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Defenses Against Disease Ch. 43. From the Tiniest Things…. Everyday we are invaded by bacteria, viruses, and non-self molecules Immune system natural protection against non-self substances 3 parts: Physical barriers skin, tight junctions, mucus layers, acidic environments
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From the Tiniest Things… • Everyday we are invaded by bacteria, viruses, and non-self molecules • Immune system natural protection against non-self substances • 3 parts: • Physical barriers skin, tight junctions, mucus layers, acidic environments • Innate Immune system non-specific reaction to all non-self molecules • Adaptive Immune system specific reaction to reoccurring non-self molecules
The White Army • Leukocytes “white blood cells”, soldiers protecting your body; patrol the blood and lymph • 6 main types: • Macrophage phagocyte (cell eater) that consume infected cells, pathogens, and non-self molecules • Monocyte become macrophages during 2nd wave of protection • Neutrophil consumes pathogens and tissue debris • Eosinophil secret enzymes to kill parasites (too big for phagocytosis) • Basophil respond to allergens, secrete histamine and cause inflammation
The White Army: Lymphocytes • Lymphocytes Groups of cells in innate and adaptive immunity • NK cells natural killer cells; kill cells infected by viruses or cancerous cells • B-Cells capture and present antigens from bacteria • Plasma cells secrete antibodies • Helper T-cells help activate other B-cells • Cytotoxic T-cells kill infected cells
Innate Immunity: Nonspecific! • Recovery time: 7-10 days • Various steps that are generally effective • Steps made to build adaptive immunity for faster response time • Reactions: • Antimicrobial peptides simplest response; pathogens interacting with inner lining of body trigger release of defenins(enzymes that destroy membranes)
Innate Immunity: Inflammation • Inflammation heat, pain, and swelling in infected area • Local only at infection site; caused by histamine • Systemic throughout the body (fever); caused by pryrogens which cause the hypothalamus to turn up the heat • Heat and swelling allow better macrophage attack at infection site and help phagocytosis
Innate Immunity: Inflammation • Steps: • Infection occurs; macrophages at site detect pathogens • Cytokines and histamine are released; inflammation starts and blood vessels dilate • Neutrophils and monocytes drawn towards site (chemokines) and pass through permeable blood vessels • Neutrophils consume bacteria and die in the process (pus) • Monocytes change to macrophages as 2nd wave attack • Infection clears up; inflammation stops
Innate Immunity: Complement Systemand Interferons • Complement system 30 proteins that recognize and attach to pathogens • Membrane attack complex after proteins attach; attack complexes bind to them and attack pathogen membranes • Enzymes will produce holes in plasma membrane • Cell cannot maintain homeostasis with ions freely flowing; Pathogen swells and lyses • Interferons released by cells infected with a virus; help block viruses from attaching to new hosts • Activated RNA degrading enzymes to stop all protein synthesis
Innate Immunity: Natural Killer Cells • NK cells target cells infected by viruses/cancer • Identify infected cells by the number of MHC (major histocompatibility complex) proteins on their surface • Normal cell high number • Infected/Cancer protein synthesis inhibited so low number • Releases perforin to degrade holes in cell’s membrane; cell swells and lyses • Also secretes proteases (degrades proteins) into the cell which causes apoptosis
Adaptive Immunity: Specific Defense! • All methods in innate immunity are generalized; but each attack on our system allows us to build a strong adaptive immunity • Antigen non-self molecule that generates antibodies; can be any organic molecule but mostly large proteins • Antigens are recognized by: • B-cells come from bone marrow; produce antibodies • T-cells mainly in Thymus; can help spread antigen info (helper T-cells) and kill infected cells (cytotoxic T-cells)
Adaptive Immunity: Two Ways to Play • Antibody-mediated (humoral) B-cells change into plasma cells to release large amounts of antibodies • Cell-mediated T-cells become active and kill infected cells • Both methods follow the same pattern: • Antigen is recognized • Lymphocytes are activated • Antigen is removed from the body • Memory cells made to prepare for future infections
Antibody-Mediated Immunity: Receptors • Antigens must be recognized first • B and T cells are covered with thousands of receptors for antigens • B-cell receptors 2 heavy chains (transmembrane) and 2 light chains; 2 variable regions on the end react to specific antigen(s) • 10 trillion B-cells with 100 million different receptors • T-cell receptors 2 short chains (transmembrane) with 1 variable region • Variable region only reacts to small part of antigen (epitope), so one antigen can react to multiple receptors
Antibody-Mediated Immunity: Antibodies • Immunoglobulins (Ig) complex molecules made of 2 heavy chains and 2 light chains; have a constant region and a variable region • Classes: • IgM B-cell receptors • IgG most abundant; used after 2nd infection • IgA secreted in specific parts of the body; block pathogens from binding to cells • IgE secreted by plasma cells; bind to basophils and mast cells to release histamine; allergic response • IgD works with IgM; still unclear of function
Antibody-Mediated Immunity: Lymphocyte Activation • Dendritic cell engulfs pathogen • Lysosome degrades pathogen; antigens are isolated • Dendritic cell presents antigens on its membrane through class II MHC proteins; now a APC (antigen-presenting cell) • Antigen presented to CD4+ T-cell; T-cell activated • Interleukins from T-cell promote rapid division; some cells become helper T-cells and activate more lymphocytes (effector T-cells)
Antibody-Mediated Immunity: Lymphocyte Activation 6) B-cells present antigens on their cell surface and link with helper T-cells; when matched the B-cell becomes activated 7) B-cells divided rapidly. Some cells become plasma cells and some become memory B-cells 8) Plasma cells secrete antibodies which bind to antigens; inhibits pathogens and make them easier to find for phagocytosis 9) Memory B-cells stay in body to create a faster response if a second infection occurs
Antibody-Mediated Immunity: Cleaning Up • Antigens removed from body two ways • Neutralization antibodies bind to antigens inhibiting them from infecting cells; filtered from body with time or consumed • Agglutination pathogens are stuck together by antibodies; unable to move • Both methods result in increased phagocytosis by the complement system
Antibody-Mediated Immunity: Memory Cells • Immunological memory built from memory B-cells and memory helper T-cells after primary immune response (3-14 days) • Secondary Immune response less antigen is needed to react with immune system so reaction is faster; flood of IgG antibodies • Related antigens can set off reaction of similar antibodies
Building Immunities • Active immunity you build your own antibodies • Vaccination dead or weak form of the pathogen gives your body the antigen needed to make the antibody but not the disease • Passive immunity antibodies given directly • IgG mother to fetus • IgA breast milk • Weaker form because effect only last a month
Cell-Mediated Immunity: Cytotoxic T-Cells • System best for viruses • Pathogen antigens released from infected cell • B-cell picks up antigens to become an APC • APC and CD+8 T-cell link and cytokines secreted by helper T-cell trigger response • CD+8 T-cell divides to make cytotoxic T-cells and memory cytotoxic T-cells • Cytotoxic T-cells find antigen on class I MHC proteins; bind to infected cell • Cytotoxic T-cell uses proteases and other enzymes to destroy infected cell
When Immune Systems Break • All systems set up an immunological tolerance; base level of what is and is not “self”; set up as fetus • Autoimmune reaction antibodies attack “self” molecules • Type I diabetes body kills own beta cells; no insulin • Lupus body attacks blood cells, platelets, mitochondria, etc… • Rheumatoid arthritis body attacks connective tissue • Multiple sclerosis body attacks myelin sheaths
Mild to Sever Reactions • Allergic reactions caused by antigens that cause B-cells to release large amounts of IgE; react with mast and basophil cells which release histamine • What does this result in? • Inflammation response • Most effect eyes, nasal and air passage ways; also stimulate smooth muscle contractions and mucus production (allergies) • Asthma restricted breathing; stopped with antihistamines • Anaphylactic shock sever reaction that can result in death; stopped with epinephrine
Mild to Sever Reactions • Suggested Homework: • Test Your Knowledge • Actual Homework: • Discuss the Concepts #1 • Interpret the Data