inflammation and hypersensitivity - block e Flashcards
inflammation triggers
pathogens
damaged cells
toxin compounds
five signs of inflammation and causes of them
heat/redness - vasodilation, widening of capillaries heats tissues and causes redness
swelling (oedema) - fluid released into tissues, increased permeability, tenderness because of increased leukocytes in area
pain - fever and proliferation of leukocytes, systemic response
loss of function - resolution, wound healing - scar tissue (non functional) - prevents movement - further damage
stages of inflammation
Inflammatory response starts when macrophages & other cells resident in the affected tissues are activated.
Innate local response – binding of PAMPs/DAMPs to PRRs
Receptor signalling – release of inflammatory mediators
Leukotrienes. Prostaglandins, Platelet activating factors. Histamine - all come from the breakdown of cell membrane phospholipids - secreted very rapidly
chemokines and cytokines and complement cascade
Pathogen-associated molecular patterns
Damage-associated molecular pattern
Pattern Recognition Receptor
inflammation mechanism
injured tissue (endothelial cells), mast cells, and macrophages secrete inflammatory signals that induce vascular changes
increased blood flow to area increases delivery of beneficial proteins and leukocytes
Increased vascular permeability allows plasma proteins to gain entry to interstitial fluid
complement (C5a) enhances the process of vasodilation & helps activate endothelial cells and mast cells (resident in tissues)
resident cells phagocytosis
can phagocyte bacteria (macrophages and dendritic cells)
cells are recruited to the injury site by a process called extravasation
key cellular components of inflammation include; neutrophils, macrophages, dendritic cells, and mast cells
induced and regulated by cytokines (TNFα, IL-1β, & IL-6) & chemokines (CXCL1 & CXCL8)
leukocyte rolling and extrvaasation
rolling adhesion
tight binding
diapedesis
migration
neutrophils make up the first wave of cells that cross the blood vessel wall to enter an inflamed tissue
inflammatory response - phagocytes
phagocytes enter area and release inflammatory mediators that induce more phagocytes
may induce fever (temp > 38)
stimulates leukocyte activity and provides a less suitable environment for some pathogens
destroys pathogens, clears dead cells, sets stage for tissue repair
causes of immune mediated disorders
failure of immune response (auto-immunity)
inappropriate response to antigens that don’t pose a threat (hypersensitivity)
two types of hypersensitivity
immediate - symptoms appear in a short space of time
delayed - can take 2-3 days for symptoms to appear
classes of hypersensitivity
type 1 - IgE mediated
type 2 - IgG or IgM mediated
type 3 - immune complex mediated
type 4 - t cell mediated
IgE mediated hypersensitivity
Ig discovered in 1960s, causes allergies
displayed by mast and basophils - binds antigen on second exposure = degranulation
vasoactive mediators = histamine, heparin, prostaglandins, leukotrienes, and proteases
IgE induces cross linking of bound mast cells and basophils with release of vasoactive mediators
includes systemic anaphylaxis and localised anaphylaxis - hay fever, hives, eczema, asthma
IgE mediated response types
immediate early response - due to release of vasoactive compounds
late phase response - mediators released during the reaction cause localised inflammation
IgG and immune complex hypersensitivity
induced by antigens that induce IgM and IgG
cutaneous reaction - arthus reaction
reaction time is 2-6 hours
pathology - necrotising vasculitis
effector cells - monocytes and neutrophils
secreted mediators - products of complement activation
type ii hypersensitivity
antibody-mediated destruction of cells by IgG and IgM
antibody bound to cell-surface antigen can induce death of this cell by 3 mechanisms; complement system (create pores in cell membrane), antibody-dependent cell-mediated cytotoxicity (ADCC), the bound antibody can serve as an opsonin (attracts phagocytic cells to bind and phagocytose cell
when excessive or misdirected = damaging
type ii mechanism
surface antigen present on target cell
IgG Fc portion bind receptor on NK, MAC, and neutrophils
IgG/IgM binds to create an immune complex
complement activated
includes blood transfusion reactions, haemolytic disease of the new born and autoimmune anaemia
IgG type ii examples
Haemolytic disease of the new-born
Haemolytic disease when Rh- mother carrying a Rh+ baby
Can be prevented by the administration of Rhogam at time of delivery.
A Rh- mother pregnant by a Rh+ father – danger of developing a response to the Rh antigen that the foetus may have inherited from father
Can lead to mother rejecting the Rh+ foetus
RBCs from the foetus can enter the maternal circulation during pregnancy, but certainly at birth.
Results in the mother producing anti Rh+ antibodies
rhogam prevents b cell activation and memory formation
immune complex hypersensitivity
mediated by immune complexes and results in complement activation
usually immune complexes are important or clearance of antigen by phagocytes
in some cases large numbers can result in tissue damage
severity depends on - size of immune complexes, levels of immune complexes present, and the distribution within the body
immune complexes
normal part of adaptive immune response
recognised by Fc receptors on phagocytes and engulfed
cleared by RBCs in spleen or kidney and/or by complement activation which leads to lysis of the cells with the immune complexes
type ii hypersensitivity
failure to clear immune complexes = disorders in phagocytotic machine or irregularities in the antigen
when they are not cleared they can be deposited into the blood vessels or tissues
uncleared complexes can bind to mast cells, neutrophils and macrophages
Ab-Ag lattices
antigens create them
some have high affinity for certain tissues and are sometimes highly charged
complement elicits localised vasodilation and attracts neutrophils
results can be blood vessel inflammation (vasculitis), tissue damage (glomerulonephritis and arthritis)
arthus reaction
immune complexes deposited near antigen admin site induce arthus reaction
localised event - large immune complexes precipitate close to injection site of antigen
lytic enzymes from neutrophils (frustrated phagocytosis) and tissue damage also mediated by the complement membrane-attack complex
generalised type III reactions such as serum sickness occur when immune complexes are deposited throughout
t cell mediated hypersensitivity
only type that is purely cell mediated
initiated by t cells (CD4+ Th1 cells)
reaction takes 1-2 days
recruits macrophages
sensitisation phase and an effector phase (initiates on 2nd exposure)
contact dermatitis (poison ivy/oak)
type iv
after sensitisation T-cells, clonally expand and differentiate into effector T-cells
effector phase – 2nd exposure – T-cells secrete a variety of cytokines;
IFNγ, TNFα & TNFβ
these cytokines recruit and activate macrophages
macrophages (professional APC) – very good at presenting antigen = exasperates the response
Th17 helper T-cells and CD8+ T-cells also contribute
granuloma
the heightened phagocytic activity leads to a build-up of lytic enzymes from macrophages in the area of infection
a prolonged DTH response becomes destructive to the host and results in a visible granuloma
continuous activation of macrophages
induces them to adhere closely
fuse to form multinucleated giant cells
can displace normal tissue cells
forms nodules - continue to release lytic enzymes, destroying tissue and blood vessels, and cause necrosis
