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After this class, you should be able to:
Tuesday February 21st, 2017 Class 28 Learning Goals Innate Immunity After this class, you should be able to: Describe the relative importance of the different parts of the innate immune system in terms of the number and types of infections prevented Predict the overall health effect of mutations in innate immune cells Define and identify an epitope Explain how a single group of cells can all have the same initial DNA…but then create a huge random diversity in the shape of a single type of protein
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What % of pathogens are stopped by passive barriers?
Eyes Blinking wipes tears across the eye. Tears contain the antibacterial enzyme lysozyme. Ears Hairs and ear wax trap pathogens in the passageway of the external ear. Nose The nasal passages are lined with mucus secretions and hairs that trap pathogens. Digestive tract Pathogens are trapped in saliva and mucus, then swallowed. Most are destroyed by the low pH of the stomach. Answer: 5 Airways (lining of trachea) Instead of reaching the lungs, most pathogens are trapped in mucus and swept up and out of the airway by the cilia. Ciliated cells Mucus-secreting cells
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1) How do platelets in the bloodstream limit infection?
Peer Instruction 1) How do platelets in the bloodstream limit infection? Blood vessel Red blood cell Platelet
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1) Neutrophils and macrophages help to stop infections. How?
Peer Instruction Granules contain pathogen-killing molecules Neutrophils arrive, begin removing pathogens by phagocytosis. Some newly arrived leukocytes mature into macrophages Pseudopodia engulf bacteria Lysosomes digest bacteria Macrophage Initiate tissue repair Vesicles secrete recruiting and fever signals
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1) How do mast cells signaling help to fight infections?
Peer Instruction 1) How do mast cells signaling help to fight infections? Mast cells at the site secrete signaling molecules that: -constrict blood vessel at wound -dilate blood vessels near wound Granules contain signaling molecules Nucleus Mast cell 2) How can the same signal cause two different responses?
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1) Will organisms with only innate immune systems live long?
Peer Instruction Pathogens stopped by mucous membranes Pathogens stopped by physical barriers Pathogens stopped by innate immune cells Internal pathogens that are new or have evolved rapidly to change their external molecular shapes 1) Will organisms with only innate immune systems live long? 2) Why are the external molecular shapes (aka epitopes) of parasites important to understanding immunity? 3) Will a strong adaptive immune system react to all shapes?
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3 2 Answer: 3 is probably the best 1 4
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1) What kind of biomolecule is this?
Peer Instruction 1) What kind of biomolecule is this? Light-chain Gene in a Single Immune Cell: Adaptive immune cell 2) What part of this is molecule is likely to have a uniform structure/function between different versions? 3) What part of this molecule does the unique binding with a specific epitope?
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2) Is this gene processing a permanent change in the cell?
1) How is an individual antibody protein created? Peer Instruction Start with DNA containing full set of V, J, and C segments. Light-chain Gene in a Single Immune Cell: Recombined DNA that has been cut and rejoined. mRNA: One V segment joins with one J segment and the C segment by recombination. Processed mRNA: Translation results in a protein with a unique amino acid sequence. 2) Is this gene processing a permanent change in the cell? Light-chain protein:
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Each antibody has a light chain and a heavy chain.
Peer Instruction Light-chain DNA: Heavy-chain DNA: Each antibody has a light chain and a heavy chain. Light chain: 40 ‘V’ regions, 5 ‘J’ regions, and 1 ‘C’ region Heavy chain: 51 ‘V’, 27 ‘D’, 6 ‘J’, and a C 1) How many possible antibody shapes are there? 2) The machinery that cuts the V, D and J regions is sloppy and inconsistent in making exact cuts. Is this good or bad for antibody diversity? Is this good or bad for your health?
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Concept Questions A physician’s assistant notes that “the most important cell in the entire immune system isn’t an immune cell; it’s a common skin cell”. Do you agree or disagree? Why? What are the health consequences for an individual born with: A mutation that inactivates all platelets A mutation that stops cell crawling in all immune cells A mutation that allows bacteria or viruses to move through skin cells A mutation that prevents innate immune cells from sending signals In three sentences (max), give a guide for deciding whether something is an epitope or not. Eventually, immune B cells compose a group of many thousands of cells. Each cell is 99.9% or more similar in terms of DNA to each other. However, there is a single gene that when compared to other B cells is less than 10% similar. How can this be? How did it happen?
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After this class, you should be able to:
Wednesday, February 22nd, 2017 Class 29 Learning Goals Adaptive Immunity After this class, you should be able to: Explain how the human adaptive immune system can prevent infections in the first patient infected (in other words: without evolving to stop that particular parasite). Compare and contrast the roles of B cells, T cells and dendritic cells in the adaptive immune system. Compare and contrast the humoral and cell-mediated responses. Examine the role of MHC proteins across different cell types.
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Peer Instruction Binding prevented Uninfected host cell Antibody Virus Antigen epitope Explain two ways that antibodies fight pathogens in the ‘humoral response’ Neutrophil Neutrophils naturally recognize and ingest anything bound by many antibodies
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B-cell activation Peer Instruction Foreign peptide B-cell receptors B-cell binds and presents antigen. B-cell MHC protein 2. The MHC-peptide complex interacts with complementary receptors on a helper T-cell, activating it. Why is B-cell activation good for fighting against a particular parasite? Activation B-cell Cytokines 3. Cytokines from the activated helper T-cell activate the B-cell. Helper T-cell B-cell clonal expansion Plasma cells Antibodies
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Explain the cellular system of B-cell activation.
Peer Instruction Foreign peptide B-cell receptors B-cell binds and presents antigen. B-cell MHC protein B-cell Cytokines B-cell activation Activation Helper T-cell B-cell clonal expansion Plasma cells Antibodies
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How do killer T-cells fight pathogens in the ‘cell mediated’ response?
Peer Instruction Killer c T-cell Virus-infected host cell Granules How do killer T-cells fight pathogens in the ‘cell mediated’ response? Virus particle
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2) How does a dendritic cell help against viruses?
Peer Instruction 1) Why is a dendritic cell like a ‘street sweeper’? Dendritic cells in the lymph nodes absorb a sampling of all protein available in the body MHC MHC proteins on dendritic cell present proteins Antigen Antibody-derived receptors on T-cells may bind to dendritically-presented proteins 2) How does a dendritic cell help against viruses? Cytotoxic ‘killer’ T-cells Clonal expansion Killer T cells leave lymph node -> into blood stream
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Concept Questions NASA is worried about Martian parasites. Before a Mars landing, patients were exposed to preserved Martian air. Why would this help? What cells would be activated? If NASA could predict the proteins on the outer surface of a Martian virus, what would be the best way to help astronauts protect themselves through adaptive immunity? Explain your answer. Grow thicker skin Create B cells with the DNA for all possible antibodies Create and many more B cells each with a different VDJ region Use gene therapy to give the same VDJ region to all B cells What cell would be most important in the response to the Ebola virus? What cell would be most important in the response to a poison molecule in the bloodstream? What cell would be most important in the response to a rapidly changing parasite? Diagram the input information and final products of the: Humoral response Cell-mediated response Predict three consequences of a failure to transport MHC proteins to the plasma membrane.
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