Module 5 Flashcards
how many complement pathways are there
alternative pathway
classical pathway
lectin pathway
what are the initators for the 3 pathways
classic
alternate
mannose binding lectin
classic - immune complexes, apoptotic cells, certain viruses and GN bacteria, CRP bound to ligand
Alternate- bacteria, fungi, viruses, tumor cells,
microbes with terminal mannose groups
classical pathway stage 1 and stage 2
antibody mediated pathway
stage 1 is recognition
-C1 (qrs) recognizes IgM or 2 IgG
-C1q binds Fc portion of IgG or IgM
-C1r and C1s attach forming C1- first enzyme of the pathway
-C1 - now active splits C4 into C4a and C4b, C2 into C2A and C2b
-C4b binds to proteins and carbs on antigen surface and C2a FORMS c4B2a known as C3 convertase - NOW ACTIVATED
Stage 2 - amplification or proteolytic complement cascade
-now C3 convertase splits molecules of C3 into C3a and C3b
stage 3 of classical pathway
MAC ATTACK
-C3b binds C4b2a to make C4b2a3b (C5 convertase)
-C5 convertase splits C5 into C5a and C5b
-C5b binds C6, C7, C8 and C9 to make c5b6789 (MAC)
-C5bC6C7C8 polymerizes C9 to form a tube that allows ions to flow into and out of cells. Causes cell to burst due to Na and H2O coming
CELL LYSIS
example of classical pathway
- transfusion of group O blood
C9 forms a pore in the donor RBC causing them to burst causing agglutination reactions
alternative pathway stages
- non antibody initiated pathway
-activated by microbial/mammalian cell surfaces (plants, yeast, bac)
-C1, C2 and C4 do not participate
STEP 1 -other serum proteins are converted causing C3 to activate
STEP 2-c3b and factor B combine to form C3b,B = C3 convertase
Regulation
- Factor H prevents C3b and Factor B from getting close it competes for a binding site on C3b eventually leading to C3 inactivation
mannose binding lectin pathway stages
1)-homologous to c1q structure
-calcium dependent lectins: collectins (collagenous lectins)
2)-MASP enzymes activate complement by interacting with two serine proteases called MASP1 MASP2 which then activates C4 and C2
FUNCTIONS OF PATHWAYS
1- cell lysis by MAC which leads to osmotic lysis of a cell
2-participate in immunity or other functions
when the host defends against infections what complement proteins are responsible for what
opsonization
chemotaxis and leukocyte activation
lysis of bacterial and mammalian cells
opsonization - covalent bonds between C3 and C4
chemotaxis and leukocyte activation - C3a, C4a, and C5a- anaphylatoxin receptors
lysis of bacterial and mammalian cells C5-C9 MAC
where there is interface between innate and adaptive immunity what complement proteins are responsible for what
antibody augmentation
responses
immunological memory enchantment
antibody augmentation - C3b and C4b bound to immune complexes and AG
responses - C3 receptors on B cells and AG presenting cells
immunological memory enchantment C3b and C4b bound to immune complexes and AG, C3 receptors on follicular dendritic cells
during disposal of waste what complement proteins are responsible for what
clearance of immune complexes from tissues
clearance of apoptotic cells
C1q - bonded bits of C3 and C4
what happens if there are abnormal changes in the complements
- cause tissue damage
-intravascular thrombosis
-abnormal levels in RA, lupusw
what can cause elevated complement levels
-inflammatory conditions
trauma myocardial infraction
testing is of limited significance
what can cause decreased complement levels
-if the complement was already recently activated
-if the complement is being consumed
-if there is a component of the pathway that is absent (opsonic , lytic activities)
patient is more susceptible to infection
what are other soluble immune response mediators
known as biological response modifiers - modulate your own immune response
there are four main sources of brms secreted by mononuclear leukocytes
-b lymph secrete AB
-t lymph secret soluble mediators
-nk cell secrete IFN ALPHA
-monocyte/macrophages secrete interferons, interleukins,
they have therapeutic uses
active - microbial or chemical to modulate - vaccinate
adoptive - using soluble mediators
passive - transfer of pre form antibodies
what are cytokines
mediators of immune response
-synthesized or secreted by cells of innate or adaptive immunity
-transmit signals between cells
-INNATE
-mediate early inflammatory reactions
-stimulate adaptive immune response
ADAPTIVE
-stimulate prolif/diff of AG-stimulated lymph
-active effector cells like macrophages
what are interleukins
mediators of immune response
-type of cytokine
-made by and act on lymphocytes
-function to mediate interactions between leukocytes but dont bind AG
-modulate inflammation and immunity by regulating growth, mobility, and lymphoid cell differentiation
what are interferons
mediators of immune response
-interfere with viral response and keep them from multiplying
-natural defense to microbes, tumors and AG
-signal neighboring UNINFECTED cells to destroy RNA and reduce protein synthesis and tell INFECTED cells to undergo apoptosis
-enhance gene expression
-inhibit cell proliferation
-increase immune effector cell
clinical use
-antiviral agents
-immunomodulators
-antineoplastic agents
what are type 1 interferons
- early innate immune response to viral infections
-IFN ALPHA AND BETA
GAMMA
-principle macrophage activating cytokine
-stimulates MHC class 1/2
-promotes differentiation of CD4+ to helper T cell type
-acts on B cells to switch IgG subclasses
-activates neutrophils
-stimulates NK cell activity
-used in clinical to increase cytokines
What is tumor necrosis factor
Mediators of the Immune Response
-principle mediator of acute inflammatory response to GN bacteria
-induces apoptosis and gene transcription
-actively recruits neuts and monocytes to infection sites and get rid of bacteria
-if TNF is low - acute inflammation is induced using leuko and endothelium
if middle level of TNF - inflammation is mediated
if increased TNF - severe disease state (septic shock from GN)
what are chemokines
Mediators of the Immune Response
-family of cytokines
-stimulates leukocyte movement from blood to tissue at site of infection
-regulates migration of PMNs in tissues
what are Hematopoietic Stimulator
Mediators of the Immune Response
-stem cell factor: acts on immature stem cells in bone marrow and thymus to promote proliferation
what are acute phase proteins
- produced by innate immune system
-NONSPECIFIC INDICATOR of inflammatory process
importance of CRP
-differentiates between bacterial (high crp) and viral infection
-good for treatment monitoring
-can reflect long or short term disease activity and response to drugs
in cardiovascular disease - crp and ldl are high
CRP is a better predictor of cardiovascular events than ldl
