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Bio 1202 Final.docx

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Biology 1202B
Michael Gardiner

Lecture 24: Immunology (Chapter 44) Disease has plagued all organisms for billions of years The word vaccination comes from vacca (cow), used cowpox to defend against smallpox What causes disease? o Pathogens o Protozoa o Viruses o Parasites o Bacteria o Protein o Fungi The immune system: made up of innate and adaptive immunity 3 lines of defence against invasion o Physical barrier: prevent entry of pathogen Mucus membranes have environments that are hostile to pathogens (stomach, reproductive tract, epithelium tissues) nd o Innate immune system (2 line of defence): generalized internal chemical, physical and cellular reactions against pathogens that have survived the physical barrier o Adaptive (or acquired) immune system: most complex line of defence, reaction is specific to a foreign substance Most organisms recognize unique pathogen-associated molecular patterns (PAMPs) found on microbial organisms, using host molecules called pattern recognition receptors (PRRs) once specific PRRs are activated by PAMP, various components of innate or acquired immune responses are activated Innate Immunity Innate immunity: immediate, nonspecific response targets invading pathogens and has no memory of prior exposure to that specific pathogen invertebrates only have innate o Inflammation: creates an internal condition that inhibits or kills many pathogens o Specialized cells: engulf or kill pathogens or infected body cells (macrophages, neutrophils, complement proteins) Bacterial induction of inflammation: o A break in the skin introduces bacteria, which reproduces o Activated macrophages engulf the pathogens and secrete cytokines and chemokines o Activated mast cells release histamine which dilate local blood vessels and increase their permeability. Cytokines also make the blood vessel wall sticky, causing neutrophils to attach o Chemokines (from the macrophage) attract neutrophils, which pass between cells of the blood vessel wall and migrate to the infection site o Neutrophils engulf the pathogens and destroy them Signs of inflammation: heat, redness, swelling (due to dilation of blood vessels), pus (dead neutrophils), pain (migration of macrophages and neutrophils) In addition to inflammation, there is another nonspecific defence mechanism, the complement system interacting soluble plasma proteins that circulate in the blood and are normally inactive. They are activated when they recognize molecules on the surface of pathogens o They create a pore, and the bacteria cant maintain osmotic balance, so the cell swells and lyses The innate immunity system is often unable to distinguish between viral pathogen and host cells, so some go undetected. Strategies to identify viruses: o RNA Interference (RNAi): interferes with the cells ability to transcribe and translate genes, triggered by dsRNA Most viruses have dsRNA, so RNAi inhibits it, eliminating impact of the virus o Interferon: viral dsRNA may cause the infected host cell to produce two cytokines (alpha interferon and beta interferon) interferon binds to cell surface receptors, triggering changes to gene expression pattern in the cell They can affect ribonucleases, which degrade cellular RNA, thus protein synthesis, so replication of the viral genome will stop o Apoptosis: programmed cell death, pathogens may trigger abnormal cell activity that activates apoptotic responses o Natural killer (NK) cells: a type of lymphocyte, circulate in the blood and kill target host cells activated by recognition of cell surface receptors or by interferons secreted by virus infected cells NK cells are not phagocytes They secrete granules containing perforin, which creates pores in the cells membrane, so cell swells and ruptures, and proteases, which degrade proteins, and activate enzymes that degrade DNA and trigger apoptosis Lecture 25: Immunology (Chapter 44) Hematopoietic stem cells: form all the blood cells Bone marrow is a source of stem cells Adaptive Immunity Specifically recognize foreign molecules and clears them from the body since the reaction is specific, it may take several days to become effective Antigen: any foreign substance that can elicit an adaptive immune response (generates antibodies) most are macromolecules Antigens are recognized by two types of lymphocytes o B lymphocytes (B cells): differentiate from stem cells in the bone marrow. Released into the blood and carried to capillary beds in the lymphatic systems o T lymphocytes (T cells): produced by the division of stem cells in the bone marrow. Released into the blood and carried to the thymus, where they differentiate We know that lymphocytes recognize antigens because leukocytes (WBCs) in mice were killed by irradiation, and mice couldnt develop an adaptive immune response. Injecting lymphocytes from normal mice into these irradiated mice restored the adaptive immune response Two types of adaptive immune responses: o Antibody mediated immunity (AMI, humoral immunity) o Cell-mediated immunity (CMI) Antibody-mediated immunity (AMI, humoral): a protein produced by the body in adaptive immunity to destroy the antigen o Lymphocyte recognizes and binds to antigen, activated lymphocyte clears antigen from the body o Activated lymphocytes differentiate into memory cells that circulate in the blood, ready to initiate a rapid immune response (immunological memory) o Each B and T cell have receptors (BCRs and TCRs), which bind to a portion of the antigen called the epitope BCRs: 2 identical light chains, 2 identical heavy chains TCRs: alpha and beta chain chains are held together by disulphide bonds and form a Y shape o 2 general phases: T Cell activation: dendritic cell engulfs and degrades a pathogen, becoming an antigen presenting cell (APC) APC secretes interleukins which activate secretion of cytokines, clonal cells differentiate into helper T cells B cell activation and antibody production: B cell displays the antigen on the cell surface, TCR on a helper T cell binds to the antigen interleukins from the T cells stimulate the B cell to produce a clone of cells, clonal cells differentiate into plasma cells, memory B cells BCR and TCR antibody diversity: These proteins are encoded by different genes, diversity, portions of the DNA segments are randomly chosen and joined together, genetic rearrangement o Each antibody type has the same AA sequence in the constant region of the heavy chain/ light chain, but the variable regions differ in the heavy and light chains o The variable regions of the chains from the specific antigen binding site In humans, there are 5 classes of antibodies (classes are determined by the constant regions) o Lecture 26: Applications of Immunology (Chapter 44) Allergies: allergens are antigens that elicit hypersensitivity or allergic reaction o Allergens induce a B cell to secrete an overabundance of IgE antibodies, which bind to receptors on mast cells (which produces histamine) o Histamine produces a severe inflammation, usually in tissue directly exposed to the allergen Asthma: sever response to allergens causes constriction of airways,
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