Basic_Immunology_Introduction.ppt
- 1. 1. Basic Immunology. Introduction COURSE OF CLINICAL IMMUNOLOGY 2015-2016
- 2. WHY DO WE NEED AN IMMUNE SYSTEM? We encounter many thousands of microbes every day – many harmless, many beneficial but some that cause disease. The immune system defends us against infections caused by the huge variety of microorganisms we encounter, including viruses, bacteria, fungi and parasites. Microbes divide rapidly, each division allowing genetic variation and change.Thus microbes can change within days or even hours. It takes years for humans to reproduce and generate genomic variation. The immune system has developed elegant mechanisms that facilitate somatic change without genomic variation in response to infection and other stimuli. THE MAJOR DEFENCE MECHANISMS AGAINST INFECTIONS Microorganisms come in all shapes and sizes, with some penetrating into cells and others entering the body but remaining outside the cells. Thus the immune system has had to develop several different mechanisms to recognise and kill microbes depending on their characteristics. From the immune systems point of view, microbes can be divided according to type of infection caused. Extracellular infection ◆ Bacteria enter tissues but usually remain outside the cells. However, as they are smaller than cells of the immune system, specialised immune cells can
- 3. ingest, kill and digest the bacteria. ◆ Multi-cellular parasites also remain outside cells, however, as they are larger than immune cells, they cannot be ingested and so additional immune mechanisms are required to fight infection. Intracellular infection ◆ Viruses enter the cytoplasm, hijack the host cells protein synthesis machinery and assemble new virus particles, which bud from the cell surface and infect new cells. Immune mechanisms which act in the extracellular space are ineffective once virus enters the cells. ◆ Intra-vesicular organisms (e.g. Mycobacteria) are taken up into cells but remain within vesicles, never entering the cytoplasm. Immune mechanisms that kill virus-infected cells are ineffective as the organisms are in a different cell compartment – therefore requiring an additional immune strategy. Infecting organisms must first breach the body’s natural defences (skin, mucous membranes etc.). The pathogen then faces the two major types of immune response, the innate immune response, and the adaptive or specific immune response. When thinking about how these systems work it is helpful to consider (1) the recognition phase where the microorganism/pathogen is recognised as foreign, and (2) the effector phase, which kills the organism.
- 4. The innate immune response is immediately available to fight pathogens without the requirement for prior exposure to the pathogen. This is the first line of defence against pathogens, recognising microbes by the presence of molecular patterns not present on mammalian cells. Innate immunity is moderately effective at controlling infection and does not improve with repeated exposure to a particular organism. The adaptive immune response is refined and expanded after infection, taking several days to provide protection on first exposure to a particular pathogen. The cells and molecules produced are highly specific for the pathogen. The adaptive immune system remembers when a microbe has previously invaded the body resulting in a rapid and efficient removal of the pathogen on the second and third time that it invades the body (immunological memory). Innate and adaptive immunity depend on white blood cells or leucocytes. Innate immunity involves granulocytes and macrophages. Adaptive immune responses depend on lymphocytes, which provide the lifelong immunity that can follow exposure to disease or vaccination. However, the two systems do not operate independently – there are many examples of co-operation. Killing of microorganisms by the adaptive immune response frequently depends upon linking antigen-specific recognition to activation of effector mechanisms
- 5. that are also used in the innate response. Together, the innate and adaptive immune systems provide an amazing defence system. Despite the fact that we are surrounded by a multitude of potentially pathogenic microorganisms, we rarely succumb to infection. Many infections are eliminated by the innate immune system and cause no disease. Infections that cannot be resolved by innate immunity trigger adaptive immunity, which usually eliminates the infection (often before we are aware of it) and generates immunological memory. WHAT HAPPENS WHEN THE IMMUNE SYSTEM GOES WRONG? The immune system is only apparent when it goes wrong, and virtually any clinical presentation may be the sign of an underlying immunological disorder. The immune system must find a balance between producing a life-saving response to infection and tissuedamaging reactions. It is also essential that the immune system only mounts a vigorous response to pathogens that pose a threat, and ignores our own tissues, as well as environmental substances including foods and medicines. Immunodeficiency diseases Immunodeficiency means a failure of the immune system to protect us from infection. It may be primary (due to an intrinsic defect in the immune system)
- 6. or secondary, (due to drugs, infection, malnutrition etc.). Overactivity of part of the immune system The immune response can cause incidental tissue damage as well as the intended removal and/or destruction of microorganisms. Additionally the immune system may fail to distinguish between pathogens and innocuous stimuli such as pollen or self-tissue. In this case a vigorous immune response causes disease. Allergy An over-response to environmental stimuli, which pose no threat, is called allergy. Several different immune mechanisms may be involved. The most common mechanism causes rapid responses varying in severity from hayfever to potentially fatal anaphylactic shock. Autoimmunity Autoimmune diseases can affect any tissue in the body, and occur when the immune system fails to distinguish between self (which should be ignored) and non-self (which should be attacked). Many autoimmune diseases can be diagnosed by testing for immune products (antibodies) against self-tissues in patients’ blood. Transplantation
- 7. Transplantation involves transfer of cells, tissues or solid organs from one person to another. As the transplanted tissue is seen as non-self, the immune system attempts to eliminate it. Powerful immunosuppression has been required to make clinical transplantation a reality. Transplantation of bone marrow, kidney, pancreas, liver, heart and lung are now routine treatments for irreversible organ failure. VACCINATION Vaccination is one of the great success stories of immunology. By generating an adaptive immune response that leads to immunological memory, people can be protected from severe disease. Vaccination has led to the eradication of smallpox, and the World Health Organization aims to eradicate poliomyelitis in the near future. The incidence of many severe infectious diseases has been hugely reduced by vaccination campaigns. Clinical immunology is the specialty that focuses on diagnosis and treatment of immune mediated disease. An understanding of the immune system and how it works is essential for treating patients with these disorders. However, immunological disorders impinge on all medical specialties to a greater or lesser degree. Thus all healthcare professionals require some understanding of basic and clinical immunology.