The Lymphatic and Immune System PDF

THE LYMPHATIC AND IMMUNE SYSTEM Chapter 21 21.1 – Anatomy of the Lymphatic and Immune Systems      Immune system – cells and organs that destroy pathogens Lymphatic system – vessels, cells, and organs that bring excess fluid to the bloodstream and filters pathogens from the blood Lymph – inters...

THE LYMPHATIC AND IMMUNE SYSTEM Chapter 21 21.1 – Anatomy of the Lymphatic and Immune Systems      Immune system – cells and organs that destroy pathogens Lymphatic system – vessels, cells, and organs that bring excess fluid to the bloodstream and filters pathogens from the blood Lymph – interstitial fluid in the lymphatic system Dietary lipids and fat-soluble vitamins are absorbed and travel in lymphatic vessels to the liver Lymph node – major staging area for development of critical immune response 21.1 - Structure       Open ended capillaries which feed into larger vessels and eventually into the subclavian vein Capillaries are simple squamous endothelial cells We have 500-600 lymph nodes along those vessels Lymph is not pumped – it moves by breathing, muscle contraction, and body movements One way valves keep it moving toward the heart (like veins) Areas with no lymph vessels are bone marrow, CNS, teeth, and cornea 21.1  Larger vessels are similar to veins with 3 tunics and valves 21.1 – Organization of Immune Function        Barrier defenses – skin and mucous membranes, prevent invasion Innate immune response – rapid, but non specific cells Adaptive immune response – slower response of lymphocytes All leukocytes come from the red marrow (myeloid or lymphoid) Phagocytic – ingest pathogens Lymphocytes – coordinate adaptive immunity Granular – help mediate immune response against parasites and pathogens like bacteria and viruses 21.1 - Lymphocytes      B cells – produce plasma cells (group of proteins that bind to specific molecules known as antigens). B cells differentiate into plasma cells after attaching to an antigen Antigen – a chemical structure on the surface of a pathogen that binds a B or T cell T cells – can secrete chemokines to bring other immune cells to the area or destroy cells infected with intracellular pathogens Plasma cells – can secrete the soluble antibodies Natural Killer cells – innate immune response, contains cell killing granules, first line of defense against virus and some cancers 21.1 – Lymphoid Organs and Development     Bone marrow – B cells develop in red bone marrow, yellow bone marrow is energy storage (fat cells) Thymus – gland between the sternum and aorta where the T cells mature, it begins shrinking at birth and may totally be gone at age 120 Secondary lymphoid organs – lymph nodes, spleen, and lymphoid nodules. Collecting sites for lymphocytes, have many fixed macrophages, and blood from cells may directly enter tissues Germinal centers – nodes and nodules have sites for rapidly dividing B cells and plasma cells 21.1 – Secondary Organs      Lymph Nodes – remove debris and pathogens (filter of lymph), dendritic cells and macrophages kill many pathogens, many B and T cells are present Afferent lymphatic vessels – enter the lymph node Efferent lymphatic vessels – leave the lymph node Spleen – extensive vascularization, known as “filter of the Blood”, holds many dendrites and macrophages Lymphoid nodules – dense cluster of lymphocytes without a fibrous capsule, found in respiratory and digestive tracts (tonsils) 21.1    Tonsils – important in developing immunity to oral pathogens, swelling is due to an active immune response to infection, they may be removed if they interfere with breathing and/or swallowing Mucosa-associated lymphoid tissue (MALT) – lymphoid follicles on GI tract, breast tissue, lungs, and eyes. Important for immune response Bronchus-associated lymphoid tissue (BALT) – lymphoid follicles on the bronchii effective against inhaled pathogens 21.2 – Barrier Defenses and the Innate immune Response 21.2    Barrier defenses – most basic, continuously working (skin and sweat, mouth, stomach, mucosal surfaces, and normal flora) Innate immune response – rapid, nonspecific, not always effective Adaptive immune response – slower to develop, highly specific, very effective at attacking a wide variety of pathogens 21.2 - Barriers       Skin – to dead and dry for bacteria to grow Sweat – wash away pathogens, lower pH, contain toxic lipids Oral salivary glands – rich in lysosome Stomach – very acidic to kill pathogens Mucosal surfaces – traps microbes and debris so they get removed Normal flora – prevent pathogens from growing on mucosal surfaces 21.2 – Innate Immune Cells     Macrophage – phagocyte that will roam or take a fixed position, first line of defense, they cooperate with the lymphocytes Neutrophils – phagocyte that is attracted via chemotaxis, they are like the reinforcements, they also cooperate with lymphocytes Monocyte – differentiates into a macrophage or dendritic cell Natural killer cells – induce apoptosis in an infected cell by releasing the fas ligand to bind to the fas molecule on the infected cell or by releasing perforins and granzymes. 21.2     Perforins – protein that puts holes in membranes of infected cells Granzymes – protein-digesting enzyme that enters through the hole and triggers apoptosis intracellularly Both the granules and the fas ligand are effective against virally infected cells Pattern recognition receptor – membrane bound receptor to recognize pathogens or molecules released by stressed or damaged cells, how innate immune system knows what to attack, limited by pathogens encountered and finite membrane space 21.2      Cytokine – signaling molecule allowing 2 nearby cells to communicate Chemokine – attract cells to them from longer distances Interferons – secreted by infected cells to tell nearby cells to make antiviral proteins Opsonization – tagging a pathogen for phagocytosis by binding an antibody or antimicrobial protein Complement system – series of proteins in the blood that opsonize a pathogen, diffuse to draw phagocytes to the area, and form pores in the plasma membrane (classic and alternate pathways) 21.2 – Inflammatory Response       Phagocytic cells responding to an injured area due to mast cells releasing histamine, leukotrienes, and prostaglandins Histamine causes vasodilation and capillary permeability, swelling Leukotrienes attract neutrophils and increase permeability Prostaglandins cause vasodilation and increase pain sensitivity (NSAID’s inhibit prostaglandin production) Acute inflammation – short term response to injury Chronic inflammation – ongoing inflammation due to foreign bodies, persistent pathogens, and autoimmune disease (rheumatoid arthritis) 21.3 – The Adaptive Immune Response: T Cells     Can specifically recognize and attack a wide variety of pathogens, 100 trillion different receptors Primary adaptive response – first infection has worse symptoms because adaptive immune system needs to become effective Secondary adaptive response – next infection is most likely eliminated before you notice a symptom, this is immunological memory Autoimmune disease - adaptive immune response begins to attack your “self” cells 21.3 – T Cell-Mediated Immune Responses      In control of adaptive immune response Variable region is specific for binding to a single particular antigen Antigens – the region on a pathogen that binds to a receptor Carb antigen – bacteria and RBC Protein antigen – viruses and worm parasites 21.3 – T Cells     T cells only recognize antigens on the surface of an antigen presenting cell A cell’s enzymes will cleave an antigen into small pieces and present it on the membrane attached to a major histocompatibility complex (MHC) molecule The antigen presentation is recognized by T cells The antigen presenting cell either takes in extracellular antigens ( class II) or a pathogen (class I) that it breaks down to smaller antigens in the lysosome 21.3      Many human cells can express class I MHC molecules Only professional antigen presenting cells can express class II MHC. macrophages, dendrites, and B cells Macrophage – presents at infection site, stimulates phagocytosis Dendrite – bring antigen to regional lymph nodes B cells – stimulate antibody secretion 21.3 – Development and Differentiation        T cell tolerance – eliminating T cells that might attack one’s own body Only 2% of T cells successfully mature from a thymocyte, 2 steps Positive selection – thymocyte is presented with an MHC, those that don’t bind undergo apoptosis Negative selection – thymocyte is presented with a self antigen, those that bind undergo apoptosis The thymocyte is then mature and is either a helper T cell or a cytotoxic T cell Helper T cells bind to class II antigen expression Cytotoxic T cells bind to class I Antigen expression 21.3 – Mechanism of T Cell Response    Clonal expansion – a mature T cell recognizes an antigen and divides rapidly by mitosis, leads to a strong response against a pathogen The cloning leads to an effector T cell (kill pathogen) and a memory T cell (long lived to react if antigen is encountered again) Clonal selection – the process of the antigen binding only to the T cell with that specific receptor 21.3 – T Cell Types      Helper T cells – secrete cytokines to enhance other immune responses, 2 types Th1 cells – regulate activity of macrophages and other T cells Th2 cells – regulate activity of B cell differentiation into plasma cells that make antibody Cytotoxic T cells – kill target cells by inducing apoptosis like NK cells Regulatory T cells – suppress other T cell immune responses 21.4 – B Cells and Antibodies      Antibody – a secreted form of a B cell receptor, there are 5 classes B cells can recognize unprocessed antigens and don’t need MHC and antigen presenting cells B cells mature in the bone marrow Central Tolerance - cells that bind to “self” cells are eliminated in bone marrow Peripheral Tolerance – a mature B cell that does bind to a “self” cell will not elicit the response from a Th2 cell to make antibody, that cell will undergo apoptosis 21.4 – B Cells    Mature B cells differentiate into plasma cells Plasma cells secrete antibody until they die, terminal differentiation Final B cell left is a memory B cell, they react like a memory T cell 21.4 – Antibody Structure 21.4 – 5 Classes of Antibody     IgM – 5 four chained structures, largest molecule, first made during primary response, great for binding and activating complement, class of antibody can change over time IgG – late response and main antibody of secondary response in the blood, able to cross placenta to the fetus, and enter the interstitial fluid IgA – 4 chain monomer in blood and 8 chain in exocrine secretions, only antibody to exit and protect the surface, present in mother’s breast milk to protect the infant from disease IgE – associated with allergies and anaphylaxis, Fc receptor binds strongly to mast cells, causes mast cells to degranulate 21.4 - Response Time   Initial response takes a few days and is weak Secondary exposure has no delay in response and is much stronger 21.4 - Immunity    Active immunity – resistance to a pathogen acquired Vaccine – killed or weak pathogen that stimulates the body to produce memory cells without suffering through an initial exposure Passive immunity – transfer of antibodies to an individual, fetal development or injection, does not lead to immunological memory 21.5 – The Immune Response Against Pathogens   Ideally the immune response will rid the body of a pathogen Seroconversion – as antibody levels rise in the blood pathogen levels decline and vice versa 21.5 – Mucosal Immune Response   Major barrier for pathogens with IgA and sometimes IgM in secretions to neutralize pathogens Neutralization – coating a pathogen to make it impossible to bind to a receptor, constantly protects the body, basis for protection due to vaccines 21.5      The body uses a wide variety of responses to fight a bacteria The cause of leprosy is resistant to lysosomes and is killed by nitric oxide inside the macrophage Fungal infections are largely opportunistic and attack during a suppressed immune response, we fight them like bacteria Parasites are attacked by eosinophils after the IgE labels it and flushed out by degranulation of the mast cells by the IgE Viruses are fought by NK cells, interferons, and cytotoxic T cells. Antibody is ineffective because it can’t get inside the cell to the virus. 21.5 – Evasion by Pathogens        Pathogens have evolved to avoid the immune response Cell wall to resist enzymes Resistant to certain drugs (MRSA) Multiple strains and differing antigens Mutation like the flu because it is a sloppy virus Genetic recombination – combining gene segments from 2 different pathogens Immunosuppressive molecules can impair immune function, viruses are good at this 21.6 – Diseases Associated with Depressed or Overactive Immune Response     Too weak or too strong can lead to a state of disease Immunodeficiency may be acquired or inherited Severe combined immunodeficiency disease (SCID) – most serious inherited type, affects both B and T cells, most die in first year of life, the “boy in the bubble” had SCID for 12 years, bone marrow transplant works or now gene therapy is the upcoming treatment HIV/AIDS – wipes out immune system, Seroconversion never wipes it away. It infects and kills helper T cells, die of opportunistic infection, virus mutates often so vaccine is 30 years coming and more time is needed 21.6 - Hypersensitivities     Immediate (Type 1) – IgE binds to mast cells causing degranulation, reactions are rapid, treated with antihistamine and epinephrine Type 2 – mismatched blood transfusion Type 3 – systemic disease, antigens and antibodies will accumulate along blood vessel linings causing inflammation Delayed (Type 4) – standard cellular immune response so it takes 24-72 hours for the response of symptoms (Tb test) 21.6 – Autoimmune Response     Tolerance breaks down and the immune system attacks a person’s own body Trigger is often unknown Treat with immunosuppressive drugs and anti-inflammatories Autoimmune disease is more rare in countries with high infectious disease rates 21.7 – Transplantation and Cancer Immunology      Organ transplant must match MHC alleles and not just blood type, infiltration of T cells in the first week indicate the transplant will likely fail A healthy immune system can control some cancers Cancers often proliferate due to mutation, body needs a new response There are positive outlooks for some cancer vaccines in the future Immune system can cause some complications, but that is outweighed by staying alive