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UNIT VII- NERVOUS & IMMUNE CHAPTERS 35, 37, 38* REVIEW WARM-UP 1. Contrast the functions of B cells and T cells. 2. What are memory cells? 3. How do vaccines work? 4. How does HIV affect the immune system? WARM-UP 1. Draw and label the parts of a neuron. 2. Describe saltatory conduction. 3. Explain how a nerve impulse is transmitted across a neuron. WARM-UP 1. What happens at the synapse? 2. Choose 1 neurotransmitter. Describe its action. 3. What is the role of the following structures in the human brain? a) Brainstem b) Cerebellum c) Cerebrum d) Corpus callosum NERVOUS SYSTEMS CHAPTERS 37, 38* YOU MUST KNOW The anatomy of a neuron. The mechanisms of impulse transmission in a neuron. The process that leads to release of neurotransmitters, and what happens at the synapse. How the vertebrate brain integrates information, which leads to an appropriate response. Different regions of the brain have different functions. TWO REGULATORY SYSTEMS • Nervous System • Endocrine System • Fast! • Slower to start • Short duration effect • Longer duration effect • Electric (ionic) signals …but also chemicals (neurotransmitters) • Chemical signals (hormones) • Affects nearby cells (local) • Affects any cell (long distance) NS & ES ARE RELATED 1. Neurosecretory Cells • In brain, but secrete hormones • Ex: epinephrine as hormone & neurotransmitter 2. Each system affects outcome of other • Ex: suckling…neurons…oxytocin…more milk • Ex: chemoreceptors detect glucose in blood…pancreas secretes insulin/glucagon NS & ES ARE RELATED 3. Feedback Mechanisms • Positive • Ex: suckling/oxytocin • Negative • Ex: calcium levels/ PTH/calcitonin ORGANIZATION OF THE NERVOUS SYSTEM Central nervous system (CNS) = brain + spinal cord Peripheral nervous system (PNS) = nerves throughout body Sensory receptors: collect info Sensory neurons: body CNS Motor neurons: CNS body (muscles, glands) Interneurons: connect sensory & motor neurons Nerves = bundles of neurons Contains motor neurons +/or sensory neurons PERIPHERAL NERVOUS SYSTEM Peripheral nervous system Somatic nervous system Autonomic nervous system Sympathetic division Parasympathetic division Enteric division NEURON = DENDRITE + CELL BODY + AXON Fig. 48-5 STRUCTURAL DIVERSITY OF NEURONS Dendrites Axon Cell body Portion of axon Sensory neuron Interneurons Cell bodies of overlapping neurons 80 µm Motor neuron NEURON • cell body: contains nucleus & organelles • dendrites: receive incoming messages • axons: transmit messages away to other cells • myelin sheath: fatty insulation covering axon, speeds up nerve impulses • synapse: junction between 2 neurons • neurotransmitter: chemical messengers sent across synapse • Glia: cells that support neurons • Eg. Schwann cells (forms myelin sheath) SCHWANN CELLS AND THE MYELIN SHEATH MAKE A MAD MAD, MAD NEURON • http://learn.genetics.utah.edu/content/neuroscience/madneuron/ BIOFLIX: HOW NEURONS WORK HTTP://MEDIA.PEARSONCMG.COM/BC/BC_0MEDIA_BIO/BIOFLIX/BIOFLIX.HT M?C8ENEURONS MEMBRANE POTENTIAL: DIFFERENCE IN ELECTRICAL CHARGE ACROSS CELL MEMBRANE Microelectrode –70 mV Voltage recorder Reference electrode GATED ION CHANNELS OPEN OR CLOSE IN RESPONSE TO 3 KINDS OF STIMULI • Stretch–gated - in cells that sense stretch; open when membrane mechanically deformed • Ligand–gated - at synapses; open/close when specific neurotransmitter binds to channel • Voltage–gated - in axons; open/close when membrane potential changes • Gated ion channels are responsible for generating the signals of the nervous system MEMBRANE POTENTIAL the outside of the cell is more positive the difference in charge while it is not “firing” is called the “resting potential” Action Potential Cartoon –Self-Guided http://outreach.mcb.harvard.edu/animations/actionpotential_ short.swf Action Potential Video https://www.youtube.com/watch? v=U0NpTdge3aw VOLTAGE-GATED ION CHANNELS • Resting state…more (+) outside than inside VOLTAGE-GATED ION CHANNELS • Stimulus causes Na channels to open VOLTAGE-GATED ION CHANNELS • Once enough Na+ moves in, membrane is “depolarized” VOLTAGE-GATED ION CHANNELS • Next, K+ gates open to allow them to move out…just as Na+ gates close… ”repolarization” VOLTAGE-GATED ION CHANNELS The Na+/K+ pump (using ATP) maintains a negative potential inside the neuron. ACTION POTENTIALS (NERVE IMPULSES) ARE THE SIGNALS CONDUCTED BY AXONS Resting potential: membrane potential at rest; polarized Na+ outside, K+ inside cell Voltage-gated Na+ channel = CLOSED Nerve impulse: stimulus causes a change in membrane potential Action potential: neuron membrane depolarizes All-or-nothing response Na+ channels open Na+ enters cell K+ channels open K+ leaves cell PROPAGATION OF THE ACTION POTENTIAL • How related to neuron? • As Na+ ions move in, the potential “flip-flops” triggering K+ gates to open • Meanwhile the Na+ ions diffuse over to next area causing the “flipflop” in charge • And it goes on and on… PROPAGATION OF THE ACTION POTENTIAL CONDUCTION OF AN ACTION POTENTIAL NERVE IMPULSE ANIMATION HTTPS://WWW.YOUTUBE.COM/WATCH?V=9EUDB4TN3B0 5:41 SALTATORY CONDUCTION: NERVE IMPULSE JUMPS BETWEEN NODES OF RANVIER (UNMYELINATED GAPS) SPEEDS UP IMPULSE Saltatory conduction speed: 120 m/sec BIOFLIX: HOW SYNAPSES WORK HTTP://MEDIA.PEARSONCMG.COM/BC/BC_0MEDIA_BIO/BIOFLIX/BIOFLIX.HT M?8APSYNAPSES CELL COMMUNICATION: NEUROTRANSMITTER RELEASED AT SYNAPSES AXON (PRESYNAPTIC CELL) DENDRITE (POSTSYNAPTIC CELL) NEUROTRANSMITTERS • Chemicals released from vesicles by exocytosis into synaptic cleft • Diffuse across synapse • Bind to receptors on neurons, muscle cells, or gland cells • Broken down by enzymes or taken back up into surrounding cells • Types of neurotransmitters: • Excitatory: speed up impulses by causing depolarization of postsynaptic membrane • Inhibitory: slow impulses by causing hyperpolarization of postsynaptic membrane EXAMPLES OF NEUROTRANSMITTERS • Acetylcholine (ACh): stimulates muscles, memory formation, learning • Epinephrine: (adrenaline) fight-or-flight • Norepinephrine: fight-or-flight • Dopamine: reward, pleasure (“high”) • Loss of dopamine Parkinson’s Disease • Serotonin: well-being, happiness • Low levels Depression • GABA: inhibitory NT • Affected by alcohol NERVOUS SYSTEM DISORDERS • LSD/mescaline – bind to serotonin and dopamine receptors hallucinations • Prozac – enhances effect of serotonin by inhibiting uptake after release • Morphine, heroin – bind to endorphin receptors decrease pain perception • Viagra – increase NO (nitric oxide) effects maintain erection • Alzheimer’s Disease (AD) – develop senile plaques, shrinkage of brain tissue MOUSE PARTY HTTP://LEARN.GENETICS.UTAH.EDU/CONTENT/ADDICTION/MOUSE/ MOUSE PARTY Mini-Poster Presentation: Drug: which drug and background information Neurotransmitter(s) Involved Action of Drug Summary Illustration: mouse drug affects REFLEXES • Simple, automatic response to a stimulus • Conscious thought not required • Reflex arc: 1. Stimulus detected by receptor 2. Sensory neuron 3. Interneuron (spinal cord or brain stem) 4. Motor neuron 5. Response by effector organ (muscles, glands) KNEE-JERK REFLEX EVOLUTION OF NERVOUS SYSTEMS VERTEBRATE BRAIN IS REGIONALLY SPECIALIZED Major Regions: forebrain, midbrain, hindbrain • • • Forebrain cerebrum Midbrain brainstem Hindbrain cerebellum HUMAN BRAIN Structure Function Cerebrum • Information processing (learning, emotion, memory, perception, voluntary movement) • Right & Left cerebral hemispheres • Corpus callosum: connect hemispheres Brainstem *Oldest evolutionary part* •Basic, autonomic survival behaviors •Medulla oblongata –breathing, heart & blood vessel activity, digestion, swallowing, vomiting •Transfer info between PNS & CNS Cerebellum • Coordinate movement & balance • Motor skill learning Human Brain Structure Function Cerebrum • Information processing (learning, emotion, memory, perception, voluntary movement) • Right & Left cerebral hemispheres • Corpus callosum: connect hemispheres Brainstem *Oldest evolutionary part* •Basic, autonomic survival behaviors •Medulla oblongata –breathing, heart & blood vessel activity, digestion, swallowing, vomiting •Transfer info between PNS & CNS Cerebellum • Coordinate movement & balance • Motor skill learning Human Brain Structure Function Cerebrum • Information processing (learning, emotion, memory, perception, voluntary movement) • Right & Left cerebral hemispheres • Corpus callosum: connect hemispheres Brainstem *Oldest evolutionary part* •Basic, autonomic survival behaviors •Medulla oblongata –breathing, heart & blood vessel activity, digestion, swallowing, vomiting •Transfer info between PNS & CNS Cerebellum • Coordinate movement & balance • Motor skill learning Human Brain Structure Function Cerebrum • Information processing (learning, emotion, memory, perception, voluntary movement) • Right & Left cerebral hemispheres • Corpus callosum: connect hemispheres Brainstem *Oldest evolutionary part* •Basic, autonomic survival behaviors •Medulla oblongata –breathing, heart & blood vessel activity, digestion, swallowing, vomiting •Transfer info between PNS & CNS Cerebellum • Coordinate movement & balance • Motor skill learning GREY MATTER: NEURON CELL BODIES, UNMYELINATED AXONS WHITE MATTER: FATTY, MYELINATED AXONS CHAPTER 35 WARM-UP 1. Define the following terms: • Pathogen • Antigen • Antibody • Allergen • Vaccine 2. What are lymphocytes? Where do B cells and T cells mature? CH. 35 REVIEW WARM-UP 1. What is the difference between innate vs. adaptive immunity? 2. Contrast the functions of B cells and T cells. 3. How are antigens recognized by immune system cells? 4. What are memory cells? 5. How does HIV affect the immune system? Chapter 35 THE IMMUNE SYSTEM WHAT YOU MUST KNOW: • Several elements of an innate immune response • The differences between B and T cells relative to their activation and actions. • How antigens are recognized by immune system cells • The differences in humoral and cell-mediated immunity • Why Helper T cells are central to immune responses TYPES OF IMMUNITY Innate Immunity • Non-specific • All plants & animals Adaptive Immunity • Pathogen-specific • Only in vertebrates • Involves B and T cells PLANT DEFENSES • Nonspecific responses • Receptors recognize pathogen molecules and trigger defense responses • Thicken cell wall, produce antimicrobial compounds, cell death • Localize effects FIGURE 43.2 Pathogens (such as bacteria, fungi, and viruses) INNATE IMMUNITY (all animals) • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors • Rapid response ADAPTIVE IMMUNITY (vertebrates only) • Recognition of traits specific to particular pathogens, using a vast array of receptors • Slower response Barrier defenses: Skin Mucous membranes Secretions Internal defenses: Phagocytic cells Natural killer cells Antimicrobial proteins Inflammatory response Humoral response: Antibodies defend against infection in body fluids. Cell-mediated response: Cytotoxic cells defend against infection in body cells. Barrier Defenses: •Skin •Mucous membranes •Lysozyme (tears, saliva, mucus) Antimicrobial Proteins: • Interferons (inhibit viral reproduction) • Complement system (~30 proteins, membrane attack complex) Innate Immunity (non-specific) Natural Killer Cells: •Virus-infected and cancer cells Inflammatory Response: • Mast cells release histamine • Blood vessels dilate, increase permeability (redness, swelling) • Deliver clotting agents, phagocytic cells • Fever Phagocytic WBCs: •Neutrophils (engulf) •Macrophage (“big eaters”) •Eosinophils (parasites) •Dendritic cells (adaptive response) NONSPECIFIC DEFENSES FIRST LINE OF DEFENSE • Skin • Antimicrobial proteins • Mucous membranes • Cilia • Gastric juice • Symbiotic Bacteria • Temperature NONSPECIFIC DEFENSES SECOND LINE OF DEFENSE • Inflammatory Response • Injury breaking the skin introducing pathogens • Histamine is released causing increase blood flow to area • Causes redness, swelling, warmth, and pain • Vasodilation (dilation of the blood vessels) • Caused by histamine • Phagocytes pass through capillary walls into tissues to ingest and destroy pathogens NONSPECIFIC DEFENSES SECOND LINE OF DEFENSE • Phagocytes destroy the pathogens and the injury begins to heal. • Neutrophil; Macrophage • Natural killer cells • Attack pathogen-infected cells • Effective at killing cancer cells and virus-infected cells NONSPECIFIC DEFENSES SECOND LINE OF DEFENSE • Complement • A group of about twenty proteins that “complement” defense reactions. • Help to destroy foreign or infected cell by promoting cell lysis • Interferon • Molecules secreted by viral infected cells that stimulate neighboring cells to produce proteins that help them defend against viruses SPECIFIC DEFENSES THIRD LINE OF DEFENSE A RESPONSE AIMED SPECIFICALLY AT THE PATHOGEN • Lymphocyte = white blood cell of the immune system • React to antigens • Two types – B cells • Made in the bone marrow • A part of the humoral immune response • Produce antibodies • Plasma cell- B cells that release specific antibodies • Memory cell- long-lived B cells that do not release their antibodies, they circulate in the body and respond quickly to eliminate any subsequent invasion by the same antigen. SPECIFIC DEFENSES THIRD LINE OF DEFENSE A RESPONSE AIMED SPECIFICALLY AT THE PATHOGEN • T cells • Made in the bone marrow, mature in the Thymus (T for thymus) • A part of the cell-mediated response • Destroy infected cells • Cytotoxic T cells (killer T cells); Helper T cells; Suppressor T cells COMPARING IMMUNE RESPONSES-PG 20 Type of cell Function Macrophage Engulfs and kills pathogens Neutrophil Engulfs and destroys pathogens Natural killer cell Punctures infected cells Helper T cell Activates cytotoxic T cells Cytotoxic T cell Punctures labeled infected cells B cell Labels invaders for destruction by macrophages Plasma cell Releases antibodies Memory cell Stores information about a pathogen PHAGOCYTOSIS INFLAMMATORY RESPONSE LYMPHATIC SYSTEM: INVOLVED IN ADAPTIVE IMMUNITY ADAPTIVE RESPONSE Lymphocytes (WBCs): produced by stem cells in bone marrow • T cells: mature in thymus • helper T, cytotoxic T • B cells: stay and mature in bone marrow • plasma cells antibodies • Antigen: substance that elicits lymphocyte response • Antibody (immunoglobulin – Ig): protein made by B cell that binds to antigens Fig. 43-9 Antigenbinding site Antigenbinding site Antigenbinding site Disulfide bridge C C Light chain Heavy chains Variable regions V V Constant regions C C Transmembrane region Plasma membrane chain chain Disulfide bridge B cell (a) B cell receptor Cytoplasm of B cell Cytoplasm of T cell (b) T cell receptor T cell Fig. 43-9a Antigenbinding site Antigenbinding site Disulfide bridge Variable regions C C Light chain Constant regions Transmembrane region Plasma membrane Heavy chains B cell (a) B cell receptor Cytoplasm of B cell Fig. 43-9b Antigenbinding site Variable regions V V Constant regions C C Transmembrane region Plasma membrane chain chain Disulfide bridge Cytoplasm of T cell (b) T cell receptor T cell THE ANTIGEN RECEPTORS OF B CELLS AND T CELLS • B cell receptors bind to specific, intact antigens • The B cell receptor consists of two identical heavy chains and two identical light chains • The tips of the chains form a constant (C) region, and each chain contains a variable (V) region, so named because its amino acid sequence varies extensively from one B cell to another • Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane • Each T cell receptor consists of two different polypeptide chains • The tips of the chain form a variable (V) region; the rest is a constant (C) region • T cells can bind to an antigen that is free or on the surface of a pathogen MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) • Proteins displayed on cell surface • Responsible for tissue/organ rejection (“self” vs. “nonself”) • B and T cells bind to MHC molecule in adaptive response • Class I: all body cells (except RBCs) • Class II: displayed by immune cells; “non-self” Fig. 43-11 Top view: binding surface exposed to antigen receptors Antigen Class I MHC molecule Antigen Plasma membrane of infected cell • Class I MHC molecules are found on almost all nucleated cells of the body • They display peptide antigens to cytotoxic T cells Fig. 43-12 Infected cell Microbe Antigenpresenting cell 1 Antigen associates with MHC molecule Antigen fragment Antigen fragment 1 Class I MHC molecule 1 T cell receptor (a) 2 2 Cytotoxic T cell Class II MHC molecule T cell receptor 2 T cell recognizes combination (b) Helper T cell • Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells • Dendritic cells, macrophages, and B cells are antigen-presenting cells that display antigens to cytotoxic T cells and helper T cells LYMPHOCYTE DEVELOPMENT • The acquired immune system has three important properties: • Receptor diversity • A lack of reactivity against host cells • Immunological memory GENERATION OF LYMPHOCYTE DIVERSITY BY GENE REARRANGEMENT • Differences in the variable region account for specificity of antigen receptors • The immunoglobulin (Ig) gene encodes one chain of the B cell receptor • Many different chains can be produced from the same Ig chain gene by rearrangement of the DNA • Rearranged DNA is transcribed and translated and the antigen receptor formed Fig. 43-13 DNA of undifferentiated B cell V37 V38 V39 V40 J1 J2 J3 J4 J5 C Intron 1 DNA deleted between randomly selected V and J segments DNA of differentiated B cell V37 V38 V39 J5 Intron C Functional gene 2 Transcription pre-mRNA V39 J5 Intron C 3 RNA processing V39 J5 mRNA Cap C B cell receptor Poly-A tail V V V 4 Translation V C C Light-chain polypeptide V Variable region C C Constant region B cell C ORIGIN OF SELF-TOLERANCE • Antigen receptors are generated by random rearrangement of DNA • As lymphocytes mature in bone marrow or the thymus, they are tested for self-reactivity • Lymphocytes with receptors specific for the body’s own molecules are destroyed by apoptosis, or rendered nonfunctional AMPLIFYING LYMPHOCYTES BY CLONAL SELECTION • In the body there are few lymphocytes with antigen receptors for any particular epitope • The binding of a mature lymphocyte to an antigen induces the lymphocyte to divide rapidly • This proliferation of lymphocytes is called clonal selection • Two types of clones are produced: short-lived activated effector cells and long-lived memory cells Fig. 43-14 Antigen molecules B cells that differ in antigen specificity Antigen receptor Antibody molecules Clone of memory cells Clone of plasma cells • The first exposure to a specific antigen represents the primary immune response • During this time, effector B cells called plasma cells are generated, and T cells are activated to their effector forms • In the secondary immune response, memory cells facilitate a faster, more efficient response Primary immune response to antigen A produces antibodies to A. Antibody concentration (arbitrary units) Fig. 43-15 Secondary immune response to antigen A produces antibodies to A; primary immune response to antigen B produces antibodies to B. 104 103 Antibodies to A 102 Antibodies to B 101 100 0 7 Exposure to antigen A 14 21 28 35 42 Exposure to antigens A and B Time (days) 49 56 ACQUIRED IMMUNITY DEFENDS AGAINST INFECTION OF BODY CELLS AND FLUIDS • Acquired immunity has two branches: the humoral immune response and the cell-mediated immune response • Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies • Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells • Helper T cells aid both responses Fig. 43-16 Humoral (antibody-mediated) immune response Cell-mediated immune response Key Antigen (1st exposure) + Engulfed by Gives rise to Antigenpresenting cell + Stimulates + + B cell Helper T cell + Cytotoxic T cell + Memory Helper T cells + + + Antigen (2nd exposure) Plasma cells Memory B cells + Memory Cytotoxic T cells Active Cytotoxic T cells Secreted antibodies Defend against extracellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins. Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells. Fig. 43-16a Humoral (antibody-mediated) immune response Key + Antigen (1st exposure) Stimulates Gives rise to Engulfed by Antigenpresenting cell + + B cell Helper T cell + Memory Helper T cells + Plasma cells + Antigen (2nd exposure) Memory B cells Secreted antibodies Defend against extracellular pathogens + Fig. 43-16b Cell-mediated immune response Key + Antigen (1st exposure) Engulfed by Antigenpresenting cell Stimulates Gives rise to + + Helper T cell Cytotoxic T cell + Memory Helper T cells + + Antigen (2nd exposure) + Active Cytotoxic T cells Memory Cytotoxic T cells Defend against intracellular pathogens MC EXAMPLES • 26. The brain coordinates the circulatory and respiratory systems of the human body. The control of breathing, for example, involves neural pathways among the structures represented in the figure above. One important stimulus in the control of breathing is an increase in blood CO2 concentration, which is detected as a decrease in blood • pH.Which of the following best describes the physiological response to an overall increase in cellular respiration in the body? • (A) In response to depleted blood CO2 levels, the pH sensors send signals directly to the rib muscles, resulting in an increase in the rate of CO2 uptake by the lungs and a decrease in CO2 utilization by the brain. • (B) In response to low blood pH, the pH sensors send a signal to the brain, which then sends a signal to the diaphragm, resulting in an increased rate of breathing to help eliminate excess blood CO2 . • (C) In response to high blood pH, the pH sensors send a signal directly to the lungs, resulting in a slower rate of breathing, and the lungs send a signal back to the heart once CO2 availability has been restored. • (D) In response to an increased rate of breathing, the rib muscles send a signal to the brain, which then sends a signal to the heart, resulting in a decrease in heart activity and slower flow of blood through the body. MC EXAMPLE • 27. Thyroxin is a hormone that increases metabolic activities within various tissue targets. Low levels of circulating thyroxin trigger the secretion of thyroid-stimulating hormone (TSH) from the anterior pituitary. TSH secretion then stimulates thyroxin production and release by the thyroid gland. The increased level of circulating thyroxin inhibits further secretion of TSH from the anterior pituitary. • Based on the information provided, which of the following can most likely be concluded about the TSH-thyroxin loop? • (A) A person taking thyroxin to supplement low thyroxin secretion will produce more TSH. • (B) Increased thyroxin production would cause elevated ribosomal activity in the anterior pituitary. • (C) The structure of the loop would lead to elevated thyroid and tissue activity due to positive feedback. • (D) The feedback mechanism would maintain relatively constant levels of thyroxin throughout tissue targets. MC EXAMPLE • Antigen invader B-cell meets antigen B-cell differentiates into plasma cells and memory cells plasma cells produce antibodies antibodies eliminate antigen. The preceding sequence of events is a description of A. Cell mediated immunity B. Humoral immunity C. Nonspecific immunity D. Phagocytosis E. Cytotoxic T-cell maturation • A man contracts the same flu strain for the second time in a single winter season. The second time he experiences fewer symptoms and recovers more quickly. Which cells are responsible for this rapid recovery? A. Helper T-cells B. Cytotoxic T-cells C. Memory cells D. Plasma cells MC EXAMPLE • Which of the following cells is most closely associated with phagocytosis? • Neutrophils • Plasma cells • B cells • Memory cells • LFRQ • The immune system is the body's defense against foreign invaders and is divided into specific and nonspecific immunity, and humoral and cell mediated immunity. Answer 3 of the 4 following questions: • Describe the primary immune response and how an invading antigen is met, dealt with, and eliminated. Describe the cells involved and how they are created. • Describe the mechanism by which the immune system deals with viruses, invaders that make it inside our cells • Define nonspecific immunity, and list 3 examples of nonspecific defense mechanisms in humans • Define the term vaccination, and describe how a vaccination works.