inflammation and repair Flashcards
4 major signs of inflammation
heat, redness, swelling, pain
name immunes cells in circulation
monocytes, leukocytes (neutrophils, basophils, eosinophils), platelets, lymphocytes
name 3 cells that recognize infection and produce inflammatory mediators
macrophages, dendritic cells, mast cells
what inflammatory mediators are released by macrophages, DCs, mast cells?
amines, cytokines (IL-1, IL-6, IL-12, IL-18)
what is different about capillaries in normal vs inflammation?
normal: most capillaries are empty
inflamation: vasodilation -> blood flows through most capillaries (hyperemia)
what is hyperemia?
increased blood flow
what is transudate? exudate?
transudate: Fluid that exits the capillaries under normal circumstances.
exudate: fluid containing metabolites and proteins
what changes in pressure happen during acute inflammation?
increase in hydrostatic pressure in all areas of microcirculation, and decrease in colloidal osmotic pressure
what is edema? (part of inflammation)
local swelling at the site of injury
what is histamine’s role?
increases vasodilation in arterioles and endothelial contraction in venules (leaky venules)
give an example of a delayed prolonged response?
sunburn
what is margination?
during inflammation when RBCs are clustered at the center and larger leukocytes become pressed against the venule wall
what protein is responsible for leukocytes slowing down? and stopping?
slow down = selectins
adhesion = integrins
what induces selectins?
cytokines and histamine
what is PECAM-1 (CD31)?
adhesion molecule found on the neutrophil and the endothelial cell wall that helps pull neutrophil through the gap between the endothelium wall
what kind of receptors on leukocytes sense chemokines
G-protein coupled receptors
what cells are recruited by chemokines?
TH1 and TH2
what cells are the first to arrive at site of inflammation
neutrophils
where do neutrophils come from? how long do they last?
bone marrow; die after a few days
what do NETs do?
Traps the microbe and stops the bacteria from travelling to other tissues
what are the precursors of macrophages?
monocytes
what are macrophage’s roles?
phagocytose bacteria, produce inflammatory mediators,
synthesize molecules for blood clotting, cell growth, tumor growth, collagen production, antibacterial defenses… ,
initiation of the immune response,
cleanup operations,
induction of general effects like fever, acute phase reaction, cachexia, loss of appetite
what are other names for macrophages?
microglial cells in CNS, interstitial dendritic cells, alveolar macrophages in lungs, kupffer cells in liver, osteoblasts in bones
what immune cells are involved in allergic and immune reactions
eosinophils and basophils
name 3 macrophages types and their role
classically activated macrophage: attack microbes
wound-healing macrophages: tissue repair
regulation macrophages: anti-inflammatory
steps of inflammatory reactions from day to day
day 1: edema
day 2: neutrophils
day 3: monocytes/macrophages
what do TLRs detect? what do they trigger?
detect pathogens, trigger inflammation
what do lectins detect?
fungal polysaccharides
describe the steps of phagocytosis
- recognition: PRRs recognize PAMPs (ex IgG, C3b), complement components
- engulfment: by phagosome
- killing and digestion: through lysosomal enzymes with free radicals
- extrusion
what are vasoactive mediator’s role?
Lead to vasodilation and increase the vascular permeability
name 2 vasoactive amines and their origin
histamines: released by degranulation of mast cells, basophils, platelets
serotonin: released by platelets
what are plasma proteases (type of vasoactive mediators) role?
increase permeability and edema
what are C reactive proteins and what do they do
involved in inflammatory processes and play an important role in various disease states
3 roles of complement?
lysis of bacteria,
chemotaxis,
opsonization
briefly describe the complement activation pathways
classical pathway: C1 binding to antibodies -> triggers vasodilation, edema, MAC
lectin pathway: triggered by microbe; use of mannose-binding lectin
alternative pathway: triggered by microbe; generates C3b
what is the outcome of all the complement pathways?
C3 is cleaved, C3a and C5a are released, C3b opsonin and C5a chemoattractant are also released, C5b-C9 form the MAC
what are kinin and role?
coagulation proteins made in the liver involved in pain signaling
name kinins. what receptors do they act on?
bradykinin, prostaglandin, 5-HT, histamine. act on free nociceptor nerve ending
what are prostaglandins made from?
plasma membrane component called arachidonic acid. made bvy enzyme COX-1
what do anti-inflammatory drugs act on?
inhibit COX-1 and COX-2 or lipoxygonase
most common anti-inflammatories
NSAIDs: aspirin and ibuprofen
what do prostaglandins do?
cause vasodilation, inhibit platelet aggregation and increase vascular permeability
name the chemokines receptors on leukocytes
CXCR, CCR
what cytokines cause fever
IL-1, IL-6, TNF
on what brain region do prostaglandin act to cause fever?
vasomotor center of the hypothalamus
why do we have fever?
increased temperature speed up leukocyte migration and reduces virulency of microbes
what effect can interleukins have on the liver?
induction of acute phase protein synthesis
what effect do interleukins and TNF have on the bone marrow?
increase production of leukocytes in a prolonged immune response
what is acute-phase reaction? what triggers it?
systemic reaction: fever, change in sleep, decreased appetite, decreased blood pressure, neutrophilia. triggered by IL-1 and TNF
what are IL-1 and TNF endothelial effects?
increase adhesion molecules, increase coagulation
what are IL-1 and TNF fibroblast effects?
increased fibroblast proliferation, increased collagen synthesis, increased collagenase
what are IL-1 and TNF leukocyte effects?
increase cytokine secretion
what is PAF and its effect?
platelet-activating factor: increase permeability, platelet aggregation, vasoconstriction, chemotaxis, GFs, clotting, fibrinogen
what are nitric oxide’s effect?
released by macrophages, reduces adhesion, increases vasodilation
where does the fluid escaped from vasculature during inflammation go after?
reabsorbed by lymphatic system
which cells clean-up after inflammatory process?
macrophages
4 things caused by acute inflammation
infarction, bacterial infections, toxins, trauma
what are the features of acute inflammation?
vascular changes, increased permeability & vasodilation, increased expression of adhesion molecules, neutrophils recruitment, mediators
what can cause scarred tissue after acute inflammation?
excess pus formation
what are the causes of chronic inflammation
viral infections, chronic infections, persistent injury, autoimmune disease, progression from an acute inflammation
what type of cells play an important role in chronic inflammation?
macrophages and lymphocytes
what are features of chronic inflammation?
mononuclear cell infiltration (monocytes), angiogenesis, fibrosis
what is the outcome of chronic inflammation?
scarred tissue
what are classically vs alternatively activated macrophages involved in?
classically: microbial actions and inflammation
alternatively: tissue repair and anti-inflammatory effects
explain the positive feedback loop involving macrophages and lymphocytes
macrophages release cytokines at the site of injury which activates lymphocytes, which in turn can release cytokines to activate macrophages
in chronic inflammation, what causes tissue injury and fibrosis?
activated macrophages
what effects does TNF-alpha have?
endothelial activation, angiogenesis, chondrocyte and osteoblast activation, prostaglandin formation, increase the release of proinflammatory cytokines
what is a granuloma?
ball of lymphoid cells containing macrophages and a giant cell in the center and T cells and fibroblasts in the shell surrounding
when are granulomas formed? what is their role?
when there is a foreign body that the immune system cannot get rid of during chronic inflammation.
to prevent the microbe from replicating and spreading in the rest of the body.
what happens in the middle of a granuloma once the macrophages kill the bacteria?
caseous necrosis
what cytokine promotes formation of granulomas?
IL-1
what is serous inflammation?
blisters; it self resolves and doesn’t have fibrin
in what disease is fibrinous inflammation often seen?
pneumonia
why does fibrin develop in alveoli during pneumonia?
to trap the bacteria in the alveolus, preventing it from spreading
in pneumonia, what cells lyse the fibrin strands trapping the bacteria?
macrophages
what is an abscess? how does it resolve? what causes it?
a hole with liquefactive necrosis (pus made of white blood cells). usually heals but scarred tissue remains. caused by bacteria infection.
what is an ulcer? what causes them?
erosion on the surface of the skin or organ. superficial caused by inadequate blood flow
what is an example of membranous inflammation?
diphtheria infection in the back of the troat causing formation of a thick membrane which can impair breathing
describe the 4 outcomes of inflammation
- resolution (usual)
- disharge of pus from excessive exudate and increased neutrophils
- chronic inflammation from persistent causal agent
- repair and organization (from excessive necrosis
how does repair work?
Fibroblasts fill the site of injury and lay down connective tissue, forming a scar
what is regeneration?
when the injured or dead cell can be replaced by a cell of the same type.
what is a labile cell?
cell that is continuously cycling. constant turnover of cells like in the epidermis
what is a stable cell? name an example
not in constant turnover, but there can be turnover if necessary, however, can’t fix extensive damage. ex: hepatocytes
what is a permanent cell? give an example
cells that can’t be replaced when they die. ex: neurons: only axons can be regenerated or other neurons can grow to compensate for loss of innervation
what is replacement?
when the damaged tissue cannot be repaired or regenerated
what is healing by primary intension? what cells does it involve?
small wounds; leads to no scar or hairline scar.
macrophages, angiogenesis, endothelial precursor, fibroblasts (secrete collagen)
what is healing by secondary intention?
A greater wound will cause the granulation of the tissue and will leave a larger scar
what is granulation and how does it form?
new blood vessels and fibroblasts grow and secrete collagen and elastin fibres into granulation tissue.
what is a keloid and how is it formed?
overactive collagen deposition
what are differentiated myofibroblasts? in what process do they participate?
fibroblast precursor. is contractile. important for tissue remodelling ex wound contraction
