CPAT3201 - Lectures 1-2

What is inflammation?

the reaction of vascularised living tissues to local injury/infection, characterized by movement of fluid and leukocytes from blood into affected tissue

What are the two main categories of inflammation?

acute and chronic inflammation

What is the role of the inflammatory response?

to localise and eliminate microorganisms, damaged cells, foreign particles, or antigens, offering a survival advantage

What are the key characteristics of acute inflammation?

rapid onset, relatively short-lived, involves the movement of fluid and neutrophils from the blood into the affected tissue

What are the major cell types involved in inflammation?

neutrophils, endothelial cells, macrophages, fibroblasts

What are the cardinal signs of inflammation?

redness, heat, swelling, pain

What mechanisms cause redness and heat during inflammation?

increased blood flow - hyperaemia, due to vasodilation and the opening of dormant capillaries

What causes swelling during inflammation?

fluid movement - exudation, from the blood into the tissue which increases tissue's fluid content

What causes pain during inflammation?

increased sensitivity of pain receptors - hyperalgesia, due to the production of mediators like prostaglandins

What is exudation in the context of inflammation?

the movement of fluid (containing plasma proteins) from the blood into affected tissue due to increased vascular permeability

What is the difference between exudate and transudate?

exudate is a protein-rich fluid that results from increased vascular permeability during inflammation, transudate is a fluid with low protein content that moves from the blood due to hydrostatic pressure

What is oedema?

accumulation of fluid extra-vascularly in tissues

What is pus?

inflammatory exudate containing viable and dead neutrophils, cell debris

What is hyperaemia?

the passage of larger-than-normal volumes of blood through a tissue, often caused by vasodilation and the opening of dormant capillaries

What are the causes and effects of vasodilation in acute inflammation?

vasodilation causes hyperaemia and allows more blood to flow into the capillary bed, leading to redness and heat in the affected area

What happens during mild or moderate acute inflammation in terms of exudation?

exudation occurs through inter-endothelial gaps in post-capillary venules due to endothelial cell contraction, either immediately and transiently or delayed and prolonged

What happens during more severe inflammation in terms of exudation?

damage to endothelial cells in all microvessels - immediate, prolonged response

How does inflammation lead to oedema?

oedema occurs when fluid accumulates outside the blood vessels in the tissues, often due to exudation from increased vascular permeability during inflammation

What is the normal physiological control of fluid movement in the microcirculation?

low protein concentration in interstitial fluid, high protein in plasma, hydrostatic pressure drives fluid in arteriole across endothelial wall, blood meets high resistance in capillary to move fluid out

What is transudation?

where fluid, low in protein and cells, passively moves from blood vessels into tissues through pores in cell membranes, due to changes in hydrostatic pressure

What are the key mediators of inflammation?

histamine, kinins, prostaglandins, leukotrienes, complement fragments (C3a, C5a), and cytokines

What role does histamine play in inflammation?

increases vascular permeability in post-capillary venules, allowing fluid and proteins to leak out

How do prostaglandins contribute to pain during inflammation?

sensitise pain receptors (nociceptors), lowering their threshold for activation, thus increasing pain perception

How does inflammation relate to tissue healing?

helps initiate tissue repair mechanisms by promoting the removal of damaged cells and supporting the repair process

What are some complications of inflammation?

acute inflammation = appendicitis or meningitis, chronic inflammation = tuberculosis or arthritis

What is the role of macrophages in inflammation?

degrade fibrin and debris, kill microorganisms, secrete cytokines to regulate the inflammatory response

What happens during the exudation process in acute inflammation?

move fluid and plasma proteins from blood vessels into tissues, accompanied by neutrophil emigration (leading to swelling and pain)

What is the significance of fibrin in inflammation?

fibrin is part of the coagulation system and helps form a barrier to limit the spread of infection, aiding tissue healing

What are the primary roles of neutrophils in inflammation?

to kill microorganisms (especially bacteria) and release chemotactins to attract other neutrophils and macrophages.

True or false. Neutrophils are terminally differentiated and cannot proliferate.

true

What are the stages of neutrophil emigration, and what mediates each stage?

rolling (selectins), adhesion (integrins), emigration (integrins)

How does margination of neutrophils occur?

circulating neutrophils touch the vessel walls, roll along the endothelium, and adhere to the endothelium, a process induced by vasoactive mediators and cytokines

What are the mechanisms by which neutrophils kill microorganisms?

phagocytosis and NETs

What is phagocytosis?

neutrophils engulf microorganisms into a phagosome

What are Neutrophil Extracellular Traps (NETs)?

neutrophils release DNA with antimicrobial proteins to trap and kill bacteria

What does NETs mean?

neutrophil extracellular traps

How do neutrophils form NETs?

neutrophils rupture their nucleus, release DNA, and bind granule proteins to it, forming NETs that trap pathogens

What are pattern recognition receptors (PRRs)?

receptors that recognize pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and trigger immune responses (antimicrobial host defences and initiate adaptive immune responses)

What are examples of PAMPs?

lipids, proteins, nucleic acids

What are examples of DAMPs?

ATP, RNA, DNA

What is the role of Toll-like receptors (TLRs)?

they recognise components of pathogens and play a critical role in pathogen detection and immune response initiation

What are the primary roles of macrophages in inflammation?

to kill microorganisms, phagocytose and degrade debris, and produce cytokines to regulate immune responses

What are the structural properties of macrophages?

a single-lobed nucleus, no obvious cytoplasmic granules, prominent endoplasmic reticulum and Golgi apparatus, and abundant mitochondria

What are the biochemical properties of macrophages?

thye have large protein synthesis capacity and derive energy from both aerobic respiration and anaerobic glycolysis

How do macrophages differ from neutrophils in terms of lifespan and function?

they are long-lived, can proliferate and differentiate (but neutrophils are short-lived and cannot proliferate)

What are cytokines and how do they function?

proteins produced by immune cells that modify the activity of other cells involved in the immune or inflammatory reaction, they can stimulate or inhibit cellular functions

What are the types of cell signalling by cytokines?

autocrine, paracrine, endocrine

What is autocrine cell signalling by cytokines?

a cell signals itself

What is paracrine cell signalling by cytokines?

a cell signals nearby cells

What is endocrine cell signalling by cytokines?

a cell releases a hormone that travels to distant target cells

What are the roles of Interleukin-1 (IL-1) and tumour necrosis factor (TNF) in inflammation?

tissue damage and diseases like arthritis

How are monocytes and macrophages related?

monocytes are precursor cells that differentiate into macrophages once they migrate from the bloodstream into tissues

How do monocytes and macrophages differ in appearance?

monocytes have a single-lobed nucleus with slight indentation, while macrophages have a single-lobed nucleus with more defined cytoplasm

What is the lifecycle of a monocyte?

they are produced in the bone marrow at a rate of ~100,000 cells per second, circulate in the blood for 2-3 days, and can remain in tissues for months or years

What are the structural and biochemical properties of neutrophils?

they have a multi-lobed nucleus, two types of cytoplasmic granules, no endoplasmic reticulum or Golgi apparatus. They have limited protein synthesis capacity and rely on anaerobic glycolysis for energy.

What happens to neutrophils after they perform their function in inflammation?

they die, often releasing NETs to trap and kill pathogens