Fundamentals Of Biology II
Fundamentals Of Biology II BIOL 11100
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This 5 page Class Notes was uploaded by Gordon Beier Jr. on Saturday September 19, 2015. The Class Notes belongs to BIOL 11100 at Purdue University taught by David Bos in Fall. Since its upload, it has received 54 views. For similar materials see /class/207827/biol-11100-purdue-university in Biological Sciences at Purdue University.
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Date Created: 09/19/15
Immunity Focus Questions 1 What are the most common routes of entry and invasion of pathogenic organisms What simple protection mechanisms do these routes of entry have in common What types of immune defense meet organisms that make it past the initial protection mechanisms How are signaling and coordination achieved across the various immune components The common routes of pathogen entry into the body are through the respiratory system the digestive system and through cuts lesions in the skin All of these routes of entry are lined with epithelial tissue which is specialized to form a lining and covering for body parts Epithelial tissue cells are tightly packed together often in multiple layers with little or no extracellular spaces or substances between them As such they form a nearly impenetrable barrier In addition epithelial cells have a variety of functions that aid in stopping pathogenic attack such as the production of acid mucous or enzymes that breakdown cell wall components If a pathogen should make it past these defenses both innate and adaptive immune components await Innate immune components are the first to respond because these components circulate as llready to go molecules and require no activation Adaptive immunity on the other hand involves cells and molecules that circulate in immature or inactive forms and are only activated by stimulation from innate immunity or directly from pathogen detection The innate and adaptive components of immunity are highly integrated and work closely together This is only possible because of cell signaling through paracrine and hormone regulators Primary among the signaling molecule of the immune system are the cytokines including interferons which are proteinbased molecules each of which serves multiple function and signals multiple cell types Which components levels of the immune system have the ability to specifically identify objects and cells as being foreign or native How What are specific examples of how it happens Although the epithelium does not distinguish foreign or native cells and molecules both innate and adaptive immunity do They do this through finding and recognizing foreign antigens on the surface of invading cells Antigens are any molecule that provokes an immune attack Detection of a foreign body can be through recognition of an entire antigen or an specific part of it an epitope The mechanism of recognition between innate and adaptive immunity is different bases on the cellularmolecular level and specifics of detail that is recognized The innate immune components recognize broad classes and types of foreign molecules called pathogen associated molecular patterns PAMPs Vertebrate organisms often recognize PAMPs as a molecules that are not made at all in the native body For example double stranded RNA lipopolysaccharide and mannosetype carbohydrates are not made at all by humans and the innate immune system recognizes these as molecules that arise in other foreign organisms It is important to point out that the innate immune components recognize the entire classes of these molecules not specific patterns or sequences in these molecules and they do so through PAMP binding to pattern recognition receptors or PRRs PAMP binding to PRRs can result either in stimulation of phagocytic endocytic pathways or cell signaling systems that alert the immune system This system is in contrast to the adaptive immune system which distinguishes native from foreign substances based on specific parts or sequences of foreign proteins through the use ofT cell receptors B cell receptors S and MHC molecules For example the adaptive immune system surveys and recognizes all proteins both foreign and native and it distinguishes the difference foreign or native based on the specific sequence of amino acids or a specific shape on part of an intact protein What are the main components of innate immunity and how do they fight infection The main components of innate immunity are 1 three types of leukocytes aka white blood cells 2 the inflammatory response and 3 the complement system The three types of39 are r g r39 quot and natural killer NK cells Neutrophils are the most abundant leukocyte and usually the first to detect and combat pathogens They work by ingestin through phagocytosis foreign objects and cells and killing them with lysosomes Macrophages are very large cells and also 39 D foreign I 39 U quotquot 39 0 also stimulate the adaptive immune system by presenting parts of the proteins from foreign cells to T cells discussed later NK cells work by inducing apoptosis in foreign cells This cell death results in the foreign cell breaking up into membranebound bits which are phagocytosed by macrophages The inflammatory response involves a number of changes brought about by the release of cytokines by damaged cells These cytokines attract neutrophils to the site of damage chemotaxis and cause the blood vessels to dilate and become more quotleakyquot which allows the incoming neutrophils and macrophages to get out of the blood stream into the damaged tissues Also the inflammatory response raises the temperature either locally or throughout the entire body which makes it harder for bacteria to grow Inflammation also stimulated the liver to pull iron out of the blood stream and store it This also makes it harder for bacteria to grow because they need large amounts of iron and this mechanism deprives them of a needed resource The complement system consists of functionally relates proteins which circulate in the blood These proteins are rapidly and easily activated through proteolysis a common mechanism of protein activation remember and once activated these proteins work to stimulate the adaptive immune system In addition complement proteins directly attack pathogens by forming the Membrane Attack complex which forms a pore in the membrane of the pathogen allowing fluid to enter the cell causing it to swell and burst Finally complement proteins act as opsonins which is when a special quotmarkerquot protein attaches to the surface of a cell That marker is readily recognized by macrophages and other cells and the effect of opsonization is to dramatically increase the rate of phagocytosis Dendritic cells DCs are also a main component of innate immunity and a key link between innate and adaptive immunity DCs are specialize to bind to PAMPs using PRRs then migrate to lymph nodes where they act as an antigen presenting cell APC In fact DCs don t really combat the pathogens like NK cells or macrophages they primarily alert the adaptive immune system to the infection They do so through processing the ingested pathogen and displaying fragments of it s proteins on MHC class II molecules to helper T cells That interaction activated the T cells which up regulate and coordinate activities of the adaptive immune system 4 Adaptive immunity works mostly through lymphocytes What are lymphocytes What kinds of Equot lymphocytes exist and what is their general mechanism of operation Lymphocytes are basically leukocytes with a special class of cellular receptors on the surface of the cell which detects and recognizes very specific epitopes or specific sequences of amino acids in short peptides There are B lymphocytes or B cells and T lymphocytes Tcells Lymphocytes circulate in the blood in a quotnaivequot form meaning that they haven t been exposed to or found a pathogen with an epitope that they recognize Each B cell and T cell expresses B cell receptors BCR and T cell receptors TCR respectively All of the TCRs on a T cell are identical similarly all of the BCRs on a B cell are identical and each TCR and BCR has very specific binding properties for a specific epitope However the BCRs on each B cell are different from the BCRs on every other B cell and the same goes for T cells The specific epitope for a TCR or BCR remains unknown as long as the cell is naive and has not been exposed to an epitope it can bind to When a naive B or T cell encounters a pathogen with epitopes that bind to its receptorusually with the help of an APC like a dendritic cell or macrophage then the lymphocyte clonally produces thousands of copies of itself a process called clonal expansion Clonal expansion produces two types of cells some are each capable of fighting the specific type of pathogen the original nai39ve cell encountered and other retain a longterm memory of that pathogen and quickly respond if that pathogen invades again in the future What are the types of T cells How do T cells recognize objects as foreign or native How do they fight foreign pathogens There are two types ofT cells the Helper T cells which have CD4 receptors on their surface and the Cytotoxic or Killer T cells which have CD8 receptors on their surface T cells in general detect specific sequences of amino acids which are bound to MHC proteins on other cells MHC proteins function is to bind protein fragments peptides and then travel to the surface of the cell where a T cell recognizes the MHCpeptide complex If the sequence of amino acids in the peptide is recognized as foreign by the T cell then the attack begins Nai39ve killer T cells bind to MHC class peptide complexes which are produced on almost all cells of the body When they find a peptide that is foreign the killer T cell goes through clonal expansion and copies of that T cell directly attacks any cell that presents that specific foreign peptide that was originally detected because the cell that presents such a peptide is infected with a virus or bacteria that lives inside that cell Killer T cells attack infected cells by inducing apoptosis much the same way that NK cells do Macrophages come and clean up the mess Nai39ve helperT cells bind to MHC class peptide complexes which are presented to them on cells specialized for phagocytosis and destruction of foreign pathogens like macrophages and dendritic cells They don t attack those cells because those cells have that foreign antigen not because they were infected but because they are specialized for ingesting destroying and presenting foreign cells and molecules Instead helper T cells go through clonal expansion and its clones secrete cytokines activating and alerting B cells and innate immune components Helper T cell clones stimulate a powerful and coordinated response When naive T cells go through clonal expansion most of the cells are functional and are involved in the immediate immune defense However a part of the cloned cells are quotmemory cells and they remain in circulation for a long period of time probably most of your remaining lifetime These quotrememberquot the specific attack and the specific pathogen so that if it is ever encountered again the next response will be much faster so fast in fact you probably won t know it if you got infected from that pathogen again How is the mechanism of B cell recognition of foreign antigens different from that ofT cells What are immunoglobulins and how do they relate to B cells Whereas T cells detect and bind to a short peptide bound to an MHC protein B cells recognize intact protein lipid or carbohydrate antigens or epitopes directly on the surface of pathogens When nai39ve B cells detect a foreign body they go through clonal expansion The clones are specialized not to attack cells but to secrete lots of proteins called immunolgobulins lgs aka antibodies The lgs are identical to the BCRs on the surface of the original nai39ve cell that detected the pathogen except they aren t bound to the surface of the cell they are secreted into the blood stream There they bind to copies of the specific antigen or epitope that originally stimulated the naive B cell Several different lgs are known which are produced by different types of B cells These lgs can neutralize antigens ability to proceed through their normal life cycle prevent them from infecting cells act as opsonins or agglutinate pathogens cause them to stick together lgs work in conjunction macrophages and other phagocytic cells of innate immunity B cells also produce memory cells similar to the way T cells do B cells that are not memory cells but participate in the immediate immune response are called plasma cells How is the great diversity ofT cell receptors TCRs and immunoglobulin achieved At any given time there are thousands and millions ofdifferent specific lgs and TCRs circulating in your body and each of them binds only to a very specific antigen or epitope The body is always randomly producing these throughout your lifetime through a process called somatic recombination also known as somatic rearrangement or VDJ recombination Key to understanding somatic rearrangement is the structure of the genes that code for the lgs or TCRs Each lg or TCR is made up one copy from each of the different parts of the gene The parts are called segments and there are 4 different segments V J D C Each segment comes in multiple copies and each copy of each segment is slightly different from the others There are about 50 different V variable segments 30 different D diversity segments 5 different joining segments and two different C constant segments In the process of somatic recombination we ll choose one from each of the four segments and join them together The recombining of V D J segments happens during B cell or T cell maturation and represents a permanent change in the DNA of that cell C segment selection and joining occurs as an mRNA transcription modification during splicing In the rearrangement process a D and a J segment are randomly chosen and joined together the DNA between the two selected segments is deleted then a V segment is randomly chosen and joined to the DJ DNA again deleting the DNA between the selected V region and the D part of the gene After the cell matures and begins gene transcription of the receptor the VDJ part of the gene is transcribed along with both C regions During the modifications to the mRNA that includes intron removal one of the two C regions is deleted along with the introns The other C region is spliced together with the VDJ to make the full gene with the VDJC components Because each unit of the V J D segments is composed of a different sequence of nucleotides random selection and inclusion of these units make a different gene and mRNA every time and hence a protein an g or TCR with its own special binding site structure I know I know somatic recombination is hard and you still don t understand It s hard to explain too Keep going over it and you ll get it eventually didn t get it the first time either Dr Bos David H Bos 2010 This material can be used for nonprofit educational purposes if properly attributed All other uses are prohibited unless written permission is granted
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