acute inflammation Flashcards
What characterizes acute inflammation?
The presence of edema and neutrophils in tissue
What are the two primary triggers for acute inflammation?
Infection (to eliminate pathogens) and tissue necrosis (to clear necrotic debris).
What type of immune response is acute inflammation?
It is an immediate response with limited specificity, part of innate immunity.
What are Toll-like receptors (TLRs) and where are they found?
TLRs are present on innate immune cells (e.g., macrophages, dendritic cells) and are activated by pathogen-associated molecular patterns (PAMPs
What does CD14 recognize?
CD14 (a co-receptor for TLR4)recognizes lipopolysaccharide (a PAMP) on the outer membrane of gram-negative bacteria
What is the result of TLR activation?
Upregulation of NF-κB, a transcription factor that activates immune response genes and produces immune mediators.
How do TLRs contribute to chronic inflammation?
TLRs are also present on adaptive immune cells (e.g., lymphocytes), where they mediate chronic inflammation.
What releases arachidonic acid (AA) from the phospholipid membrane?
Phospholipase A2 releases AA.
What are the two pathways that act on arachidonic acid, and what do they produce?
1.Cyclooxygenase produces prostaglandins (PGs).
- 5-lipoxygenase produces leukotrienes (LTs).
What do prostaglandins PGI2, PGD2, and PGE2 mediate?
Vasodilation and increased vascular permeability.
What additional functions does PGE2 mediate?
PGE2 also mediates pain and fever.
What does leukotriene LTB4 do?
LTB4 attracts and activates neutrophils.
What do leukotrienes LTC4, LTD4, and LTE4 mediate?
Vasoconstriction, bronchospasm, and increased vascular permeability (slow-reacting substances of anaphylaxis).
Where are mast cells commonly found?
Mast cells are widely distributed throughout connective tissue.
What are the three main ways mast cells can be activated?
1.Tissue trauma.
2.Complement proteins C3a and C5a.
3.Cross-linking of cell-surface IgE by antigen.
What is the immediate response of mast cell activation?
Release of preformed histamine granules, which mediate vasodilation of arterioles and increased vascular permeability
What is the delayed response of mast cell activation?
Production of arachidonic acid metabolites, particularly leukotrienes.
What is the role of complement proteins in inflammation?
Complement proteins are proinflammatory serum proteins that “complement” inflammation by enhancing immune responses.
What are the three pathways of complement activation?
1.Classical pathway: C1 binds IgG or IgM bound to antigen.
2.Alternative pathway: Microbial products directly activate complement.
3.Mannose-binding lectin (MBL) pathway: MBL binds to mannose on microorganisms to activate complement.
What are the key functions of complement components?
C3a and C5a (anaphylatoxins): Trigger mast cell degranulation, causing histamine-mediated vasodilation and increased vascular permeability.
C5a: Chemotactic for neutrophils.
C3b: Acts as an opsonin for phagocytosis.
MAC (Membrane Attack Complex): Lyses microbes by creating a hole in the cell membrane.
What is the Hageman factor (Factor XII), and how is it activated?
Hageman factor is an inactive proinflammatory protein produced in the liver. It is activated upon exposure to subendothelial or tissue collagen
What systems are activated by the Hageman factor?
Coagulation and fibrinolytic systems
Complement system
Kinin system associated with bradykinin
What is the role of bradykinin in inflammation?
Bradykinin mediates vasodilation, increased vascular permeability (similar to histamine), and pain.
What causes redness (rubor) and warmth (calor) during inflammation?
Redness and warmth are due to vasodilation, which increases blood flow. Key mediators are histamine, prostaglandins, and bradykinin.
How does swelling occur in inflammation and what are the key mediators ?
Swelling is caused by fluid leakage from postcapillary venules into the interstitial space (exudate). Key mediators are:
Histamine: Causes endothelial cell contraction.
Tissue damage: Leads to endothelial cell disruption
What mediates pain during inflammation?
Bradykinin and PGE2 sensitize sensory nerve endings, causing pain.
What triggers fever during inflammation?
Pyrogens (e.g., bacterial LPS) cause macrophages to release IL-1 and TNF, increasing cyclooxygenase activity in hypothalamic perivascular cells. This leads to increased PGE2 and a higher temperature set point.
What causes margination of neutrophils during inflammation?
Vasodilation slows blood flow in postcapillary venules, allowing neutrophils to marginate from the center to the periphery.
How do neutrophils roll along the vessel wall?
Selectins (“speed bumps”) on endothelial cells bind sialyl Lewis X on leukocytes:
P-selectin: Released from Weibel-Palade bodies, mediated by histamine.
E-selectin: Induced by TNF and IL-1.
What mediates firm adhesion of neutrophils to the vessel wall?
Cellular adhesion molecules (ICAM and VCAM) on the endothelium (upregulated by TNF and IL-1) bind integrins on leukocytes (upregulated by C5a and LTB4).
What are the clinical features of leukocyte adhesion deficiency?
Delayed separation of the umbilical cord.
Increased circulating neutrophils.
Recurrent bacterial infections without pus formation.
How do neutrophils transmigrate and move toward the site of inflammation?
Neutrophils transmigrate across postcapillary venules and are attracted by:
Chemical attractants: Bacterial products, IL-8, C5a, and LTB4
What enhances phagocytosis by neutrophils?
Opsonins such as IgG and C3b enhance phagocytosis.
What is Chediak-Higashi syndrome?
An autosomal recessive protein trafficking defect impairing phagolysosome formation. Clinical features include:
Increased risk of pyogenic infections.
Neutropenia.
Giant granules in leukocytes.
Defective primary hemostasis.
Albinism.
Peripheral neuropathy.
What is the most effective mechanism for destroying phagocytosed material?
O2-dependent killing via the oxidative burst, generating HOCl (bleach) in phagolysosomes:
NADPH oxidase: Converts O2 to O2ꜙ.
Superoxide dismutase (SOD): Converts O2ꜙ to H2O2.
Myeloperoxidase (MPO): Converts H2O2 to HOCl.
What causes CGD, and what is its inheritance pattern?
CGD is due to a defect in NADPH oxidase and can be inherited as X-linked or autosomal recessive.
What are the clinical features of CGD?
Recurrent infections and granuloma formation.
may preseent with fever and sevral abscess formation
Infections by catalase-positive organisms such as:
Staphylococcus aureus
Pseudomonas cepacia
Serratia marcescens
Nocardia
Aspergillus
How is CGD diagnosed?
Using the Nitroblue Tetrazolium (NBT) test:
DHR floow ccytometry shows absence of fluoroscene
Normal: Dye turns blue (functional NADPH oxidase).
CGD: Dye remains colorless (defective NADPH oxidase).
What is the defect in MPO deficiency?
Defective conversion of H2O2 to HOCl due to myeloperoxidase (MPO) deficiency.
What are the clinical features of MPO deficiency?
1.Increased risk for Candida infections.
2..Most patients are asymptomatic.
How does the NBT test appear in MPO deficiency?
Normal, because the respiratory burst (O2 to H2O2) is intact
What mechanism is used in O2-independent killing?
Enzymes in secondary granules, such as:
Lysozyme in macrophages.
Major basic protein in eosinophils.
What happens to neutrophils after resolving the inflammatory stimulus?
Neutrophils undergo apoptosis and disappear within 24 hours.
When do macrophages predominate in inflammation, and how do they arrive?
Macrophages predominate 2-3 days after inflammation begins. They arrive via margination, rolling, adhesion, and transmigration.
What mechanisms do macrophages use to destroy phagocytosed material?
Phagocytosis (augmented by opsonins).
O2-independent killing via enzymes in secondary granules (e.g., lysozyme).
What are the four possible outcomes of the inflammatory process managed by macrophages?
Resolution and Healing: Anti-inflammatory cytokines (IL-10, TGF-β).
Continued Acute Inflammation: IL-8 recruits additional neutrophils.
Abscess Formation: Acute inflammation surrounded by fibrosis mediated by macrophages.
Chronic Inflammation: Macrophages present antigens to CD4+ helper T cells, promoting chronic inflammation.
what are the innate immune cells ?
macrophages and dendritic cells
what are the mediators of acute inflammation ?
toll like receptors
arachidonic acid
mast cells
complement
hageman factor
which complement activate mast cell degranulation ?
C3a and C5a
