11_Immunology Lecture 1 by a prof of chem.pptx

Immunology lecture

1. OVERVIEW OF IMMUNE SYSTEM The immune system deals with host immune response to foreign antigen (no- nself ). Immune system is vital for survival because our environment is teeming with potentially deadly microbes and the immune system protect us from infectious pathogens. IMMUNITY generally is the condition wherein an individual is secured against a particular disease. Such individual is not susceptible to the invasive or pathogenic effects of microorganism or the toxic effects of antigenic substances to which he is immune . Normally the immune system is a protective/defensive mechanism of the body against anything that is foreign or non-self.

2. Anomalies that may occur with the immune system include the following: Immunodeficiency states : which renders the individual susceptible to infections and possibly tumours . Hypersensitivity reactions : wherein there is overwhelming allergic reaction to a foreign substance e. g. bee sting, incompatible blood etc Autoimmunity : the immune system loses its ability to distinguish self from non-self , resulting in immune reactions against the individual’s tissues and cells.

3. The mechanisms of protection against infections fall into two broad categories. Innate immunity ( also called natural, or native, or non-specific immunity ), refers to defense mechanisms that are present even before infection and that have evolved to specifically recognize microbes and protect individuals against infections . Adaptive immunity ( also called acquired, or specific, immunity ) consists of mechanisms that are stimulated by (“adapt to”) microbes and are capable of recognizing microbial and nonmicrobial substances . Innate immunity is the first line of defense , because it is always ready to prevent and eradicate infections. Adaptive immunity develops later, after exposure to microbes, and is even more powerful than innate immunity in combating infections. By convention, the term “immune response” refers to adaptive immunity.

4. Natural Kill Cells HUMORAL HUMORAL INNATE (Non specific) Bacterial polysaccharides Alternate pathway ADAPTIVE (Specific)) Neutralization of toxins ANTIBODY Neutralization of virus in circulation IFN α + β Viral inhibition Bacteria lysis COMPLEMENT Activation Chemotactic factors Neutrophils Antimicrobial activities e. g phagocytosis and extracellular killing CELLULAR Anti tumour activities e. g direct killing ADCC B cells Macrohages CELLULAR T cells Lysis of tumour cells Helper or Suppressor Facilitation of adhesion (Opsonization) IL-2 INf-y Antigen presentation Lymphohokine activation e IL-2

5. INNATE IMMUNITY The major components of innate immunity are epithelial barriers that block entry of microbes , phagocytic cells (mainly neutrophils and macrophages), dendritic cells , natural killer (NK) cells , several plasma proteins, including the proteins of the complement system. The two most important cellular reactions of innate immunity are: inflammation , the process in which phagocytic leukocytes are recruited and activated to kill microbes, and anti-viral defense , mediated by dendritic cells and NK cells . Leukocytes and epithelial cells that participate in innate immunity are capable of recognizing components of microbes that are shared among related microbes and are often essential for the infectivity of these pathogens (and thus cannot be mutated to allow the microbes to evade the defense mechanisms ).

6. These microbial structures are called pathogen associated molecular patterns . Leukocytes also recognize molecules released by injured and necrotic cells , which are sometimes called danger-associated molecular patterns . The cellular receptors that recognize these molecules are often called pattern recognition receptors . The best-defined pattern recognition receptors are a family of proteins called Toll-like receptors (TLRs) that are homologous to the Drosophila protein Toll . Different TLRs are specific for components of different bacteria and viruses . TLRs are located on the cell surface and in endosomes , so they are able to recognize and initiate cellular responses to extracellular and ingested microbes.

7. Other microbial sensors are located in the cytoplasm , where they recognize bacteria and viruses that may have colonized cells . Upon recognition of microbes, the TLRs and other sensors signal by a common pathway that leads to the activation of transcription factors, notably NF- κB (nuclear factor κB ). NF- κB turns on the production of cytokines and proteins that stimulate the microbicidal activities of various cells , notably the phagocytes. Other cellular receptors bind microbes for phagocytosis ; these include receptors for mannose residues, which are typical of microbial but not host glycoproteins , and receptors for opsonins such as antibodies and complement proteins that coat microbes.

8. Epithelia of the skin, gastrointestinal and respiratory tracts provide mechanical barriers to the entry of microbes from the external environment . Epithelial cells also produce anti-microbial molecules such as defensins , and lymphocytes located in the epithelia combat microbes at these sites . If microbes do breach epithelial boundaries, other defense mechanisms are develop to ensure protection and defense.

9. Monocytes and neutrophils are phagocytes in the blood that can rapidly be recruited to any site of infection; monocytes that enter the tissues and mature are called macrophages . Dendritic cells produce type I interferons , anti-viral cytokines that inhibit viral infection and replication. Natural killer cells provide early protection against many viruses and intracellular bacteria . The proteins of the complement system are some of the most important plasma proteins of the innate immune system.

10. In innate immunity the complement system is activated by microbes using the alternate and lectin pathways ; in adaptive immunity it is activated by antibodies using the classical pathway. Lung surfactant is also a component of innate immunity, providing protection against inhaled microbes. The early innate immune response not only provides the initial defense against infections but is also involved in triggering the subsequent, more powerful adaptive immune response.

11. ADAPTIVE IMMUNITY The adaptive immune system consists of lymphocytes and their products, including antibodies . The receptors of lymphocytes are much more diverse than those of the innate immune system , but lymphocytes are not inherently specific for microbes , and they are capable of recognizing a vast array of foreign substances. There are two types of adaptive immunity: humoral immunity , which protects against extracellular microbes and their toxins, and cell-mediated (or cellular) immunity , which is responsible for defense against intracellular microbes . Humoral immunity is mediated by B (bone marrow–derived) lymphocytes and their secreted products, antibodies (also called immunoglobulins, Ig), and cellular immunity is mediated by T (thymus-derived) lymphocytes . Both classes of lymphocytes express highly specific receptors for a wide variety of substances, called antigens.

12. TISSUES OF THE IMMUNE SYSTEM The tissues of the immune system consist of the GENERATIVE ( also called the Primary, or Central ) lymphoid organs, in which T and B lymphocytes mature and become competent to respond to antigens and the PERIPHERAL ( or Secondary ) lymphoid organs, in which adaptive immune responses to microbes are initiated . Generative Lymphoid Organs The principal generative lymphoid organs are the thymus where T cells develop, and the bone marrow, the site of production of all blood cells and where B lymphocytes mature.

13. Peripheral Lymphoid Organs The peripheral lymphoid organs consist of the lymph nodes, spleen and the mucosal and cutaneous lymphoid tissues. The tissues are organized to concentrate: antigens , antigen presenting cells (APC) and lymphocytes in a way that optimizes interaction among these cells and the development of adaptive immune responses . Within the peripheral lymphoid organs, T lymphocytes and B lymphocytes are segregated into different areas . In lymph nodes , the B cells are concentrated in discrete structures called Follicles , located around the periphery or Cortex of each node. If the B cells in a follicle have recently responded to an antigen, this follicle may contain a central region called Germinal Center.

14. The T lymphocytes are concentrated in the Paracortex , adjacent to the follicles. The follicles contain the follicular dendritic cells that are involved in the activation of B cells and the paracortex contains the dendritic cells that present antigens to T lymphocytes . In the spleen , T lymphocytes are concentrated in the periarteriolar lymphoid sheaths surrounding small arterioles , and B cells reside in the follicles. Each T and B lymphocyte is genetically programmed to recognize only one antigenic determinant , by means of antigen-specific receptor on its surface and hence, these cells display exquisite antigen specificity.

15. In unprimed individuals, the number of lymphocytes that can react to any given specific antigen are extremely small. When challenged with an antigen, e. g. in the form of a microbial infection, antigen-specific lymphocytes divide and expand to effectively handle the offending organism . Such clonal expansion of T and B lymphocytes is a complex multi-step process involving both differentiation and cell division . As such, it takes at least few days, sometimes weeks, before the process is completed. Because of this requirement, specific immune responses are better suited as the second line of defense , which eventually becomes the major protective mechanism.

16. There are multiple interconnections and “cross-talk” among the various components of the innate and adaptive immunity: The complement cascade , an important nonspecific humoral component , can be triggered directly by an invading organism (the alternate pathway ) or by antibodies formed in the course of a specific immune response. Complement in turn, plays important role in modulating the function of neutrophils and macrophages.

17. Macrophages are not only important effector cells in the expression of innate immunity, but also, as antigen-presenting cells , they play important role in triggering specific immune responses mediated by B and T lymphocytes. The T lymphocytes , in turn, mediate cellular immunity and in addition they regulate the function of antibody-producing B cells as well as that of macrophages and NK cells.

18. The physiologic significance of these interactions is often evident when a genetic or acquired disease selectively destroys just one component of the interrelated networks, as seen in the Acquired Immunodeficiency Syndrome (AIDS). In this syndrome, the destruction of a subset of T cells by the human immunodeficiency virus (HIV) produces a cascade of effects that eventually cripples almost the entire host defense apparatus.