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Semester 3: Immunology
Overview of immune system: non-specific and specific immunity, immune cells, organs
Overview of Immune System
Non-Specific Immunity
Non-specific immunity, also known as innate immunity, provides the first line of defense against pathogens. It includes physical barriers such as skin and mucous membranes, as well as cellular defenses involving phagocytes, natural killer cells, and the complement system. This type of immunity does not target specific pathogens but rather reacts to all invaders in a similar manner.
Specific Immunity
Specific immunity, or adaptive immunity, is characterized by the ability to recognize and remember specific pathogens. It involves lymphocytes, specifically B cells and T cells, which respond to distinct antigens. B cells produce antibodies that neutralize pathogens, while T cells attack infected cells and help regulate the immune response.
Immune Cells
The immune system comprises various types of cells, including: - B cells: responsible for antibody production. - T cells: involved in cell-mediated immunity. - Macrophages: phagocytic cells that engulf pathogens. - Dendritic cells: antigen-presenting cells that activate T cells. - Natural killer cells: attack tumor and virus-infected cells.
Immune Organs
Key organs involved in the immune system include: - Bone marrow: site of blood cell production including B cells. - Thymus: maturation site for T cells. - Lymph nodes: filter lymph and store immune cells. - Spleen: filters blood, removes pathogens, and recycles iron.
Antigens: immunogenicity, haptens, epitopes, immunoglobulins structure and function
Antigens: immunogenicity, haptens, epitopes, immunoglobulins structure and function
Antigens
Antigens are substances that induce an immune response. They can be proteins, polysaccharides, or nucleic acids. The ability of an antigen to provoke a response is known as immunogenicity.
Immunogenicity
Immunogenicity reflects the ability of an antigen to stimulate an immune response. Factors influencing immunogenicity include the foreignness of the antigen, its molecular size, chemical composition, and the presence of adjuvants.
Haptens
Haptens are small molecules that cannot elicit an immune response on their own. However, when attached to a larger carrier protein, they can provoke an immune response. This interaction is critical for the development of certain allergies.
Epitopes
Epitopes are specific regions on an antigen recognized by the immune system, particularly by antibodies. They can be linear or conformational. The diversity of epitopes contributes to the specificity of the immune response.
Immunoglobulins Structure
Immunoglobulins, or antibodies, consist of two heavy chains and two light chains. They have a Y-shaped structure which allows them to bind to specific antigens through their variable regions.
Immunoglobulins Function
Immunoglobulins play crucial roles in immune defense. They neutralize toxins, opsonize pathogens for phagocytosis, and activate the complement system. Different classes of immunoglobulins (IgG, IgA, IgM, IgE, IgD) fulfill various functions in the immune response.
T and B cell receptors, maturation, activation, differentiation, proliferation, effector mechanisms
T and B cell receptors, maturation, activation, differentiation, proliferation, effector mechanisms
T Cell Receptors
T cell receptors are proteins found on the surface of T cells that recognize antigens presented by major histocompatibility complex molecules. They play a critical role in the adaptive immune response.
B Cell Receptors
B cell receptors are membrane-bound immunoglobulins on B cells that bind to specific antigens. Upon binding, they initiate B cell activation and differentiation into plasma cells.
Maturation of T Cells
T cells mature in the thymus, where they undergo positive and negative selection processes to ensure self-tolerance and functional capability.
Maturation of B Cells
B cells mature in the bone marrow, where they undergo gene rearrangement resulting in diverse antigen receptors and also develop self-tolerance.
Activation of T Cells
T cell activation requires the recognition of processed antigens by T cell receptors in conjunction with co-stimulatory signals, such as CD28 binding to B7 on antigen-presenting cells.
Activation of B Cells
B cell activation can occur through direct antigen binding to B cell receptors or through helper T cells providing second signals. This also involves cytokines.
Differentiation of T Cells
Activated T cells can differentiate into various subsets such as helper T cells, cytotoxic T cells, or regulatory T cells, each with distinct functions in the immune response.
Differentiation of B Cells
Upon activation, B cells differentiate into plasma cells that produce antibodies or into memory B cells that provide long-term immunity.
Proliferation of T Cells
Following activation, T cells undergo clonal expansion, leading to a rapid increase in the number of specific T cells capable of targeting the antigen.
Proliferation of B Cells
Similarly, activated B cells also proliferate, generating a large population of antibody-secreting plasma cells.
Effector Mechanisms of T Cells
Effector T cells can directly kill infected or cancerous cells through the release of perforin and granzymes or can activate other immune cells through cytokines.
Effector Mechanisms of B Cells
Plasma cells secrete large quantities of antibodies that neutralize pathogens, opsonize bacteria for phagocytosis, and activate the complement system.
Clonal selection theory, immunoglobulin gene rearrangements, class switching
Clonal Selection Theory, Immunoglobulin Gene Rearrangements, Class Switching
Clonal Selection Theory
Clonal selection theory explains how the immune system recognizes and responds to specific antigens. According to this theory, each lymphocyte expresses a unique receptor that recognizes a specific antigen. When an antigen is encountered, the lymphocyte with the correct receptor is activated, undergoing clonal expansion to produce a population of identical cells. This population differentiates into effector cells that eliminate the pathogen and memory cells that provide long-lasting immunity.
Immunoglobulin Gene Rearrangements
Immunoglobulin gene rearrangement is a crucial process in B cell development that generates diverse antibodies. During this process, gene segments that encode immunoglobulin chains (heavy and light chains) are randomly rearranged through somatic recombination. This results in unique antigen-binding sites for each B cell. The process occurs in the bone marrow and is essential for the adaptive immune response, allowing the immune system to recognize a wide array of pathogens.
Class Switching
Class switching refers to the process by which activated B cells change the isotype of their immunoglobulin (Ig) from IgM to other classes such as IgG, IgA, or IgE. This occurs after a B cell is activated and is dependent on signals from T helper cells and cytokines. Class switching allows the immune response to adapt to different types of infections, enhancing the effectiveness of the immune system. The switch is facilitated by DNA recombination events that replace the constant region of the Ig heavy chain, while preserving the variable region.
Complement system, cytokines, cell-mediated immunity
Immunology
Complement System
The complement system is a part of the innate immune response that enhances the ability of antibodies and phagocytic cells to clear pathogens. It consists of a series of proteins found in the blood and tissue fluids. When activated, they lead to opsonization of pathogens, recruitment of inflammatory cells, and the lysis of pathogens through the formation of the membrane attack complex. There are three pathways of activation: classical, lectin, and alternative. Each pathway converges on a central cascade that promotes inflammation and enhances immune responses.
Cytokines
Cytokines are small signaling proteins released by cells that have a specific effect on the interactions and communications between cells in the immune system. They play crucial roles in mediating and regulating immunity, inflammation, and hematopoiesis. Major types of cytokines include interleukins, interferons, tumor necrosis factors, chemokines, and growth factors. Cytokines can have pro-inflammatory or anti-inflammatory effects, and their balance is critical for maintaining homeostasis and responding appropriately to infections or injuries.
Cell-Mediated Immunity
Cell-mediated immunity is a form of immunity that does not involve antibodies but rather relies on the activation of T-cells and the release of cytokines in response to antigens. It is essential for fighting off intracellular pathogens, such as viruses and certain bacteria, as well as for tumor surveillance. Major components of cell-mediated immunity include helper T-cells, cytotoxic T-cells, and memory T-cells. The activation of these cells occurs through the recognition of antigens presented by major histocompatibility complex molecules on antigen-presenting cells.
MHC: organization, function, antigen processing, presentation, hypersensitivity reactions
MHC: organization, function, antigen processing, presentation, hypersensitivity reactions
Organization of MHC
MHC molecules are divided into two main classes: Class I and Class II. Class I MHC molecules are present on all nucleated cells and present endogenous antigens to CD8+ T cells. Class II MHC molecules are primarily expressed on professional antigen-presenting cells (APCs) and present exogenous antigens to CD4+ T cells.
Function of MHC
The primary function of MHC molecules is to bind and present peptide antigens to T cells, which is crucial for the activation of the adaptive immune response. MHC molecules ensure that T cells can recognize and respond to specific pathogens or abnormal cells.
Antigen Processing
Antigen processing involves the breakdown of protein antigens into peptide fragments. For Class I MHC, this occurs in the cytoplasm through proteasomal degradation, while for Class II MHC, antigens are taken up by endocytosis and processed in endosomal/lysosomal compartments.
Antigen Presentation
Antigen presentation is the display of peptide-MHC complexes on the surface of cells. Class I MHC presents to CD8+ T cells, while Class II MHC presents to CD4+ T cells. This interaction is critical for T cell activation and the subsequent immune response.
Hypersensitivity Reactions
Hypersensitivity reactions are exaggerated immune responses that can lead to tissue damage. These reactions can be categorized into four types: Type I (immediate), Type II (cytotoxic), Type III (immune complex-mediated), and Type IV (delayed-type). MHC molecules play a role in the development and regulation of these immune responses.
Immunological diseases: autoimmunity, immunodeficiency, HIV pathogenesis
Immunological diseases: autoimmunity, immunodeficiency, HIV pathogenesis
Autoimmunity
Autoimmunity occurs when the immune system mistakenly attacks the body's own tissues. This dysfunction can lead to various autoimmune diseases such as rheumatoid arthritis, lupus, and multiple sclerosis. The pathogenesis of autoimmunity often involves genetic predisposition, environmental triggers, and loss of immunological tolerance.
Immunodeficiency
Immunodeficiency refers to the impaired ability of the immune system to respond effectively to pathogens. This can be classified into primary immunodeficiencies, which are inherited, and secondary immunodeficiencies, which can be caused by external factors such as infections, malnutrition, or medical treatments. Examples include severe combined immunodeficiency (SCID) and acquired immunodeficiency syndrome (AIDS).
HIV Pathogenesis
HIV (Human Immunodeficiency Virus) targets CD4+ T cells, leading to a progressive decline in the immune function. The virus integrates its genetic material into the host cell's DNA and replicates, which ultimately results in the depletion of CD4+ cells. This immunological failure is responsible for the increased susceptibility to opportunistic infections and certain cancers in AIDS patients. Antiretroviral therapy can help manage HIV infection, but it does not eradicate the virus.
Oncogenes, tumor antigens, cancer immunotherapy
Oncogenes, Tumor Antigens, Cancer Immunotherapy
Oncogenes
Oncogenes are mutated forms of normal genes called proto-oncogenes. These mutations lead to unregulated cell growth and division, contributing to cancer progression. Key oncogenes include RAS, MYC, and EGFR. Understanding the role of oncogenes provides insight into molecular pathways driving cancer.
Tumor Antigens
Tumor antigens are substances expressed on the surface of cancer cells that trigger immune responses. They can be categorized as tumor-specific antigens (TSAs) found only on cancer cells, and tumor-associated antigens (TAAs) that are present in normal cells but overexpressed in tumors. Examples of TAAs include HER2/neu and prostate-specific antigen (PSA). Studying tumor antigens aids in the development of targeted therapies.
Cancer Immunotherapy
Cancer immunotherapy harnesses the body's immune system to fight cancer. It includes various approaches such as monoclonal antibodies, checkpoint inhibitors, and cancer vaccines. Checkpoint inhibitors block proteins that prevent T cells from attacking cancer cells, while vaccines stimulate the immune system to recognize and fight tumor antigens. Immunotherapy has shown promising results in various cancers, transforming treatment strategies.
Vaccines: types, vaccine technology, monoclonal and polyclonal antibodies production
Vaccines: types, vaccine technology, monoclonal and polyclonal antibodies production
Types of Vaccines
Vaccines can be classified into several types: live attenuated vaccines, inactivated or killed vaccines, subunit, recombinant, or conjugate vaccines, and mRNA vaccines. Live attenuated vaccines use a weakened form of the germ that causes a disease. Inactivated vaccines contain germs that have been killed and cannot cause disease. Subunit vaccines include only parts of the virus or bacterium. Recombinant vaccines are created using genetic engineering, while mRNA vaccines use synthetic mRNA to teach cells to produce an antigen.
Vaccine Technology
Vaccine technology has evolved significantly, with multiple platforms being utilized including viral vector vaccines, protein-based vaccines, and DNA vaccines. Viral vector vaccines use a harmless virus to deliver genetic material from the pathogen, which then stimulates an immune response. Protein-based vaccines use purified proteins from the pathogen, whereas DNA vaccines involve inserting a piece of DNA from the pathogen into the host to elicit an immune response.
Monoclonal Antibodies
Monoclonal antibodies are lab-made molecules that can mimic the immune system's ability to fight off pathogens. They are produced by creating identical copies of a single type of immune cell, called a B cell, which produces a specific antibody. These antibodies can be used for both therapeutic and diagnostic purposes.
Polyclonal Antibodies
Polyclonal antibodies are produced by several different B cell lineages, meaning they recognize multiple epitopes on the same antigen. They are typically obtained from the serum of immunized animals and have diverse applications in research, diagnostics, and treatment.
Production Methods
For monoclonal antibodies, the hybridoma technique involves fusing an antibody-producing B cell with a myeloma cell to create a hybrid cell that can proliferate indefinitely. Polyclonal antibodies are produced by immunizing an animal and then isolating the serum.
Applications in Medicine
Both monoclonal and polyclonal antibodies play crucial roles in therapeutic applications, including cancer treatment, autoimmune diseases, and infectious diseases. They are also key components in diagnostic tests.
Experimental models, immunological techniques including ELISA, RIA, flow cytometry
Immunology
Experimental Models
Experimental models in immunology are critical for understanding immune responses in vivo. Common types of models include animal models like mice, rats, and rabbits, which are used to study disease processes and the effects of therapeutic interventions. These models can mimic human diseases, allowing researchers to explore pathology and test treatments.
Immunological Techniques
Immunological techniques are essential for detecting and quantifying molecules related to the immune response. They include several key methods that are widely used in research and clinical settings.
ELISA
Enzyme-linked immunosorbent assay (ELISA) is a plate-based assay technique designed to detect and quantify proteins, antibodies, or hormones. ELISA is valued for its sensitivity, specificity, and ability to handle multiple samples simultaneously. It employs an antigen-coated surface, where samples are added, followed by enzyme-linked secondary antibodies for signal detection.
RIA
Radioimmunoassay (RIA) is a sensitive technique used to measure concentrations of antigens by the use of radioactively labeled antibodies. It's particularly useful in detecting hormones, drugs, and other substances at very low concentrations. Despite its sensitivity, concerns about radioactivity have led to its decline in favor of safer alternatives.
Flow Cytometry
Flow cytometry is a powerful technique used to analyze the physical and chemical characteristics of cells or particles in a fluid as they pass through a laser. This method allows for the rapid quantification and sorting of cells based on specific markers identified using fluorescently labeled antibodies. It is widely used in immunology for cell counting, biomarker detection, and functional assays.
