acute + chronic inflammation Flashcards
How immune system work?
2 different systems?
what 3 things do they do?
how is the system activated?
Fight off pathogens (e.g. bacteria, viruses, parasites, fungi), neutralize toxins, remove cancerous cells
Activated by antigens - foreign proteins on the surface
Innate vs adaptive
Innate vs adaptive
3 key differences?
Innate
Fast
Non-specific
No memory
Adaptive
Slower
Specific to pathogen
Memory
Inflammation definition
what is it? what does it do?
Defensive process that a living body initiates against infection and damaged tissues
Recruits cells and molecules from the circulation to where they are needed to eliminate offending agents
Terms ending in the suffix ‘-itis’ denote inflammation
Why is inflammation important?
what if not controlled properly?
Inflammation can be inappropriately triggered or poorly controlled – can cause tissue injury
Inflammation will continue until the triggers are removed
Understanding the pathogenic mechanisms is important in diagnosing inflammatory processes and treatment
Inflammation: Triggers
4 main thinsg and examples of them>
Physical agents
Extreme temperatures, electric shock, radiation, mechanical injuries (e.g. splinters, dirt, sutures, dentures)
Chemical agents
Chemical burns, irritants, drugs, products of metabolism, tissue necrosis
Biological agents
Bacteria, viruses, fungi, parasites, toxins
Immune reactions
Abnormal inflammatory responses to normal tissue (e.g. autoimmune diseases) or foreign tissue (e.g. allergens)
Usually seen in chronic inflammation
Inflammation: Clinical signs
5 main things?
functional impairment pain tissue swelling redness warmth
Inflammation: Morphological patterns
what does pus contain?
what other things can happen?
how can there be tissue scarring?
Suppurative or purulent inflammation, abscess
Pus consists of neutrophils, dead cells, tissue fluid
Ulcers
Serous inflammation (e.g. blister)
Fibrinous inflammation (extensive leakage of fluid from blood vessels therefore allow the fibrinogen into tissue which can lead to a blood clot and therefore lead to tissue scarring
Types of inflammation (2)
Chronic inflammation
Acute inflammation
Acute inflammation
what is it? examples
Acute inflammation
A rapid response to deliver leukocytes and plasma proteins to sites of infection or tissue injury; short duration
e.g. Acute appendicitis, acute bronchitis, abscess
Chronic inflammation
what is it? examples?
Chronic inflammation
Inflammation of prolonged duration (weeks or months), in which inflammation, tissue injury and attempts at repair co-exist, in varying combinations
e.g. Tuberculosis infection, autoimmune diseases
Acute inflammation: Characteristics
what kind of immune response is involved? main cell involved? how large of a scale is this? obvious clinical signs? what else happens?
Innate immune response – occurs within minutes or hours, lasts for hours or days
Main cell: neutrophil
Mostly local, can be systemic (e.g. fever, neutrophilia)
Exudation of fluid and plasma proteins (edema) + emigration of leukocytes
Obvious clinical signs – calor, rubor, tumor, dolor etc
Purpose of acute inflammation (5)
what does it do at the site?
what does it tell the body to do?
what does it create conditions for?
what else does it do?
Alert the body - hence send chemical signals like cytokines to help activate adaptive immunity
Limit spread of infection or injury
Protect injured site from becoming infected
Eliminate dead cells/tissues - via macrophages
Create conditions required for healing
Purpose of acute inflammation – the 5 Rs
Recognition of injury Recruitment of leukocytes Removal of causative agent Regulation (closure of inflammatory response) Resolution/Repair of affected tissue
Termination of acute inflammation
when does this occur?
4 ways this occurs
why does this occur?
Very important
Occurs when causative agent is removed
Reaction resolves rapidly
Mediators broken down and dissipated
Leukocytes have short life span in tissues
Anti-inflammatory mechanisms activated
Control response and prevent it from causing excessive damage to host tissues
Outcomes of acute inflammation
what is the best outcome?
what is suppurative or purulent inflammation? what is this caused by and what can it become?
what does the repair by scarring/fibrosis depend on?
how can it become a chronic inflammation?
Complete resolution (best outcome) Causative agent removed early, limited tissue damage, cells at site able to regenerate
Abscess – Suppurative/purulent inflammation
Caused by certain types of bacteria
Can become chronic if not reabsorbed/drained
Repair – healing by scarring/fibrosis
Greater extent of tissue destruction, native tissue unable to regenerate (e.g. myocardial infarction)
Highly depend on tissue regeneration ability (labile vs stable vs permanent tissues) -> if tissue can’t regenerate it will be replaced by connective tissue synthesised by fibroblast cells that are present to patch up injury site which leads to scarring
Progression to chronic inflammation
Causative agent could not be removed
Main events of acute inflammation vascular events (small vessels + capillaries)
what does mast cells produce and effect of this?
what happens to blood vessels to help molecules? (3)
Histamine produced by mast cells – attract more mast cells therefore more histamine -> amplification
Vasodilation & stasis – widening of internal diameter of blood vessels
Increased blood volume to injured area; slowing down of blood flow -> therefore neutrophil + monocyte can get out and migrate to the site
Endothelial cells contraction - increased vascular permeability
Fluid and cells leak out of the walls of the blood vessels
Endothelial cells express adhesion molecules for leukocytes to bind
Main events of acute inflammation
cellular events - neutrophil, macrophage
what happens to leukocytes?
what do integrin do?
how do they reach the site? how do they move to the site?
what happens at site?
Margination of leukocytes - adhere to walls of blood vessels
Rolling, integrin activation, adhesion - roll along blood vessels -> catch + release adhesion molecules on the walls of blood vessels. Also, integrin molecules on the leukocytes will be activated therefore bind very tightly to adhesion molecules
Transmigration through endothelium -> move out + transmigrate out of the blood vessels into the surrounding tissue through the gaps made by contraction of endothelial cells
Chemotaxis to inflamed site -> leukocytes migrate to inflamed sites by chemotaxis (moved to area of increased distress molecules)
Activation and phagocytosis
Effect of acute inflammation events
Recruitment and exudation of leukocytes and plasma proteins from the blood vessels to the inflamed site to deal with infection/damage
Leukocytes recruited: Neutrophils
what are these?
what do they do? (4)
what do they become?
Neutrophils (first responders)
Phagocytose pathogens and dead tissues
Release granule content to counteract histamine, release more chemokines to attract more leukocytes etc
Generate reactive oxygen/nitrogen species, proteases
Form Neutrophils Extracellular Traps (NETs)
Short lived; becomes pus
Leukocytes recruited: Macrophages and others
what do they differentiate from?
what do they do? What do they release?
two other leukocytes? when are they used?
Macrophage
Differentiate from monocytes
Phagocytosis
Releases factors that promote tissue repair (TGF-β)
Other leukocytes
Eosinophils (parasite infections, allergies)
Lymphocytes (viral infections) -> adaptive immunity
Important mediators
what effects do tnye have?
how are they connected?
what does mast cells release? (2) what causes mast cells to release these?
other mediators?
C5a (Complement)
Stimulates release of reactive oxygen species (chemical warfare)
Attracts neutrophils and monocytes
Increase vascular permeability
Cause mast cells to release histamines and TNF- α
Histamine (vasoactive amines)
Vasodilation
Contraction of endothelial cells
Tumour Necrosis Factor alpha (TNF- α)
Stored in mast cells (small quantities), released by macrophage
Cause endothelial cells to produce adhesion molecules for leukocytes
Other mediators: IL-6, IL-8, lipid-derived mediators (e.g. prostaglandins), serotonin, kinins
Chronic inflammation: Characteristics
what is this leaning towards with immune response?
main cells involved? (3)
what may it follow? if not?
what does it co-exist with?
what is the main things involved with this? (4)
Leaning toward adaptive immune response – lasts weeks to months
Main cells: Macrophage, lymphocytes, plasma cells
May follow acute inflammation (if infectious agent not removed); or slow, insidious onset
Co-exists with tissue damage and repair attempts
More tissue destruction; cellular infiltrates; blood vessel proliferation and connective tissue deposition (scarring)
Chronic inflammation: Causes
3 main things, give examples of them
Persistent infections
E.g. tuberculosis, viral or parasitic infections
Persistent exposure to injurious agents
Silicosis in the lungs, atherosclerosis in vessels
Immune-mediated
Autoimmune diseases – triggered by self-antigens
Allergies – triggered by harmless environmental substances
Chronic inflammation: Mediators
3 main group mediators
give examples and their effects
Mediators of acute inflammation e.g. TNF-α (if out of control, it will lead to prolonged state of inflammation)
Interferon gamma (IFN-γ)
Produced by T-cells and NK cells
Activates macrophages, increases microbicidal activity
Chemokines
IL-17, IL-12
Different types of chronic inflammation
4 types
Non-specific chronic inflammation
Autoimmune chronic inflammation - rheumatoid arthirtis
Chronic suppurative inflammation
Chronic granulomatous inflammation
Non-specific chronic inflammation
when does this develop?
example - what is it caused by? inflammatory cells involved?
what is ulceration?
Develops when acute inflammation fails to eliminate causative agent
Gastritis, gastric ulcer caused by Helicobacter pylori or non-steroidal anti-inflammatory drugs (NSAIDs)
Inflammatory cells: lymphocytes, plasma cells
Ulceration: Loss of surface cells or tissue necrosis – oral mucosa, stomach, intestines, genitourinary tract
Non-specific chronic inflammation
Helicobacter pylori-associated gastritis
what does this avoid?
what is recruited to inflammation sites? what do they release? what is the effect of this and why?
what happens in long term?
H. pylori evades both innate and adaptive immune responses
Neutrophils recruited to inflammation site – release Reactive Oxygen/Nitrogen Species & proteases
Can’t harm H. pylori in gastric mucus, but harms normal tissues (gastric epithelial cells) -> as innate can’t tell between friend or foe
Infection persists, becomes chronic gastritis (as adaptive can’t remove it either)
Autoimmune chronic inflammation
what is this? example
inflammatory cells involved?
key charcateristics?
Immune response to self-antigens
e.g. Rheumatoid arthritis, Crohn’s disease
Inflammatory cells: macrophages, lymphocytes
Mechanisms complex, not completely understood
Insidious start
Progressive, persistent chronic inflammation, tissue damage
Autoimmune chronic inflammation
Rheumatoid arthritis
where does it take place?
what happens there? (2)
what is the effect of this?
what do 70% of patients have?
Chronic inflammation in synovium (lining of joints)
Swelling: expansion of synovium by inflammatory cell infiltrate
Pannus formation: fibrin deposition
Massive bone damage and joint destruction
~70% of patients have anti-rheumatoid factor (later found to be autoantibodies against Fc portion of IgG)
Chronic suppurative inflammation
what is this? examples?
inflammatory cells involved?
how does it start?
how is it resolved clinically?
Persistent suppurative (pus forming) inflammation
Pilonidal disease abscess, empyema, osteomyelitis
Inflammatory cells: mainly neutrophils, eosinophils (if parasite)
Starts as acute suppurative inflammation – local pus accumulation cannot be clear spontaneously (abcess)
Surgical procedure: Incision and drainage
Chronic suppurative inflammation
Abscess
how is it often caused? how?
what must be done to fully heal?
what is an abscess?
Often caused by pyogenic (pus forming) bacteria
Fibrosis walled off a localized focus of acute inflammation – localized collection of purulent inflammation
Often have to be lain open to heal (incision and drainage)
Central area of necrotic leucocytes & tissue cells; zone with neutrophils; fibroblast proliferation and fibrotic area (walled around the abscess)
Chronic suppurative inflammation
what is created when causative agent cannot be eradicated? why? what do these characteristically consist of?
inflammatory cells?
Causative agent cannot be eradicated - granuloma formation to isolate and prevent spread of agent -> therefore it is walled off by connective tissue therefore form granulomas which will isolate + prevent spread of causative agent
Inflammatory cells: epitheloid cells, giant cells, lymphocytes
Granulomas characteristically consists of:
Macrophages (epitheloid cells, giant cells)
Lymphocytes
Fibroblast, collagen (main component of connective tissue)
Necrotic tissue may or may not be present
Langhans giant cell - what is this?
Multiple nuclei in horseshoe shape due to macrophages merging
Chronic suppurative inflammation
causes
example of different ones
Immune granulomas: associated with persistent T cell activation
Infections: difficult to eradicate infectious agents
Bacterial: TB, leprosy, syphilis
Parasitic: Schistosomiasis
Autoimmune disease: response against self antigens
Rheumatoid arthritis, Crohn’s disease
Foreign body granulomas
Talc, sutures, fibres, silica
No T cell activation
Unknown aetiology: Sarcoidosis
Chronic granulomatous inflammation: To note
what happens after macropage fail to eradicate the agent? what do they do?
what is the effect of this?
T cell activation after macrophage fails to eradicate causative agent
Switch from innate to adaptive immunity
T cells activate macrophage – morphology change Epitheloid cells (look like epithelial cells) Macrophage fusion – multinucleated (Langhans) giant cell
Persistent inflammation causes significant tissue damage (mostly caused by macrophage)
Granulomatous inflammation: Outcomes (TB)
what causes this? what is often the case with this? what can you see in x-rays?
what happens to the causative agents? when is there an issue?
Causative agent (Mycobacterium tuberculosis) eradicated
Tissue healing
Often scarring/fibrosis
Calcium deposits in scarred tissue – x-ray visible
Causative agent persists
‘Walled off’ by fibrous tissue
Infection kept in check by T cells and macrophage (bacteria slow dividing) hence equilibrium
Calcium deposition (calcification)
TB reactivation when immunity compromised (steroids, HIV) therefore agent breaks off and infects cells again
Healing and repair
when does it start?
what happens with chronic inflammation?
Starts at time of injury, even when there is ongoing inflammation
In chronic inflammation, injury, inflammation and repair co-exists
Healing and repair
primary and secondary intention
what is the primary intention? what molecules must be involved?
what is secondary intention? what is damaged and example?
Primary intention: Cell regeneration
Injury limited to epithelial layer (labile); Stable tissues if growth factors and cytokines TNF-a, IL-6 present, but not a true regeneration
e.g. small wounds, clean, uninfected surgical incision closed by surgical sutures
Secondary intention: Cell regeneration (epithelium) and fibrous repair (patching and scaring)
More extensive tissue loss; permanent (non-dividing) tissue type
e.g. large wounds, abscesses, ulcerations, ischemic necrosis
Healing and repair
Key players
cells?
other? (3)
what 4 other things are crucial?
Cells
e.g. macrophages, lymphocytes, platelets, endothelial cells, fibroblast etc
Cytokines, growth factors, enzymes
Extracellular matrix
Structural proteins (e.g. collagens)
Adhesive glycoproteins (e.g. cadherins) hence bind cells together
Proteoglycans and hyaluronan -> lubriction and strength
Healing and repair: Steps
what must first happen if there is a cut?
what will happen to the cells/skin after this?
what will be brought here and why?
what happens in ealry stage of repair?
how is wound surface area reduced?
how is scaffold formed for tissue regeneration?
Haemostasis – blood clot forming (coagulation pathways)
Stops bleeding; scaffold for migration of cells involved in repair and regeneration
Epithelial cell regeneration/proliferation
Stratified epithelia with stem cells on basal layer (stem cells can differentiate to replace upper layer)
Fibroblast, myofibroblast, endothelial cells, stromal stem cells form fibrous scar tissue
Angiogenesis (to provide cells to site)
Formation of new blood vessels
Granulation tissue
New fibroblast and small blood vessels forming on wound surface in the early phase of repair (24-72h)
Pink, soft, granular, accompanying oedema
Myofibroblast/ wound contraction
Reduction of wound surface area/ gap closure by the action of myofibroblast
Collagen synthesis and remodeling
Deposition of collagen and linking of collagen fibres
hence form scaffold for tissue regeneration
