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Immunology Bundle

by: Jenna Nicole

Immunology Bundle BIO 4251

Jenna Nicole
GPA 3.3

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About this Document

These notes cover the first exam comprehensively from the first day of class.
Dr. Marriott
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This 11 page Bundle was uploaded by Jenna Nicole on Tuesday August 2, 2016. The Bundle belongs to BIO 4251 at University of North Carolina - Charlotte taught by Dr. Marriott in Fall 2016. Since its upload, it has received 7 views. For similar materials see Immunology in Biology at University of North Carolina - Charlotte.


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Date Created: 08/02/16
Immunology Notes st 1 Lecture 8/23/16 2 main barriers to infection Skin Mucous membranes in lungs and intestines with chemical barriers such as stomach acid This is innate immunity Two types of immunity Innate & Adaptive Innate immunity does not improve in memory or show specificity or improve upon exposure again Adaptive immunity takes time which is a downside Takes about a week for adaptive immunity to really get going Innate & Adaptive immunity work hand in hand together Innate immunity holds things in check until adaptive immunity comes in HIV & AIDS attacks adaptive immunity nd 2 Lecture 8/25/16 Fig 2-11 Physical barrier in terms of mucus in the lungs and intestines Lysosomes in tears= anti-microbial enzyme Innate barriers= immediate & non-specific but at the downside of no memory Adaptive system improves with each exposure and becomes faster and strong but takes up a week to respond Adaptive immune system is organized - Primary & secondary lymphoid organs Primary =bone marrow (especially in the long bones), and the thymus We generate our immune cells in these primary lymphoid organs Lymph nodes – prominent in armpits, groin & neck Spleen = large central organ Lymphoid organs Adenoids, tonsils, peyer’s patches, gut associated lymphoid tissue, mucosal associated lymphoid tissue ^ all connected by bloodstream and lymphatic system Once generated in thymus & marrow, these immune cells go to the secondary lymphoid organs where they hang out and look for foreign challenges Lungs, GI & urinary-genital tracts has so many secondary because of their lack of physical barriers Immune cells= for now lets call them leukocytes Most important (immune cell) type of leukocytes is the lymphocute which have the signature of adaptive immunity Each individual lymphocyte has a specific receptor on its surface looking for a particular type of foreign particle Whenever a leukocyte encounters the particular particle their receptor looks for, they enter the cell cycle The daughter cells will go on to become memory cells and the cells necessary to fight the encountered challenge All leukocytes are generated from stem cells in bone marrow Pluripotent stem cells give rise to all blood cell types Hematopoesis is the process in which stem cells give rise to blood cells Hematopoesis has two pathways Myeloid pathway aka myeloid progenitor Lymphoid pathway aka lymphoid progenitor Myeloid pathway cells are important in innate immunity and play a role in generating the adaptive responses Growth factors, signaling molecules (cytokines) direct the development of cells during hematopoiesis Stromal cells= generic term for packing cells, these “direct traffic” by producing cytokines and growth factors Fig 2-6 b part 1 Lymphocyte 20-40% of all leukocytes in bloodstream, in lymphatic system they comroise almost all 3 main types B lymphocytes (B-Cells) T lymphocytes (T-Cells) Natural killer cells *Natural killer cells are weird in respect to the fact they don’t have specific receptors* B Cells B cells at rest look rather unremarkable but on the surface they have immunoglobulins (aka anti-bodies) that are membrane bound with each B cell having a different immunoglobulin When at rest and not activated they’re called a naïve lymphocyte *If a B-cell recognizes a foreign particle it goes into G1 and becomes a lymphoblast (DNA synthesis) then ultimately enters clonal expansion* Clones will have immunoglobulins identical to mother cell Clonal cells will then devlop into effector cells (i.e. plasma cell) Fig 2-6 B part 3 Highly developed ER & golgi apparatus for protein synthesis. Proteins made are immunoglobulins for secretion Effector cells are nothing enormous immunoglobulin factories often called plasma cells Some of the daughter cells will become memory cells Each time a particular challenge is encountered, clonal expansion occurs to make effector and memory cells and it takes around a week for this to happen T Cells A T-cell has a receptor called a T-cell receptor It does not recept for immunoglobulins Each T-cell has its own specific receptor The same way a B-cell activates upon encounters, so does a T-cell T- cells are picky eaters and a MHC molecule has to serve up a foreign particle to it Other leukocytes express MHC and serve up particles to a T-cell basically saying “like this?” Once T-cell is activated it also makes effector and memory cells Two types of T- cells Cytotoxic and Helpter T- Cells How do you distinguish a T-Cell from a B-Cell? They’re distinguishable by their expression of molecules on their surface called CD molecules (cluster of differentiation molecules) and there’s about 350 of these CD molecules Cytotoxic T cells express CD8 while Helper T cells express CD4 Natural killer cells Lack specific receptors and are involved more in innate immune response Lymphoid Pathway Gives rise to T and B cells Myeloid pathway makes monocytes > macrophage Monocytes circulate in bloodstream When monocyters enter into tissues they become macrophages and macrophages can be tissue specific Macrophages use pseudopodia to drag whole bacteria into the cell to be broken down *the lysosome and phagosome will fuse together to form the phagolysome* Angry macrophages make bleach Macrophages are a type of innate immunity With anti-body molecules tagged, phagocytosis works 10 to 100x better Opsinization is the term for tagging of foreign particles with anti-body Macrophages make MHC molecules with chunks of particle spat out and this brings the T cells its food to generate the adaptive immune response Macrophages are important in both innate and adaptive immune response Dendritic Cells Also scarf up things but instead of cell eating they prefer cell drinking and they’re especially good at serving up foreign particles to T cells Very mobile After pinocytosis they run to nearest secondary lymphoid organ to serve up with MHC the foreign particle to the T cells and they also produce a lot of signaling molecules (cytokines) Both dendritic cells and macrophages produce cytokines Neutrophils, eosinophils, and basophils are all lumped together as granulocytes Neutrophils are phagocytic with highly developed lysosomes and produce anti- microbial substances Neutrophils are usually the first cell to arrive at the site of infection 50-70% of your white blood cells are neutrophils making this cell type the most common Lecture Notes 8/30/16 Neutrophils tend to arrive at the site of infection/damage first Neutrophils are phagocytic with digestion enzymes Eosinophils are only 1-3% of WBC’s in blood steam and they’re more specific than neutrophils and hypothesized to be used in defense against parasitic worms Basophils are not phagocytic and are <1% of circulating WBC’s and play a key role in responses like allergies and they have granules full of cytokines Mast cells (not generated by hematopoiesis) have lots of granules that are important in allergy responses as well as being scattered in bodily cells they contain things like histamine in their granules and are similar to basophils In bone marrow self-reactive B cells are eliminated In thymus self-reactive T cells are eliminated Thymocytes= developing T cells Almost 98% of all T cells are killed off in thymus to eliminate self reactive cells You’re outnumbered 10:1 by the amount of bacteria that you carry around Look at reactive oxygen and nitrogen species Your immune system uses an innate system from prehistoric times to recognize particular, inherent and unchangeable microbial motifs, this system is composed of TLR’s (toll like receptors) TLR’s trigger the reactive oxygen and nitrogen reactions By activating macrophages, TLR’s tell them to start pumping MHC TLR’s activate your innate immunity! Immunology 9/1/16 Lecture Notes In the primary lymphoid organs selection for potentially harmful cells occurs. Review notes. Reach chapters 2 & 3 this weekend and type up those notes! Innate immune cells like macrophages and dendritic cells play dual roles in innate and adaptive immunity. Foreign Particles Foreign particles are actually antigens Antigens are just things that can provoke an immune response They can be our own stuff, self-antigens, but most typically if its going stark an immune response it’s going to be foreign Antigens=remember it doesn’t have to be foreign but typically it will be alien aka non-self It’s antigens that T & B lymphocytes are going to recognize Two Types of Challenges Your body has to deal with two particular type of different challenges -Extracellular (outside) challenges such as bacteria or parasitic worms -Intracellular (internal) challenges such as viruses and some bacteria (like TB and leprosy causing bacteria) Distinct arms of each system (innate & adaptive) to deal with the intra vs extra cellular pathogen Two Distinct Arms of Adaptive Immunity Extracellular Challenges Secreted antibody molecules produced by plasma B cells are churning out immunoglobulins which are designed to deal with extracellular challenges This arm of adaptive immunity is called the humoral arm Humoral= think antibodies & extracellular challenge Intracellular Challenges Antibodies can’t get at intracellular challenges Second defense mechanism that is tailor made to deal with compromised cells (virally infected cells, cancer cells, etc.) use the cytotoxic T cells (killer T cells) to kill any compromised host cells This arm is called the cell mediated arm / cell mediated immunity *These antigens will activate the T & B cells and give us our adaptive immunity* What makes an antigen good at provoking an immune response? An antigen that provokes a good immune response is called an immunogen To describe how good it is at provoking an immune response is called its immunogenicity Not all antigens are equal when it comes to immunogenicity Lipids & nucleic acids (3 ) = Least immunogenic of biological macromolecules Polysaccharides (Carbohydrates) (2 ) = A bit more immunogenic, better than lipid & nucleic acids Proteins (1 ) = the most immunogenic antigens! Primary focus on protein antigens Not all proteins are equal, some are better immunogens than others The properties of the protein influence the immunogenicity as well as recipient factors Whatever organism is responding will also influence how immunogenic a protein is Factors of Protein Immunogenicity 1- How foreign is this protein to the organism mounting the immune response? The closer an immunogen is to being self the weaker the response. Needs to be foreign. 2- Size. The size of a protein will also be a factor in its immunogenicity. A protein that is 100,00 Daltons (100 kDa) is an ideal size of a protein in terms of its immunogenicity. Any larger or smaller it doesn’t tend to be as good. Needs to be right size. 3- The actual composition of that protein is going to play a role. The chemical composition is a factor in its immunogenicity (primary structure). Organization and folding also plays a role. The protein organization at 4 levels will influence immunogenicity. A certain degree of organization and structure. 4- It is how easily your immune cells can tear the protein structures apart. When the macrophages and dendritic cells rip up (processing) plays a role in determining how good of an immunogen it is. The ability of our immune cells to process and show these antigen chunks to our immune cells. All four of these things are needed to activate our immune response. Two way street. Not only is the protein itself important. It turns out we can influence a particular proteins immunogenicity depending on the recipient. Recipient Factors 1- Genotype. The genotype of a recipient will govern the expression of particular immune molecules. Genotype also plays a role in expression of B and T cells receptors. 2- How we deliver the protein. How much and where? If you give too much of an immunogen your immune system just ignores it. The dose of the immunogen plays a key role. Too little is a weak response. Too much and your immune system just ignores it and becomes tolerate. 3- Route of administration. How you deliver the immunogen plays an important role. *Adjuvant is the “extra” stuff we put in vaccines besides just the protein. It is what will jack up our immune response to a particular antigen* Only 1 FDA approved adjuvant used for decades. Works by activating immune cells via toll like receptors to start expressing more molecules like MHC. Also promotes a bigger response to a particular protein antigen. It is important to remember that these lymphocytes and their particular antigen receptors, each one of those receptors is seeing and recognizing an antigen. It doesn’t see the whole thing, instead each individual T and B cell is only going to recognize a little part of a protein structure. These little parts that the T or B cells can recognize is called a particular epitope. This epitope is a little part of the whole antigen that is seen by a particular T or B cell. A particular protein can have many different epitopes that are recognized by different T or B cells. T and B cells recognize completely different epitopes B Cell Epitopes Immunoglobulins like to recognize the native protein bits as it comes floating along. Only for soluble proteins. The immunoglobulin likes to tag/stick onto the foreign part. An exposed/external epitope. B cells like exposed epitopes composed of hydrophilic residues. You can have a sequential or non-sequential epitope due to its protein folding. Epitopes can be either sequential or non-sequential. B cells will recognize external, exposed motifs. B cells combine soluble proteins. Epitopes they see have to be accessible/exposed so they’re hydrophilic. Can be either sequential or non- sequential. T Cell Epitopes T cells like to respond to internal strings of amino acids. This tells you because its hidden away in the center of the protein that you’ve got to pull apart the protein. T cells like internal epitope. They look for hydrophobic epitopes. They will recognize sequential and only sequential epitopes. T cells respond to linear hydrophobic epitopes. The MHC molecule is what will serve up these internal peptide chunks. It is a tri-molecular structure. When a T cell receptor is interacting with the antigen epitope and the MHC structure it is a tri-molecular structure. Antibodies A monoclonal antibody is where antibodies are identical in their specificity A polyclonal antibody is where antibodies are not identical in their specificity Structure of Antibody Molecule See figure 4-6 2 different constant regions for a light chain 5 different constant regions for a heavy chain About the first 110 amino acids of a light chain and heavy amino acids of a heavy change on each arm show tremendous variability between antibodies Within this variable region, there are even more variable regions known as hypervariable regions These hypervariable regions make up the antigen binding site (the area where this molecule will bind to antigen epitopes) Fc regions (constant region of the heavy chains) are actually what will elicit the biologic response September 8 2016 Immunology The constant region of the heavy chain will make up the FC region and this is important for the antibody. FAB region recognizes and grabs a hold of the protein antibody molecule. The FC region is important because it has a biological effect. There were 5 different constant regions that were found in the heavy chain- alpha, delta, nu, gamma, epsilon Immunoglobulin G secreted as antibody monomer which can elicit the big three responses IgD is membrane bound and can serve as the membrane bound antigen receptor for B cells IgM when it’s a monomer can also be membrane bound, expressed by naïve B cells and serve as the antigen specific receptor IgE is important in allergies IgM when secreted in its solid form is secreted as a pentamer which many binding sites (1 class of antibody that is secreted by a plasma cell) this molecule is huge however and tends to be limited to the bloodstream IgA dimer is found typically in the bodies secretions (tears, mucous and breastmilk) this works together to gum together potentially pathogenic organisms and this works as a preemptive strike (secreted across the epithelial layer) IgD and IgM have a tail that allows them to insert into the plasma membrane The tail of an immunoglobulin of IgD or IgM has an hydrophobic tail with amino acid residues that allows for them to insert into the plasma membrane, this cytoplasmic tail is short Ig alpha and Ig beta are the two heterodimer polyleptide chains that together allow a membrane bound immunoglobulin to function as a receptor can interact with the membrane bound immunoglobulin molecules and unlike the membrane bound immunoglobulin molecule it has long cytoplasmic tails The plasma cell doesn’t just stop at producing IgM it can switch production to IgG or IgA, but you can only mess around with only one end of the antibody molecule The antibody molecule shows tremendous diversity on one end with the other end staying pretty constant You produce between to 10 to 100 billion different antibody molecules In immunology, one gene does not encode 1 polypeptide when it comes to the light and heavy chains It turns out light and heavy chains are composed of multiple gene segments from gene families that are “cut and pasted” together V and J gene segments will encode the variable region of the light chain with the C gene segment encoding the constant region In the heavy chain, the D gene segment stands for diversity gene segment For the heavy chain, it turns out that the V, D and J gene segments together form the variable region of the heavy chain V, D and J has multiple gene segments for a heavy chain Leader sequence encodes the signal peptide when we translate this into a protein Random V-J joining For the heavy chain with the V, D, J joining, there are 2 recombination events needed The first recombination event is random D-J joining The second recombination even is when a D-J segment joins up with a V so V > D-J joining to form V-D-J segment Recombination Signal Sequences (RSS’s) direct the flow of traffic and come in 1 of 2 forms, one turn and two turn The one turn must find the two turn to combine with 4 sets of enzymes you need to know are going to be required for recombination events in developing B cells 1 Rag 1 a specific enzyme to cut DNA (in lymphocytes) 2 Rag 2 a specific enzyme to cut DNA (in lymphocytes) 3 TDT (in lymphocytes) 4 Double stand break repair enzymes (not specific to lymphocytes) Allelic exclusion is where you shut off the machinery for re-arranging the genes, this is why there is only 1 antigenic specificity per B cell Table 5-2 7 mechanisms that contribute to antibody diversity The first mechanism is multiple gene segments present in germline DNA The second is that those gene segments are combined randomly The third mechanism of diversity is this combination of the different heavy and light chains The fourth mechanism of diversity


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