Chapter 17: Immunology and Serology VEE PDF

Chapter 17 IMMUNOLOGY AND SEROLOGY 1  Learning Outcomes 1.Define immunology 2.Define serology 3.Define antigen and antibody 4.Describe the general characteristics of antigens 5.Describe the general characteristics of antibodies 6.Evaluate the characteristics and functions of...

Chapter 17 IMMUNOLOGY AND SEROLOGY 1  Learning Outcomes 1.Define immunology 2.Define serology 3.Define antigen and antibody 4.Describe the general characteristics of antigens 5.Describe the general characteristics of antibodies 6.Evaluate the characteristics and functions of the five classes of antibodies 2  Learning Outcomes 7. Describe natural immunity 8. Know the components of the natural immune system 9. Describe acquired or adaptive immunity 10.Know the components of the acquired or adaptive immunity (active, passive) and (Humoral and Cell Immunity) 11.Define inflammation 12.Cite the hallmarks of inflammation 13.Define sensitivity 14.Define specificity 3  Overview of Immunology and Serology Immunology is defined as: ◦ The study of the molecules, cells, organs, and systems. The immune system's responsibility is to protect the body from harmful substances and disease-causing changes, such as: 1. Fighting Germs 2. Neutralizing harmful substances 3. Fighting disease-causing changes 4. Healing Damage ◦ https://www.youtube.com/watch?v=PzunOgYHeyg 4  Overview of Immunology & Serology In Fighting germs: The immune system identifies and removes disease-causing germs, like bacteria, viruses, parasites, and fungi. In neutralizing harmful substances: The immune system recognizes and neutralizes harmful substances from the environment. In Fighting disease-causing changes, The immune system fights disease-causing changes in the body, such as cancer cells. In healing damage, the immune system heals the damage that intruders cause. 5  Overview of Immunology & Serology The immune system uses a variety of mechanisms to perform these tasks, including: 1. Innate immunity is a non-specific, rapid response that occurs within minutes or hours of an attack. It involves cells like phagocytes, mast cells, basophils, and eosinophils, as well as the complement system. 2. White Blood Cells are a key part of the immune system. Some types of white blood cells, called phagocytes, destroy invading organisms, while others, called lymphocytes, help the body remember and destroy invaders 3. Natural barriers- The body has natural barriers, like the skin, mucous membranes, tears, earwax, mucus, and stomach acid, that help prevent microorganisms from entering the body 6  Overview of Immunology and Serology Serology is a division of immunology that specializes in laboratory detection and measurement of specific antibodies that develop in the blood during a response to exposure to a disease-producing antigen. ◦ Blood-banking techniques use serologic methods to determine blood group antigens and antibodies in the blood of a patient or blood donor. 7  Overview of Immunology and Serology The function of the immune system is to recognize “self” from “nonself” and to defend the body against nonself substances. Non-self materials can be as diverse as life-threatening infectious microorganisms or a lifesaving organ transplant. 8  Overview of Immunology and Serology Desirable consequences of immunity include natural resistance to, recovery from, and acquired resistance to infectious disease. A deficiency or dysfunction of the immune system can cause many disorders, such as acquired immunodeficiency syndrome (AIDS). Undesirable consequences of immunity include allergies, rejection of transplanted organs, and development of an autoimmune disorder: a condition in which the body attacks itself as a foreign substance, as occurs in insulin-dependent (Type 1) diabetes and pernicious anemia. 9  Overview of Immunology and Serology Many factors, including the general health and age of a person, are important considerations in the defense against disease. The ability to respond immunologically to disease is age- related. Although non-specific and specific body defenses are present in the fetus and newborn, many defenses are incompletely developed at birth, which increases the risk of developing infectious diseases. Other factors that can influence body defenses are genetic predisposition to disorders, nutritional status, and a person’s method of coping with stress. 10  Antigens and Antibodies An antigen is a substance that stimulates antibody formation and can bind to an antibody. 11  Antigens and Antibodies ◦ Cellular antigens of importance in immunology are major histocompatibility complex (MHC) tissue antigens (or human leukocyte antigens [HLAs]), autoantigens, and blood group antigens. ◦ In most cases, the normal immune system responds to foreign antigens by producing antibodies. ◦ Antibody produced in response to the foreign antigen is found in the plasma and in other body fluids and react with the foreign antigen in some observable way. ◦ Antibody is usually specific for the antigen against which it is formed. ◦ The antibody formed in response to a foreign antigen, such as a flu vaccination, can protect an individual from subsequent infections by that specific antigen. 12  Antigens and Antibodies Foreign antigenic substances are recognized by lymphocytes and plasma cells. Lymphocytes, specifically B cells, are the primary immune cells that recognize foreign antigenic substances, and when activated, they differentiate into plasma cells which then produce antibodies against those antigens; effectively marking them for destruction by the immune system Each specific type of antigen stimulates the production of equally specific antibodies by various body tissues. 13  Antigens and Antibodies If an antibody has been formed against a foreign antigenic substance, a good way to identify the infecting organism is to identify the antibody produced in response to it. This is the basis for immunologic and serologic determinations. ◦ If a known antigen is combined with a patient’s serum containing antibodies against a specific antigen, a reaction will be observed. ◦ If a specific antibody is not present in the patient’s serum, no reaction should be observed. ◦ https://youtu.be/qCRwuxDpthY?si=LCPQkMwFAMxkEr2j 14  Antigens and Antibodies Nature of antigens ◦ An antigen is generally described as a substance that, when injected into an animal, is recognized as foreign and, provided immunologically active cells are present, provokes an immune reaction or response. ◦ This immune response is the production of antibodies, substances that usually protect the body against the foreign antigen. ◦ At times, antibodies are not protective and cause allergic reactions such as hay fever or anaphylactic shock. 15  Antigens and Antibodies Antigenicity is influenced by: ◦ Molecular size, foreignness, shape of the molecule, and chemical composition. ◦ In addition, the antigenicity of a foreign substance is also related to the route of entry. ◦ Intravenous (vein) and intraperitoneal (administered through the peritoneum, a thin membrane that lines the abdominal cavity and contains the abdominal organs) routes have stronger stimuli than subcutaneous (fatty tissue l located under the dermis and above the muscle) and intramuscular routes (upper arm deltoid muscle, middle of thigh, or upper buttocks). 16  Characteristics of Antibodies Antibodies are proteins produced in response to foreign antigenic stimuli. ◦ Whether a cell-mediated response or an antibody response occurs depends on how the antigen is presented to the lymphocytes; many immune reactions display both responses. Antibodies (immunoglobulins [Ig]) are found in the gamma globulin fraction of serum or plasma. 17 Characteristics of Antibodies Antibodies resulting from antigenic stimulation within the same species are called alloantibodies or isoantibodies. Antibodies resulting from exposure to antigenic material from another species are called heteroantibodies. 18  Antibodies Immunoglobulins (Ig): also called antibodies, are proteins produced by plasma cells and secreted into body fluids in response to antigen exposure. Immunoglobulins circulate in the blood and make up approximately 10% to 15% of serum protein. An antigen entering the body triggers the production of immunoglobulins that can react specifically with areas found on that antigen. 19 Classes of Antibodies (Ig) Five Ig classes of antibodies with different molecular weights and biologic activity occur in human blood and body fluids. 20  Classes of Immunoglobulins 21 Classes of Antibodies (Ig) ◦IgA: 13% of total immunoglobulin ◦IgD: 1% of total immunoglobulin ◦IgE: Trace of total immunoglobulin ◦IgG: 80% of total immunoglobulin ◦IgM: 6% of total immunoglobulin 22  Antibody Structure ◦All the immunoglobulins have a similar chemical structural configuration. ◦The common configuration is a monomer composed of two identical heavy chains and two identical light chains connected by disulfide bonds or bridges in the hinge region. ◦The chemical structure of the heavy chains is responsible for the differences in the classes of antibodies. Light chains are of only two types, kappa and lambda, and are common to all immunoglobulin classes. 23  Classes of Immunoglobulins Immunoglobulin G (IgG) ◦It is the antibody in the highest concentration in blood and helps prevent infection. ◦It is also called gamma globulin or immune globulin. ◦IgG is produced by plasma B cells and helps prevent infections by multiplying and attacking foreign substances. It also neutralizes bacterial toxins in the blood and tissues. ◦Once produced, IgG remains in the blood for a long time and provides long-lasting immunity. 24  Classes of Immunoglobulins Immunoglobulin M (IgM) ◦ Largest antibody, approximately 5 times larger than IgG. ◦ It is the first antibody produced by the body in response to a foreign antigen or germ and is a key part of the immune system's defense against infection. ◦ IgM antibodies are produced by plasma cells as part of the body's adaptive immune response. They provide short-term protection while the body produces other antibodies. IgM plays a key role in agglutinating bacteria, activating the complement cascade, and protecting against infections. ◦ It is the first class of antibodies to be produced by newborns after birth. ◦ Detection: A positive IgM result may indicate that a person currently has an infection or has had one in the last 6 months. For example, a positive IgM result may indicate that a person has hepatitis A. 25  Classes of Immunoglobulins Immunoglobulin A (IgA) ◦ Second most abundant Ig in the blood. ◦ IgA protects the body from microbial invasion, especially in the respiratory, digestive, and genitourinary tracts. It's the most common antibody in secretions, such as saliva, tears, and breast milk, and is also found in the blood (secretory antibody). ◦ A doctor may order an IgA test to diagnose problems with the immune system, intestines, and kidneys. It can also help check for autoimmune conditions, such as arthritis, lupus, and celiac disease ◦ IgA deficiency is a genetic condition that can cause frequent infections, allergies, and digestive and autoimmune problems. Most people with an IgA deficiency don't have any symptoms. 26  Immunoglobulin A (IgA) Immunoglobulin A (IgA) is an antibody found in breast milk that helps protect infants from infection and shapes their intestinal microbiota: Protection from infection IgA binds to viruses and bacteria in the infant's mouth, nose, Eustachian tubes, and gastrointestinal tract, preventing them from entering the body. Intestinal microbiota IgA helps shape the infant's gut microbiota and promotes a healthy relationship between the infant and its microbes. Immune system development IgA helps infants overcome the normal delay in producing their immune factors. 27  Classes of Immunoglobulins IgD is not fully understood Immunoglobulin D (IgD) ◦Present in very small amounts in blood. ◦The function of Immunoglobulin D (IgD) remains largely unclear in the immune system, as it is primarily found on the surface of naive B cells and only small amounts circulate in the blood, with its exact role in antigen recognition and B cell activation still being investigated; despite its presence in most vertebrates, its specific function is considered a puzzle in immunology 28  Immunoglobulin D (IgD) Low serum levels: Only small amounts of soluble IgD can be detected in the blood, further complicating studies on its function. Potential roles in B cell development: Some research suggests IgD may play a role in B cell maturation, helping to regulate the transition from immature to mature B cells. Possible role in mucosal immunity: Recent studies indicate that IgD might be involved in mucosal immune responses, potentially interacting with basophils to modulate inflammation 29  Classes of Immunoglobulins Immunoglobulin E (IgE) ◦Least common immunoglobulin in blood. ◦IgE binds to eosinophils, basophils, and mast cells (tissue basophils). ◦IgE is involved in allergic reactions such as hay fever and food allergies. ◦Increased in many parasitic infections. 30  Immunoglobulin E (IgE) Allergic reactions: When the body encounters an allergen, such as pollen or peanuts, it produces IgE antibodies to fight off the "threat". This causes allergy symptoms like sneezing, itching, wheezing, or asthma. In severe cases, it can lead to anaphylactic shock, a life- threatening allergic reaction. Parasitic infections: IgE contributes to the body's immune response to parasitic infections. Other functions: IgE also plays a role in autoimmune processes and venom protection. 31  Immunoglobulin E (IgE) IgE is one of five classes of immunoglobulins, along with IgM, IgG, IgD, and IgA. It's produced by plasma cells and is found predominantly in tissues, where it's attached to mast cells and basophils. A doctor may recommend an IgE test if you have persistent allergy symptoms, unexplained skin conditions, or suspected parasitic infections. The test involves taking a blood sample and measuring the amount of IgE in your blood. 32  Antigens and Antibodies A simple Mnemonic to memorize and remember the Antibodies and Their Function. EASIEST WAY TO MEMORIZE THEM. https://youtu.be/1IN4KhNSMKs?si=qEJsF_OdUIJb5G9c 33 Production of Antibodies The response to an antigenic or foreign substance is referred to as an IMMUNE RESPONSE. An antibody response has the following four phases: 1. Lag phase: no detectable antibody 2. Log phase: antibody titer increases ( a blood test that measures the amt of antibodies in the blood) 3. Plateau phase: antibody titer stabilizes 4. Decline: antibody is broken down (catabolized) Note: Immunity is not immediate; when first infected, the person is ill by the disease. Antibodies require about 2 weeks to develop sufficiently, after which subsequent exposure to the antigen will elicit an effective secondary antigen-antibody response, resulting in protective immunity. 34 Production of Antibodies Primary response ◦ When a foreign antigen is first introduced, the antibody cannot be detected until about 10 to 14 days after stimulation, and the concentration of antibody (antibody titer) is greatest at about 20 days, after which it gradually decreases. ◦ The subclass of antibody associated with the primary response is IgM. 35 Production of Antibodies ◦ Secondary response aka (anamnestic response is ◦ a second rapidly increased production of antibodies in response to an immunogenic substance after serum antibodies from a first response can no longer be detected in the blood) ◦ Time: a secondary response has a shorter lag phase, a longer plateau phase, and a more gradual decline in antibody titer than a primary response. ◦ Type of antibody: Although some IgM antibody is formed in a secondary response, the IgG class is the predominant type formed. ◦ Antibody titer: in a secondary response, antibody concentrations reach a higher titer. The plateau levels in a secondary response are typically tenfold or more than the plateau levels in the primary response 36 Immune Complexes ◦The non-covalent bonding of an antigen with its respective, specific antibody is called an immune complex. ◦ Under normal circumstances, this process does not lead to a pathologic consequence. ◦ It can be viewed as a major host defense against the invasion of foreign antigens. ◦ In unusual circumstances, an immune complex persists and is deposited in endothelial or vascular structures, where it causes inflammatory damage. 37 Body Defenses Against Microbial Disease Before a pathogen can invade the human body, it must overcome the general resistance provided by the body’s immune system, which consists of nonspecific and specific defense mechanisms. A. Microbiota (Normal Flora) ◦ Normal flora, are bacteria usually found in certain parts of the body, such as the throat and intestines. ◦ Normal flora regulate the following: ◦ Innate immune functions and homeostasis ◦ Adaptive immune functions in the intestines ◦ Systemic innate and adaptive immune functions ◦ Disruption of the host normal flora, especially in the gut, is associated with many autoimmune diseases. 38 Body Defenses Against Microbial Disease ◦ First line of defense: A. Unbroken skin and mucosal membrane surfaces- These surfaces are important because they form a physical barrier to many microorganisms. B. Normal Flora- consists of bacteria that are found usually in certain parts of the body such as the throat and intestines. These microorganisms eliminate foreign microorganisms from the body. C. Other types of first-line defenses against microbial invasion include secretions such as mucus, earwax, lactic acid in sweat, stomach acid, saliva, and tears. 39 Body Defenses Against Microbial Disease ◦ Second line of defense: Natural immunity ◦ Natural (innate or inborn) resistance is one of the two ways the body resists infection if microorganisms have penetrated the first line of defense. ◦ Natural immunity has a nonspecific mechanism consisting of particular cells (neutrophils, tissue basophils, macrophages) and soluble substances in the blood (complement, lysozyme, interferon). Neutrophils, monocytes, and macrophages can engulf bacteria Complement proteins, soluble protein components, are the major fluid component of NATURAL IMMUNITY. Lysozymes and interferon aka NATURAL ANTIBIOTICS Interferons are a family of proteins produced rapidly by many cells in response to viral infection; and block the replication of viruses in cells. 40  Natural Immunity (Innate) Non-Specific Available quickly inflammation is the body's immune system's response to an irritant, such as an injury, infection, or toxic chemical. The five cardinal signs of inflammation are: Redness Caused by increased blood flow and the number of red blood cells passing through the injured area Heat Caused by increased blood flow carrying heat from the core to the extremities Swelling Caused by fluid accumulating outside blood vessels Pain Caused by chemical mediators like bradykinin, serotonin, and prostaglandins, as well as tissue distortion from swelling 41 Body Defenses Against Microbial Disease ◦ Third line of defense: Acquired or adaptive immunity ◦ Allows the body to recognize, remember, and respond to a specific stimulus, an antigen. ◦ There are two types of acquired or adaptive immunity: ACTIVE AND PASSIVE ◦ Active immunity: host produces an antibody (VACCINATION) ◦ Results from natural exposure in response to a natural infection or from an intentional vaccination with an antigen-bearing microorganism. Active immunity should stimulate the production of antibodies in a person with the disease ◦ Passive immunity: Host does not produce an antibody ◦ Antibodies from the mother: Include a baby receiving antibodies from its mother through the placenta or breast milk, providing immediate protection without the body needing to produce its antibodies. Antibody injections (snake venom, A person receives an injection of antibodies to protect against a toxin Artificial infusion of serum (This serum is produced in animals, usually horses, to treat toxins from Clostridium botulinum, Clostridium tetani, and Corynebacterium diphtheriae). 42 43 Body Defenses Against Microbial Disease Third line of defense: Acquired or adaptive immunity ◦ Humoral-mediated immunity ◦ Acts as a primary defense against bacterial infection ◦ It can be natural immunity: the person builds antibodies as the result of an infection with a microorganism ◦ It can be active immunity: the body produces antibodies after exposure to a foreign antigen (vaccination may be needed to increase the pool of memory cells) ◦ It can be passive: The body receives antibodies made by someone else. This can happen naturally, like when a mother's antibodies cross the placenta to the fetus, or artificially, like when someone with agammaglobulinemia receives gamma globulin.. 44 Body Defenses Against Microbial Disease Third line of defense: Acquired or adaptive immunity ◦ Cell-mediated immunity: ◦ Responsible for body defense: ◦ Contact sensitivity, such as poison ivy dermatitis ◦ Immunity to viral and fungal antigens ◦ Rejection of foreign tissue grafts Note: Cell-mediated immunity is moderated by links between T lymphocytes and phagocytic cells such as monocytes- macrophages. A classic example of cell-mediated immunity is the body's response to a viral infection, where cytotoxic T cells directly kill virus-infected cells, effectively eliminating the virus before it can replicate further; another example is the skin reaction to poison ivy, which is a type of delayed-type hypersensitivity reaction triggered by T cells interacting with the allergen. 45 How do antibodies work video https://youtu.be/_N1xX49AqwQ?si=HWvfLsvS8BXABcSX 46  Complement Complement is a heat-labile series of 18 plasma proteins. ◦ Proteins of the classic activation pathway and their terminal sequence are called components. ◦ Normally, complement components are present in the circulation in an inactive form. ◦ When an antigen and matching antibody join one another, the classic complement activation pathway is triggered. ◦ Once a complement pathway is activated, the cascading pathway results in the ultimate formation of the membrane attack complex that disrupts cellular membranes. ◦ https://youtu.be/E4dZ5w3D9ZM? si=r4iScsKG2yzLPfGU 47  Cells and Cellular Activities of the Immune System ◦ The entire WBC system is designed to defend the body against disease. ◦ Each cell type has a unique function and in many cases acts in cooperation with other cell types. ◦ Leukocytes (WBCs) can be functionally divided into the general categories of: 1. Granulocytes (Natural Immunity) 2. Monocytes-macrophages (Natural Immunity) 3. Lymphocytes—plasma cells (Acquired Immunity) 48 Cells and Cellular Activities of the Immune System ◦ Role of granulocytes and mononuclear cells: Phagocytosis 1. Chemotaxis 2. Adherence 3. Engulfment 4. Phagosome formation and fusion 5. Digestion and destruction ◦ Damage to tissues by trauma or microbial invasion releases substances to initiate phagocytosis. 49 Phagocytosis Video https://youtu.be/Q84-mP0cGWQ?si=vSH9hSjeIQ8d5MbD 50  Test Sensitivity and Specificity Sensitivity: refers to the lower limit of detection, or the lowest concentration capable of being detected by a test method. Failure to detect small amounts of a substance in a test will result in a false-negative result. Specificity: refers to the ability to detect only the substance for which the test is designed. Reaction with other substances (cross- reactivity) decreases the specificity of the test and can cause false positive results. 51  Principles of Immunologic and Serologic Methods Agglutination: the visible clumping or aggregation of cells or particles as a result of a reaction with a specific antibody. ◦IgM is the antibody class that reacts best in agglutination reactions because of its large size. ◦Antigen-coated particles become linked together and form visible clumps when reacted with sufficient antibodies. In most cases, the presence of agglutination indicates a positive test. 52  Principles of Immunologic and Serologic Methods Immunofluorescent assays ◦ Direct immunofluorescent assay ◦ In the direct technique, a conjugated antibody is used to detect antigen–antibody reactions that can be seen with a fluorescent microscope. ◦ Indirect immunofluorescent assay (IFA) ◦ Most widely used for the detection of diverse antibodies, the IFA is based on the fact that antibodies (immunoglobulins) not only react with homologous antigens but also can act as antigens and react with antiimmunoglobulins. Enzyme immunoassays ◦ Enzyme immunoassay (EIA) uses enzyme molecules that can be conjugated to specific monoclonal or polyclonal antibodies. ◦ Includes the enzyme-linked immunosorbent assay (ELISA) ◦ MANY MORE……. 53  Immunologic and Serologic Testing for Bacterial and Viral Diseases- To name a few Lyme Disease- PCR Syphilis- Antibody test Acquired Immunodeficiency Syndrome (HIV)-HIV antibodies, rapid tests, Western blot Infectious Mononucleosis-RAPID TESTS Hepatitis-testing acute/chronic antibodies 54