Immunology and Serology - 01 Intro to Immunology

IMMUNOLOGY AND SEROLOGY INTRODUCTION TO IMMUNOLOGY OUTLINE • • • • History and Definition of Terms o Nobel Prizes Awarded for Immunologic Studies o Brief History of Immunology Immunity and the Immune System o Two General Types of Immunity o Immunization Cells and Organs of the Immune System o Major Lineages o Two Types of Immune System Organs Definition of Terms HISTORY AND DEFINITION OF TERMS NOBEL PRIZES AWARDED FOR IMMUNOLOGIC STUDIES 1700 Edward Jenner 1885 Louis Pasteur 1901 Emil von Behring 1905 Robert Koch 1908 Paul Ehrlich Elie Metchnikoff 1912 Alexis Carrell 1913 Charles Richet 1919 Jules Bordet 1930 Karl Landsteiner 1945 Sir Alexander Fleming; Sir Ernst Borischain; Lord Howard Walter Floray 1949 Salk and Sabin 1951 Max Theiler 1952 Selman Abraham Waksman 1957 Daniel Bovet 1959 Severo Ochoa; Arthur Kornberg 1960 Sir Frank Macfarlane Burnet; Sir Peter Brian Medawar 1965 Francois Jacob; Andrei Lwoff; Jacques Monod 1966 Payton Rous 1968 Robert Holley; Har Gobind Khorana; Marshall Nirenberg 1969 Max Delbruck; Alfred Hershey; Salvador Luria 1972 Rodney Porter; Gerald Edelman 1975 David Baltimore; Renato Dulbecco; Howard Martin Ternin 1975 Kohler 1977 Rosalyn Yallow Vaccination of cowpox against smallpox Reported live attenuated vaccine against rabies Antiserum therapy esp. against diphtheria Tuberculosis Theories of Immunity (Cellular & Humoral) Phagocytosis Organ grafting Anaphylaxis Theories of Immunity / Complement Human Blood groups Penicillin Development of polio vaccine Yellow Fever vaccine Streptomycin as first antibiotic effective against TB Antihistamine research Mechanism of biological synthesis of DNA and RNA Acquired Immunological Tolerance Genetic control of enzymes and viruses synthesis Tumor-inducing viruses Genetic code and its function in protein synthesis Replication mechanism and genetic structure of viruses Chemical structure of Immunoglobulins Interaction between tumor viruses and genetic material of the cell First monoclonal antibody Radioimmunoassay of peptide hormones 1978 Werner Arber; Daniel Restriction Nathans; Hamilton Smith enzymes/application to • 1980 Baruj Benacerraf; Jean Dausset; George Snell 1983 Barbara McClintock 1984 Cesar Milstein; George Kohler; Niels Jerne 1987 Susumo Tonegawa 1989 J. Michael Bishop; Harold Varmus; 1990 Joseph Murray; E. Donnell Thomas 1996 Peter Doherty; Rolf Zinkernagel problems of molecular genetics Immunogenetics and Histocompatibility Mobile genetic elements (transposons) Hybridoma Technology / Monoclonal antibodies Immunoglobulin genetics ab diversity Cellular origin of retroviral oncogenes Organ & Cell Transplantation Specificity of cell mediated immune defense (dual recognition) 1997 Stanley Prusiner Prions as a new biological principle of infection 1999 Gunter Blobel Signal transduction Durham and Gruber Agglutination Graber and Williams Immunoelectrophoresis Isihazaka IgE Isaacs and Lindenmann Interferons Edward Jenner Smallpox vaccine Kraus Precipitation 2005 Frazer Development of human papilloma virus vaccine BRIEF HISTORY OF IMMUNOLOGY IMMUNOLOGY • • • • • Started as science of immunity Began in Ancient China o To protect people from sickness (smallpox) o Used inhalation of dried smallpox crust for protection o The initial practice was rejected In Turkey, Europe o Wife of British Ambassador, Lady Montague introduced variolation o Variolation - using a common needle, collect lesion of smallpox virus from infected person and transferred to a healthy person wanting immunization; rejected due to no scientific basis ▪ She tried them to her children Edward Jenner introduced a safer version o Introduced cross-immunity (creation of permanent immunity upon exposure/recovery form other disease or infection) o Observed milkmaids with cowpox who did not acquire smallpox after recovering from cowpox o Used for creating generean vaccine ▪ Helped in eradicating smallpox Louis Pasteur o Father of immunology o Furthered the study of immunology o Used Jenner's studies for discovering more vaccines o Contributions ▪ Rabies vaccine ▪ Pasteurization - heating to kill bacteria ▪ Various vaccine ▪ IMMUNITY AND THE IMMUNE SYSTEM • • • • Immunology - area of biology that is concerned with the process by which all living organisms defend themselves against infection. o Preventive aid to mankind (vaccines) o Focuses on immunizing techniques; prevention Serology - deserved equal recognition as immunology o Focuses on detection or diagnosis of diseases Immunity - ability of an organism to recognize and defend itself against specific pathogen or antigens. Immune system is part of the lymphatic system o Advantages ▪ Defends against diseases and infections ▪ Allows recovery against diseases and infections o Disadvantages ▪ May develop into autoimmune diseases/disorders ▪ Hypersensitivity & allergies ▪ Transplant rejection TWO GENERAL TYPES OF IMMUNITY • • Natural/Innate Immunity (non-specific) o External (epithelial barriers) o Internal Defense (phagocytosis, inflammation) Acquired/Adaptive Immunity (specific) NATURAL/INNATE IMMUNITY • • • Inborn immunity Anatomical Barriers (external) – first line of defense o Mechanical Factors ▪ Skin ▪ Mucus ▪ Saliva ▪ Tears o Chemical Factors ▪ Fatty acids ▪ Lysozymes ▪ Defensins ▪ Surfactants o Biological Factors ▪ Normal flora of the skin and GIT Humoral barriers to infection o Aka biochemical factors, body fluids for non-specific immunity o Humoral factors play an important role in inflammation, characterized by edema and phagocytic cells. These factors are found in the serum or at the site of infection. o B1. Non specific plasma proteins: ▪ Complement system - Once activated complement can lead to increased vascular permeability, recruitment of phagocytic cells, and lysis and opsonization if bacteria. ▪ Coagulation system - Some products of the coagulation system can contribute to the nonspecific defenses because of their ability to increase vascular permeability and act as chemotactic agents for phagocytic cells. ▪ Lactoferrin and transferrin ▪ Interferons - proteins that can limit virus replication in cells. ▪ Betalysin - heat stable, found in serum only bec. it is released by platelets during coagulation. • Properdin - serum protein that exerts bactericidal and viricidal effects in the presence of C3 and magnesium. o B2. Interleukins (IL) ▪ Interleukin 1 - regulation of immune responses, inflammatory reactions, and hematopoiesis; T-cell activation factor ▪ Interleukin 2 - activates cytotoxic T cell, NK cells and LAK cells ▪ Interleukin 3 - stimulates hematopoietic cells ▪ Interleukin 4 - activates B cell ▪ Interleukin 5 - also known as eosinophil differentiation factor (EDF); regulates eosinophil growth and activation ▪ Interleukin 6 - also referred to as B-cell stimulatory factor-2 (BSF-2); final differentiation of B-cells; shares functions with IL-4 and IL-6, IFN beta 2. ▪ Interleukin 7 - stimulates maturation of early B and T cells. ▪ Interleukin 8 - known asneutrophil chemotactic factor; activates neutrophils; principal inflammatory cytokine. ▪ Interleukin 9 - proliferation of T cells, thymocytes, mast cells ▪ Interleukin 10 - inhibition of cytokine synthesis ▪ Interleukin 11 - stimulates megakaryocytopoiesis; regulates hematopoiesis ▪ Interleukin 12 - stimulation and maintenance of Th1 cellular immune responses against various intracellular pathogens, such as Leishmania, Toxoplasma, Measles virus, and Human immunodeficiency virus 1 (HIV); activates NK cells ▪ Interleukin 17 - o proinflammatory cytokine produced by activated memory T cells ▪ Interleukin 24 - plays important roles in tumor suppression, wound healing and psoriasis ▪ Interleukin 27 - regulates the activity of B and T lymphocytes ▪ Interleukin 28 - plays a role in immune defense against viruses ▪ Interleukin 29 - plays a role in host defenses against microbes ▪ Interleukin 31 - may play a role in inflammation of the skin ▪ Interleukin 32 - induces monocytes and macrophages Cellular barriers to infection o These cells are the main line of defense in the nonspecific immune system. o Neutrophils o Macrophages ▪ Tissue macrophages: • Liver: Kupffer cells • Kidney: Mesengial macrophage • Lung: Alveolar macrophage • Lymph nodes: dendritic cells • Spleen: Splenic macrophage • Skin: Langerhan’s cells • Brain and CNS: Microglial cells • Connective tissue: Histiocytes • Small intestines: Payer’s patches • Mast cells o o o o o Dendritic cells Natural killer (NK) and lymphokine activated killer (LAK) cells Eosinophils Basophils Monocytes IMMUNIZATION • • • ADAPTIVE/ACQUIRED IMMUNITY • • • • • third line of defense o Affords protection against re-exposure to the same pathogen Lymphocytes - cells responsible for the specific immune response o found in blood and lymph Types o B – cells – mature in marrow o T – cells – mature in thymus o Helper / Cytotoxic/Killer / Suppressor / Memory Types of Acquired/Adaptive Immunity o Active Immunity – result of actual infection ▪ Naturally Acquired Active Immunity – exposure to antigen • immunity may be life long or temporary • body generates immune response to antigen ▪ Artificially Acquired Active Immunity – through vaccination • body generates immune response to antigen • immunity may be life long or temporary o Passive Immunity – result of transmission of antibodies ▪ Naturally Acquired Passive Immunity – natural antibodies • antibodies pass from mother to fetus via placenta ▪ Artificially Acquired Passive Immunity – injection of antibodies • immunity is short-lived Types of Specific Immunologic Reactions o Adaptive can be Cellular (cell-mediated) and Humoral (antibody-mediated) o Humoral Immunity ▪ involves B cell activation ▪ production of antibodies in blood plasma and lymph ▪ B cells that are stimulated are called plasma cells will actively secrete antibodies ▪ Antibodies are found in ECF(blood plasma, lymph, mucus, etc) and surface of B cells ▪ Defense against bacteria, bacterial toxins, and viruses that circulate freely in body fluids before they enter cells o Cellular Immunity ▪ action of T cells ▪ active against cancer cells and transplanted tissues ▪ kills cell through lysis ▪ important in viral and fungal infections and in infections caused by AFB Process of inducing immunity naturally or artificially by vaccination or administration of antibody Vaccination - A type of active immunization wherein any vaccine or toxoid is administered for prevention of disease Herd Immunity - For every type of disease, there is a recommended percentage of immunized population to achieve herd immunity VACCINES • Proteins, polysaccharides or nucleic acids delivered to the immune system to induce specific responses that inactivate, destroy or suppress the pathogen FOUR TYPES OF COVID-19 VACCINES • • • • There are four categories of vaccines in clinical trials: whole virus, protein subunit, viral vector and nucleic acid (RNA AND DNA). Some of them try to smuggle the antigen into the body, others use the body’s own cells to make the viral antigen Whole Virus o Many conventional vaccines use whole viruses to trigger an immune response. There are two main approaches. Live attenuated vaccines use a weakened form of the virus that can still replicate without causing illness. Inactivated vaccines use viruses whose genetic material has been destroyed so they cannot replicate, but can still trigger an immune response. Both types use well-established technology and pathways for regulatory approval, but live attenuated ones may risk causing disease in people with weak immune systems and often require careful cold storage, making their use more challenging in low-resource countries. Inactivated virus vaccines can be given to people with compromised immune systems but might also need cold storage. Protein Subunit o Subunit vaccines use pieces of the pathogen - often fragments of protein - to trigger an immune response. Doing so minimises the risk of side effects, but it also means the immune response may be weaker. This is why they often require adjuvants, to help boost the immune response. An example of an existing subunit vaccine is the hepatitis B vaccine. Nucleic Acid o Nucleic acid vaccines use genetic material – either RNA or DNA – to provide cells with the instructions to make the antigen. In the case of COVID-19, this is usually the viral spike protein. Once this genetic material gets into human cells, it uses our cells' protein factories to make the antigen that will trigger an immune response. The advantages of such vaccines are that they are easy to make, and cheap. Since the antigen is produced inside our own cells and in large quantities, the immune reaction should be strong. A downside, however, is that so far, no DNA or RNA vaccines have been licensed for human use, which may cause more hurdles with regulatory approval. In addition, RNA vaccines need to be kept at ultra-cold temperatures, -70C or lower, which could prove challenging for countries that don’t have specialised • cold storage equipment, particularly low- and middleincome countries. Viral Factor o Viral vector vaccines also work by giving cells genetic instructions to produce antigens. But they differ from nucleic acid vaccines in that they use a harmless virus, different from the one the vaccine is targeting, to deliver these instructions into the cell. One type of virus that has often been used as a vector is adenovirus, which causes the common cold. As with nucleic acid vaccines, our own cellular machinery is hijacked to produce the antigen from those instructions, in order to trigger an immune response. Viral vector vaccines can mimic natural viral infection and should therefore trigger a strong immune response. However, since there is a chance that many people may have already been exposed to the viruses being used as vectors, some may be immune to it, making the vaccine less effective. Cytokine Family Growth Factors M_CSF Chemical messengers that regulate the immune system, orchestrating both innate and adaptive response to infection Cytokine Primary Activity Family Cell Type Interferons Alpha Leukocytes Antiviral, antiproliferative, enhance MHC I, NK Activity Beta Fibroblasts, Same epithelial cells Gamma T Cell, NK cells Antiviral, enhance MHC I & II, antiproliferative TNF Alpha Macrophage, Activate macrophages lymphocytes and cytotoxic cells; Induces IL-1, IL-6, Acute Phase Proteins Beta T Cells Active Macrophages; Induces IL-1, IL-6 Interleukins IL-1 Most cells, Induces inflammation, macrophages, DC fever & sepsis, activate TNF-alpha IL-2 T Cells Induces proliferation and maturation of T cells IL-6 Most cells B cell stimulation, mediator of acute phase reactions IL-10 T Cells, monocytes/ Inhibits IFN-Gamma & ILmacrophages 12 productions IL-11 Bone marrow Induces stromal cells, immunosuppression, mesenchymal cells synergistic effects on hematopoiesis IL-12 Dendritic cells, induces production of macrophages, B IFN-Gamma, TNF-Alpha, cells IL-2 IL-15 T cells, fibroblasts, Induces production of microglia, epithelial peripheral blood, cells maturation of NK cells IL-23 Macrophages, DC Same as IL-12, differentiates CD4 T Cells to TH17 Monocytes G-CSF Macrophages GM-CSF T cells, macrophages Activity Proliferation of macrophage precursors Proliferation, differentiation, activation of neutron Proliferation of granulocytes and macrophage precursors CELLS AND ORGANS OF THE IMMUNE SYSTEM MAJOR LINEAGES • • CYTOKINES • Primary Cell Type • two major lineages: myeloid precursor and lymphoid precursor Myeloid Precursor o mast cells o monocytes o PMN (polymorphonuclears) o rbc o platelets o dendritic cells o macrophages Lymphoid Precursor o T cell o B cell o NK TWO TYPES OF IMMUNE SYSTEM ORGANS • • Primary – maturation sites o Bone Marrow ▪ central organ where all immune cells are born ▪ B cells maturation o Thymus ▪ T cell maturation Secondary – activation sites o Lymph Nodes o Lymphatics o Spleen o MALT (Mucous Associated Lymphoid Tissues) ▪ Tonsils ▪ Peyer’s patches ▪ Appendix • • • • • • • • • • • • • • • The organs of the immune system are stationed throughout the body. They are generally referred to as lymphoid organs because they are concerned with the growth, development, and deployment of lymphocytes, the white cells that are the key operatives of the immune system. The blood and lymphatic vessels that carry lymphocytes to and from the other structures can also be considered lymphoid organs. Lymph nodes – are small, bean-shaped with clusters in the neck, armpit, abdomen, and groin. Each lymph node contains specialized compartments which contains platoons of B lymphocytes, T lymphocytes and other cells. Spleen - fist-sized organ at the upper left of the abdomen, which contains two main types of tissue: the red pulp and the white pulp. Like the lymph nodes, the spleen is subdivided into compartments that specialize in different kinds of immune cells. Phagocytes are large white cells that can engulf and digest microorganisms and other antigenic particles. Important phagocytes are monocytes (Links to an external site.) and macrophages. Dendritic cells are irregularly shaped white blood cells found in the spleen and other lymphoid organs. Neutrophils are not only phagocytes but also granulocytes, they contain granules filled with potent chemicals which can destroy microorganisms. Mast cell is a noncirculating counterpart of the basophil. Located in the lungs, skin, tongue, and linings of the nose and intestinal tract, the mast cell is responsible for the symptoms of allergy. DEFINITION OF TERMS • • • • • • Acquired immunodeficiency syndrome (AIDS): A lifethreatening disease caused by a virus and characterized by breakdown of the body's immune defenses. Agammaglobulinemia: An almost total lack of immunoglobulins, or antibodies. Allergen: Any substance that causes an allergy. Allergy: An inappropriate and harmful response of the immune system to normally harmless substances. Anaphylactic shock: A life-threatening allergic reaction characterized by a swelling of body tissues including the throat, difficulty in breathing, and a sudden fall in blood pressure. Antibody: A soluble protein molecule produced and secreted by B cells in response to an antigen, which is capable of binding to that specific antigen. • • • • • • • • • • • • • • Antigen: Any substance that, when introduced into the body, is recognized by the immune system. Antigen-presenting cells: B cells, cells of the monocyte lineage (including macrophages as well as dendritic cells), and various other body cells that "present" antigen in a form that T cells can recognize. Antinuclear antibody (ANA): An autoantibody directed against a substance in the cell's nucleus. Antiserum: Serum that contains antibodies. Antitoxins: Antibodies that interlock with and inactivate toxins produced by certain bacteria. Appendix: Lymphoid organ in the intestine. Attenuated: Weakened; no longer infectious. Autoantibody: An antibody that reacts against a person's own tissue. Autoimmune disease: A disease that results when the immune system mistakenly attacks the body's own tissues. Rheumatoid arthritis and systemic lupus erythematosus are autoimmune diseases. B cells: Small white blood cells crucial to the immune defenses. Also known as B lymphocytes, they are derived from bone marrow and develop into plasma cells that are the source of antibodies. Bone marrow: Soft tissue located in the cavities of the bones. The bone marrow is the source of all blood cells. Complement: A complex series of blood proteins whose action "complements" the work of antibodies. Complement destroys bacteria, produces inflammation, and regulates immune reactions. Complement cascade: A precise sequence of events usually triggered by an antigenantibody complex, in which each component of the complement system is activated in turn. Constant region: That part of an antibody's structure that is characteristic for each antibody class. Co-Stimulation: The delivery of a second signal from an antigen-presenting cell to a T cell. The second signal rescues the activated T cell from anergy, allowing it to produce the lymphokines necessary for the growth of additional T cells. Cytokines: Powerful chemical substances secreted by cells. Cytokines include lymphokines produced by lymphocytes and monokines produced by monocytes and macrophages. Cytotoxic T cells: A subset of T lymphocytes that can kill body cells infected by viruses or transformed by cancer. Dendritic cells: White blood cells found in the spleen and other lymphoid organs. Dendritic cells typically use threadlike tentacles to enmesh antigen, which they present to T cells. Epitope: A unique shape or marker carried on an antigen's surface, which triggers a corresponding antibody response. Graft-versus-host disease (GVHD): A life-threatening reaction in which transplanted immunocompetent cells attack the tissues of the recipient. Helper T cells: A subset of T cells that typically carry the T4 marker and are essential for turning on antibody production, activating cytotoxic T cells, and initiating many other immune responses. Hematopoiesis: The formation and development of blood cells, usually takes place in the bone marrow. • • • • • • • • • • • • • • • • • • • • • Histocompatibility testing: A method of matching the self antigens (HLA) on the tissues of a transplant donor with those of the recipient. The closer the match, the better the chance that the transplant will take. Human leukocyte antigens (HLA): Protein in markers of self used in histocompatibility testing. Some HLA types also correlate with certain autoimmune diseases. Hybridoma: A hybrid cell created by fusing a B lymphocyte with a long-lived neoplastic plasma cell, or a T lymphocyte with a lymphoma cell. A B-cell hybridoma secretes a single specific antibody. Hypogammaglobulinemia: Abnormally low levels of immunoglobulins. Idiotypes: The unique and characteristic parts of an antibody's variable region, which can themselves serve as antigens. Immune complex: A cluster of interlocking antigens and antibodies. Immune response: The reactions of the immune system to foreign substances. Immunoassay: A test using antibodies to identify and quantify substances. Often the antibody is linked to a marker such as a fluorescent molecule, a radioactive molecule, or an enzyme. Immunocompetent: Capable of developing an immune response. Immunoglobulins: A family of large protein molecules, also known as antibodies. Immunosuppression: Reduction of the immune responses, for instance by giving drugs to prevent transplant rejection. Immunotoxin: A monoclonal antibody linked to a natural toxin, a toxic drug, or a radioactive substance. Inflammatory response: Redness, warmth, swelling, pain, and loss of function produced in response to infection, as the result of increased flood flow and an influx of immune cells and secretions. Interleukins: A major group of lymphokines and monokines. Langerhans cells: Dendritic cells in the skin that pick up antigen and transport it to lymph nodes. Lymph: A transparent, slightly yellow fluid that carries lymphocytes, bathes the body tissues, and drains into the lymphatic vessels. Lymphatic vessels: A bodywide network of channels, similar to the blood vessels, which transport lymph to the immune organs and into the bloodstream. Lymph nodes: Small bean-shaped organs of the immune system, distributed widely throughout the body and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymphoid organs: The organs of the immune system, where lymphocytes develop and congregate. They include the bone marrow, thymus, lymph nodes, spleen, and various other clusters of lymphoid tissue. The blood vessels and lymphatic vessels can also be considered lymphoid organs. Lymphokines: Powerful chemical substances secreted by lymphocytes. These soluble molecules help direct and regulate the immune responses. Macrophage: A large and versatile immune cell that acts as a microbe-devouring phagocyte, an antigen-presenting cell, and an important source of immune secretions. • • • • • • • • • • • • • • • • • • • • • • Major histocompatibility complex (MHC): A group of genes that controls several aspects of the immune response. MHC genes code for self markers on all body cells. Mast cell: A granule-containing cell found in tissue. The contents of mast cells, along with those of basophils, are responsible for the symptoms of allergy. Monoclonal antibodies: Antibodies produced by a single cell or its identical progeny, specific for a given antigen. As a tool for binding to specific protein molecules, monoclonal antibodies are invaluable in research, medicine, and industry. Monokines: Powerful chemical substances secreted by monocytes and macrophages. These soluble molecules help direct and regulate the immune responses. Natural killer (NK) cells: Large granule-filled lymphocytes that take on tumor cells and infected body cells. They are known as "natural" killers because they attack without first having to recognize specific antigens. Nucleic acids: Large, naturally occurring molecules composed of chemical building blocks known as nucleotides. There are two kinds of nucleic acids, DNA and RNA. OKT3: A monoclonal antibody that targets mature T cells. Opsonize: To coat an organism with antibodies or a complement protein so as to make it palatable to phagocytes. Peyer's patches: A collection of lymphoid tissues in the intestinal tract. Phagocytes: Large white blood cells that contribute to the immune defenses by ingesting microbes or other cells and foreign particles. Plasma cells: Large antibody-producing cells that develop from B cells. Polymorphs: Short for polymorphonuclear leukocytes or granulocytes. Protozoa: A group of one-celled animals, a few of which cause human disease (including malaria and sleeping sickness). Rheumatoid factor: An autoantibody found in the serum of most persons with rheumatoid arthritis. RNA (ribonucleic acid): A nucleic acid that is found in the cytoplasm and also in the nucleus of some cells. One function of RNA is to direct the synthesis of proteins. Serum: The clear liquid that separates from the blood when it is allowed to clot. This fluid retains any antibodies that were present in the whole blood. Severe combined immunodeficiency disease (SCID): A life-threatening condition in which infants are born lacking all major immune defenses. Spleen: A lymphoid organ in the abdominal cavity that is an important center for immune system activities. Stem cells: Cells from which all blood cells derive. The bone marrow is rich in stem cells. Subunit vaccine: A vaccine that uses merely one component of an infectious agent, rather than the whole, to stimulate an immune response. Superantigens: A class of antigens, including certain bacterial toxins, that unleash a massive and damaging immune response. Suppressor T cells: A subset of T cells that turn off antibody production and other immune responses. • • • • • • • • • T cells: Small white blood cells that orchestrate and/or directly participate in the immune defenses. Also known as T lymphocytes, they are processed in the thymus and secrete lymphokines. Thymus: A primary lymphoid organ, high in the chest, where T lymphocytes proliferate and mature. TIL: Tumor-infiltrating lymphocytes. These immune cells are extracted from the tumor tissue, treated in laboratory, and reinjected into the cancer patient. Tissue typing: See histocompatibility testing. Tolerance: A state of nonresponsiveness to a particular antigen or group of antigens. Tonsils and adenoids: Prominent oval masses of lymphoid tissues on either side of the throat. Toxins: Agents produced by plants and bacteria, normally very damaging to mammalian cells, that can be delivered directly to target cells by linking them to monoclonal antibodies or lymphokines. Vaccine: A substance that contains antigenic components from an infectious organism. By stimulating an immune response (but not disease), it protects against subsequent infection by that organism. Variable region: That part of an antibody's structure that differs from one antibody to another.