L3: Innate Immunity----Inflammation

What is the importance of innate immunity?

It provides a non-specific defense against pathogens and plays a crucial role in the early stages of immune response.

What are the primary cells involved in innate immunity?

Neutrophils and natural killer cells are primarily phagocytes that target bacteria and other pathogens.

What is the role of neutrophils in inflammation?

Neutrophils primarily phagocytose bacteria and other pathogens. They are among the first cells attracted to a site of injury

What is the role of macrophages in innate immunity?

Macrophages bridge innate and adaptive immunity by activating T cells, phagocytosing dead cells and bacteria, and secreting cytokines

What do dendritic cells do?

Dendritic cells are antigen-presenting cells that activate T cells and secrete cytokines.

What are exogenous causes of inflammation?

Physical injuries, chemical agents, and biological agents such as bacteria, viruses, and parasites.

What are endogenous causes of inflammation?

Endogenous causes of inflammation include immune reactions (hypersensitivity), circulation disorders (thrombosis), and metabolic product depositions (uric acids)

Name some diseases associated with chronic inflammation.

Diseases associated with chronic inflammation include metabolic syndrome, arthritis, Alzheimer’s disease, asthma, ulcerative colitis and inflammatory bowel disease, colon, breast, and lung cancers, eye disorders, cardiovascular disease, and gingivitis

What can lead to acute inflammation?

Infarction, bacterial infection, toxins, and trauma.

How do mast cells contribute to inflammation?

Mast cells secrete histamine, leading to increased blood flow and inflammation.

What is the purpose of vascular changes during inflammation?

To increase blood flow and vascular permeability, allowing immune cells to reach the site of infection.

How does vascular permeability change during inflammation?

Vascular permeability increases, leading to leakage of exudate into the tissue

Describe the process of neutrophil margination and rolling.

Neutrophils get close to the blood vessel wall (margination), then bind selectin ligand to E- or P-selectin on the endothelium and chemokine receptors on neutrophils bind to chemokines (like IL-1 secreted by macrophages) presented by proteoglycans on the endothelium, activating the neutrophils (rolling)

Explain the process of neutrophil adhesion and transmigration.

Neutrophils adhere by binding β2 integrin to ICAM-1, then transmigrate from the blood vessel to the tissue

What attracts neutrophils to the site of infection during chemotaxis?

Cytokines produced by Langerhans cells and macrophages attract neutrophils to the site of infection

What happens during the leukocyte activation stage of inflammation?

Neutrophils are initially activated to kill microbes, followed by the activation of monocytes, which have multi-potential functions

How do IFN-γ, IL-4, and IL-10 affect monocyte/macrophage function?

IFN-γ enhances the killing ability of monocytes, IL-4 promotes tissue repair and barrier immunity, and IL-10 cleans up cell debris during resolution

What occurs during phagocytosis?

Phagocytes engulf pathogens, forming phagosomes that fuse with lysosomes to form a phagolysosome, and digesting the contents with lysozyme before releasing them as exocytic vesicles

What triggers the resolution of inflammation?

Granulocytes secrete lipoxin to initiate termination, resolvins and protectins stop neutrophil recruitment, macrophages engulf apoptotic neutrophils and release TGF-β, pro-inflammatory cytokines decrease, and anti-inflammatory cytokines increase

What are the outcomes of inflammation resolution?

Normal tissue repair, fibrosis, or pus formation can occur depending on the extent of tissue damage.

What characterizes chronic inflammation?

Persistent stimuli, mainly the presence of macrophages, often resulting in tissue destruction.

What happens during fibrosis as an outcome of inflammation?

Fibrosis occurs when inflamed tissue is damaged and cannot regenerate, leading to fibrous scarring by collagen and functional repair

What role does histamine play in the inflammatory response?

produced by mast cells and basophils, increases the permeability of blood capillaries via H1 receptors, facilitating the inflammatory response.

What are the functions of TNFα and IL-1?

They induce fever, promote the production of acute-phase proteins, and stimulate other inflammatory mediators.

What is the function of prostaglandins in inflammation?

Prostaglandins are eicosanoid inflammatory mediators that induce vasodilation, increase capillary permeability, and cause pain and fever during inflammation.

What is the role of leukotrienes in inflammation?

Leukotrienes induce chemotaxis and extra-vascularization of immune cells.

What is the role of platelet-activating factor in inflammation?

Platelet-activating factor induces platelet aggregation, activates neutrophils, and serves as a strong chemoattractant for eosinophils, contributing to edema.

What are the plasma mediators?

Bradykinin, plasmin, thrombin and complement proteins

What is bradykinin's role in inflammation?

Bradykinin is produced by the kinin system and increases vascular permeability, causes smooth muscle contraction, and contributes to the inflammatory response.

How does plasmin contribute to inflammation?

Plasmin activates the fibrinolytic system to degrade fibrin, leading to increased vascular permeability and attracting leukocytes during inflammation.

What is thrombin's function in the coagulation process?

Thrombin converts soluble fibrinogen into insoluble fibrin, playing a crucial role in blood clotting during inflammatory responses.

What is the significance of the complement system in inflammation?

Complement proteins enhance inflammation by inducing histamine release (C3a and C5a), mediate opsonization (C3b), act as strong chemoattractant (C5b), and induce bacteria lysis (MAC)

What distinguishes acute inflammation from chronic inflammation in terms of cells involved?

Acute inflammation primarily involves neutrophils, while chronic inflammation involves monocytes, macrophages, and lymphocytes.

What are the potential outcomes of acute inflammation?

Resolution, abscess formation, or progression to chronic inflammation.

What are the potential outcomes of chronic inflammation?

Chronic inflammation can lead to tissue destruction, fibrosis, and necrosis over time due to prolonged immune responses.

What is Sepsis Syndrome?

A whole-body inflammatory response to infection that can lead to multi-organ failure.

How does sepsis syndrome affect blood pressure?

It can cause shock due to loss of blood pressure from vasodilation and fluid leakage into tissues.

What is the relationship between septicemia and inflammation?

Septicemia triggers the release of inflammatory cytokines like TNFα and IL-1, contributing to systemic inflammation.