University:
American Career College
Course:
MA700 | Clinical Procedures and Pharmacology
Academic year:

2021
Views:

228

Pages:

53
Author:

VNever

Introduction to the Immune System: Innate and Adaptive immunity Terminology of Immunity  The term immunity is derived from the Latin word immunitas, which was formerly referred to the protection from legal prosecution offered to Roman senators during their occupations in office.  Nowadays, immunity means protection from disease and, more specifically, infectious disease. Terminology cont.    Immune system is the components such as organs, cells and molecules responsible for immunity. Immune response is the collective response against foreign substances. Immunology is the study of the immune system components and immune response to pathogenic and non-pathogenic molecules and study of immune system role in disease. History First reports of immune system goes back to Thucydides in 430 B.C. Lady Mary Worley Montagu is also famous for her letters to Royal college of London. His brother was died from small pox. She saw that Muslims and Chinese perform variulation against small pox. Both of her children underwent variulation in 1718 in Turkey. History In 1500s Turkish and Chinese physicians performed variolation through inhalation method. It was explained by Razi. A Smallpox Victim Edward Jenner found that milkmaids were Immune to small pox Edward Jenner inoculating James Philip with cowpox (1798) History  Louis Pasture (1822–1895 French), one of the most productive scientists introduced the word “Vaccination” for “Immunization” based on Jenner studies.  Vaccination    Rabies Anthrax Chicken pox's Immunologists are the predominant Medicine Nobel Prize Winners The Norwegian Nobel Institute in Oslo From 1901- 2020, more than 20 prizes were won for immunological studies The Nobel Prize in Medicine 2018 The Nobel Prize in Physiology or Medicine 2018 was awarded jointly to James P. Allison and T. Honjo "for their discovery of cancer therapy by inhibition of negative immune regulation." Physiologic function of immune system    The most important physiologic function of the immune system is prevention or eradication of infections. Thus, individuals with defective immune responses are susceptible to serious, often lifethreatening infections. Conversely, stimulating immune responses against microbes through vaccination is the most effective method for protecting individuals against infections. Roles of immune system in health and disease Beneficial and harmful roles   Vaccination has led to the worldwide eradication of smallpox, the only disease that has been eliminated from civilization by human intervention. Unfortunately, interruptions of vaccination programs in developing countries and in regions of social conflict have led to local reemergence of some infectious diseases, such as polio. Effectiveness of vaccination for common infectious diseases in US Beneficial and harmful roles   In the 1980s, the appearance of acquired immunodeficiency syndrome (AIDS) emphasized immune system role in defending against infection. These patients has suppressed immune response and are susceptible for pathogens and even nonpathogenic microorganisms. Beneficial and harmful roles    In addition to protection against pathogens, immune system is involved in combating against cancer. It performs immunesurveilance and prevents the growth of some tumors. Moreover, some cancers can be treated by stimulating immune responses against tumor cells. Immune responses also participate in the clearance of dead cells and in initiating tissue repair. Beneficial and harmful roles    Immune system is a double edged sword. In contrast to beneficial roles, abnormal immune responses cause inflammatory diseases. The immune response is the major barrier to success of organ transplantation. Beneficial and harmful roles     The products of immune cells (such as antibodies) can be used for treatment and diagnosis in clinical laboratory. Antibodies can block or eliminate potentially harmful molecules such as toxins. Engineered immune cells may be used for treatment of immunologic diseases and cancers. Due to therapeutic and diagnostic properties, immunology has captured the attention of clinicians and scientists, specially at the current Corona virus infections. Main questions could be 1. 2. 3. What types of immune responses protect individuals from infections? What are the important characteristics of immune system, and what mechanisms are responsible for these characteristics? How immune system components find pathogens and respond to them? Innate and adaptive immunity combat with pathogens Innate and adaptive immunity  Host defenses are grouped under: – – Innate immunity, which provides immediate protection against microbial invasion Adaptive immunity, which develops more slowly and provides more specialized defense against infections. Innate immunity   Innate immunity, or natural immunity or native immunity, is always present in healthy individuals (hence the term innate), prepared to block the entry of microbes and to rapidly eliminate the entered microbes. In innate immunity, the first line of defense is provided by epithelial barriers of the skin and mucosal tissues and by cells and natural antibiotics present in epithelia, all of which function to block the entry of microbes. Adaptive immunity   Adaptive immunity, also called specific immunity or acquired immunity, requires expansion and differentiation of lymphocytes in response to microbes before it can provide effective defense; i.e. it adapts to the presence of microbial invaders. Innate immunity is phylogenetically older, and the adaptive immune response was evolved later. Adaptive immunity    Innate immune responses trigger and enhance adaptive immune responses against the infectious agents. The adaptive immune system consists of lymphocytes and their products, such as antibodies. Adaptive immunity is important for defense against pathogens resistant to innate immunity. Adaptive immunity   The mechanisms of innate immunity recognize common structures shared by microbes, but the cells of adaptive immunity (lymphocytes) express specific receptors for a variety of infectious and noninfectious substances. Any substance that is specifically recognized by lymphocytes or antibodies is called an antigen. Innate and adaptive immunity interactions  Adaptive immunity helps and greatly enhances the functions of the innate immunity to eliminate microbes and foreign molecules.  For example: Antibodies (as a component of adaptive immunity) bind to microbes and coat them. Phagocytes as a component of innate immunity, recognize, ingest and destroy the antibody coated microbes.   Types of adaptive immunity  The two types of adaptive immunity, called humoral immunity and cell-mediated immunity, are mediated by different cells and molecules and provide defense against extracellular and intracellular microbes, respectively. Types of adaptive immunity Humoral immunity   Humoral immunity is mediated by proteins called antibodies, which are produced by B lymphocytes. Secreted antibodies enter the circulation and mucosal fluids to neutralize and eliminate microbes and microbial toxins that are present outside host cells, in the blood, extracellular fluid, and in the lumens of mucosal organs such as the gastrointestinal and respiratory tracts. Antibodies combat with extracellular pathogens   One of the main functions of antibodies is to stop microbes that are present at mucosal surfaces and in the blood, from gaining access to and colonizing host cells and connective tissues. In this way, antibodies prevent establishment of infections. However, antibodies cannot gain access to microbes that live inside infected cells. T cells combat with intracellular pathogens     Defense against intracellular microbes is called cell-mediated immunity because it is mediated by T lymphocytes. Some T cells activate phagocytes to destroy the ingested microbes (intracellular vesicles). Other T cells kill host cells that are harboring infectious microbes in their cytoplasm. In both cases, the T cells recognize microbial antigens that are displayed on host cell surfaces, which indicates there is a microbe inside the cell. Antigen recognition by lymphocytes   The specificities of B cells and T cells differ in some important respects. Most of T cells recognize only protein antigens, whereas B cells and antibodies are able to recognize many different types of molecules, including proteins, carbohydrates, nucleic acids, and lipids. How to induce immunity against a special pathogen  Immunity may be induced in an individual by infection or vaccination (active immunity) or conferred on an individual by transfer of antibodies or lymphocytes from an actively immunized individual (passive immunity). Active immunity   In active immunity, an individual exposed to the antigens of a microbe mounts an active response to eradicate the infection and develops resistance to later infection by that microbe. Such an individual is said to be immune to that microbe, in contrast with a naive individual, not previously exposed to that microbe’s antigens. Passive immunity    In passive immunity, a naive individual receives antibodies or cells (e.g., lymphocytes, feasible only in animal experiments) from another individual already immune to an infection. The recipient acquires the ability to combat the infection for as long as the transferred antibodies or cells last. Passive immunity is therefore useful for rapidly conferring immunity even before the individual is able to mount an active response, but it does not induce long-lived resistance to the infection. Passive immunity   The only physiologic example of passive immunity is seen in newborns, whose immune systems are not mature enough to respond to many pathogens but who are protected against infections by acquiring antibodies from their mothers through the placenta and breast milk. Clinically, passive immunity is limited to treatment of some immunodeficiency diseases with antibodies pooled from multiple donors, and for emergency treatment of some viral infections and snakebites using serum from immunized donors. Properties of adaptive immune responses Several properties of adaptive immune responses are crucial for the effectiveness of these responses in combating infections. Specificity and Diversity   The adaptive immune system is capable of distinguishing a special antigen among millions of different antigens. This is called specificity. The total collection of lymphocyte specificities, which is called lymphocyte repertoire is extremely diverse. Specificity and Diversity   The diversity of the lymphocyte repertoire, which enables the immune system to respond to a vast number and variety of antigens, also means that very few cells, perhaps 1:100,000 or 1:1,000,000 lymphocytes, are specific for any one antigen. Thus, the total number of naive (not activated) lymphocytes that can recognize and react against any one antigen ranges from about 1000 to 10,000 cells in the body. Lymphocytes are unique cells  The basis for this remarkable specificity and diversity is that lymphocytes express clonally distributed receptors for antigens, meaning that the total population of lymphocytes consists of many different clones (each made up of one cell and its progeny), and each clone expresses a specific antigen receptor that is different from the receptors of all other clones. Clonal selection  The clonal selection hypothesis, formulated in the 1950s, correctly predicted that clones of lymphocytes specific for different antigens develop before an encounter with these antigens, and each antigen elicits an immune response by selecting and activating the lymphocytes of a specific clone. Clonal selection Clonal expansion   To mount an effective defense against microbes, these few cells have to expanded to give rise to a large number of lymphocytes capable of destroying the microbes (clonal expansion). The remarkable effectiveness of immune responses is attributable to several features of adaptive immunity, including the marked expansion of the pool of lymphocytes specific for any antigen upon exposure to that antigen, and selection mechanisms that preserve the most useful lymphocytes. Memory   The adaptive immune system mounts larger and more effective responses to repeated exposures to the same antigen. This feature of adaptive immune responses implies that the immune system remembers exposure to antigen, and this property of adaptive immunity is therefore called immunologic memory. Primary & Secondary immune response   The response to the first exposure to antigen, called the primary immune response, is initiated by lymphocytes called naive lymphocytes that are seeing antigen for the first time. The term naive refers to these cells being immunologically inexperienced, not having previously responded to antigens. Subsequent encounters with the same antigen lead to responses called secondary immune responses that usually are more rapid, larger, and better able to eliminate the antigen than primary responses. Primary & Secondary immune response Primary & Secondary immune response   Secondary responses are the result of the activation of memory lymphocytes, which are longlived cells that were induced during the primary immune response. The term memory arose because of the realization that these cells must remember previous encounter with antigen since they respond better upon subsequent encounters. Immunologic memory and vaccination   Immunologic memory optimizes the ability of the immune system to combat persistent and recurrent infections, because each exposure to a microbe generates more memory cells and activates previously generated memory cells. Memory also is one of the reasons why vaccines confer long-lasting protection against infections. Clonal expantion   When lymphocytes are activated by antigens, they undergo proliferation, generating many thousands of clonal progeny cells, all with the same antigen specificity. This process, called clonal expansion, rapidly increases the number of cells specific for the antigen encountered and ensures that adaptive immunity keeps pace with rapidly proliferating microbes. Specialization    Immune responses are specialized, and different responses are designed to defend best against different classes of microbes. Immune response to fungi, bacteria, virus and parasites are different. Immune response to extracellular and intracellular pathogens are different. Hemeostasis  All immune responses are self-limited and decline as the infection is eliminated, allowing the system to return to a resting state, prepared to respond to another infection. Non-reactivity to self antigens   The immune system is able to react against an enormous number and variety of microbes and other foreign antigens, but it normally does not react against the host’s own potentially antigenic substances or self antigens. This unresponsiveness to self is called immunological tolerance, referring to the ability of the immune system to coexist with (tolerate) potentially antigenic self molecules, cells, and tissues.