Lecture 4 - Soluble Mediators of the Immune System PDF

The Immune System Soluble Mediators of the Immune System The Complement System Complement – a group of plasma proteins (20) that are activated in the presence of foreign substances Complement activation enhances & amplifies inflammation Bacteria & some other cell types are lys...

The Immune System Soluble Mediators of the Immune System The Complement System Complement – a group of plasma proteins (20) that are activated in the presence of foreign substances Complement activation enhances & amplifies inflammation Bacteria & some other cell types are lysed by complement activation Complement activation enhances both innate & adaptive defenses Innate, Internal Defenses Complement activation pathways  Classical pathway: requires antibodies Antibodies bind to target (antigen) Complement protein C1 binds to the antibody- antigen complex (complement fixation)  Alternative pathway: complement factors interact with microorganism glycocalyx  Lectin Pathway: employs mannose binding protiens. All three pathways lead to a cascade of protein activation, leading to activation of C3 Complement Cascade C3 is the start of the; Final Common Pathway  C3 cleaves to form C3a & C3b  C3a (& C5a) enhance inflammation by increasing histamine release, increasing vascular permeability & stimulating chemotaxis  C3b coats bacterial membrane supplying adhesion points (opsonization)  C3b initiates the cascade forming the membrane attack complex (MAC)  The MAC forms a hole in the cell membrane & enhances Ca2+ influx  cell lysis Inadvertent Effects of Complement Activation The complement system can cause significant tissue damage in response to abnormal stimuli. In these infectious or autoimmune conditions, the inflammatory or lytic effects of complement may contribute significantly to the pathology of the disease. Complement activation is also associated with intravascular thrombosis, which leads to ischemic injury to tissues. Deficiencies of Complement Low levels of complement suggest one of the following biological effects:  Complement has been excessively activated recently.  Complement is currently being consumed.  A single complement component is absent because of a genetic defect. If regulatory components are absent, excess activation may occur at the wrong time or at the wrong site. The potential consequences of increased activation are excess inflammation and cell lysis and consumption of complement components. Complement deficiency can also cause increased susceptibility to pyogenic infections (e.g., Haemophilus influenzae, Streptococcus pneumoniae) Deficiencies of Complement Other Soluble Mediators of the Immune Response Cytokines- control a variety of cellular responses thereby regulating the immune response.  Interleukins- regulate growth, mobility and differentiation of lymphoid cells.  Interferons- interfere with viral replication.  Tumor Necrosis Factor- mediates acute inflammatory response to infectious microbes. Hematopoietic stimulators:  Stem cell factor  Colony stimulating factors  Transforming growth factors  Chemokines Other Soluble Mediators of the Immune Response Other Soluble Mediators of the Immune Response Acute Phase Proteins A group of glycoproteins associated with the acute-phase response are collectively called acute-phase proteins or acute-phase reactants. The various acute-phase proteins rise at different rates and in varying levels in response to tissue injury (e.g., inflammation, infection, malignant neoplasia, various diseases or disorders, trauma, surgical procedures, drug response). The increased synthesis of these proteins takes place shortly after a trauma and is initiated and sustained by proinflammatory cytokines.