Ch.2 Acute Inflammation pt.3 Flashcards
collection of soluble proteins (pre-made) and their membrane receptors that function mainly in host defense against microbes and in pathologic inflammatory reaction
Complement System
Innate
Inflamation will caused the trigger and release of chemokine TNF & Il-6 which will trigger an ____ ___ ____ in the liver. What does this response release?
Acute Phase response; releases pre-made complement protiens from the liver.
The critical step in complement activation is the _____ ____ of the third (and most abundant) component, C3
Proteolytic Cleavage
What complement pathway?
which is triggered by fixation of C1 to antibody (IgM or IgG formed adaptively) that has combined with antigen.
*req pre-formed antibodys
Classical
C1- antibody (IgM & IgG)
What complement pathway?
which is triggered by microbial surface molecules (e.g.,endotoxin, or lipopolysaccharide [LPS]), complex polysaccharides, and other substances, in the absence of antibody.
Alternative pathway
C3B innate ability to bind surface microbs
Which Complement pathway?
plasma mannose-binding lectin binds to carbohydrates on microbes and activates C1, also without a role for antibody
Lectin Pathway
MBL binds to mannose on microb
All three patways of the complement actiation lead to the formation of an enzyme called?
C3 convertase
Splits C3 into C3a & C3b
What does C3B go on to do?
Bind to other fragments and produce C5 Convertase.
What does C5 convertase do?
Cleaves C5 into C5a & C5b
C5b binds the late components (C6-C9), culminating in the formation of the ____
Membrane attack complex MAC
Function of Complement:
C3a and C5a are ____ they trigger mast cell degranulation resulting in histamine mediated vasodialation and increase in vascular permeability
Inflamation (1)
Anaphylotoxins
Function of complement:
When C3b and cleavage products are fixed to microbial walls, they act as ____ promoting phagocytosis by neutrophils & macrophages.
The leukocytes have receptors for the _____
Opsinins!
Opsinization & phagocytosis (2)
Function of complement:
assembly of the MAC on cells creates holes in the cell membrane that allow intracellular water and ions to leak out, resulting in the** death (lysis) of the cells**
Cell Lysis (3)
What kind of thin-walled microbes are verys suseptible to complement induced cell lysis?
Neisseria bacteria
Meningococci and Gonococci
Complement activation is heavily controled by ____ protiens that prevent healthy tissue from being injured at sites of complement activation
Regulatory Proteins
What complement regulatory protien?
blocks the activation of C1, the first protein of the classical complement pathway.
Inherited deficeny= hereditary angioedema
C1 inhibitor (C1 INH)
What complement regulatory protien?
____prevents formation of C3 convertases and ____ **inhibits formation of the membrane attack complex.**
paroxysmal nocturnal hemoglobinuria (PNH)
Decay accelerating factor (DAF) and CD59
What complement regulatory protien?
plasma protein that promotes the inactivation of the C3 convertase
Deficency causes what?
Factor H
Excessive complement activation
Proinflamatory protien produced by the live in an inacitve from APP
Hangeman Factor (XII)
Link btwn coagulation cascade & inflmation
What activate the Hangeman Factor?
Coming into contact with exposed sub-endothelium or collagen
Kinin clevaes high molecular weight kinogen (HMWK) to bradykinin which mediations vasodialation and increased vasculare permeability + pain
Kinin System
Hageman factor promotes activity of what 3 things?
- coagulation (intrinsic) and fibronolytic systems
- activates complement
- kinin system
Vasodialator of arterioles+ mild constrictor of post capillary venules
pooling of blood in capillaries to send lots of leukocyte rich blood to tissues.
Ties with PGE2 to lower pain threshold and chronic pain
Bradykinin
Pt. with antihypertensive medications have lots of cough, what can this be linked to?
Bradykinin
Similar to prostoglandis, ___ has a function in intial constriction of any feta vessles that eventually close
Bradykinin
Work on nerve endings, lower pain threshold, more pain. Peripheral nervous syste.
Neuropeptides
What common feature of inflmmation?
accelerated release of cells from the bone marrow postmitotic reserve pool (caused by cytokines, including TNF and IL-1) and is therefore associated with **increased numbers of immature neutrophils in the blood (“band” cells), referred to as a shift to the left
Leukocytosis
Most bacterial infections induce an increase in the blood neutrophil count
Neutrophelia
Viral infections, such as infectious mononucleosis, mumps, and German measles, cause an **absolute increase in the number of lymphocytes **
no fever BUT very Fatigued. Chronic inflmation
Lymphocytosis
allergies and parasitic infestations, blood eosinophils increase
Eosinophillia
Certain infections (typhoid fever and infections caused by rickettsiae, and certain viruses and protozoa) are associated with a **decreased number of circulating white cells
Leukopenia
Protiens sythesized by the liver and released on a contiunous basis at a homeostatic level.
Pre-preared, released all at once during inflmatory reaction (TNF and IL-6 trigger this)
Acute Phase Reactants
Ferritin, fibrogen, hepcidin, CRP, AA amyloid are all examples of what?
Actue phase protiens
What acute phase protien?
Binds bacterial polysachrdes then activates complemenet.
Detected in serum= inflamation , prognosis!
C-Reactive Protien
less= less infection. NSAIDs mask reduce levels & mask
What can be detected in the serum of patients with chronic inflmatory conditons like CAD, RA, obesity, cigarette smoker?
High levels of CRP
What acute phase protien?
Binds to iron and takes it away from microbs so they can use it for oxygen. Stored in macrophages of liver+ bone.
Ferritin
During an infection binding of Iron away from microbs by ferritin results in what?
Temporary iron defficency
What acute phase protien?
Has antibactieral properties as well as iron trapping function.
Can cause anemia in chronic inflamation
Hepcidin
4
The rate of accumulation of erythrocytes, if theres is ongoing inflammation elevation is proportionate to APPP secreation.
APP bind to cell membrane and neutralize (-) charge, causing stacks.
Erythrocyte Sedementation Rate
Chronic inflmation; vasculitis, endocarditis, surgery; all evelvate
What are the two hallmarks of acute inflammatory reaction’s?
- Vasodialation of small blood vessles
- accumulation of leukocytes & fluid in extravascular tissues (exudate)
What kind of accute inflammation?
marked by the accumulation of serumlike protein-rich exudates in body cavities lined by the peritoneum, pleura, or pericardium or spaces created by tissue injury.
Serous Inflamation
What kind of accute inflammation?
characterized by the deposition of fibrin as a result of the local activation of coagulation.
large increases in vasccular permeability so high MW molecules like Fibrogen accumulate within exudates; fibrin forms.
Fibrinous Inflamation
What kind of accute inflammation?
Characterized by the production of pus, an exudate consisting of neutrophils, the liquefied debris of necrotic cells, and edema fluid.
Purulent (Suppurative) Inflammation, Abscess
Infection with bacteria that cause liquifactive necrosis, ex. Staph, cause ____ inflamation
Pyogenic pathogens= pus producing
Purulent inflamation
A common example of an acute Purulent (suppurative) inflammation
appendicitis
localized collections of pus caused by suppuration within a tissue, an organ, or confined space.
Abcesses
What kind of accute inflammation?
a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue
only occure when tissue necrosis and inflamtion occur near surface.
Ulcers
most common in mucosa of mouth stomach, intestine, GI tract, skin.
What outcome of accute inflamation?
Tissue cleared of microbs, IL-1/6 no longer coming from macrophages, regeneraton capacity not exceeded
involves removal of cellular debris and microbes by macrophages and resorption of edema fluid mainly through lymphatics.
Compete reslution
What outcome of accute inflamation?
Occurs after substantial tissue destruction, when the inflammatory injury involves tissues that are incapable of regeneration, or when there is abundant fibrin exudation in tissue or in serous cavities (pleura, peritoneum) that cannot be fully cleared. (TGF-Beta)
Scar Formation
Healing by connective tissue replacement (scarring, or fibrosis)
What outcome of accute inflamation?
acute inflammatory response cannot be resolved because of either the persistence of the injurious agent or some interference with the normal process of healing.
Progression to chronic inflamation
