.

   • Plasma Protein Responses: Mast cell degranulation can stimulate the synthesis and release of plasma proteins, further modulating the inflammatory process and contributing to immune activation at the local level.

Purpose of the compliment cascade in inflammation

The complement cascade serves multiple essential purposes in the immune system's defense against pathogens and maintaining overall health. Here are the key purposes of the complement cascade:

pathogen recognition and opsonization

inflammation

direct pathogen killing

clearance of immune complexes

Modulation of Immune Responses

the complement cascade plays a critical role in pathogen recognition, opsonization, inflammation, direct pathogen killing, immune complex clearance, and immune response modulation. Its multifaceted functions are integral to the body's ability to combat infections, maintain immune homeostasis, and protect against a wide range of pathogens

Complement cascade - Pathogen Recognition and Opsonization

1. The complement cascade helps identify and tag pathogens for elimination by the immune system. It recognizes unique molecular patterns on pathogens and coats them with complement proteins, particularly C3b, a process known as opsonization.

2. Opsonization enhances phagocytosis, facilitating the uptake and destruction of pathogens by immune cells such as macrophages and neutrophils.

complement cascade - inflammation

1. The complement cascade helps trigger and amplify the inflammatory response. Certain complement components, such as C3a and C5a, act as anaphylatoxins, promoting the recruitment and activation of immune cells to the site of infection.

2. Inflammation facilitates the removal of pathogens, increases blood flow to the affected area, and creates an environment conducive to immune cell activity and tissue repair.

complement cascade - direct pathogen killing

1. The complement cascade can directly lyse pathogens through the formation of the membrane attack complex (MAC). The MAC creates pores in the pathogen's membrane, leading to cell lysis and destruction of the invader.

2. This direct killing mechanism is particularly effective against certain types of bacteria and enveloped viruses.

complement cascade - Clearance of Immune Complexes

1. The complement system aids in the clearance of immune complexes, which are complexes formed by antigens and antibodies. Complement proteins can bind to these complexes and facilitate their removal from circulation.

2. Proper clearance of immune complexes helps prevent autoimmune reactions and maintain immune system balance.

complement cascade - Modulation of Immune Responses

1. Complement proteins play a role in modulating immune responses by interacting with other components of the immune system. They can influence the activation, differentiation, and function of various immune cells, contributing to the overall immune response.

2. The complement system integrates with other immune pathways, such as the coagulation cascade and the adaptive immune response, to coordinate an effective defense against pathogens.

Opsonization

Helps identify and tag pathogens for elimination by the immune system and coats them with complement proteins, particularly C3b.

Inflammation

Helps trigger and amplify the inflammatory response, certain complement components, such as C3a and C5a, act as anaphylatoxins, promoting the recruitment and activation of immune cells to the site of infection.

Initiation Phase of the complement cascade

Activates the complement cascade in response to the presence of pathogens or immune complexes, identifies and marks the target for destruction.

1. Purpose: The initiation phase activates the complement cascade in response to the presence of pathogens or immune complexes. This phase identifies and marks the target for destruction.

2. Classical Pathway: Activated by antigen-antibody complexes, initiating the cascade when antibodies bind to pathogens.

3. Lectin Pathway: Triggered by lectin binding to pathogen surfaces, especially those with specific sugars.

4. Alternative Pathway: Provides a rapid response by directly recognizing pathogen surfaces.

Amplification Phase of the complement cascade

Enhances the complement response, rapidly increasing the opsonization and inflammatory processes.

1. Purpose: The amplification phase enhances the complement response, rapidly increasing the opsonization and inflammatory processes.

2. Enzymatic Reactions: Formation of C3 convertase enzyme and cleavage of C3 into C3a and C3b.

3. Opsonization: C3b coats the pathogen surface, facilitating phagocytosis, and clearance by immune cells.

Cascade Convergence Phase of the complement cascade

Integrates the different pathway activations and amplifies the complement response.

1. Purpose: The convergence phase integrates the different pathway activations and amplifies the complement response.

2. C5 Cleavage: Cleavage of C5 into C5a and C5b, leading to the formation of the membrane attack complex (MAC).

3. MAC Formation: MAC formation initiates the direct killing of pathogens through pore formation in their membranes.

Terminal Phase of the complement cascade

Executes the final steps of the complement cascade to eliminate pathogens effectively.

1. Purpose: The terminal phase executes the final steps of the complement cascade to eliminate pathogens effectively.

2. MAC Assembly: MAC insertion into pathogen membranes disrupts their integrity, causing cell lysis.

3. Anaphylatoxins Release: Release of anaphylatoxins like C3a and C5a promotes inflammation, immune cell recruitment, and modulation of the immune response.

The clotting cascade

Helps contain the injury site by forming a mesh-like clot composed of fibrin, platelets, and other proteins.

The clotting cascade's functions in inflammation include restricting the spread of pathogens, facilitating antigen removal, controlling bleeding, and providing a supportive framework for tissue repair and healing. This coordinated response helps contain damage, promote immune cell activity, and support the restoration of tissue integrity following injury or inflammation.

role of preventing spread of inflammation in clotting cascade

1.     Prevents Spread to Adjacent Tissue:

1. Role: The clotting cascade helps contain the injury site by forming a mesh-like clot composed of fibrin, platelets, and other proteins.

2. Process: This clotting mechanism physically blocks the spread of pathogens, toxins, or damaged components to surrounding healthy tissues, limiting the extent of damage and maintaining tissue integrity.

role of trapping Antigens at the Site for Removal - clotting cascade

Aids in the entrapment and localization of antigens, pathogens, and debris at the site of injury or inflammation.

Role: The clotting cascade aids in the entrapment and localization of antigens, pathogens, and debris at the site of injury or inflammation.

1. Process: By forming a clot, the cascade effectively traps antigens and other harmful substances, making it easier for immune cells like macrophages and neutrophils to access and remove these unwanted elements, facilitating the clearance of pathogens and promoting tissue cleaning.

role of stopping Bleeding in the clotting cascade

One of the primary functions of the clotting cascade is to halt bleeding at the site of injury, preventing excessive blood loss.

1. Role: One of the primary functions of the clotting cascade is to halt bleeding at the site of injury, preventing excessive blood loss.

2. Process: The cascade's series of enzymatic reactions lead to the formation of a stable blood clot, sealing off damaged blood vessels and maintaining hemostasis. This process is crucial for preventing further tissue damage and maintaining blood circulation.

role of providing a Frame for Repair and Healing in the clotting cascade

A temporary framework that supports the migration and proliferation of cells involved in tissue regeneration.

Role: The fibrin mesh formed as a result of the clotting cascade provides a structural scaffold for tissue repair and healing.

1. Process: The fibrin clot acts as a temporary framework that supports the migration and proliferation of cells involved in tissue regeneration, such as fibroblasts and endothelial cells. It facilitates the deposition of extracellular matrix components and promotes the repair and remodeling of damaged tissues, aiding in the healing process.

Kinin (Bradykinin) cascade

The actions of bradykinin in the kinin cascade, such as vasodilation and leukocyte chemotaxis, play critical roles in orchestrating the body's inflammatory response, facilitating immune cell recruitment, pathogen clearance, and tissue repair at the site of injury or infection.

• Short-Lived and Localized: The effects of the kinin cascade, including vasodilation and leukocyte chemotaxis, are typically transient and confined to the immediate vicinity of the inflammatory stimulus.

• Vasodilation Mechanisms: Vasodilation induced by bradykinin involves increased vascular permeability, smooth muscle contraction, and nerve stimulation, creating an environment that facilitates the immune response.

• Leukocyte Movement: Leukocyte chemotaxis ensures the recruitment of immune cells to the site of inflammation, promoting the clearance of pathogens and the restoration of tissue homeostasis.

Vasodilation as a part of the Kinin (Bradykinin cascade)

The widening of blood vessels, which leads to increased blood flow to the affected area.

1. Vasodilation is the widening of blood vessels, which leads to increased blood flow to the affected area. Bradykinin, a key component of the kinin cascade, plays a crucial role in promoting vasodilation during inflammation.

2. Function:

   • Vasodilation enhances blood flow to the site of injury or infection, delivering immune cells, nutrients, and oxygen needed for repair and immune response.

   • Increased vascular permeability allows plasma proteins and immune cells to exit the bloodstream and reach the site of inflammation, aiding in defense against pathogens.

Leukocyte Chemotaxis as a part of the Kinin (Bradykinin cascade)

Is the process by which white blood cells, particularly leukocytes, are attracted to and migrate towards the site of inflammation in response to chemical signals; directs immune cells to the site of injury or infection.

1. Leukocyte chemotaxis is the process by which white blood cells, particularly leukocytes, are attracted to and migrate towards the site of inflammation in response to chemical signals. Bradykinin is a potent chemoattractant for leukocytes.

2. Function:

   • Leukocyte chemotaxis directs immune cells to the site of injury or infection, where they can engulf pathogens, remove debris, and modulate the immune response.

   • The presence of leukocytes at the site of inflammation helps contain and eliminate pathogens, contributing to the resolution of the inflammatory process.

Red Blood Cells (Erythrocytes) - cell-mediated response

Primarily transport oxygen (O2) to tissues in the body and play a crucial role in cellular respiration.

1. Function: Red blood cells primarily transport oxygen (O2) to tissues in the body and play a crucial role in cellular respiration.

2. Role in Cell-Mediated Response: While red blood cells are not directly involved in immune responses, their function in oxygen transport supports the overall metabolic needs of immune cells during inflammation.

Platelets (Thrombocytes) Cell-mediated response

Essential for blood clotting and hemostasis, preventing excessive bleeding at the site of injury.

1. Function: Platelets are essential for blood clotting and hemostasis, preventing excessive bleeding at the site of injury.

2. Role in Cell-Mediated Response: Platelets contribute to the formation of blood clots, which help seal damaged blood vessels, control bleeding, and provide a temporary scaffold for cell migration during tissue repair.

Mast Cells Cell-mediated response

Tissue-resident immune cells that contain granules rich in inflammatory mediators like histamine.

1. Function: Mast cells are tissue-resident immune cells that contain granules rich in inflammatory mediators like histamine.

2. Role in Cell-Mediated Response: Mast cells play a key role in the immediate inflammatory response by degranulating and releasing histamine and other vasodilators. This leads to increased vascular permeability, vasodilation, and the characteristic symptoms of inflammation like swelling, redness, and itching.

Neutrophils (Cell-mediated response)

Early responders that phagocytize and eliminate pathogens.

Monocytes (Macrophages) (Cell-mediated response)

Trigger plasma protein responses, engage in long-term healing and cleanup depending on the severity of the infection.

Eosinophils (Cell-mediated response)

Involved in parasitic infections and allergic reactions, regulate mast cell responses.

Basophils (Cell-mediated response)

Contribute to the B cell antibody response and are associated with allergic reactions.

Natural Killer Cells (Cell-mediated response)

Granulocyte-free cells that target infected cells, particularly virus-infected cells and some cancers.

Phagocytosis

Phagocytosis is a crucial process in the immune response, involving the ingestion and destruction of foreign invaders by specialized immune cells. phagocytosis, facilitated by chemotaxis, opsonization, lysosomes, and the process of apoptosis, is a vital immune response mechanism for eliminating pathogens, maintaining tissue integrity, and regulating inflammation in the body.

Chemotaxis (as a part of Phagocytosis)

The process by which immune cells are guided to the site of infection or inflammation.

1. Chemotaxis is the process by which immune cells are guided to the site of infection or inflammation. The complement cascade plays a significant role in chemotaxis, attracting leukocytes to the site of injury and initiating the process of phagocytosis.

2. Starting the Process: Chemical signals released at the site of infection attract leukocytes, signaling them to move towards the source of the signal and begin the phagocytosis process.

Opsonization (as a part of Phagocytosis)

The process of labeling pathogens with molecules that enhance their recognition and ingestion by phagocytic cells.

1. Opsonization is the process of labeling pathogens with molecules that enhance their recognition and ingestion by phagocytic cells.

2. Recognition and Ingestion: Leukocytes, such as monocytes and neutrophils, recognize opsonized pathogens through specific receptors and engulf them through phagocytosis, forming a phagosome.

3. Fusion and Destruction: The phagosome fuses with lysosomes, which contain digestive enzymes and antimicrobial substances, resulting in the destruction and degradation of the engulfed material.

Lysosomes (as a part of Phagocytosis)

Specialized organelles containing enzymes that aid in digestion and breakdown of engulfed material during phagocytosis.

1. Lysosomes are specialized organelles containing enzymes that aid in digestion and breakdown of engulfed material during phagocytosis.

2. Phagosome Formation: The fusion of the phagosome (containing the ingested pathogen) and the lysosome forms a phagolysosome, where the pathogen is degraded by enzymes and reactive oxygen species (ROS).

3. Importance in Phagocytosis: Lysosomes play a central role in the killing and digestion of pathogens, helping to eliminate the threat and prevent further infection.

Apoptosis (as a part of Phagocytosis)

A programmed cell death mechanism crucial for maintaining tissue homeostasis and removing damaged or unnecessary cells.

1. Apoptosis is a programmed cell death mechanism crucial for maintaining tissue homeostasis and removing damaged or unnecessary cells.

2. Implications: In cases of excessive or prolonged inflammation, cells may undergo apoptosis as a regulatory mechanism to prevent the spread of damage and promote resolution of the inflammatory response.

3. Role of Phagocytosis: Phagocytic cells like monocytes and macrophages play a role in engulfing apoptotic cells and cell debris, contributing to tissue cleanup and resolution of inflammation.

Cytokines

A diverse group of proteins that play essential roles in mediating the immune response and creating a complex communication network within the body.

Cytokines are a diverse group of proteins that play essential roles in mediating the immune response and creating a complex communication network within the body.  Cytokines, including interleukins, TNF-α, interferons, and chemokines, create a complex network of communication within the immune system, regulating immune responses at both local and systemic levels. These cytokines can have pro-inflammatory or anti-inflammatory effects, orchestrating the immune response to maintain immune homeostasis and combat infections or inflammatory conditions.

Interleukins

Act as signaling molecules to regulate immune cell growth, differentiation, activation, and function in a paracrine or autocrine manner.

1. Source: Interleukins are produced by various immune cells, primarily T cells, B cells, macrophages, and dendritic cells.

2. Local Role: Interleukins act as signaling molecules to regulate immune cell growth, differentiation, activation, and function in a paracrine or autocrine manner.

3. Systemic Effect: Some interleukins, such as IL-2, have systemic effects on the entire immune system, coordinating responses to infections or foreign antigens.

4. Inflammation: Interleukins can have pro-inflammatory (e.g., IL-1, IL-6) or anti-inflammatory (e.g., IL-10) properties, balancing the immune response.

Tumor Necrosis Factor-alpha (TNF-α)

Promotes inflammation, apoptosis (cell death), and activates immune cells to combat pathogens at the site of infection.

1. Source: TNF-α is primarily produced by macrophages, monocytes, and T cells in response to infection, inflammation, or injury.

2. Local Role: TNF-α promotes inflammation, apoptosis (cell death), and activates immune cells to combat pathogens at the site of infection.

3. Systemic Effect: Systemic release of TNF-α can lead to fever, weight loss, and tissue damage in conditions like sepsis or autoimmune diseases.

4. Inflammation: TNF-α is a pro-inflammatory cytokine, inducing the expression of other inflammatory mediators.

Interferons

Help inhibit viral replication in infected cells and activate immune responses to control viral spread.

1. Source: Interferons are primarily produced by virally infected cells, dendritic cells, and natural killer cells in response to viral infections.

2. Local Role: Interferons help inhibit viral replication in infected cells and activate immune responses to control viral spread.

3. Systemic Effect: Interferons can induce an antiviral state in neighboring cells, enhancing immune surveillance against viral infections.

4. Inflammation: Interferons are typically pro-inflammatory, promoting an antiviral response and modulating immune function.

Chemokines

Regulate leukocyte migration to the site of inflammation by functioning as chemoattractants.

1. Source: Chemokines are secreted by various cell types, including immune cells, endothelial cells, and fibroblasts, in response to inflammation or infection.

2. Local Role: Chemokines regulate leukocyte migration to the site of inflammation by functioning as chemoattractants.

3. Systemic Effect: Chemokines play a role in coordinating immune cell recruitment and activation systemically during inflammation.

4. Inflammation: Chemokines are primarily pro-inflammatory, promoting the recruitment and activation of immune cells to combat pathogens at the site of infection.

Acute Inflammation

A rapid and localized immune response triggered by tissue injury, infection, or foreign invaders like bacteria or viruses.

1. Cause: Acute inflammation is a rapid and localized immune response triggered by tissue injury, infection, or foreign invaders like bacteria or viruses.

2. Manifestations:

   • Redness, swelling, heat, and pain at the site of injury or infection.

   • Increased vascular permeability, leading to the influx of immune cells, such as neutrophils and macrophages, to combat pathogens.

   • Tissue repair and resolution of inflammation occur once the immune response successfully eliminates the threat.

   • Well-regulated, self-limiting response aimed at restoring tissue homeostasis.

Cytokine Storm

Is an exaggerated and uncontrolled systemic inflammatory response characterized by the overproduction of pro-inflammatory cytokines.

1. Cause: A cytokine storm is an exaggerated and uncontrolled systemic inflammatory response characterized by the overproduction of pro-inflammatory cytokines. This response can be triggered by conditions like severe infections, sepsis, or certain autoimmune disorders.

2. Manifestations:

   • Excessive release of cytokines, such as interleukins (IL-6, IL-1), interferons (IFN-γ), and tumor necrosis factor-alpha (TNF-α), leading to systemic inflammation.

   • Severe inflammation, hyperactivation of immune cells, and widespread tissue damage throughout the body.

   • Manifestations can include fever, organ dysfunction, multi-organ failure, and even life-threatening complications.

   • Dysregulated and uncontrolled immune response that can be harmful rather than protective.

Comparison of acute inflammation and cytokine storm

• Cause: Acute inflammation is a localized response triggered by tissue damage or infection, whereas a cytokine storm is a systemic and dysregulated immune response resulting in uncontrolled inflammation.

• Manifestations: Acute inflammation typically presents as a localized response with redness, swelling, and heat, whereas a cytokine storm can lead to systemic manifestations, multi-organ dysfunction, and severe complications.

• Regulation: Acute inflammation is part of the body's normal defense mechanism and is self-limiting, while a cytokine storm lacks control and regulation, leading to excessive inflammation and tissue damage.

Results of Chronic Inflammation

Chronic inflammation is a persistent and prolonged inflammatory response that can have adverse effects on the body, leading to tissue damage, immune system dysfunction, and the development of various chronic diseases. Here is an organized explanation of chronic inflammation, its associations, mediators, and the consequences of deficient or excessive inflammatory responses:

Can lead to persistent damage to cells and tissues, impairing their function and potentially promoting disease progression.

1. Damaged Cells: Chronic inflammation can lead to persistent damage to cells and tissues, impairing their function and potentially promoting disease progression.

2. Weakened Immune System: Over time, chronic inflammation can dysregulate the immune system, leading to immune suppression or dysfunction, making the body more susceptible to infections and diseases.

Association of chronic diseases with chronic inflammation

1. Chronic inflammation is associated with a range of chronic diseases, including:

   • Periodontitis: Chronic gum disease characterized by inflammation and tissue damage around the teeth.

   • Obesity: Chronic low-grade inflammation in adipose tissue contributes to metabolic dysfunction and obesity-related complications.

   • Diabetes Mellitus (DM): Chronic inflammation is implicated in insulin resistance and complications associated with diabetes.

   • Alzheimer's Disease: Neuroinflammation is a key feature in the pathogenesis of Alzheimer's disease.

   • Insulin Resistance: Chronic inflammation plays a role in the development of insulin resistance, a precursor to type 2 diabetes.

   • Frailty: Chronic inflammation may contribute to frailty in older adults, affecting overall health and functional decline.

dietary factors - Mediators of Chronic Inflammation

Phytochemicals and antioxidants from fruits, vegetables, and other sources can help balance inflammation and reduce oxidative stress associated with chronic inflammation.

Gut Microbiome - Mediators of Chronic Inflammation:

The composition and diversity of gut microbiota can influence inflammatory responses, with dysbiosis or imbalance potentially contributing to chronic inflammation.

Consequences of Inappropriate Inflammatory Responses:

1. Deficient Inflammatory Response to Infection: When the inflammatory response is insufficient or delayed, the body may struggle to effectively combat infections, increasing the risk of severe illness or complications.

2. Hyperactive Inflammatory Response: Overactive or dysregulated inflammatory responses can lead to autoimmune diseases, allergies, chronic pain and alloimmunity, where the immune system mistakenly targets healthy tissues or reacts excessively to harmless substances.

Inflammation in Acute Pain

In response to tissue injury serves a protective function by promoting healing and tissue repair.

1.     Acute pain is typically a symptom of tissue damage or injury and is accompanied by an acute inflammatory response. Inflammation in response to tissue injury serves a protective function by promoting healing and tissue repair. During this acute phase, the release of inflammatory mediators such as prostaglandins, cytokines, and chemokines sensitizes nerve endings, leading to pain perception as a warning sign of potential harm.

transition from acute to chronic pain r/t inflammation

1.     In some cases, acute pain may persist or transition to chronic pain due to various factors, including unresolved inflammation. Chronic pain conditions often involve a dysregulated inflammatory response characterized by persistent low-grade inflammation in the absence of ongoing tissue damage.

inflammatory contributors to Chronic pain conditions

Such as arthritis, fibromyalgia, and neuropathic pain are associated with sustained inflammation and neuroimmune interactions.

1.     Chronic pain conditions such as arthritis, fibromyalgia, and neuropathic pain are associated with sustained inflammation and neuroimmune interactions. In chronic pain states, pro-inflammatory mediators continue to be released, sensitizing pain pathways, altering neural signaling, and perpetuating pain perception.

neuroplastic changes r/t inflammation

1.     Prolonged inflammation can induce neuroplastic changes in the central nervous system, affecting pain processing pathways and promoting sensitization of pain receptors. This results in an amplification of pain signals and a lowered pain threshold, contributing to the persistence of chronic pain.

Inflammatory Mediators and Pain Sensitization

Inflammatory mediators such as bradykinin, prostaglandins, and cytokines can sensitize nociceptors.

Resolution of Inflammation

Involves the restoration of tissue homeostasis, clearance of inflammatory cells, and regeneration of damaged tissue structures.

1.     Inflammatory mediators such as bradykinin, prostaglandins, and cytokines can sensitize nociceptors (pain-sensing nerve fibers), leading to hyperalgesia (increased sensitivity to pain) and allodynia (pain in response to normally non-painful stimuli). This inflammatory-induced sensitization plays a significant role in amplifying and perpetuating chronic pain conditions.

Fibrosis

The excessive accumulation of fibrous connective tissue in response to chronic inflammation or tissue damage.

Granuloma Formation

The immune system attempts to wall off substances it perceives as foreign but is unable to eliminate.

Autoimmunity

The immune system mistakenly targets the body's own tissues, leading to chronic inflammation and tissue damage.

Role of the Complement System

Enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells, promoting inflammation.

Classical Pathway

Initiated by antigen-antibody complexes, leading to complement activation and inflammation.

Alternative Pathway

Triggered by direct binding of complement proteins to pathogen surfaces in the absence of antibodies.

Lectin Pathway

Activated by the binding of mannose-binding lectin (MBL) to mannose residues on pathogens.

Systemic Effects of Inflammation

Manifestations that extend beyond the local site of infection or injury, affecting organ systems throughout the body.

Fever

A systemic response characterized by an elevation in body temperature, often triggered by pyrogens released during inflammation.