L4: Inflammation Flashcards
types of inflammation?
accute inflammation - innate immunity/natural
stimulus detected by the cells that heal it and end the stimulus?
chronic inflammation- adaptive immunity/aquired.
ongoing stumulus- cells try to heal but ongoing stimulus= more cells recruited and therefore increase inflammation and causes changes to cell so becomes a cycle. therefore increase disease
the 4 mechanisms by which immune systen causes tissue damage + inflammation?
type 1: immediate hypersensitivity e.g: allergic rhinitis, asthma, systemic anaphylaxis/ immune mechanism: igE antibody in response to allergens. mechanism of injury: bind to mast cells and basophils causing degranulation. release cytokines, histamines etc.
Type 2: antibody-mediated, e.g., drug allergies, autoimmune diseases, haemolytic anemia, Graves disease, etc. Immune mechanism: IgM and IgG target ag on the cell surface of ECM components. Mechanism of injury: opsonisation and phagocytosis of cells. Complement and Fc receptor-mediated recruitment and activation of leukocytes, e.g., neutrophils, and macrophages.
type 3: immune complex eg: serum sickness, systemic lupus, erthematosus? immune mechanism: immune complexes of circulating antigens and IgM or IgG. mechanism of injury: complement and fc receptor mediated recruitment and activation leukocytes.
type 4: T cell mediated. e.g: contact dermatitis, graft rejection, rheumatoid arthritis, asthma etc. immune mechanism: cd4 (delayed-type hypersensitivity) and cd8: t cell mediated cytolysis. mechanism of tissue injury: 1. macrophage activation: cytokine-mediated inflammation. 2. direct target cell lysis. cytokine-mediated inflammation?
importance of inflammation?
no inflammation= no adaptive immune response
triggers for inflammation?
infections (B,V +P) +microbial toxins
trauma: blunt and penetrating
physical and chemical agents (thermal injury, infaceation???_ environmental chemicals.)
tissue necrosis
foreign bodies: splinters, dirt, satures.
Immune response (hypersensitivity reactions).
functions of inflammation?
alert body to threat of tissue injury, neutralise/destory harmful agent, limit extent of tissue injury and prepare area for repair.
acute inflammation physiological responses and symptoms?
physiological response: increase blood flow symptom: heat (colo.r), redness.
vasodilation symptoms( redness (rubor) and swelling (tumor)
release of soluble mediators: pain (dolor)
extravasation of fluid: swelling (tumor), pain (dolor)
i.e: cells, fluids, proteins into intestinal space.
cellular influx (chemotaxis): pain (dolor), swelling (tumor)
increased cellular metabolism: pain (dolor), swelling (tumor), heat (colo.r)
phases of acute inflammation?
initiation: induction of the response e.g: stepping on a nail - tissue insult leads to pain, redness and swelling.
amplification: dependent on extent of tissue injury
destruction phagocytic, enzymatic and non enzymatic mechanisms.
termination: resolution of inflammation, anti-inflammatory mediators
the mechanism behind acute inflammation?
Physical trauma results in pain, redness, and swelling due to tissue damage and the subsequent activation of the inflammatory response.
Capillary Rupture and Tissue Damage:
The trauma causes capillary rupture, leading to local tissue damage.
Damaged cells release damage-associated molecular patterns (DAMPs) and other inflammatory mediators.
Recruitment of Mediators and Proteins:
Inflammatory mediators, pain mediators, and clotting proteins (e.g., fibrin and platelets) are recruited to the site of injury.
Blood coagulation occurs, forming a clot that helps seal the wound and prevents further bleeding.
Entry of Pathogens or Debris:
Ruptured capillaries can allow bacteria, debris, or other foreign substances to enter the tissue.
These substances release pathogen-associated molecular patterns (PAMPs), which further activate the immune system.
Activation of Immune Responses:
Complement activation: The complement cascade is triggered, leading to pathogen opsonization, membrane attack complex formation, and recruitment of immune cells.
Antibodies: If pre-existing antibodies recognize the pathogen, they bind and help neutralize it or enhance phagocytosis.
Neutrophil and Macrophage Recruitment:
Neutrophils and macrophages are activated and recruited to the site. They perform phagocytosis to clear pathogens and debris.
These cells produce pro-inflammatory cytokines (e.g., TNF-α, IL-1, IL-6), amplifying the immune response.
Cytokines and Inflammation:
Cytokines and complement activation increase vascular permeability and facilitate the influx of additional immune cells (e.g., monocytes, lymphocytes) from the capillaries into the site of inflammation.
This process contributes to the characteristic redness, swelling, and warmth of inflammation.
2 main cell types causing acute inflammation?
mast cells: activated by cd3/c5a, tissue trauma, decreased oxygen tension and IgE/ allergen causing granule release e.g: histamine.
macrophages: TLR ligation leads to signalling in macrophages and production of 5 major pro inflammatory cytokines.
the pro inflammatory cytokines produced by macrophages?
macrophages produce: IL-12,IL-8 (CXCL8) a chemokine recruiting neutrophils)
-RESPONSES:
UPREGULATING VASCULAR ADHESION MOLECULES (allowing plasma proteins like complement proteins and immune cells like neutrophils and macrophages to leave the blood into affected tissue causing swelling (edema)). allows leukocytes to adhere to vessel wall and migrate out of bloodstream into the tissue. DONE BY TNF-ALPHA, IL-1 AND IL-6.
INCREASED VASCULAR PERMEABILITY: TNF-ALPHA, IL-1
VASODILATION: TNF-ALPHA, IL01,-IL-6
(increased blood flow to site of infection/injury so area becomes red and warm. more oxygen, immune cells and nutrients can reach affected area and cause increased pressure and swelling.
INDUCE MATURATION OF DENDRITIC CELLS: TNF-ALPHA, IL-6, IL-1
The acute phase response?
IL-6, IL-1 and TNF cause hepatocytes of the liver to release:
- serum amyloid protein (inhibiting fever)
- C reactive protein (a marker of systemic inflammation)
- mannose binding protein which along with crp aids removal of microorganisms
fibrinogen: in blood clotting.
these are all acute phase proteins that promote repair, activate the immune system and contain infection or injury.
Inflammatory mediators produced locally at the site
of inflammation can act systemically eg on hepatocytes
of the liver leading to the “acute phase response”.
C reactive protein is used clinically
as a surrogate marker of systemic inflammation
what happens with tissue damage?
tissue damage, low oxygen tension and trauma. so degranulation of mast cells, vasoactive agents e.g: histamine is released. vasodilation occurs of capillaries?. gaps between the tight junctions of vasciular endothelial cells are forming i.e: increased vascular permeability to let the fluid in. regulation of adhesion molecules. cell flowing in bloodtsream e.g: neutrophil. when it sees the upregulation of adhesion molecule it gets stuck and knows to migrate to the sites of inflammation called diapedesis. i.e: the neutrophils squeeze between endothelial cells to exist the blood stream and enter tissue. complement is activated. chemotaxis occurs (il-8 coming out of macrophages?). phagocytosis occurs of the microorganisms.
Five Inflammatory Cascades?
contribute mediators for the acute inflammatory cascade:
1. Complement
2. Coagulation
3. Bradykinin
4. Arachidonic acid
5. Free Radicals
pathways in some detail?
through endothelial damage:
activation of the clotting cascade produces? plasmin which leads to complement activation.
(1)
degradation products of fibrin after thrombin will also increase vasciular permeability, neutrophils and chemotaxis.
bradykinin pathway: mediators are called kinins- potent mediators that cause pain. increased vasicular permeability, vasocdilation, pain, smooth muscle contraction. (3)
arachidonic acid: cell membrane damage releases membrane phospholipids acts on?? phospholipase. get arachdionic acid. 2 pathways after. lipoxygenase pathway producing leukotriene A4 that producesleukotrienes for neutrophil chemotaxis and bronchial smooth muscle contraction.
cycloxygenase pathway gives prostoglandins for increased vascular permeability, vascular dilation, neutrophil chemotaxis. (4)
respiratory burst after phagocytosis produces free radicals (5)
h2o2 + cl- by mpo gives ocl- +h20
2o2- + 2H+ by superoxide dismutase t h2o2 + o2
??? process is confusing for me
acute and chronic cells?
acute can develop into chronic. acute by trauma, bacterial infections, tissue injury etc. tissue resident mast cells, macrophages , neutrophils. deominated by neutrophils coming from blood supply. if stimulus not removed then develops into chronic where adaptive system cells are dominating. angiogenesis, mononuclear cells, can get fibrosis.
