Immune System PDF

Presentation Title Goes Here Online: Overview of the Immune System Nonspecific Defenses and Innate Immunity Specific Defenses and Adaptive Immunity Immunizations Disorders of the Immune Objectives: Explain the function of the immune system in the body. List the organs and tissues of the immune syste...

Presentation Title Goes Here Online: Overview of the Immune System Nonspecific Defenses and Innate Immunity Specific Defenses and Adaptive Immunity Immunizations Disorders of the Immune Objectives: Explain the function of the immune system in the body. List the organs and tissues of the immune system, and provide a function for each. Describe the barriers to entry that keep pathogens out of the body. Summarize the inflammatory response. Describe the roles of the complement system and natural killer cells in nonspecific immunity. Summarize the role of lymphocytes in adaptive immunity. Distinguish between the antibody response and the cellular response. Explain what factors of the immune system contribute to transplant rejection. Summarize the role of vaccines in providing immunity against diseases. Distinguish between active and passive immunity. 1 DD Month 20XX 2 Overview of the Immune System Pathogens are 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 Immune system fight infections and cancer. contains the lymphatic organs: the red bone marrow, thymus, lymph nodes, and spleen Lymphoid tissue may also be found in the tonsils and appendix 3 Lymphatic Organs Red bone marrow—produces blood cells In children, most bones have red bone marrow. In adults, reduced to some bones e.g skull, sternum, ribs, Lymphocytes differentiate into either: B lymphocytes (B cells) Complete maturation in bone marrow Produce antibodies T lymphocytes (T cells) Complete maturation in thymus Kill antigen-bearing cells 4 Lymphatic Organs Thymus Larger in children and shrinks as we age Plays role in maturation of T cells Only about 5% of T cells ever leave the thymus Lymph nodes Small, ovoid structures occurring along lymphatic vessels Filter lymph and keep it free of pathogens and antigens Sinuses lined by macrophages that engulf and destroy pathogens Instrumental in fighting infections and cancer due to many lymphocytes Swollen lymph nodes may indicate the body is fighting an infection. 5 Lymphatic Organs Spleen: Filters blood and is made of: Red pulp: Blood passing through sinuses is filtered of pathogens, debris, and worn-out red blood cells Sinuses are lined with macrophages White pulp: Lymphocytes are actively engaged in fighting infections and cancer One can survive without a spleen but more susceptible to infections 6 Cells of the Immune System Variety of Immune System Cells: Nonspecific immunity—indiscriminate Specific immunity—specific antigen Antigen —any molecule that stimulates the immune system 7 Cells of the Immune System Cells Function(s) Macrophages Phagocytize pathogens; inflammatory response and specific immunity Mast cells Release histamine, which promotes blood flow to injured tissues; inflammatory response Neutrophils Phagocytize pathogens; inflammatory response Natural killer cells Kill virus-infected and tumor cells by cell-to-cell contact B lymphocytes Involved in the process of specific immunity by producing plasma cells and memory B cells Plasma cells Produce specific antibodies Memory cells Long-lived cells that may produce new B and T cells in the future T lymphocytes Regulate immune response; produce cytotoxic T cells and helper T cells Cytotoxic T cells Kill virus-infected and cancer cells Helper T cells Coordinate the adaptive immune responses play a role in the immune system’s ability to distinguish between the cells of our body (self) and pathogens in the body (nonself). 8 Nonspecific Defenses and Innate Immunity Innate immunity is the first line of defense Is present before any exposure to pathogens and is effective from the time of birth It involves fast nonspecific responses to pathogens Innate immunity consists of: Barriers to entry Inflammatory response Complement system Natural killer cells Barrier Defenses Barrier defenses include the skin and mucous membranes of the respiratory, and reproductive tracts. Mucus traps and allows for the removal of microbes The low pH of skin and the digestive system prevents growth of many bacteria The cells of the epidermis harden and die as they progress to the outer layer of the skin 10 The Inflammatory Response Series of events that occur whenever the tissue is damaged Inflamed area: Redness, heat, swelling, and pain Mast cells release chemicals Histamine causes capillaries to dilate and become more permeable Increased permeability allows fluid to escape, causing swelling Swollen area stimulates nerve endings resulting in pain Neutrophils are phagocytic white blood cells. Migrates to the site of the injury Encloses pathogens in vesicle for digestion inside the cell 11 Natural Killer Cells Kill cells that are not recognized as “self” Use same methods as T cells to kill cells Not specific—do not increase in numbers when exposed to specific antigen, no memory or previous contact Adaptive Immunity 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 In adaptive immunity, receptors provide pathogen-specific recognition The adaptive response relies on two types of lymphocytes, or white blood cells Immunity usually lasts for some time. Once we recover from measles, we usually don’t get it again. Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells They both have unique receptor proteins that can bind to foreign molecules Adaptive immunity defends against infection of body fluids and body cells Acquired immunity has two branches: the humoral immune response and the cellmediated 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 15 Specific Defenses and Adaptive Immunity Respond to antigens: Antigen can be part of a pathogen, foreign cell, or cancer cell We have become immune when our body has learned to destroy a particular antigen Distinguishes “self” from “nonself” Our immune system does not respond to molecules on the surface of our own cells. Lymphocytes have plasma membrane receptors for antigens—like a lock and a key. We have lymphocytes for any possible type of antigen. What is an antigen? Antigens are substances that can cause an immune response to produce antibodies from a B or T cell Antigen receptors Exposure to the pathogen activates B and T cells with antigen receptors specific for parts of that pathogen B cells and T cells have receptor proteins that can bind to foreign molecules Each individual lymphocyte is specialized to recognize a specific type of molecule Mature B cell Mature T cell Antigen Recognition by B Cells and Antibodies Each B cell antigen receptor is a Y-shaped Antigenbinding site Antigenbinding site B cell antigen receptor C little among B cells, whereas the variable regions differ greatly V The constant regions of the chains vary V V V Disulfide bridge C molecule with two identical heavy chains and two identical light chains Variable regions Constant regions C C Light chain Transmembrane region The variable regions provide antigen specificity Heavy chains B cell Plasma membrane Cytoplasm of B cell What is an antibody? Antigen receptor Antibody Binding of a B cell antigen receptor to an antigen is an early step in B cell activation B cell This gives rise to cells that secrete a soluble form of the protein called an antibody or immunoglobulin (Ig) Secreted antibodies are similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane Antigen Epitope Pathogen (a) B cell antigen receptors and antibodies Antibody C Antibody A Antibody B Antigen (b) Antigen receptor specificity Antigen Recognition by T Cells Each T cell receptor consists of two different polypeptide chains (called a and b) The tips of the chain form a variable (V) region; the rest is a constant (C) region Antigenbinding site T cell antigen receptor T cells bind to antigens fragments that are presented on the host cell V C C Variable regions Constant regions Transmembrane region Disulfide bridge a chain T cell and B cell antigen receptors are functionally different V T cell b chain Cytoplasm of T cell Plasma membrane 20 The Function of Antibodies Antibodies : Immunoglobulin proteins that are capable of combining with a specific antigen Antigen–antibody reaction can take several forms May produce complexes of antigens combined with antibodies (immune complexes) that mark antigens for destruction 21 B Cells and the Antibody Response Each B cell can only bind to a specific antigen. Give rise to plasma cells that produce antibodies The antigen that fits its receptor binding site B-cell receptor (BCR) If an antigen does bind to the BCR, that particular B cell is activated, divides, and produces plasma cells and memory cells. Stimulated by secretions are called cytokines 22 Characteristics of B Cells They provide an antibody response to a pathogen. They are produced and become mature in bone marrow. They reside in lymph nodes and the spleen; they circulate in blood and lymph. They directly recognize antigens and then undergo cell division. Cell division produces antibody-secreting plasma cells, as well as memory B cells. 23 B Cells and the Antibody Response, cont. Plasma cells are large with an extensive rough endoplasmic reticulum for making and secreting antibodies specific to the antigen. Memory B cells—responsible for long-term immunity If the same antigen enters the system again, memory B cells divide and quickly produce plasma cells pumping out antibodies. Once the threat passes, development of new plasma cells stop and those present undergo apoptosis (programmed cell death). 24 T Cells and the Cellular Response Some regulate immune response Others directly kill cells bearing antigens When T cells leave the thymus, they have unique T cell receptors (TCRs). Unlike B cells, T cells Do not produce antibodies and cannot recognize an antigen without help. The antigen must be presented to them by an antigen-presenting cell (APC). After a macrophage phagocytizes a virus, it is digested in a lysosome. An antigen from the virus is combined with an MHC “self” protein and moved to the cell surface for presentation to a T cell. The T cell is now activated and divides to produce more T cells—either cytotoxic or helper T cells. As the infection wanes, T cells undergo apoptosis. 25 Characteristics of T Cells They provide a cellular response to virusinfected cells and cancer cells. Antigen must be presented to a T cell in groove of an MHC* protein. Cytotoxic T cells destroy nonself antigenbearing cells. Helper T cells secrete cytokines that control the immune response. *MHC = major histocompatibility complex. MHC molecules present antigens MHC (major histocompatibility complex) molecules are cell-surface proteins that display the antigen fragments on the cell surface In infected cells, MHC molecules bind and transport antigen fragments to the cell surface, a process called antigen presentation Displayed antigen fragment MHC molecule T cell T cell antigen receptor Antigen fragment Pathogen Host cell (a) Antigen recognition by a T cell Top view A T cell can then bind both the antigen fragment and the MHC molecule Antigen fragment MHC molecule Host cell (b) A closer look at antigen presentation This interaction is necessary for the T cell to participate in the adaptive immune response 27 T Cell Response Types of T cells: Cytotoxic T cells Storage vacuoles contain perforins (perforate cell membrane) or granzymes (delivered into pore to cause apoptosis). Responsible for responses to virus-infected and cancer cells Helper T cells Regulate immunity by secreting cytokines Signal chemicals that stimulate various immune cells to perform their functions Macrophages, B cells, other T cells HIV infects helper T cells, making the AIDS patient susceptible to infections 28 Cytotoxic T Cells and the Cellular Response ku.ac.ae Cytotoxic T Cells lyse Infected Host Cells Cytotoxic T cell Accessory protein Class I MHC molecule Infected cell 1 Released cytotoxic T cell Antigen receptor Perforin Pore Antigen fragment 2 Dying infected cell Granzymes 3 ku.ac.ae Helper T Cells have a central role in Humoral and Cell-Mediated Responses Antigenpresenting cell Antigen fragment Pathogen Class II MHC molecule Accessory protein Antigen receptor 1 Helper T cell Cytokines Humoral immunity B cell + 3 + + 2 + Cytotoxic T cell Cellmediated immunity Cytotoxic T Cells: A Response to Infected Cells Cytotoxic T cells are the effector cells in the cell-mediated immune response Cytotoxic T cells recognize fragments of foreign proteins produced by infected cells and possess an accessory protein that binds to class I MHC molecules The activated cytotoxic T cell secretes proteins that disrupt the membranes of target cells and trigger apoptosis ku.ac.ae Cytotoxic T Cells lyse Infected Host Cells Cytotoxic T cell Accessory protein Class I MHC molecule Infected cell 1 Released cytotoxic T cell Antigen receptor Perforin Pore Antigen fragment 2 Dying infected cell Granzymes 3 Activation of B Cells The humoral response is characterized by secretion of antibodies by B cells Activation of the humoral immune response involves B cells and helper T cells as well as proteins on the surface of pathogens In response to cytokines from helper T cells and an antigen, a B cell proliferates and differentiates into memory B cells and antibody secreting effector cells called plasma cells Antibodies do not kill pathogens; instead they mark pathogens for destruction ku.ac.ae Activation of a B cell in the Humoral Immune Response Antigen-presenting cell Class II MHC molecule Antigen receptor Pathogen Antigen fragment B cell + Accessory protein Cytokines Activated helper T cell Helper T cell 1 Memory B cells 2 Plasma cells 3 Secreted antibodies HUMORAL IMMUNE RESPONSE CELL-MEDIATED IMMUNE RESPONSE Antigen (1st exposure) Taken in by Stimulates Gives rise to Antigenpresenting cell B cell Cytotoxic T cell Helper T cell Memory helper T cells Antigen (2nd exposure) Plasma cells Secreted antibodies Memory B cells Memory cytotoxic T cells Defend against extracellular pathogens Defend against intracellular pathogens and cancer Active cytotoxic T cells ku.ac.ae 36 Tissue Rejection: Tissue Transplants and Immune Response Certain organs could be transplanted easily from one person to another if the body does not reject them. Rejection occurs because cytotoxic T cells and antibodies bring about the destruction of foreign tissues in the body. Organ rejection can be controlled by carefully selecting the donor and administering immunosuppressive drugs. Best if donor organ comes from person with the same type of MHC proteins Some drugs work by inhibiting response of T cells to cytokines to weaken the immune response 37 Immunizations Vaccines—substances that usually do not cause illness but cause the immune system to respond to them Pathogens or their products that have been treated so they are not virulent Proteins produced by genetically engineered bacteria Types of immunity: Active Passive Newer technologies, such as those being used against COVID-19, are using messenger RNA (mRNA) molecules to produce specific parts of the virus to act as antigens. 38 mRNA Vaccines Using the mRNA of the S protein of SARS-CoV-2, researchers were able to develop a new method of producing vaccines in response to the pandemic. 39 Active Immunity Promoted by immunization After a vaccine is given, the antibody titer in the blood can be measured. Primary response is the first response to this antigen. Secondary response is faster and produces more antibodies. “Booster” dose of vaccine Active immunity depends on the presence of memory B cells and memory T cells. Usually long lasting but a booster may be required after several years 40 Active Immunity Due to Immunization 41 Passive Immunity Prepared antibodies (immunoglobulins), are not produced by the individual’s plasma cells Temporary—no memory cells Newborns receive antibodies from their mother across the placenta or through breastfeeding Only lasts a few months Injections of gamma globulins (portion of blood that contains antibodies) are given to patients unexpectedly exposed to an infectious disease. 42 Disorders of the Immune System Immune system cannot distinguish self from nonself Some pathogens have evolved to diminish the effectiveness of host immune responses Effect can range from minor to sometimes fatal Exaggerated - Allergy Self-Directed – Autoimmune disease Diminished Immune – Immune deficiency 43 Allergies Hypersensitivities to substances that ordinarily would not cause an immune response. Pollen, food, animal hair, and so on. Allergens—antigens in an allergy Regulated by cytokines secreted by both T cells and macrophages 44 Allergic Responses Immediate allergic responses: Caused by receptors on mast cells in tissues Allergens trigger release of histamine Can occur within seconds of exposure Symptoms can vary with the extreme of anaphylactic shock (sudden life-threatening drop in blood pressure) Delayed allergic response Initiated by memory T cells at the site of allergen contact in the body Skin test for tuberculosis (TB) Positive test result is red hardened skin at test site Shows previous exposure to TB Contact dermatitis to poison ivy, jewelry, cosmetics, and so on. 45 Autoimmune Diseases When cytotoxic T cells or antibodies attack the body’s own cells Cause unknown Myasthenia gravis Neuromuscular junctions do not work properly, and muscular weakness results. Multiple sclerosis (MS) Myelin sheaths of nerve fibers break down causing various neuromuscular disorders Systemic lupus erythematosus Various symptoms prior to death due to kidney damage Rheumatoid arthritis Joints are affected 46 AIDS: Acquired Immunodeficiency syndrome HIV (human immunodeficiency virus) lives in and destroys helper T cells Body is able to maintain adequate T cell numbers for some time Without therapy, T cell number eventually drops Person unable to fight off viruses, fungi, and bacteria that a normal person fights every day HIV transmitted by: Sexual contact with an infected person including vaginal or rectal intercourse or oral/genital contact Needle-sharing among intravenous drug users Babies born to females who are infected with HIV 47 HIV Infection As of 2020, an estimated 37.7 million people worldwide were living with HIV There were 1.5 million new HIV infections in 2020, a 23% decline from 2010 Heterosexual contact and IV drug use account for greatest percentage of increase in new cases Total deaths attributed to HIV/AIDS is over 36.3 million 48 AIDS The number of deaths have dropped by 39% since 2010 due to more widespread access to antiviral medications. Advances in treatment have reduced serious complications and have prolonged life. The sooner drug therapies have begun, the better the chances that HIV will not destroy the immune system. Some new strains are drug-resistant. AIDS vaccine trials are underway RV144 is a vaccine that finished Phase III trials in 2009 Phagocytic Cells of the Immune System A white blood cell engulfs a microbe, then fuses with a lysosome to destroy the microbe There are different types of phagocytic cells Neutrophils engulf and destroy pathogens Macrophages are found throughout the body Dendritic cells stimulate development of adaptive immunity Eosinophils discharge destructive enzymes Natural killer cells: circulate through the body and detect abnormal cells. They release chemicals leading to cell death(apoptosis), inhibiting the spread of virally infected or cancerous cells Presentation Title Goes Here DD Month 20XX ku.ac.ae 50 Helper T Cells: A Response to Nearly All Antigens 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 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 ku.ac.ae Helper T Cells have a central role in Humoral and Cell-Mediated Responses Antigenpresenting cell Antigen fragment Pathogen Class II MHC molecule Accessory protein Antigen receptor 1 Helper T cell Cytokines Humoral immunity B cell + 3 + + 2 + Cytotoxic T cell Cellmediated immunity Cytotoxic T Cells: A Response to Infected Cells Cytotoxic T cells are the effector cells in the cell-mediated immune response Cytotoxic T cells recognize fragments of foreign proteins produced by infected cells and possess an accessory protein that binds to class I MHC molecules The activated cytotoxic T cell secretes proteins that disrupt the membranes of target cells and trigger apoptosis Which of the following is required to activate a cell-mediated or humoral immune response to a foreign molecule? a) cytokines secreted by helper T cells b) perforins secreted by cytotoxic T cells c) granzymes secreted by cytotoxic T cells d) antibodies secreted by plasma cells e) complement proteins secreted by the liver © 2021 Pearson Education, Ltd. Which defensive chemical is improperly matched with its function? a) perforins—lysis b) antibodies—pathogen neutralization c) histamines—dilate capillaries d) cytokines—immune cell stimulation e) lysozymes—cause fevers © 2021 Pearson Education, Ltd. What is the correct sequence in which the following occur during a primary humoral immune response? 1. B cell activation 2. helper T cell activation 3. plasma cell differentiation and proliferation 4. antibody secretion 5. presentation of antigen on class II MHC proteins a) 5, 2, 1, 4, 3 b) 4, 5, 2, 1, 3 c) 5, 1, 2, 3, 4 d) 4, 5, 3, 1, 2 e) 5, 2, 1, 3, 4 © 2021 Pearson Education, Ltd. What is “matched” between donor tissue and recipient in order to increase the likelihood of a successful transplantation? a) antigens b) allergens c) Toll-like receptors d) MHC proteins e) antibodies © 2021 Pearson Education, Ltd. A synonym for an effector B cell is a(an) _____ cell. a) plasma b) memory c) tolerant d) immune e) suppressor © 2021 Pearson Education, Ltd. Thank You ku.ac.ae