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Innate Immunology Review.docx

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University of Ottawa
Dr Kingswell

Immunology Review The main goal of the immune system  distinguish self from non-self! - This does NOT mean it can distinguish good from bad! What is “good” or “bad” for the body is subjective to us. The body can only differentiate what is from our own body from what is foreign. - This is an essential topic in understanding autoimmunity and transplants. A transplanted bone marrow may be good for the body, but the body does not know this – it only recognizes it as foreign. In autoimmunity, the body fails to recognize itself - The immune system recognizes foreign pathogens through ANTIGENS (from “ANTIbody GENeration.” These are usually proteins that the body can recognize as foreign. - Note that usually, when we say something RECOGNIZES ANTIGEN it actually means it recognizes a PART of a protein, not the whole part  When the body recognizes something as foreign, it DESTROYS! Self Recognition – MHC molecules - MHC molecules are membrane proteins that allow for T cells (and natural killer cells) to recognize the cell itself and the proteins they carry. Think of them as scaffolds for which they hold up antigens. Note that T cells recognize both the MHC molecule itself and the antigen it presents - MHC molecules are made up of protein that is constant (the scaffold part) + a pocket that is variable, which is where protein (either foreign or self) goes - MHC molecules are not stable without a protein in their pockets! MHC class I molecules - These are found on all cell types. It’s each cell’s “citizenship ID.” - MHC class I molecules help for CD8+ T cells (see about these cells below) to “taste” what’s in their cytoplasm. Proteins are degraded and added to the MHC proteins as they’re being built in the ER MHC class II molecules - these are only found on cells of the immune system. It’s like their “employee” badge and used to communicate with CD4+ T cells - MHC class II molecules are formed in endosomes where there is a protein that is needed stabilize the pocket. Proteins phagocytosed and maintained in endosomes merge with the endosome with the MHC class II molecule and they combine to form a protein, which is presented on the cell surface Communication - Cells can communicate through receptors at close distance, or cytokines at long distances - Cytokines are chemical messengers (like hormones) that cause a response to another cell. These signals might be “Make antibodies!” or “activate!” - Chemokines are a group of cytokines that trigger migration to an area of the periphery or a tissue. Basically, they are cytokines where the signal is “Come hither!” The Innate Immunity Overview  Cells of the innate immunity are able to do multiple things: - recognize foreign pathogens and cancer cells (phagocytosis or cytotoxicity) - think of them as bouncers at a club – no idea or the wrong idea, you’re out! - remove cellular debris - present parts of foreign pathogens (antigens) to other cells (antigen-presenting cells or APCs) - start inflammation - all of these cells are produced in the bone marrow - they do this on a regular basis, therefore it’s your body’s INITIAL RESPONSE to invasion  These cells can recognize parts of foreign pathogens that are evolutionarily conserved. They are not geared towards a specific microbe such as Salmonella. They are able to distinguish bacteria in general as well as other microbes - For example: Gram-negative bacteria have a molecule on their outer surface called lipopolysaccharides (LPS). LPS is an example of pathogen-associated molecular pattern (PAMP). Cells of the innate immunity can recognize these PAMPs through pattern recognition receptors (PRRs). For example, Toll-like receptor 4 (TLR-4) is a receptor on cells of the innate immunity that can bind these bacteria. When bacteria is bound, the TLR undergoes a protein cascade inside the cell that eventually goes to the nucleus and starts making cytokines and chemokines (see below!) which “tattle-tale” on the bacteria, calling in reinforcements.  Antigen Presenting cells - These cells are specifically designed to present antigens to T cells and activate them. - All cells have antigen presented on their cell membrane, but these cells do it to ACTIVATE T cells. *Analogy – these are like the sailors inside the crow’s nest watching for icebergs. Everyone’s watching for icebergs, but these guys do it for a living and can go straight to the captain! Cells of Innate Immunity - Neutrophils  the most numerous, and conduct phagocytosis of microbes (Pac-man cells) - eosinophils  defend against parasites - basophils  involved in allergic reactions - mast cells  BIGGEST COMPONENT OF ALLERGIC REACTIONS - macrophages  resident of a certain tissue (their progenitors, called monocytes, are in the periphery). Antigen-presenting cell + scavenger (phagocytoses cellular debris and microbes) - natural killer cells  the oddball from the lymphoid lineage that kills cells (often cancer cells or infected cells) with no MHC class I molecule
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