acute + chronic inflammation

Question 1

How immune system work?

2 different systems?
what 3 things do they do?
how is the system activated?

Answer 1

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

Question 2

Innate vs adaptive

3 key differences?

Answer 2

Innate
Fast
Non-specific
No memory

Adaptive
Slower
Specific to pathogen
Memory

Question 3

Inflammation definition

what is it? what does it do?

Answer 3

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

Question 4

Why is inflammation important?

what if not controlled properly?

Answer 4

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

Question 5

Inflammation: Triggers

4 main thinsg and examples of them>

Answer 5

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

Question 6

Inflammation: Clinical signs

5 main things?

Answer 6

functional impairment 
 pain
tissue swelling
redness
warmth

Question 7

Inflammation: Morphological patterns

what does pus contain?
what other things can happen?
how can there be tissue scarring?

Answer 7

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

Question 8

Types of inflammation (2)

Answer 8

Chronic inflammation

Acute inflammation

Question 9

Acute inflammation

what is it? examples

Answer 9

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

Question 10

Chronic inflammation

what is it? examples?

Answer 10

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

Question 11

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?

Answer 11

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

Question 12

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?

Answer 12

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

Question 13

Purpose of acute inflammation – the 5 Rs

Answer 13

Recognition of injury
Recruitment of leukocytes
Removal of causative agent
Regulation (closure of inflammatory response)
Resolution/Repair of affected tissue

Question 14

Termination of acute inflammation

when does this occur?
4 ways this occurs

why does this occur?

Answer 14

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

Question 15

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?

Answer 15

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

Question 16

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)

Answer 16

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

Question 17

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?

Answer 17

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

Question 18

Effect of acute inflammation events

Answer 18

Recruitment and exudation of leukocytes and plasma proteins from the blood vessels to the inflamed site to deal with infection/damage

Question 19

Leukocytes recruited: Neutrophils

what are these?
what do they do? (4)
what do they become?

Answer 19

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

Question 20

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?

Answer 20

Macrophage
Differentiate from monocytes
Phagocytosis
Releases factors that promote tissue repair (TGF-β)

Other leukocytes
Eosinophils (parasite infections, allergies)
Lymphocytes (viral infections) -> adaptive immunity

Question 21

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?

Answer 21

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

Question 22

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)

Answer 22

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)

Question 23

Chronic inflammation: Causes

3 main things, give examples of them

Answer 23

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

Question 24

Chronic inflammation: Mediators

3 main group mediators
give examples and their effects

Answer 24

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

Question 25

Different types of chronic inflammation 4 types

Answer 25

Non-specific chronic inflammation Autoimmune chronic inflammation - rheumatoid arthirtis Chronic suppurative inflammation Chronic granulomatous inflammation

Question 26

Non-specific chronic inflammation when does this develop? example - what is it caused by? inflammatory cells involved? what is ulceration?

Answer 26

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

Question 27

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?

Answer 27

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)

Question 28

Autoimmune chronic inflammation what is this? example inflammatory cells involved? key charcateristics?

Answer 28

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

Question 29

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?

Answer 29

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)

Question 30

Chronic suppurative inflammation what is this? examples? inflammatory cells involved? how does it start? how is it resolved clinically?

Answer 30

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

Question 31

Chronic suppurative inflammation Abscess how is it often caused? how? what must be done to fully heal? what is an abscess?

Answer 31

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)

Question 32

Chronic suppurative inflammation what is created when causative agent cannot be eradicated? why? what do these characteristically consist of? inflammatory cells?

Answer 32

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

Question 33

Langhans giant cell - what is this?

Answer 33

Multiple nuclei in horseshoe shape due to macrophages merging

Question 34

Chronic suppurative inflammation causes example of different ones

Answer 34

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

Question 35

Chronic granulomatous inflammation: To note what happens after macropage fail to eradicate the agent? what do they do? what is the effect of this?

Answer 35

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)

Question 36

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?

Answer 36

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

Question 37

Healing and repair when does it start? what happens with chronic inflammation?

Answer 37

Starts at time of injury, even when there is ongoing inflammation In chronic inflammation, injury, inflammation and repair co-exists

Question 38

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?

Answer 38

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

Question 39

Healing and repair Key players cells? other? (3) what 4 other things are crucial?

Answer 39

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

Question 40

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?

Answer 40

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