Overview of the Immune System

Types of immunity: innate and adaptive

Immunity refers to the body’s ability to resist or fight off infections and diseases. There are two main types of immunity: innate immunity and adaptive immunity.

1. Innate Immunity: This is the body’s first line of defense against pathogens, and it provides immediate, nonspecific protection. Innate immunity includes physical barriers (like the skin), chemical barriers (like stomach acid), and cellular defenses (like macrophages and neutrophils) that help to identify and destroy pathogens.
2. Adaptive Immunity: Also known as acquired immunity, this type of immunity develops throughout our lives as we are exposed to various pathogens. Adaptive immunity is highly specific to particular pathogens and involves the production of antibodies by B cells and the activation of T cells. Once the immune system has been exposed to a pathogen, it can “remember” it and respond more effectively upon subsequent exposure.

Both innate and adaptive immunity work together to protect the body from infections and diseases.

Cells and organs of the immune system

The immune system is composed of a complex network of cells, tissues, and organs that work together to defend the body against harmful pathogens, such as bacteria, viruses, fungi, and parasites. Here are some key components of the immune system:

1. White Blood Cells (Leukocytes): These are the main cells of the immune system and include several types, such as:
   • Neutrophils: These are the most abundant type of white blood cells and are important for fighting bacterial infections.
   • Lymphocytes: Including B cells, T cells, and natural killer (NK) cells. B cells produce antibodies, T cells directly attack infected or abnormal cells, and NK cells attack virus-infected and cancerous cells.
   • Monocytes: These cells can differentiate into macrophages and dendritic cells, which play important roles in engulfing and digesting pathogens.
   • Eosinophils and Basophils: These cells are involved in allergic reactions and defense against parasites.
2. Lymphoid Organs:
   • Bone Marrow: This is where blood cells, including immune cells, are produced.
   • Thymus: T cells mature in the thymus before entering the bloodstream.
   • Lymph Nodes: These small, bean-shaped structures filter lymph (a fluid containing white blood cells) and trap pathogens.
   • Spleen: This organ filters blood and helps in the production of antibodies and immune cells.
   • Tonsils and Adenoids: These tissues help trap pathogens entering through the nose and mouth.
3. Secondary Lymphoid Organs:
   • Mucosa-Associated Lymphoid Tissue (MALT): This includes the tonsils, Peyer’s patches in the intestines, and other lymphoid tissues associated with mucosal surfaces.
   • Lymphoid nodules: Small, localized collections of lymphoid tissue found in various organs, such as the lungs and intestines.
4. Other Immune Cells and Tissues:
   • Skin-Associated Lymphoid Tissue (SALT): Immune cells in the skin help protect against pathogens.
   • Gut-Associated Lymphoid Tissue (GALT): Immune cells in the gut help protect against pathogens in the digestive tract.
   • Bronchus-Associated Lymphoid Tissue (BALT): Immune cells in the lungs help protect against respiratory pathogens.

These cells and organs work together to recognize and respond to pathogens, helping to keep the body healthy and free from infections.

Antigens: epitopes, antigenicity, factors influencing antigenicity

Antigens are substances that can induce an immune response in the body. They are typically proteins or large polysaccharides found on the surface of pathogens or other foreign substances. Antigens are recognized by the immune system as “non-self” and trigger the production of antibodies or an immune response to eliminate them. Here are some key concepts related to antigens:

1. Epitopes (Antigenic Determinants): Epitopes are specific regions on an antigen that are recognized by antibodies or T cell receptors. Antigens can have multiple epitopes, each capable of binding to a specific antibody or T cell receptor.
2. Antigenicity: Antigenicity refers to the ability of an antigen to induce an immune response. Not all molecules are antigenic; they must possess certain characteristics to be recognized by the immune system.
3. Factors Influencing Antigenicity:
   • Size: Larger molecules tend to be more antigenic because they have more epitopes that can be recognized by the immune system.
   • Chemical Composition: Antigens with complex chemical structures, such as proteins and polysaccharides, are more likely to be antigenic.
   • Foreignness: Antigens that are foreign to the body are more likely to be recognized as non-self and trigger an immune response.
   • Degradability: Antigens that are easily degraded by enzymes are more likely to be antigenic because they can be processed and presented to immune cells.
   • Genetic Factors: Individual genetic differences can influence the immune response to antigens, making some people more or less responsive to certain antigens.
   • Adjuvants: Substances that enhance the immune response, known as adjuvants, can increase the antigenicity of a substance.

Understanding these factors is important in vaccine development, as vaccines must contain antigens that are capable of inducing a strong and specific immune response to provide effective protection against pathogens.

Antigen processing and presentation

Antigen processing and presentation are essential processes in the immune system that help the body recognize and respond to antigens. Here’s an overview of how these processes work:

1. Antigen Processing: Antigens are processed into smaller fragments that can be recognized by immune cells. This process occurs in two main ways:
   • Endogenous Antigen Processing: Intracellular pathogens, such as viruses or some bacteria, are broken down into fragments by proteases in the cytoplasm. These antigen fragments are then transported into the endoplasmic reticulum (ER) by transporter proteins such as TAP (Transporter Associated with Antigen Processing). In the ER, the fragments are loaded onto major histocompatibility complex class I (MHC-I) molecules.
   • Exogenous Antigen Processing: Antigens from extracellular pathogens, such as bacteria, are taken up by antigen-presenting cells (APCs) through phagocytosis or endocytosis. Within endosomes and lysosomes, these antigens are broken down into smaller fragments by proteases. The antigen fragments then bind to MHC-II molecules within endosomes, and the MHC-II-antigen complex is transported to the cell surface.
2. Antigen Presentation: Once the antigen fragments are bound to MHC molecules, they are presented on the surface of the APCs for recognition by T cells. There are two types of MHC molecules involved in antigen presentation:
   • MHC Class I: Present on the surface of all nucleated cells. MHC-I molecules present endogenous antigens to CD8+ T cells (cytotoxic T cells). This process allows the immune system to detect and eliminate infected or abnormal cells.
   • MHC Class II: Present on the surface of APCs such as dendritic cells, macrophages, and B cells. MHC-II molecules present exogenous antigens to CD4+ T cells (helper T cells). This process helps activate other immune cells and coordinate the immune response.

By processing and presenting antigens, the immune system can distinguish between self and non-self antigens and mount an appropriate immune response to eliminate pathogens and infected cells.

Immunoglobulins

Structure and types of immunoglobulins and biological activities

Immunoglobulins (Ig), also known as antibodies, are glycoprotein molecules produced by plasma cells (differentiated B cells) in response to specific antigens. They play a crucial role in the immune system by recognizing and binding to antigens, marking them for destruction or neutralization. Here are the main types of immunoglobulins and their biological activities:

1. Structure of Immunoglobulins: Immunoglobulins have a characteristic Y-shaped structure consisting of four polypeptide chains—two identical heavy chains (H) and two identical light chains (L), linked by disulfide bonds. Each chain has variable (V) and constant (C) regions. The antigen-binding site is located at the tips of the Y-shaped molecule and is formed by the variable regions of the heavy and light chains.
2. Types of Immunoglobulins:
   • IgG: This is the most abundant immunoglobulin in the blood, accounting for about 75-80% of all antibodies. It provides long-term immunity and is involved in neutralizing toxins, opsonization (marking pathogens for destruction), and complement activation.
   • IgM: IgM is the first antibody produced during an initial immune response to an antigen. It is typically found as a pentamer (five units) and is efficient at agglutination (clumping) of antigens, complement activation, and opsonization.
   • IgA: IgA is found predominantly in mucosal areas, such as the gut, respiratory tract, and genitourinary tract. It plays a crucial role in mucosal immunity by preventing pathogens from entering the body and neutralizing toxins.
   • IgE: IgE is involved in allergic reactions and defense against parasitic infections. It binds to allergens and triggers the release of histamine from mast cells and basophils, leading to allergic symptoms.
   • IgD: IgD is found in small amounts in the blood and is primarily found on the surface of B cells, where it functions as a receptor for antigen recognition. Its exact role in the immune response is not fully understood.
3. Biological Activities of Immunoglobulins:
   • Neutralization: Antibodies can bind to viruses or toxins, preventing them from infecting cells or causing harm.
   • Opsonization: Antibodies coat pathogens, marking them for destruction by phagocytes (e.g., macrophages and neutrophils).
   • Complement Activation: Antibodies can activate the complement system, a group of proteins that help destroy pathogens directly or enhance the inflammatory response.
   • Agglutination: Antibodies can clump pathogens together, making them more easily engulfed by phagocytes.
   • Antibody-Dependent Cellular Cytotoxicity (ADCC): Antibodies can bind to infected or abnormal cells, marking them for destruction by immune cells such as natural killer (NK) cells.

These biological activities of immunoglobulins are essential for the immune system’s ability to recognize and eliminate pathogens, contributing to overall immune protection.

Monoclonal antibodies: production and applications

Monoclonal antibodies (mAbs) are antibodies that are identical and produced by a single clone of cells. They are important tools in biomedical research and have various therapeutic applications. Here’s an overview of how monoclonal antibodies are produced and some of their key applications:

1. Production of Monoclonal Antibodies:
   • Hybridoma Technology: Monoclonal antibodies are typically produced using hybridoma technology. This involves fusing a specific antibody-producing B cell with a myeloma cell (a cancerous B cell that can divide indefinitely) to create a hybrid cell called a hybridoma. The hybridoma can produce the specific monoclonal antibody indefinitely.
   • Screening and Selection: The hybridomas are screened and selected to identify those that produce the desired monoclonal antibody. This is often done using techniques such as enzyme-linked immunosorbent assay (ELISA) or flow cytometry.
   • Expansion and Harvesting: Selected hybridomas are then expanded in culture to produce large quantities of the monoclonal antibody. The antibodies can be harvested from the culture supernatant and purified for use.
2. Applications of Monoclonal Antibodies:
   • Therapeutic Applications: Monoclonal antibodies are used in the treatment of various diseases, including cancer, autoimmune disorders, and infectious diseases. They can target specific molecules involved in disease processes, such as growth factors or cell surface receptors, and help modulate the immune response.
   • Diagnostic Applications: Monoclonal antibodies are used in diagnostic tests, such as ELISA and immunohistochemistry, to detect the presence of specific antigens or proteins in samples. They are also used in medical imaging techniques, such as positron emission tomography (PET), to target specific tissues or cells.
   • Research Applications: Monoclonal antibodies are valuable tools in research laboratories for studying the structure and function of proteins, identifying specific cell types, and investigating disease mechanisms. They are also used in the development of new therapeutic agents and vaccines.

Overall, monoclonal antibodies have revolutionized the fields of medicine and research, offering highly specific and effective tools for diagnosis, treatment, and research purposes.

Cytokines: types and immune response

Cytokines are a broad and diverse group of small proteins that play key roles in cell signaling and mediating immune responses. They are produced by various cells, including immune cells, and act on other cells to regulate immune responses, inflammation, and hematopoiesis (the formation of blood cells). Here are some types of cytokines and their roles in the immune response:

1. Interleukins (ILs):
   • IL-1: Stimulates inflammation, induces fever, and activates T and B cells.
   • IL-2: Stimulates the proliferation of T cells and promotes their differentiation into effector T cells.
   • IL-4: Promotes the differentiation of B cells into plasma cells and the production of IgE antibodies.
   • IL-6: Stimulates the production of acute-phase proteins and plays a role in inflammation.
   • IL-12: Induces the differentiation of T cells into Th1 cells and promotes the production of IFN-gamma.
2. Tumor Necrosis Factors (TNFs):
   • TNF-alpha: Plays a role in inflammation, induces fever, and stimulates the production of other cytokines.
   • TNF-beta (lymphotoxin): Involved in the regulation of immune responses and the development of lymphoid organs.
3. Interferons (IFNs):
   • IFN-alpha and IFN-beta: Antiviral cytokines that help protect cells from viral infections.
   • IFN-gamma: Stimulates the activation of macrophages and enhances the immune response against intracellular pathogens.
4. Chemokines: These cytokines are involved in the chemotaxis of immune cells, guiding them to sites of infection or inflammation.
   • CCL2 (MCP-1): Attracts monocytes and T cells to sites of inflammation.
   • CXCL8 (IL-8): Attracts neutrophils to sites of infection or inflammation.
5. Growth Factors: These cytokines stimulate the growth and proliferation of various cell types.
   • Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): Stimulates the production of granulocytes and macrophages.
   • Granulocyte Colony-Stimulating Factor (G-CSF): Stimulates the production of neutrophils.
   • Macrophage Colony-Stimulating Factor (M-CSF): Stimulates the differentiation and proliferation of monocytes and macrophages.

Cytokines play a crucial role in regulating the immune response by coordinating the activities of different immune cells. They can have pro-inflammatory or anti-inflammatory effects, depending on the context of the immune response. Dysregulation of cytokine production can contribute to the development of various immune-related disorders, such as autoimmune diseases and inflammatory conditions.

Complement system

The complement system is a complex network of proteins that plays a key role in the immune response. It is part of the innate immune system and functions to enhance the ability of antibodies and phagocytic cells to clear pathogens from the body. The complement system can be activated through three main pathways: the classical pathway, the lectin pathway, and the alternative pathway. Here’s an overview of how the complement system works:

1. Classical Pathway: This pathway is activated when antibodies (such as IgM or IgG) bind to antigens on the surface of pathogens. The bound antibodies then interact with complement protein C1, leading to a cascade of protein activations that ultimately result in the formation of the membrane attack complex (MAC). The MAC forms a pore in the membrane of the pathogen, causing cell lysis and destruction.
2. Lectin Pathway: This pathway is activated when mannose-binding lectin (MBL), a protein that binds to specific sugars on the surface of pathogens, binds to the pathogen. MBL then activates a series of complement proteins, leading to the formation of the MAC and pathogen destruction.
3. Alternative Pathway: This pathway is continuously activated at a low level in the absence of infection. It involves the spontaneous activation of complement protein C3, which leads to the formation of C3 convertase. The alternative pathway can also be triggered by certain surface structures on pathogens. Activation of the alternative pathway results in the formation of the MAC and pathogen lysis.

In addition to its role in direct pathogen killing, the complement system also plays a role in inflammation and immune regulation. Complement proteins can attract immune cells to the site of infection, enhance phagocytosis by opsonization (marking pathogens for ingestion by phagocytes), and regulate the adaptive immune response.

Dysregulation of the complement system can lead to immune-related disorders, such as autoimmune diseases (e.g., systemic lupus erythematosus) and inflammatory conditions. Therefore, the complement system is tightly regulated to prevent excessive or inappropriate activation.

Antigen-Antibody Interactions

Antibody affinity and activity: precipitation, agglutination

Antibody affinity and activity refer to the strength of binding between an antibody and its target antigen, as well as the functional outcomes of this binding. Two important functional outcomes of antibody-antigen binding are precipitation and agglutination:

1. Precipitation: Precipitation occurs when antibodies bind to soluble antigens, forming large complexes that become insoluble and precipitate out of solution. This process effectively removes the antigen from the solution, making it easier for phagocytic cells to engulf and clear the antigen. Precipitation is often used in laboratory settings to detect the presence of antigens in a sample. For example, the precipitation reaction known as the Ouchterlony double immunodiffusion assay can be used to determine the presence of specific antigens in a sample based on the formation of a visible precipitin line between antigen and antibody wells.
2. Agglutination: Agglutination occurs when antibodies bind to multiple antigens on the surface of particles or cells, causing them to clump together. This process can help neutralize pathogens by preventing them from interacting with host cells and by enhancing their phagocytosis by immune cells. Agglutination reactions are commonly used in blood typing to determine an individual’s blood type. For example, the agglutination of red blood cells in response to specific antibodies can indicate the presence of certain blood group antigens on the surface of the red blood cells.

The affinity of an antibody for its antigen is a measure of how tightly the antibody binds to the antigen. High-affinity antibodies bind strongly to their target antigens and are more effective at precipitating or agglutinating antigens. Affinity is determined by the specific amino acid sequences in the variable regions of the antibody that interact with the antigen. Affinity maturation, a process that occurs during the immune response, leads to the production of antibodies with increased affinity for the antigen over time.

Overall, precipitation and agglutination are important functional outcomes of antibody-antigen binding that play key roles in the immune response and in laboratory diagnostics.

Radioimmunoassay (RIA), ELISA, Western blotting, immunoprecipitation, immunofluorescence

These are all laboratory techniques used in immunology and molecular biology to detect and analyze proteins, antibodies, and other molecules. Here’s a brief overview of each technique:

1. Radioimmunoassay (RIA): RIA is a sensitive technique used to measure the concentration of antigens or antibodies in a sample. It involves the use of a radioactive (usually iodine-125) labeled antigen or antibody that binds specifically to the target molecule. The amount of radioactive signal is proportional to the concentration of the target molecule in the sample.
2. Enzyme-Linked Immunosorbent Assay (ELISA): ELISA is a widely used technique for detecting and quantifying proteins, antibodies, hormones, and other molecules. It involves immobilizing a target antigen or antibody on a solid surface (such as a microplate), then adding a detection antibody that is linked to an enzyme. The enzyme produces a measurable signal (e.g., color change) when a substrate is added, indicating the presence and quantity of the target molecule.
3. Western Blotting (Immunoblotting): Western blotting is used to detect specific proteins in a sample. It involves separating proteins by size through gel electrophoresis, transferring them to a membrane, and then probing the membrane with a specific antibody that binds to the target protein. The antibody is then detected using a secondary antibody linked to an enzyme or fluorescent molecule.
4. Immunoprecipitation: Immunoprecipitation is used to isolate a specific protein or protein complex from a mixture. It involves incubating a sample with an antibody that binds to the target protein, then using a secondary antibody linked to beads or a solid support to pull down the antibody-protein complex. The isolated protein can then be analyzed further.
5. Immunofluorescence: Immunofluorescence is a technique used to visualize the location of specific proteins or antigens in cells or tissues. It involves incubating the sample with a primary antibody that binds to the target molecule, then adding a fluorescently labeled secondary antibody that binds to the primary antibody. The fluorescence can be visualized using a microscope.

These techniques are valuable tools in research and diagnostics, allowing scientists to detect, quantify, and analyze specific molecules with high sensitivity and specificity.

Flow cytometry for separation of immune cells