Inflammation I Flashcards
What is a common chemical defense mechanism between all epithelial surfaces in the body?
Presence of B-defensins
What is inflammation?
A physiologic process by which vascularized tissues respond to injury
Has both soluble mediators and cellular components
What are the hallmark signs of inflammation?
Redness, Swelling, Heat and Pain
What is acute inflammation?
Rapid, shor lived (minutes to days) relatively uniform response
Characterized by the accumulation of fluid, plasma proteins, and neutrophils
What is chronic inflammation?
Longer duration and includes all of acute response
Followed by the influx of lymphocytes, macrophages and possibly ending in fibroblast growth
May results in granuloma development
What is the physiological response to tissue damage (cause of inflammation)?
Increased blood flow
Vascular permeability
Leukocyte migration into tissues and accumulation at the inflammatory foci
Activation of the leukocytes to destroy the foreign invader
What are pathogen-associated molecular patterns?
Molecules associated with groups of pathogens, that are recognized by cells of the innate immune system
Recognized by toll-like receptors (TLRs) and other PRRs
What is the plasma protease system?
Complement, kinins and clotting/fibrinolytic proteins
Initiated by bacteria through recognition of degraded bacterial cell wall products or toxins
What do the endothelial cells do in response to inflammatory stimuli?
Contract, widening the gaps between the cells and permitting the passage of blood components
What are defensins?
Pore forming proteins that are a part of the immediate response
Lyse pathogens
What are kinins?
Serum proteases whose ultimate product is bradykinin, an agent known to induce smooth muscle contraction, vasoconstriction, and increased permeability of small blood vessels
What are prostaglandins?
Oxidative derivative of fatty acid arachidonate that mediates fever, pain and vascular permeability
What are leukotrienes?
inflammatory mediates derived from arachidonic acid that mediate vasoconstriction, increases vascular permeability
Endothelial adhesiveness and neutrophil chemotaxis
What is histamine?
Vasoactive amine stored in mast cells and basophils
Promotes acute inflammation through increased vascular permeability
What are neuropeptides?
Inflammatory mediators released by neurons in response to local tissue damage
What are cytokines?
Molecules secreted by cells (leukocytes) that act locally in micro-environment by binding receptors on target cells
What is IL-1?
Major inflammatory cytokine released by monocytes and activated macrophages
Increased blood flow, fever, enhanced expression of adhesion molecules, stimulation of cytokine production from other leukocytes
What are TNF-alpha and TNF-beta?
Derived from macrophages
Similar actions to IL-1
Also induces apoptosis
What is IL-4?
Activities related to allergic inflammation - basophil development and eosinophil chemotaxis
Participates in granuloma formation
What is IL-6?
Released by T cells and endothelial cells
Promotes monocyte differentiation
Increases platelets in circulation and fibrinogen production by liver
What is gamma interfueron?
Made by T cells and NK cells
Upregulates MHC proteins
Activates macrophages, making them more efficient killers
What is IL-12?
Mad by macrophages and B cells
Stimulates proliferation of NK cells, T-helper and T-cytolytic cells
What are opsonins?
Molecules that bind to bacterial surface molecules, making them more susceptible to phagocytosis
(e.g. C-reactive protein, mannose-binding lectin)
What are some pyrogens and how do they exert their effect?
IL-1, IL-6, TNF-a, prostaglandins
Exert their effect via the temperature regulating function of the hypothalamus
What are the three different complement pathways and their activating molecules?
Alternative - C3b
Lectin - Mannose-binding lectin
Classical - Antibody (IgM, IgG, IgA)
*All bind to microbial surface
What common pathway do all three complement pathways converge on?
Activation of C3 and C5 convertases
What are the functions of C3a and C5a fragments?
C3a and C5a are anaphylatoxins, C5a is a chemotaxin
Act on blood vessels to increase vascular permeability, allows fluid leakage and extravasation of proteins and monocytes and neutrophils
What are the three phases of complement activation?
Recognition phase detects presence of infection
Enzymatic phase rapidly and extensively amplifies activation and promotes cellular inflammation and opsonization
MAC phase leads to damage of microbial membranes
What are the components of the membrane attack complex?
C5b-C9
What is the function of C3b?
Binds to CR1 on macrophages and promotes phagocytosis
How does the complement promote the clearance of immune complexes from blood?
C3b binds CR1 on erythrocytes
C3b is deposited onto circulating immune complexes
RBCs bind CB3-immmune complex and carry them to the spleen
In the spleen/liver, macrophages strip off immune complexes and degrade them
How do deficiencies in the complement system predispose an individual to infection?
Ineffective opsonization and defects in MAC
Defects in opsonization are more severe than defects in membrane attack complex
