Biology II FBI102 PDF

Assoc. Prof. Dr. Melis SÜMENGEN ÖZDENEFE 1 2  Pathogens, agents that cause disease, infect a wide range of animals, including humans  The immune system recognizes foreign bodies and responds with the production of immune cells and prot...

Assoc. Prof. Dr. Melis SÜMENGEN ÖZDENEFE 1 2  Pathogens, agents that cause disease, infect a wide range of animals, including humans  The immune system recognizes foreign bodies and responds with the production of immune cells and proteins  All animals have innate immunity, a defense active immediately upon infection  Vertebrates also have adaptive immunity 3  Innate immunity is present before any exposure to pathogens and is effective from the time of birth  It responds to a broad range of pathogens 4  Adaptive immunity, or acquired immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances  It involves a very specific response to pathogens 5  Pathogens (such as bacteria, fungi, and viruses) INNATE IMMUNITY Barrier defenses: (all animals) Skin Recognition of traits Mucous membranes shared by broad Secretions ranges of pathogens, Internal defenses: using a small set of Phagocytic cells receptors Natural killer cells Rapid response Antimicrobial proteins Inflammatory response ADAPTIVE IMMUNITY Humoral response: (vertebrates only) Antibodies defend against Recognition of traits infection in body fluids. specific to particular pathogens, using a Cell-mediated response: vast array of receptors Cytotoxic cells defend against infection in body Slower response cells. 6  Innate immunity is found in all animals and plants  In vertebrates, innate immunity is a first response to infections and also serves as the foundation of adaptive immunity 7  In insects, an exoskeleton made of chitin forms the first barrier to pathogens  The digestive system is protected by a chitin-based barrier and lysozyme, an enzyme that breaks down bacterial cell walls  Hemocytes circulate within hemolymph and carry out phagocytosis, the ingestion and digestion of foreign substances including bacteria 8  1 Pseudopodia surround pathogens. Pathogen 2 Pathogens engulfed by endocytosis. PHAGOCYTIC CELL 3 Vacuole forms. Lysosome Vacuole containing enzymes 4 Vacuole and lysosome fuse. 5 Pathogens destroyed. 6 Debris from pathogens released. 9  Hemocytes also secrete antimicrobial peptides that disrupt the plasma membranes of fungi and bacteria 10  The immune system recognizes bacteria and fungi by structures on their cell walls  Innate immune responses are distinct for different classes of pathogens 11  The immune system of mammals is the best understood of the vertebrates  Innate defenses include barrier defenses, phagocytosis, antimicrobial peptides  Additional defenses unique to vertebrates are natural killer cells, interferons, and the inflammatory response 12  Barrier defenses include the skin and mucous membranes of the respiratory, urinary, and reproductive tracts  Mucus traps and allows for the removal of microbes  Many body fluids including saliva, mucus, and tears are hostile to many microbes  The low pH of skin and the digestive system prevents growth of many bacteria 13  Pathogens entering the mammalian body are subject to phagocytosis  Phagocytic cells recognize groups of pathogens using TLRs, Toll-like receptors  TLRs recognize fragments of molecules characteristic of a set of pathogens 14 EXTRACELLULAR FLUID Lipopolysaccharide Helper protein Flagellin TLR4 PHAGOCYTIC CELL TLR5 CpG DNA TLR9 VESICLE Innate immune responses dsRNA TLR3 15  There are two main types of phagocytic cells in the mammalian body ◦ Neutrophils engulf and destroy pathogens ◦ Macrophages are found throughout the body  There are two additional types of phagocytic cells ◦ Dendritic cells stimulate development of adaptive immunity ◦ Eosinophils discharge destructive enzymes 16  Cellular innate defenses in vertebrates also involve natural killer cells  These circulate through the body and detect abnormal cells  They release chemicals leading to cell death, inhibiting the spread of virally infected or cancerous cells  Many cellular innate defenses involve the lymphatic system 17  Interstitial fluid Blood capillary Adenoid Tonsils Lymphatic vessels Thymus Tissue Lymphatic cells vessel Lymphatic Peyer’s Spleen vessel patches (in small intestine) Lymph nodes Appendix (cecum) Lymph Masses of node defensive cells18  Peptides and proteins function in innate defense by attacking pathogens or impeding their reproduction  Interferon proteins provide innate defense, interfering with viruses and helping activate macrophages  About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation 19  The inflammatory response, such as pain and swelling, is brought about by molecules released upon injury of infection  Mast cells, a type of connective tissue, release histamine, which triggers blood vessels to dilate and become more permeable 20  Activated macrophages and neutrophils release cytokines, signaling molecules that enhance the immune response  Enhanced blood flow to the site helps deliver antimicrobial peptides that result in an accumulation of pus, a fluid rich in white blood cells, dead pathogens, and cell debris from damaged tissues 21 Pathogen Splinter Movement of fluid Signaling Macro- Mast molecules phage cell Capillary Phagocytosis Red blood cells Neutrophil 1 Histamines and cytokines 2 Antimicrobial 3 Neutrophils released. Capillaries dilate. peptides enter tissue. digest pathogens Neutrophils are and cell debris. recruited. Tissue heals. 22  Inflammation can be either local or systemic (throughout the body)  Fever is a systemic inflammatory response triggered by substances released by macrophages in response to certain pathogens  Septic shock is a life-threatening condition caused by an overwhelming inflammatory response 23  Some pathogens avoid destruction by modifying their surface to prevent recognition or by resisting breakdown following phagocytosis  Tuberculosis (TB), one such disease, kills more than a million people a year 24  The adaptive response relies on two types of lymphocytes, or white blood cells  Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells 25  Antigen receptors Mature B cell Mature T cell 26  The small accessible part of an antigen that binds to an antigen receptor is called an epitope  Each individual B or T cell is specialized to recognize a specific type of molecule  The antigen receptors of B cells and T cells have similar components but they encounter antigens in different ways 27  Each B cell antigen receptor is a Y-shaped molecule with two identical heavy chains and two identical light chains  The constant regions of the chains vary little among B cells, whereas the variable regions differ greatly  The variable regions provide antigen specificity 28  Antigen- Antigen- binding binding site site Disulfide bridge Variable regions B cell Constant antigen regions receptor Light C C chain Transmembrane region Heavy Plasma chain membrane B cell Cytoplasm of B cell 29  Binding of a B cell antigen receptor to an antigen is an early step in B cell activation  This gives rise to cells that secrete a soluble form of the protein called an antibody or immunoglobulin (Ig)  Antibodies have the same Y shape as B cell antigen receptors but are secreted, not membrane bound 30  Antigen receptor Antibody B cell Antigen Epitope Pathogen (a) B cell antigen receptors and antibodies Antibody C Antibody A Antibody B Antigen (b) Antigen receptor specificity 31 32  Each T cell receptor consists of two different polypeptide chains (called  and )  The tips of the chain form a variable (V) region; the rest is a constant (C) region  T cell and B cell antigen receptors are functionally different 33  Antigen- binding site T cell Variable antigen V V regions receptor Constant C C regions Transmembrane Disulfide region bridge α chain β chain Plasma membrane T cell Cytoplasm of T cell 34  T cells bind to antigen fragments displayed or presented on a host cell  These antigen fragments are bound to cell- surface proteins called MHC molecules  MHC (major histocompatibility complex) molecules are host proteins that display the antigen fragments on the cell surface 35  In infected cells, MHC molecules bind and transport antigen fragments to the cell surface, a process called antigen presentation  A T cell can then bind both the antigen fragment and the MHC molecule  This interaction is necessary for the T cell to participate in the adaptive immune response 36 Displayed antigen T cell fragment MHC T cell antigen molecule receptor Antigen fragment Pathogen Host cell (a) Antigen recognition by a T cell Top view Antigen fragment MHC molecule Host cell (b) A closer look at antigen presentation 37  The defenses provided by B and T lymphocytes can be divided into humoral immune response and the cell-mediated immune response  In the humoral immune response antibodies help neutralize or eliminate toxins and pathogens in the blood and lymph  In the cell-mediated immune response specialized T cells destroy affected host cells 38  A type of T cell called a helper T cell triggers both the humoral and cell-mediated immune responses  Signals from helper T cells initiate production of antibodies that neutralize pathogens and activate T cells that kill infected cells  Antigen-presenting cells have class I and class II MHC molecules on their surfaces 39  Class II MHC molecules are the basis upon which antigen-presenting cells are recognized  Antigen receptors on the surface of helper T cells bind to the antigen and the class II MHC molecule; then signals are exchanged between the two cells  The helper T cell is activated, proliferates, and forms a clone of helper T cells, which then activate the appropriate B cells 40  Antigen- presenting cell Clone of activated helper T cells Pathogen Antigen fragment Class II MHC B cell Cytotoxic molecule T cell Antigen receptor Accessory protein HUMORAL CELL- Cytokines IMMUNITY MEDIATED (secretion of IMMUNITY Helper T cell antibodies (attack on by plasma infected cells) cells) 41 42  Cytotoxic T cells use toxic proteins to kill cells infected by viruses or other intracellular pathogens  Cytotoxic T cells recognize fragments of foreign proteins produced by infected cells  The activated cytotoxic T cell secretes proteins that disrupt the membranes of target cells and trigger apoptosis 43  Cytotoxic Granzymes Released T cell cytotoxic T cell Accessory protein Antigen Dying Class I receptor Perforin infected MHC cell molecule Pore Infected cell Antigen fragment 1 2 3 44 45  The humoral response is characterized by secretion of antibodies by B cells 46  Activation of B cells involves helper T cells as well as proteins on the surface of pathogens  When an antigen binds a B cell, the cell takes in a few foreign molecules by receptor- mediated endocytosis  The class II MHC protein of the B cell then presents an antigen fragment to a helper T cell, a process that is critical to B cell activation 47  An activated B cell gives rise to thousands of identical plasma cells  These begin producing and secreting antibodies  Most antigens recognized by B cells contain multiple epitopes  A variety of B cells activated by one antigen will give rise to plasma cells producing antibodies directed against different epitopes of the common antigen 48 Antigen- Pathogen presenting cell B cell Antigen Memory B cells fragments MHC Antigen CD4 receptor Cytokines Activated Plasma Secrete 1 Helper T cell 2 helper T cell 3 cells antibodies 49  Antibodies do not kill pathogens; instead they mark pathogens for destruction  In neutralization, antibodies bind to viral surface proteins preventing infection of a host cell  Antibodies may also bind to toxins in body fluids and prevent them from entering body cells 50  In opsonization, antibodies bind to antigens on bacteria, triggering phagocytosis  Antigen-antibody complexes may bind to a complement protein—which triggers a cascade of complement protein activation  Ultimately a membrane attack complex forms a pore in the membrane of the foreign cell, leading to its lysis 51 (a) Neutralization (b) Opsonization (c) Activation of complement system and pore formation Antibody Complement proteins Formation of membrane attack complex Bacterium Flow of water Virus and ions Pore Foreign Antigen Macrophage cell Blocking of ability Promotion of Activation Pore formation allows of virus to bind to phagocytosis of of the water and ions to rush a host cell bacteria by complement inside the foreign cell, macrophages and system which swells and neutrophils eventually lyses. 52 53  B cells can express five different forms (or classes) of immunoglobulin (Ig) with similar antigen-binding specificity but different heavy chain C regions  IgD is membrane bound, while the other four, IgA, IgE, IgG, and IgM are soluble 54  Both the humoral and cell-mediated responses can include primary and secondary immune responses  Memory cells enable the secondary response 55  HUMORAL IMMUNE RESPONSE CELL-MEDIATED IMMUNE RESPONSE Key Antigen (1st exposure) + Stimulates Engulfed by Gives rise to Antigen- + presenting cell + + Cytotoxic B cell Helper T cell T cell + + Memory helper T cells + + + Antigen (2nd exposure) Plasma Memory + Memory Active cells B cells cytotoxic T cells cytotoxic T cells Secreted Defend against Defend against antibodies extracellular pathogens intracellular pathogens and cancer 56  Active immunity develops naturally a pathogen invades the body and elicits a primary or secondary immune response  Passive immunity provides immediate, short- term protection  It is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk 57  Both active and passive immunity can be induced artificially  Active immunity can develop following immunization, introduction of antigens into the body  In artificial passive immunization, antibodies from an immune animal are injected into a nonimmune animal 58  Antibodies produced by an animal after exposure to an antigen are the products of many different clones of plasma cells  However, monoclonal antibodies can be prepared from a single clone of B cells grown in culture  These antibodies are identical and specific for one epitope  Monoclonal antibodies are used in many types of medical diagnoses and treatments 59 Endoplasmic reticulum of plasma cell 2 µm 60  Cells transferred from one person to another can be attacked by immune defenses  This complicates blood transfusions or the transplant of tissues or organs 61  Antigens on red blood cells determine whether a person has blood type A (A antigen), B (B antigen), AB (both A and B antigens), or O (neither antigen)  Antibodies to nonself blood types exist in the body  Transfusion with incompatible blood leads to destruction of the transfused cells 62  MHC molecules are different among genetically nonidentical individuals  Differences in MHC molecules stimulate rejection of tissue grafts and organ transplants 63  Chances of successful transplantation increase if donor and recipient MHC tissue types are well matched  Immunosuppressive drugs facilitate transplantation  Lymphocytes in bone marrow transplants may cause the donor tissue to reject the recipient 64  Some pathogens have evolved to diminish the effectiveness of host immune responses 65  If the delicate balance of the immune system is disrupted, effects can be severe 66  Allergies are exaggerated (hypersensitive) responses to antigens called allergens  In localized allergies such as hay fever, IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells 67  The next time the allergen enters the body, it binds to mast cell–associated IgE molecules  Mast cells release histamine and other mediators that cause vascular changes leading to typical allergy symptoms  An acute allergic response can lead to anaphylactic shock, a life-threatening reaction, within seconds of allergen exposure 68 IgE Allergen Mast (second exposure) cell 1 Initial exposure 2 Subsequent Vesicle exposure Histamine 3 Cross-linking triggers release of histamine 69  In individuals with autoimmune diseases, the immune system loses tolerance for self and turns against certain molecules of the body  Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, insulin-dependent diabetes mellitus, and multiple sclerosis 70 71  Moderate exercise improves immune system function  Psychological stress has been shown to disrupt immune system regulation by altering the interactions of the hormonal, nervous, and immune systems  Sufficient rest is also important for immunity 72  Inborn immunodeficiency results from a genetic or developmental defect in the innate or adaptive defenses, or both  Acquired immunodeficiency develops later in life due to exposure to chemical and biological agents 73  Pathogens have evolved mechanisms to thwart immune responses 74  Through antigenic variation, some pathogens are able to change epitope expression and prevent recognition  The human influenza virus mutates rapidly, and new flu vaccines must be made each year  Human viruses occasionally exchange genes with the viruses of domesticated animals  This poses a danger as human immune systems are unable to recognize the new viral strain 75  Some viruses may remain in a host in an inactive state called latency  Herpes simplex viruses can be present in a human host without causing symptoms 76  Human immunodeficiency virus (HIV) infects helper T cells  HIV persists in the host—despite an immune response—because it has a high mutation rate that promotes antigen variation  Over time an untreated HIV infection not only avoids the adaptive immune response, but abolishes it 77  HIV infection leads to acquired immune deficiency syndrome (AIDS)  People with AIDS are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse  The spread of HIV is a worldwide problem  The best approach for slowing this spread is education about practices that transmit the virus 78 79  The frequency of certain cancers increases when adaptive immunity is inactivated  15–20% of all human cancers involve viruses  The immune system can act as a defense against viruses that cause cancer and cancer cells that harbor viruses  In 2006, a vaccine was released that acts against human papillomavirus (HPV), a virus associated with cervical cancer 80 81