Immunology Lecture- 3
Complement System complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to destroy and clear pathogens and viruses. Consists of series of 26 serum proteins that work together activated in cascade Produced by liver, lymphocytes, and monocytes Complement proteins circulate in the blood in an inactive form. Cascade when first protein in the complement system series is activated in one reaction, triggers another reaction which trigger others and so on. Cascade activation complement proteins (C) are inactive until they are split into products. (e.g: C 1, when split, they become active ( C1a and C1b) Complement components of the innate immune system can be activated directly by microbes, can also be activated by antibodies, molecules of the adaptive system
Complement System
Functions of complement system Increase phagocytosis through opsonization or immune adherence. Create Membrane attack complex: cytolysis helps to rid the body of antibody-coated antigens (antigen-antibody complexes). Chemotaxis attracting phagocytes (macrophages and neutrophils) Enhances inflammation responses Regulate immune reactions Agglutination clustering and binding of pathogens together (sticking)
Stages in the Complement Cascade Initiation Amplification and cascade Polymerization Membrane attack
pathways Complement activation occurs by classical, alternative or lectin pathways, each of which is initiated differently. Classical activated by the presence of antibody bound to microbes Specific immune system ( depend on antibody to initiate it) Alternative activated directly when complement proteins bind to normal cell wall or surface components of microbes Lectin activated when a host serum protein binds a particular sugar (mannan) in the wall of fungi and other microbes Non specific reaction ( does not need antibody to initiate it)
Classical Pathway Rapid- Efficient Activators (complement-fixing antibody, IgG, IgM, sometimes microbe surface components) Host component that initially bind (C1 complex) Complement proteins involved C1 complex C4 C2 C3 C5 C6 C7 C8 C9 membrane attack complex
Alternative pathway Slow- less efficient Activator Bacteria or fungal cell wall Viruses Parasites surfaces Does require a specific antibody to get started Host component that initially bind C3 Complement proteins involved C3 Factor B C5 Factor D C6 Properdin C7 C8 C9 membrane attack complex
Lectin pathway Activator Mannose Host component that initially bind mannose binding lectin C5 C6 C7 C8 C9 membrane attack complex
Membrane attack complex The terminal stage of classical pathway involves creation of the membrane attack complex, (Called lytic unit) 5 terminal complement proteins (C5 through C9) associate into a membrane attack complex assembly begins with C5 cleavage into C5a and C5b fragments Forms and drills a hole in the membrane, leading to the hypotonic lysis of cells. C9 component is similar to perforin, which is produced by cytotoxic T- Cell and natural killer cells.
Some bacteria evade complement Capsules prevent C activation Surface lipid-carbohydrates prevent MAC formation Enzymatic digestion of C5a
Cytokines ( signaling protein) Cytokines ( chemical messenger) chemical substances secreted by cells that used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. Some cytokines are chemical switches that turn certain immune cell types on and off. Cytokines include lymphokines (produced by lymphocytes) monokines (produced by monocytes and macrophages). interleukins ( produced by leukocytes) interferons growth factors. Chemokines (chemically attract): Family of cytokines secreted by specific cells at site of injury or infection. Able to call or induce directed chemotaxis of immune cells to fight the microbe and help to repair the damage ( play role in inflammation) Chemokines are a promising target for new drugs to help regulate immune responses.
Interferons (IFNs) Group of Cytokines Small protein produced by certain white blood cells and tissue cells Classes: Interferon alpha lymphocytes and macrophages Interferon beta fibroblasts and epithelial cells Interferon gamma T cells Alpha IFN & Beta IFN: Cause cells to produce antiviral proteins that inhibit viral replication Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria Produced in response to viral infection microbe infection and other antigens increased nucleic acid content, immune products Bind to cell surfaces and induce expression of antiviral proteins Inhibits tumor cell growth Activates T and B cell Activates macrophages
Interferon is produced, released, and taken-up by a near-by cell, where by original cell is not protected but the recipient cell is protected. The antiviral activity of interferon.
Interleukin (IL) Group of cytokines The majority of interleukins are synthesized by helper CD4 T lymphocytes, as well as monocytes, macrophages They promote the development and differentiation of T and B lymphocytes The function of the immune system depends in a large part on interleukins Interleukin-1 ( IL-1) Source: macrophages- monocytes-dendrtitic cell B- cell Regulate immune response Inflammation reaction ( small amount induce acute phase- large amount induce fever) Play role in central nervous system Interleukin- 2 ( IL-2) stimulates produce and differentiation of T cell response immunity-boosting properties have made it a promising treatment for several illnesses. Interleukin-3 ( IL-3) Source: activated T- helper cell- NK- eosinophils- mast cell Regulate and control blood cell production differentiation and function of granulocytes and macrophages Interleukin- 4 ( IL-4) Source: macrophages, mast cell synthesis IgG1 and IgE Important role in allergic response (IgE) Interleukin- 5 (IL-5) Source: mast cells- eiosinophiles IgA production