Inflammation Flashcards
What are the 4 features of acute inflammation?
- Rubor (redness)
- Calor (heat)
- Tumor (swelling)
- Dolor (pain)
What is inflammation a response to?
Cellular injury
What is the purpose of inflammation?
Remove cause and consequence of cellular injury
What are the 6 causes of inflammation?
- Pathogen —> infection
- Allergen —> hypersensitivity (allergic reaction)
- Auto-antigens —> auto-immunity
- Physical damage —> trauma
- Extreme temperatures
- Necrosis or necroptosis (non-apoptotic cell death)
Which 6 types of disease can cause inflammation?
- Infection
- Autoimmunity
- Hypersensitivity
- Trauma
- Fibrotic disease
- Cancer
Which cells are involved in inflammation?
- Epithelial and endothelial —> release cytokines and chemokines for immune cell recruitment
- Neutrophils —> acute
- Macrophages —> chronic
- T and B lymphocytes
- Eosinophils and mast cells —> allergy
How is an acute inflammatory response activated?
Change in blood flow at site of injury —> structural changes in microvasculature —> accumulation of immune cells and proteins
Which tissues can acute inflammation effect?
Any vascularised tissue
What does tissue damage stimulate? (3)
- Inflammatory signals
- Vasodilator release
- Vascular changes
What do inflammatory signals stimulate?
Neutrophil recruitment
What are the 2 things identified via inflammatory signals?
- Foreign material
- Non-apoptotic cell death
What are the 2 vasodilators released at sites of injury?
- Histamine
- Nitrous oxide
What 2 main vascular changes occur at sites of tissue damage?
- Inc permeability
- Plasma leakage
What is the benefit of increased vascular permeability and leakage at sites of tissue damage?
- Inc antibodies
- Inc proteins
- Inc leukocyte migration
- Inc barrier —> doesn’t reach other tissues
Which 5 mediators are regulate inflammation at sites of injury?
- Histamine
- Prostaglandins
- Cytokines
- Chemokines
- Complement proteins
Which cells release prostaglandins at sites of inflammation? (2)
- Mast cells
- Leukocytes
Which cells release cytokines at sites of inflammation? (3)
- Macrophages
- Endothelial cells
- Mast cells
Which cells release chemokines at sites of inflammation? (3)
- Leukocytes
- Activated macrophages
What releases complement proteins at sites of inflammation? (3)
Plasma
(Proteins synthesised in liver)
Which cells release histamine at sites of inflammation? (3)
- Mast cells
- Basophils
- Platelets
What are the 3 functions of histamine in inflammation stimulation?
- Vasodilation
- Inc vascular permeability
- Endothelial activation
What is the function of prostaglandins in inflammation stimulation?
Vasodilation
What is the function of cytokines in inflammation stimulation?
Endothelial activation
What are the 2 functions of chemokines in inflammation stimulation?
- Chemotaxis —> immune cell recruitment
- Leukocyte activation
What are the 4 functions of complement proteins in inflammation stimulation?
- Chemotaxis —> immune cell recruitment
- Leukocyte activation
- Vasodilation
- Opsonisation —> phagocytosis
What is exudate?
Fluids, proteins and cells that have seeped out of the blood
What are the 3 stages of inflammation occurring?
- Steady state of tissue
- Damage occurs
- Immune cells recruited
How do chemokines recruit immune cells to sites of inflammation? (3)
- Released
- Diffuse —> gradient
- Leukocytes with complementary receptors migrate to chemokine source
Which immune cells are first recruited to sites of acute inflammation and how?
Neutrophils via IL-8 (CXCL8)
Which chemokine attracts neutrophils to sites of inflammation?
IL-8 (CXCL8)
What are the 4 steps of neutrophil extravasation?
- Chemo-attraction
- Rolling adhesion
- Tight adhesion
- Transmigration
How does chemo-attraction work in neutrophil extravasation to sites of inflammation?
Cytokines stimulate endothelial upregulation of adhesion molecules (eg. selectins)
—> More for neutrophils to bind to on blood vessel wall
How does rolling adhesion work in neutrophil extravasation to sites of inflammation?
Carbohydrate ligands of neutrophils bind to selectins
- Low affinity state
- eg. PSGL1 binds to P and E-selectins
What do neutrophils bind in rolling adhesion?
Selectins
How does tight adhesion work in neutrophil extravasation to sites of inflammation?
Chemokines promote low to high affinity switch in integrins
—> neutrophils bind stronger
Which 2 integrins are switched in tight adhesion of neutrophils and why?
LFA-1 and Mac-1
—> enhances binding to ligands
How does transmigration work in neutrophil extravasation to sites of inflammation?
Neutrophil cytoskeleton rearranges and pseudopodia formation (temporary extensions)
—> Diapedesis
What mediates transmigration of neutrophils?
PECAM (Platelet Endothelial Cell Adhesion Molecule)
What are the 3 functions of neutrophils at sites of inflammation?
- Pathogen recognition
- Pathogen clearance
- Cytokine secretion
How do neutrophils recognise different gram -ve bacteria?
Use TLR4 and CD14 to identify different LPS (lipopolysaccharides) of bacteria
How do neutrophils clear pathogens?
- Phagocytosis
- Netosis
Why do neutrophils secrete cytokines at sites of inflammation?
Recruits and activates other immune cells
What are 2 examples of enzymes in lysosomes?
- Lysozyme
- Elastase
What are the 3 steps of phagocytosis?
- Endocytosis —> phagosome
- Fuse with lysosome —> phagolysosome
- Enzymes kill pathogen
- Involves ROS (from phagocyte NADPH oxidase)
- Involves antimicrobial peptides (eg. defensins)
What are the parts of acute inflammation resolution?
- Neutrophil apoptosis (short half-life) and inflammatory mediator turn over
- Macrophages clear apoptotic cells
- Repair/wound healing
What are the 3 types of inflammation?
- Acute
- Chronic
- Granulomatous
What is granulomatous inflammation?
Chronic inflammation involving the formation of a granuloma
What are some disease associated with chronic inflammation?
- Rheumatoid arthritis
- Asthma
- IBS
- MS
- Psoriasis
What are some disease associated with granulomatous inflammation?
- TB
- Leprosy
- Crohn’s disease
What are the 4 stimuli of chronic inflammation?
Persistent inflammatory stimuli
1. Prolongued infection
2. Persistant toxic stimuli (allergens/pollutants)
3. Unclearable particulates (eg. silica)
4. Autoimmunity —> always self-antigens in body
Which 3 cells are involved in chronic inflammation?
- Macrophages
- T cells
- Plasma cells
When will chronic inflammation occur? (2)
- No clearance of inflammatory agent
- Bystander tissue destruction
- Concurrent tissue repair —> fibrosis and angiogenesis
How are macrophages recruited to sites of chronic inflammation?
Tissue-resident or as monocytes in blood
What are the benefits of macrophages in chronic inflammation?
- Phagocytosis
- Cytotoxic
- Anti-inflammatory chemical release
- Wound repair
What are the negative consequences of macrophages in chronic inflammation?
- Cytotoxic —> damage
- Inflammatory
- Pro-fibrotic
What are the 3 types of T cells found at sites of chronic inflammation?
- Pro-inflammatory (Th1 and Th17)
- Cytotoxic T cells
- Treg cells (Th0)
What do pro-inflammatory T cells release at sites of chronic inflammation and why? (3)
- TNF
- IL-17
- IFN-γ
- Recruits neutrophils and macrophages
- Activates macrophages
What do cytotoxic T cells release at sites of chronic inflammation and why?
- Granzymes
- Perforin
- Granule-associated proteins
- Kill infected cells
What do Treg cells release at sites of chronic inflammation and why?
- TGF-β
- IL-10
- Immunosuppressive —> regulate inflammation
How do B cells contribute to chronic inflammatory?
Generate plasma cells —> antibodies
Do B cells always travel to the site of chronic inflammation?
No - may operate remotely
What is a granuloma?
Distinct circle of aggregated macrophages
What is the trigger of granuloma formation?
Strong T cell response to resistant agents
What are the 6 differences between acute and chronic inflammation?
- Time - onset and duration
- Effects
- Predominant cells
- Chemicals released
- Prominent feature
- Outcomes
What is the difference between the onset time of acute and chronic inflammation?
- Acute —> immediate
- Chronic —> delayed
What is the difference between the duration of acute and chronic inflammation?
- Acute —> days
- Chronic —> weeks to years
What is the difference between the effects of acute and chronic inflammation?
- Acute —> vasodilation, inc vascular permeability, leukocyte response
- Chronic —> perisistent inflammation, attempts at healing
What is the difference between the predominant cells involved in acute and chronic inflammation?
- Acute —> neutrophils
- Chronic —> macrophages
What is the difference between the main chemicals released in acute and chronic inflammation?
- Acute —> histamine
- Chronic —> ongoing cytokine release
What is the difference between the prominent visual feature of acute and chronic inflammation?
- Acute —> necrosis
- Chronic —> scarring (attempt at healing)
What is the difference between the outcomes of acute and chronic inflammation?
- Acute —> complete resolution or progresses to chronic
- Chronic —> scarring and tissue function loss
What are the 3 possible positives of inflammation?
- Can clear inflammatory agent
- Removes damaged cells
- Can restore normal tissue function
What are the 3 possible negatives of inflammation
- May cause excess tissue damage
- May cause scarring
- May lose organ function —> organ failure
What does post-inflammatory wound healing lead to?
ECM deposition
What is sequelae?
Aftereffects
