Pathoma inflammation

pod2ndyear's version from 2015-08-22 18:03

2.1 inflammation

Question Answer
acute inflammation vs chronic inmlammationneutrophil vs lympthocytes gets into the interstitial space
acute inflammation characterized byedema and neutrophils
causes of acuteinfection-pahtogen or tissue necrosis(is followed by acute inflammation) the goal for both is to elimate pathogen or clear nectrotic tissue)
timing with acuteimmediate but with limited specificity (innate immunity) (in contrast with adaptive immunity which is speicfic but takes a long time)
acute inflammation is mediated by 5TLR, arachidoinc acid, mast cells, complement, hageman factor
TLRon macrophases and dendritic cells that recognize PAMPs. also part of chronic inflammation
PAMP exampleCD14 on macrophases recognize LPS on outer membrane of GN bacteria... an activated TLR upregulates NF-kapaB...activates multiple immune
arachidoinc acid released by phospholipase A2. acted on by cyclooxygenase or 5-lipooxygenase pathways.
cyclooxygenase pathway producesPG (I2,D2,E2) -mediate vasodiolation and increased vascuar. PGE2 mediates fever and pain. (pain is also mediated by bradykinin)
5-lipooxygenase pathways prodecesLeukotriene (LT) LTB4 attracks and activates neutrophils. LTC4,D4,E4-mediate vasoconstriction, bronchospasm and increased vascular
mast cellsfound in ct
3 mech that mast cells are activatedtissue trauma, complement protiens C3a and C5a, cross linking of cell srufce Ige by antigen
what happens when the mast cells are activatedimmediate response-histamin release and vasoconstrict and increased vascular (post cap venule) and Delayed response-arachidonic acid particularly leukotriens
complement fxnassist inflammation as inactive precursors
activation of complementclassical pathway-C1 binds to IgG or IgM that is boudn to antigen "GM makes classic cars" Alternate pathway- microbial products directly activate complemtnt. Mannose binding lectin- MBL binds mannos on microorganism and activates complements
Result of complement activationall pathways lead to the generation to C3a(trigger mast cell) C3b(opsonin for phagocytosis) ....C5a(chemotactic neutrophils)formation MAC(lysis by creating holes in cell membrane)
what is hageman factoran inactive proinflammatory protein produced in liver which is activated by exposure to subendotheils or tissue collogen
what does an active hageman factor activatecoaguation and fribrinytic systems, complement, kinin system(cleaves HMWKinin to braykinin for vasodialtion, increased vascurar and pain
when the common mediators work together what is the cardinal sign of inflammationrubor and calor-due to vasodialation(relaxed smooth m) mediated by HISTAMINE, PG and bradykinin. swelling-due to leakage into interstiial space from postcapillary venuels, mediated by histamine and tissue damage. Pain-mediated by bradykinin and PGE2. Fever-marophages release IL1 and TNF into blood and hit perivascular cells of hypothalmus that increase COX activity which increased PGE2=fever(raised temp)

2.1 part 2 (actue inflammating-neutrophils)

Question Answer
what are 3 phases of acute inflammationfluid, neutrophil-24 hour peak, macrophages-2-3 day peak
neutrophil phase step 1margination-vasodialating slows blood flow post capillary venuels and cells migrate from center to periphery
neutrophil phase step 2rolling-hit selectins "speed bumps" to slow down the nuetrophils.
2 types of selectinsP is from wibe-palade bodises and E is induced from TNF and IL-1
selectins bind tosialyl lewis X leukcyes -results in rolling of leukocytes (neutorphils here)
neutrophil step 3Adhesion-cellular adhesion molecules are upregulated by TNF and IL-1. they bind inigrins and aare upreguated by C5a and LTB4. all of this equals a firm adhesion to vessel wall
leukocye adhesion deficiencyautosmal rescessive defect of integrins (CD18 subunit)=delayed seperation of umbilical cord, increased neutrophil circulation, recurrent bacterial infections that lack pus(pus is dead neutrophils) formation
neutrophil step 4transmigration and chemotaxis-at the post capillary venuels and move toward chemical attratctions(bacterial prodeucts,IL-8, C5a and LTB4)
neutrophil step 5phagocytosis-consumptions enhanced by opsonin (IgG and C3b)
phagolysomomesa merged neutorphil with lysosome-"sourrounding arms' on neutrophil. its the lysome that phagocytoses
chediak-higashi syndromeprotien trafficking deffect (broken "chinies" railroad tracks) not allowing the phagolysosome to occur. sysmptoms include-increased rick of pyogenic infections, neutropenia, gian granules, defective primary hemostatsis, albinism, peripheral neropathy
neutorphil step 6destruction of phagocytosed material-O2 dependant (most effective) O2 is converted to O2minus by NADPH oxidase (oxidative burst). (O2minus is converted to H2O2 by SOD. and H2O2 is converted to HOCl by MPO.)
role of HOCL in neutrophil step 6destroys phagocytosed microbes.
CGD (chronic granulotoumous disease)poor O2 dependant killing due to NADPH oxidase. (disease affecting neutrophil step 6)
what does CDG lead toinfection and granuluoa formation with catalase -positive organisms-(Pseudomonia cepacia)
how to screen for CDGnitroblue tetrazolium test-turns blue if NADPH oxidase can convert O2 to O2minus (negative for CDG if turns blue)
MPO deficiency(neutrophil step 6 disease) defective conversion of H2O2 to HOCl. -increcreased risk of candida (NBT test is negative)
what is O2 independant killinganother way to accomplis step 6 neutrophil which is the desctrution of phagocytosed material. its less effective thouigh
neutrophil step 7resolution- nutrophils undergo apoptosis with 24 hours. =Pus (dead neutrophils within fluid)
what comes in aftter neutrophilsmacrophage-2-3 days after inflammation begins. derived from monocytes, come into cells the same way as nuetrophils.
role of macrphageingest via phagocytosis using secondary granules (lysosime) and manage situation by inducing resolution and healing(IL10 and TGFbeta), continue acute inflammation-IL8(call in more neutrophils), abcess, chronic inflammation

2.2-chronic inflammation

Question Answer
response and specificity for chronic inflamationdelayed response but specific ( part of adaptive immunity)
main type of cells present in chronic infmallamtionlyphocytes-T cells and B cells
chronic inflamation is stimlied bypersistant infection (most common), autoimmune disease, foreign matrial, CA
T cells-deveop in thymus and then undergo TCR rearrangment and becomeCD4 helper T cells(bind MHC class 2) or CD8 cytotoxic T cells(bind MHC class 1) to recognize primariily recognize antigens
how do T cells get activatedbinding of antigen/MHC complex and a second signal-B7 on APC binds CD28 on CD4 T cells "way t remember this 28/7=4"
once CD4 t cells are activated what happenssecrete cytokines (the job of CD4 is to help Bcells or CD8 T cells)
what are the 2 types of cytokinesTH1-helps the CD8 Tcells by generating IL2 and IFNgamma(macrophase activatior). TH2-helps the Bcells by producing IL4-(cass swithcing to IgG and IGE) and IL5(eosinophil chemotaxis and activation maturattio of B cells to plasma cells, and class swithcing to IgA. IL10 inhibits the TH1. review- IL10 are also made by macrophages to shut down immune response
CD8 t cells are activated bywhen an intracelluar antigen is processed and presented on MHC1 and a second signal-IL2 from CD4 TH1
once CD8 are activated how does it killsecrete perforins and granzyme to induce apoptosis. also can severet FasL which binds Fas on target cell and that also activates apoptosis
B lyphoctes undergo Ig rearrangment to becomenaive B celss that express IgM and IgD
How do B cells get activated 2binds IgM or IgD. B cells can present to CD4 helper Tcell via MHC 2 and then CD40 on B cell will bind CD40 on helper Tcell(this was the 2nd activation)
Helper T cells secreteIL4 and IL5. They help mediate B cell isotome swithching, hypermutiation and maturation to plasma cells
what is granulomoutous inflammationa supbtype of chronic inflammation.
what is the key cell for granuomtous inflammationEpitheloid histiocytes-basicly are macrophases with lots of pink cytoplasm. contain giatn cells. granulomas are deivied into two subtypes -(noncaseating and caseating_
noncaeating granulomuslack central necorsis(has nuc), assits with foreign materal, scarcoidoisis, Beryllimum exposoure, chrohn disease, and cat scratch disease
caseating granulomahas a central necrosis(lacks nuc). typicla of TB(can use the AFB stain) and fungal infections(can use a GMS stain).
steps for granuloma formationmacrophases present antigen to CD4 helper T cells. macrophased secret IL-12 inducing CD4 helper T cells to differential into TH1 subtype. the TH1 secres IFNgamma wich converts macrophases to epitheliood histiocytes and giant cells. both types of grauulomas occur in this way.