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Introduction To Immunology Dr. yasmeen taj Definition The word “Immuis” means free from burden and “immunitas” means exemption from government taxes and this provided the English terminology Immunity. Immunity is a broad definition: This is a protective or defense mechanism of our body, which leads us to a healthy life. Types Of Immunity Inborn or innate immunity: It is present at birth; This is our First Line Of Defense. Acquired or specific: It is not present at birth but becomes part of our immune system as the lymphoid system develops. 1970: WHO defined immunity as immune response to antigen ( Foreign body) in form of Humoral ( activation of B-lymhocytes) Cellular (by activation of T-lymphocytes Cells Involved in Immunity Macrophages B cells T cells Important components of innate immunity Factors that limit entry of microorganisms into the body Factor -Keratin layer of intact skin -Lysozyme in tears and other secretions -Respiratory cilia -Low pH in stomach and vagina; fatty acids in skin -Surface phagocytes (eg. alveolar macrophages) -Defensins (cationic peptides) -Normal flora of throat, colon and vagina Mode Of Action -Acts as mechanical barrier -Degrades peptidoglycan in bacteria cell wall -Elevate mucus containing trapped organisms -Retards growth of microbes -Ingest and destroy microbes -Create pores in microbial membrane -Occupy receptors which prevent colonization by pathogens Important components of innate immunity Factors that limit growth of microorganisms within the body Natural killer cells Neutrophils Macrophages and dendritic cells Inferons Complement Transferrin and lactoferrin Fever Inflammatory response APOBEC3G (apolypoprotein is RNA editing enzyme) Kill virus infected cells Ingest and destroy microbes Ingest and destroy microbes, and present antigen to helper T-cells Inhibit viral replication C3b is an opsonin, membrane attack complex creates holes in bacterial membranes Sequester iron required for bacterial growth Elevated temperature retards bacterial growth Limits spread of microbes Causes hypermutation in retroviral DNA and mRNA Macrophages and other antigen presenting cells such as dendritic cells, participate in both the innate arm and acquired arm of the immune system. They are in effect a bridge between the two arms. As part of the innate arm they ingest and kill various microbes. They also present antigens to helper T cells which is the essential first step in the activation of the acquired arm. Main Components of Innate and acquired Immunity that contribute to humoral ( antibody-mediated ) immunity and cell mediated immunity Humoral Immunity Cell mediated Immunity Innate Complement Neutrophil Acquired B cells Antibodies Macrophages Natural killer cells Helper Tcells Cytotoxic T cells Specificity Of The Immune Response -Recognition of the foreign organisms by specific immune cells -Activation of these immune cells to produce a specific response (eg,antibodies) -Response that specifically targets the organisms for destruction Major Functions Of T Cells and B cells Antibody-Mediated Immunity (B Cells) 1) Host defense against infection 2) 3) 4) (Opsonize bacteria, neutralize toxins and viruses) Allergy (hypersensitivity) eg, hay fever anaphylactic shock Autoimmunity Cell Mediated Immunity 1) Host defense against infection (especially M.tuberculosis, fungi and virus infected cells) 2) Allergy (hypersensitivity )eg poison oak 3) Graft and tumor rejection 4) Regulation of antibody response (help and suppression) Important features Of Innate and Acquired Immunity Type of Immunity Specificity Effective immediately Improves Has after exposure to After Exposure memory microbe Innate Nonspecific Yes in No No minutes Acquired Highly No--requires specific several days before becoming effective Yes Yes Active and Passive Immunity Active immunity is resistance acquired after contact with foreign antigens, eg, microorganisims This contact may consist of : Clinical or subclinical infections Immunization with live or killed infectious agents or their antigens. Exposure to microbial products (eg, toxins and toxoids) Passive immunity Passive immunity is resistance based on antibodies preformed in another host. Other forms of passive immunity are IgG passed from the mother to the fetus during pregnancy. IgA passed from the mother to the newborn during breast feeding. Passive active immunity Passive-active immunity involves giving both preformed antibodies (immune globulins) to provide immediate protection and Vaccine to provide long term protection These preparations should be given at different sites in the body to prevent the antibodies from neutralizing the immunogen in the vaccine. This approach is used in the prevention of Tetanus, Rabies and Hepatitis B Immunogen and Antigen When foreign substances (Ag) are introduced into the body, they lead to anti-foreign substance ( Anti-body ) formation Immunogenic when they are able to produce specific immune response; that they will stimulate immune cells and then give rise to immunological reaction (Humoral or cellular). Antigenic substances cannot directly yield immune response, but need some help by some proteins) and then They can react with antibodies. All immunogens are antigenic but not all antigens are immunogenic Antigen Antigen may be: A) Complete B) Incomplete Properties of antigen( Foreign substances) to be Immunogenic 1) Foreignness A) Autologous antigens are self antigens and there will be no immune response. B) Allogenic antigens are from the same species and there may be reaction, eg. Blood transfusion, kidney transplant. C) Heterologous antigens are from different species These antigens will be rejected and there will be severe immune response Chemical-Structural complexity A certain amount of chemical complexity is required; eg aminoacid Homoplymers are less immunogenic then heteropolymers containing Two or three different aminoacids Molecular Size The most potent imunogens are proteins with high molecular weight ie, above 100,000. Generally, molecules with molecular weight below 10,000 are weakly immunogenic, and very small ones eg an aminoacid are nonimmunogenic Epitope Epitopes are small chemical groups on the antigen molecule that can elicit and react with antibody The antigen has variable number of epitopes and this is called the valency of the antigen Hapten Hapten is a greek word meaning to fasten. These are partial antigens. These are not immunogenic. Hapten needs carrier proteins like albumin, globulin and synthetic polypeptide to become immunogenic. Hapten (Hp)+Carrier Protein (Cp) Hp+Cp-Ab formation against hapten Antibiotics, analgesics, penicilin and alpha-methyldopa Therefore haptens are antigenic and not immunogenic ADJUVANTS Adjuvant word is from Latin means “aiding”and these are immunopotentiating agents. These are of two types ( Ag+Ab)---Injected---->Increased immune response Today, adjuvants play an important role in the efficacy of vaccines. Stimulating the correct immune response is a must when selecting an adjuvant to use for a new vaccine. Since one adjuvant alone is rarely optimal for all antigens, it is critical to have a selection of different types of adjuvants for evaluation with your antigen. MVP offers a selection of oil emulsion based adjuvants, polymer based adjuvants and co-polymer based adjuvants. Enhance the response to immunogens with Imject Adjuvants. Adjuvants are nonspecific stimulators of the immune response. When mixed with an antigen or immunogen, adjuvants help to deposit or sequester the injected material thereby helping to increase antibody response. Adjuvants enhance the immune response to compounds that are already immunogenic; they do not confer immunogenicity to non-immunogenic haptens. To make prospective antigens more immunogenic, it is necessary to conjugate them to a carrier protein or some other complex, immunogenic molecule. Thank you