Fundamentals of Immunology
Unit-1
Introduction and Historical Background: Cells and Organs of Immune System
Definition, Overview of Immune System- Anatomical, Physiological and Inflammatory Barriers. Major Contribution of Following Scientists- Edward Jenner, Jacob Henle, Louis Pasteur, Joseph Lister, Robert Koch, Paul Ehrlich, Elie Metchnikoff, Emil Von Behring, Jules Bordet, Karl Landsteiner, Jules Freund, Peter Gorer And George Snell, Tiselius & Kabat, Gerald Eldelman & Rodeny Porter, Cesar Milstein & Georges Kohler, Peter Doherty & Rolf Zinkernagel
Hematopoiesis Formation of B-Lymphocytes and T-Lymphocytes and Its Regulation Cells of The Immune System- NK Cells. B-Lymphocytes, T-Lymphocytes, Granulocytic Cells, Dendritic Cells Primary Lymphoid Organs and their Functional Role- Bone Marrow and Thymus. Secondary Lymphoid Organs and Its Functional Role- Lymph Nodes, Spleen, Mucosal-Associated Lymphoid Tissue [MALT] Intraepithelial Lymphocytes [IEL], Cutaneous-Associated Lymphoid Tissue [CALT]
Unit-II
Antigen and Immunogen, Structure and Function of Immunoglobulins, Structure and Function of MHC:
Antigen- Definition and Its Properties. Immunogen-Definition and Its Properties Antigenecity Vs. Immunogenicity and Factors Affecting It. Haptens and Adjuvants Basic Structure of Immunoglobulin. Classes of Immunoglobulin and Its Biological Activities. Major Histocompatibility Complex [MHC] Structure, Types and Function. Regulation of
MHC Expression Production of Monoclonal Antibodies, Its Mechanism [De Novo and Salvage Pathway] and Application in Research and Health.
Unit-III
Primary And Secondary Line Of Defence [Innate And Acquired Immunity], Antigen-Antibody Interactions:
Innate Immunity Phagocytic Barriers. Antigen Presenting Cells Antigen Processing and Presentation. Acquired Immunity- B-Cell Mediated Immunity, T-Cell Mediated Immunity Its Mechanism and Regulation. Immune Memory of B-Lymphocytes
Structure of Antibody, Treatment of Antibody with Pepsin, Papain, B-Mercaptoethanol and DMSO Interaction of Antigen-Antibody Antibody Affinity, Antibody Avidity, Cross Reactivity, Precipitation Reactions and Agglutination Reactions.
Unit-IV
Immune Effector Mechanism, Allergy And Hypersensitivity:
Cytokines Properties and Its Receptors. Cytokine Secretion by Thl, Th2 And Th17 Subsets And Its Function. The Complement System: Its Components, Functions, Activation and Regulation. Complement Deficiencies
Allergy and Hypersensitivity: Gell and Coombs Classification, IgE Mediated [Type 1] Antibody-Mediated Cytotoxicity [Type II]. Immune Complex-Mediated [Type III] and Tot Mediated [Type IV] Hypersensitivity.
Unit-1: Introduction and Historical Background of Immunology
Immunology is a branch of biology that focuses on the study of the immune system, its functions, and its role in protecting the body from harmful pathogens such as bacteria, viruses, and other microorganisms. This unit serves as an introduction to the field of immunology, providing a comprehensive overview of the immune system, its components, historical developments, and the major contributors who have shaped our understanding of immunity.
Overview of the Immune System: Anatomical, Physiological, and Inflammatory Barriers
The immune system is an intricate network of cells, tissues, and organs that work together to defend the body from infections and diseases. It can be divided into two primary types of immunity:
- Innate Immunity (Non-specific Immunity): This is the body’s first line of defense, providing immediate but general protection against pathogens. It includes physical barriers like the skin and mucous membranes, as well as internal defenses such as phagocytic cells (e.g., neutrophils and macrophages) and proteins like cytokines and the complement system.
- Acquired Immunity (Specific Immunity): This immunity is developed over time as the body is exposed to different pathogens. It is highly specific and involves B-cells and T-cells. Acquired immunity is also characterized by the formation of immunological memory, which enables the body to respond more efficiently to subsequent exposures to the same pathogen.
In addition to these defense mechanisms, the body also utilizes inflammatory responses that occur when tissue injury or infection is present. Inflammation is an essential part of the immune response that helps recruit immune cells to the site of infection and promotes healing.
Historical Contributions to Immunology
The understanding of the immune system has been greatly influenced by several scientists over the years. Their work has contributed significantly to the development of immunology and laid the foundation for modern medicine and vaccine development.
- Edward Jenner: Known as the father of immunology, Jenner’s development of the smallpox vaccine in 1796 marked the beginning of the concept of immunization. His work paved the way for the development of vaccines for various infectious diseases.
- Jacob Henle: Henle is credited with recognizing the role of microorganisms in disease and proposing the germ theory of disease, which laid the groundwork for understanding the immune system’s response to pathogens.
- Louis Pasteur: A pioneer in the study of microbiology, Pasteur’s work on pasteurization and vaccine development (including vaccines for rabies and anthrax) advanced the understanding of how the immune system fights infections.
- Joseph Lister: Lister’s introduction of antiseptic techniques revolutionized surgery and contributed to the understanding of how pathogens enter the body and how infections can be prevented.
- Robert Koch: Koch’s postulates and his discovery of the tuberculosis pathogen provided crucial evidence supporting the germ theory of disease. His work demonstrated how specific microorganisms are linked to specific diseases.
- Paul Ehrlich: Ehrlich’s research on antibodies and their role in immunity earned him the Nobel Prize. He also developed the concept of the “magic bullet,” a targeted approach for treating infections, which laid the foundation for chemotherapy.
- Elie Metchnikoff: Metchnikoff discovered phagocytosis, the process by which certain cells engulf and digest pathogens, contributing to the understanding of the innate immune response.
- Emil Von Behring: Von Behring developed the first serum therapy for diphtheria, which helped treat and prevent infections caused by bacterial toxins.
- Jules Bordet: Bordet’s work on complement proteins and their role in the immune response contributed to the understanding of the complex immune system.
- Karl Landsteiner: Landsteiner’s discovery of blood groups and the Rh factor is crucial for understanding immune compatibility in organ transplantation and blood transfusions.
- Jules Freund: Freund developed Freund’s adjuvant, a substance used to enhance the body’s immune response to vaccines.
- Peter Gorer and George Snell: These scientists contributed to the discovery of the major histocompatibility complex (MHC), which plays a central role in the immune response and in organ transplantation.
- Tiselius & Kabat: Their work on the identification and characterization of immunoglobulins (antibodies) contributed to the understanding of how the immune system recognizes and neutralizes pathogens.
- Gerald Edelman & Rodney Porter: These scientists shared the Nobel Prize for their work on the structure of antibodies, which helped explain how the immune system can recognize and respond to a vast array of pathogens.
- César Milstein & Georges Kohler: Their work on the development of monoclonal antibodies revolutionized diagnostic and therapeutic applications in immunology.
- Peter Doherty & Rolf Zinkernagel: Their discovery of how the immune system recognizes virus-infected cells and the concept of “self” and “non-self” recognition was a major milestone in immunology.
Hematopoiesis and Formation of B-Lymphocytes and T-Lymphocytes
Hematopoiesis is the process by which blood cells, including immune cells, are produced in the bone marrow. This process involves the differentiation of hematopoietic stem cells into various types of blood cells, including B-lymphocytes and T-lymphocytes, which play central roles in the acquired immune response.
- B-Lymphocytes (B-cells): These cells are responsible for producing antibodies that target specific pathogens. B-cells originate in the bone marrow and undergo maturation before migrating to secondary lymphoid organs such as lymph nodes and the spleen.
- T-Lymphocytes (T-cells): T-cells originate in the bone marrow but mature in the thymus. There are two primary types of T-cells: Helper T-cells (Th cells), which assist other immune cells, and Cytotoxic T-cells (Tc cells), which destroy infected or abnormal cells.
The regulation of B-cell and T-cell formation is a complex process influenced by genetic factors and signaling molecules. The precise differentiation of these immune cells is essential for an effective immune response.
Cells of the Immune System
The immune system is composed of a variety of specialized cells, each with specific roles in immunity. These include:
- Natural Killer (NK) Cells: These are a type of cytotoxic lymphocyte that plays a key role in the innate immune response by recognizing and killing virus-infected cells and tumor cells.
- Granulocytic Cells: These include neutrophils, eosinophils, and basophils, which are involved in inflammation and the defense against bacterial infections.
- Dendritic Cells: These cells act as antigen-presenting cells (APCs) that process and present antigens to T-cells, playing a crucial role in initiating the adaptive immune response.
Primary and Secondary Lymphoid Organs
The immune system is supported by a network of primary and secondary lymphoid organs:
- Primary Lymphoid Organs:
- Bone Marrow: The site of hematopoiesis, where immune cells are generated.
- Thymus: The organ where T-cells mature and differentiate.
- Secondary Lymphoid Organs:
- Lymph Nodes: These small, bean-shaped organs filter lymph and trap pathogens, allowing immune cells to respond.
- Spleen: The spleen filters blood and removes old or damaged blood cells, as well as pathogens.
- Mucosal-Associated Lymphoid Tissue (MALT): This includes structures like the tonsils, Peyer’s patches in the intestines, and other lymphoid tissues associated with mucosal surfaces.
Additionally, Intraepithelial Lymphocytes (IEL) and Cutaneous-Associated Lymphoid Tissue (CALT) are important components of the immune system that provide localized defense in the mucous membranes and skin, respectively.
Conclusion
The study of immunology has provided significant insights into the complex mechanisms that protect the body from infections. Through the contributions of various scientists, the immune system’s components, functions, and the processes of immune responses have been thoroughly explored. Understanding the cells, organs, and molecular mechanisms involved in immunity is critical for advancing medical research and developing new therapeutic approaches, including vaccines and immunotherapies. This unit serves as a foundation for further exploration into the fascinating and crucial field of immunology.
Unit II: Antigen and Immunogen, Structure and Function of Immunoglobulins, Structure and Function of MHC
Introduction to Antigens and Immunogens
The immune system plays a crucial role in defending the body against pathogens such as bacteria, viruses, fungi, and other foreign substances. Central to the immune response are antigens and immunogens, which trigger specific immune reactions in the body.
Antigen: Definition and Properties
An antigen is any substance that can bind specifically to an antibody or a T-cell receptor. Antigens are typically foreign molecules (such as proteins, polysaccharides, or nucleic acids) found on the surface of pathogens or other foreign substances. They are recognized by the immune system as being non-self, thus initiating an immune response.
Antigens have specific properties that make them recognizable by the immune system, including:
- Size: Larger molecules tend to be more immunogenic than smaller ones.
- Complexity: Antigens with more structural complexity are generally more potent in eliciting immune responses.
- Foreignness: The immune system is better at detecting antigens that are foreign to the body, particularly when they are structurally different from self-molecules.
- Stability: Stable antigens can persist longer in the body, providing more time for immune recognition.
Immunogen: Definition and Properties
An immunogen is a type of antigen that is capable of inducing an immune response. While all immunogens are antigens, not all antigens are immunogens. Immunogens must be able to elicit both a humoral and cellular immune response, triggering the production of antibodies and the activation of T-cells.
The immunogenicity of a substance depends on several factors, including its molecular size, complexity, and its ability to be processed and presented by antigen-presenting cells (APCs).
Antigenicity vs. Immunogenicity
- Antigenicity refers to the ability of a substance to bind to an antibody or T-cell receptor.
- Immunogenicity refers to the ability of a substance to induce an immune response, including the production of antibodies and the activation of immune cells.
Factors Affecting Antigenicity and Immunogenicity:
- Dose and Route of Administration: Higher doses and the right route of administration can enhance immunogenicity.
- Genetic Factors: An individual’s genetic makeup can influence how well their immune system recognizes and responds to specific antigens.
- Adjuvants: These are substances that enhance the body’s immune response to an antigen, improving the effectiveness of vaccines.
Haptens and Adjuvants
- Haptens are small molecules that are not immunogenic on their own but become immunogenic when attached to a larger carrier molecule, usually a protein.
- Adjuvants are substances that enhance the immune response to an antigen. They are commonly used in vaccines to boost the immune system’s response.
Structure and Function of Immunoglobulins (Antibodies)
Immunoglobulins (Ig), also known as antibodies, are glycoproteins produced by B lymphocytes that play a crucial role in the immune defense. These molecules specifically bind to antigens, neutralizing pathogens or marking them for destruction by other immune cells.
Basic Structure of Immunoglobulins
Immunoglobulins have a Y-shaped structure that consists of four polypeptide chains:
- Two heavy chains (H chains) and
- Two light chains (L chains). The heavy and light chains are connected by disulfide bonds. The immunoglobulin molecule is divided into two regions:
- Fab (Fragment antigen-binding): The variable region of the antibody that binds specifically to the antigen.
- Fc (Fragment crystallizable): The constant region that interacts with various receptors on immune cells.
Classes of Immunoglobulins
There are five primary classes of immunoglobulins, each with distinct functions in immune responses:
- IgG: The most abundant immunoglobulin in the bloodstream, responsible for long-term immunity and the ability to neutralize toxins and pathogens.
- IgA: Found in mucosal areas such as the respiratory and gastrointestinal tracts, providing immune protection at the mucosal surfaces.
- IgM: The first antibody produced during an initial immune response, effective in activating the complement system.
- IgE: Involved in allergic reactions and defense against parasitic infections.
- IgD: Present on the surface of B-cells and involved in initiating B-cell activation.
Biological Activities of Immunoglobulins
Immunoglobulins perform several functions essential to the immune response:
- Neutralization: Antibodies bind to pathogens or toxins, preventing them from infecting host cells.
- Opsonization: Antibodies enhance the ability of phagocytes to engulf and destroy pathogens.
- Complement Activation: Certain immunoglobulins, like IgM and IgG, activate the complement system to destroy pathogens.
- Agglutination and Precipitation: Antibodies can cross-link antigens, causing them to clump together, making them easier for the immune system to clear.
Major Histocompatibility Complex (MHC)
The Major Histocompatibility Complex (MHC) is a critical part of the immune system that enables the presentation of antigens to T-cells, a crucial step in initiating adaptive immune responses.
Structure of MHC
MHC molecules are cell surface proteins that present processed antigens to T-cells. They are divided into two classes:
- MHC Class I: Found on the surface of all nucleated cells. These molecules present antigens from inside the cell (e.g., viral proteins) to CD8+ cytotoxic T-cells.
- MHC Class II: Found on antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B-cells. These molecules present extracellular antigens to CD4+ helper T-cells.
Types and Functions of MHC
- MHC Class I Molecules: Involved in presenting endogenous antigens, typically viral or tumor-derived peptides, to CD8+ T-cells. This is vital for the immune response against infected or cancerous cells.
- MHC Class II Molecules: Present exogenous antigens, typically from pathogens, to CD4+ T-cells. This is crucial for activating helper T-cells and initiating other immune responses, including the activation of B-cells.
Regulation of MHC Expression
The expression of MHC molecules is tightly regulated and can be influenced by various factors, including cytokines. For example, interferons can increase MHC class I expression to enhance the presentation of viral antigens.
Production of Monoclonal Antibodies
Monoclonal antibodies (mAbs) are antibodies derived from a single clone of B-cells and are highly specific to a single antigen. They are produced using hybridoma technology, where a single B-cell that produces the desired antibody is fused with a myeloma cell to create a hybrid cell (hybridoma) that can proliferate indefinitely.
Mechanisms of Monoclonal Antibody Production
- De Novo Pathway: The immune system naturally produces antibodies in response to an antigen.
- Salvage Pathway: Monoclonal antibodies can also be produced by reprogramming B-cells from an individual to produce a specific antibody against a target antigen.
Monoclonal antibodies have numerous applications in research, diagnostics, and therapeutics, including:
- Cancer treatment: mAbs can be engineered to target and destroy specific cancer cells.
- Infectious disease management: They can be used as a treatment for viral infections, including COVID-19.
- Autoimmune diseases: Monoclonal antibodies can help modulate immune responses in conditions like rheumatoid arthritis.
Conclusion
In conclusion, antigens, immunogens, immunoglobulins, and MHC molecules are key components of the immune system that work together to detect, bind, and eliminate pathogens from the body. Understanding their structure, function, and interactions is essential for advancing immunological research, vaccine development, and therapeutic strategies for various diseases. The study of these molecules not only aids in enhancing immune responses but also provides insights into managing immune-related disorders.
Unit III: Primary and Secondary Lines of Defense (Innate and Acquired Immunity), Antigen-Antibody Interactions
Introduction to Immune Defense Mechanisms
The immune system serves as the body’s defense against pathogens, harmful microorganisms, and other foreign substances. The immune defense mechanisms are broadly classified into two categories: the primary (innate) and secondary (acquired) lines of defense. Each of these immune lines is responsible for detecting, neutralizing, and eliminating these harmful agents, ensuring the body’s protection from infections and diseases.
Innate Immunity: The First Line of Defense
Innate immunity is the body’s initial, non-specific response to infection and foreign pathogens. Unlike acquired immunity, which requires prior exposure to pathogens, innate immunity is present at birth and functions immediately to protect the body.
- Phagocytic Barriers: Phagocytosis is a key process in the innate immune response, where specialized cells, such as neutrophils and macrophages, engulf and destroy invading pathogens. These immune cells recognize pathogen-associated molecular patterns (PAMPs) on the surface of microorganisms, triggering the phagocytic process.
- Antigen-Presenting Cells (APCs): Dendritic cells, macrophages, and B-cells serve as antigen-presenting cells in the innate immune system. APCs capture pathogens and process them to present foreign antigens to the adaptive immune system, acting as a bridge between innate and acquired immunity.
- Antigen Processing and Presentation: Once pathogens are engulfed by APCs, their proteins are broken down into smaller peptide fragments. These peptides are then displayed on the surface of APCs in the context of Major Histocompatibility Complex (MHC) molecules, where they can be recognized by T-cells. This process is essential for initiating adaptive immune responses.
Acquired Immunity: The Adaptive Immune System
Acquired immunity, also known as adaptive immunity, is characterized by its specificity and ability to remember previously encountered pathogens. It involves the activation of B-cells and T-cells, which work together to neutralize and eliminate pathogens.
- B-Cell Mediated Immunity: B-cells are responsible for producing antibodies, which are proteins that specifically recognize and neutralize foreign antigens. Upon encountering an antigen, B-cells differentiate into plasma cells, which secrete antibodies, and memory B-cells, which persist in the body to provide long-term immunity. This mechanism is crucial for defending against extracellular pathogens.
- T-Cell Mediated Immunity: T-cells, particularly cytotoxic T-cells (CD8+), are involved in defending against intracellular pathogens, such as viruses. These T-cells recognize infected cells through MHC class I molecules and destroy the infected cells. Helper T-cells (CD4+) regulate the immune response by secreting cytokines that promote the activation of other immune cells, such as B-cells and cytotoxic T-cells.
- Immune Memory of B-Lymphocytes: One of the defining features of acquired immunity is immune memory. Memory B-cells retain the ability to recognize and respond rapidly to previously encountered pathogens, ensuring a quicker and stronger response upon subsequent infections.
Antigen-Antibody Interactions:
Antigen-antibody interactions are central to the immune response. The specific binding between an antigen and an antibody determines the outcome of the immune reaction, and these interactions can influence the efficacy of immune defenses.
- Structure of Antibodies: Antibodies, also known as immunoglobulins, are Y-shaped proteins composed of two heavy chains and two light chains. The variable region of the antibody binds to a specific antigen, while the constant region interacts with immune cells to mediate effector functions. The different classes of immunoglobulins (IgA, IgD, IgE, IgG, IgM) have distinct functions in immune defense.
- Treatment of Antibody with Enzymes: The structure and function of antibodies can be altered by enzymatic treatments. For example:
- Pepsin: Cleaves the antibody into Fab fragments that retain antigen-binding ability but lose the ability to activate complement.
- Papain: Splits the antibody into two Fab fragments and one Fc fragment.
- B-Mercaptoethanol: Breaks disulfide bonds, leading to the dissociation of antibody chains.
- DMSO (Dimethyl sulfoxide): Can alter the conformation of antibodies, affecting their binding properties.
- Antibody Affinity and Avidity:
- Antibody Affinity: Refers to the strength of the binding between an antibody and a single antigen epitope. Higher affinity antibodies bind more tightly to their target.
- Antibody Avidity: Represents the overall strength of binding between an antibody and multivalent antigens (those with multiple epitopes). Avidity is influenced by both affinity and the number of binding sites.
- Cross-Reactivity: Cross-reactivity occurs when an antibody binds to an antigen that is structurally similar but not identical to the original target antigen. This phenomenon can be beneficial (e.g., recognizing closely related pathogens) or detrimental (e.g., autoimmune responses).
- Precipitation and Agglutination Reactions:
- Precipitation Reactions: Occur when soluble antigens bind to antibodies, forming large complexes that precipitate out of solution. These reactions are useful in diagnostic tests.
- Agglutination Reactions: Involves the clumping of antigens (such as red blood cells) when exposed to specific antibodies. This reaction is a critical tool in blood typing and pathogen identification.
Conclusion:
The immune system’s ability to differentiate between self and non-self is vital for maintaining health and fighting infections. Innate immunity provides a rapid, non-specific defense, while acquired immunity ensures a more targeted and memory-based response. The interaction between antigens and antibodies is fundamental to immune responses, providing the body with the ability to neutralize and remove pathogens efficiently. Understanding these immune processes is crucial for developing treatments for infections, allergies, and autoimmune diseases, as well as for designing vaccines and therapeutic interventions.
By deepening our knowledge of immunology, we can enhance diagnostic tools, improve disease treatments, and bolster our overall understanding of human health.
This detailed exploration of Unit 3 provides a comprehensive understanding of the immune system’s primary and secondary defense mechanisms, as well as the intricate antigen-antibody interactions. Optimized for educational purposes, this content can serve as a valuable resource for students studying immunology and related fields.
Unit-IV: Immune Effector Mechanism, Allergy, and Hypersensitivity
The immune system is a highly intricate and essential defense mechanism of the human body that protects against pathogens, toxins, and foreign substances. Unit-IV delves into the complex immune effector mechanisms, the role of cytokines, the complement system, and various forms of allergic reactions and hypersensitivity responses, providing critical insights into how the immune system functions and responds to various challenges.
Cytokines: Properties, Receptors, and Their Role in Immune Response
Cytokines are small proteins that are secreted by a wide range of cells, primarily immune cells, to mediate and regulate immunity, inflammation, and hematopoiesis. These signaling molecules play a crucial role in both innate and adaptive immune responses. Cytokines include interleukins, interferons, tumor necrosis factors (TNF), and colony-stimulating factors (CSFs).
- Properties of Cytokines:
- Small molecular weight: Cytokines typically range from 5 to 20 kDa in size.
- Pleiotropy: Cytokines can have multiple effects on various cell types. For instance, interleukin-2 (IL-2) is involved in the proliferation of T-cells, but it also affects B-cells and natural killer (NK) cells.
- Redundancy: Multiple cytokines can have similar functions. For example, IL-2, IL-4, and IL-7 all stimulate the growth of T-cells.
- Synergy and Antagonism: Cytokines can work together (synergy) or counteract each other’s effects (antagonism).
- Cytokine Receptors: Cytokine receptors are proteins located on the surface of immune cells that bind to specific cytokines and mediate their biological effects. These receptors typically belong to large families, such as the IL-1 receptor family, TNF receptor family, and Class I and Class II cytokine receptor families.
Upon binding with their ligands, cytokine receptors activate intracellular signaling pathways, which influence gene expression and modulate immune cell functions such as proliferation, differentiation, migration, and survival.
- Role of Cytokines in Immune Response: Cytokines are involved in the regulation of both T-helper (Th) cell subsets and the coordination of immune responses. For example:
- Th1 cytokines (IL-2, IFN-γ) promote cellular immunity, helping to activate macrophages and cytotoxic T-cells.
- Th2 cytokines (IL-4, IL-5, IL-13) stimulate B-cell differentiation and antibody production, playing a role in humoral immunity.
- Th17 cytokines (IL-17) are involved in the defense against extracellular pathogens and are associated with autoimmune conditions.
The Complement System: Components, Functions, Activation, and Regulation
The complement system is a vital component of the innate immune system and consists of a series of proteins that work together to fight infections, trigger inflammation, and remove pathogens and damaged cells. The complement system consists of more than 30 proteins, including enzymes, regulators, and receptors, which play significant roles in immune defense.
- Components of the Complement System: The main components of the complement system include:
- C1-C9 proteins: These are the core proteins involved in the complement cascade. The cascade is triggered by the recognition of pathogens and leads to the formation of the membrane attack complex (MAC) that disrupts the pathogen’s cell membrane.
- Complement Regulatory Proteins: These proteins (e.g., C1 inhibitor, factor H) control the complement activation to prevent damage to host tissues.
- Functions of the Complement System: The complement system performs several functions crucial for immune defense:
- Opsonization: Complement proteins coat the surface of pathogens, marking them for phagocytosis by immune cells.
- Chemotaxis: Complement proteins like C5a attract immune cells to the site of infection.
- Lysis of Pathogens: The complement system forms the MAC, which creates pores in the membranes of pathogens, leading to their lysis.
- Inflammation: Complement activation increases vascular permeability, leading to the recruitment of immune cells to the site of infection.
- Activation of the Complement System: The complement system can be activated through three primary pathways:
- Classical Pathway: Initiated by antigen-antibody complexes binding to C1.
- Alternative Pathway: Triggered by microbial surfaces and independent of antibodies.
- Lectin Pathway: Initiated by the binding of mannose-binding lectin (MBL) to specific sugars on the pathogen surface.
- Regulation of Complement Activation: The complement system is tightly regulated to avoid unwanted activation and damage to host tissues. Complement regulators, such as Factor I, CD59, and C1 inhibitor, play essential roles in modulating the activity of complement components to ensure controlled immune responses.
Allergy and Hypersensitivity: Types, Mechanisms, and Clinical Implications
Hypersensitivity reactions occur when the immune system responds excessively or inappropriately to harmless substances, leading to tissue damage. Allergies, or allergic reactions, are a common example of Type I hypersensitivity. These reactions can range from mild symptoms like sneezing to severe anaphylactic shock. Hypersensitivity reactions are classified into four types based on their mechanisms and the immune components involved.
- Type I Hypersensitivity (Immediate Hypersensitivity or Allergic Reactions):
- Mechanism: Type I hypersensitivity reactions are IgE-mediated. The first exposure to an allergen (e.g., pollen, dust mites) stimulates the production of IgE antibodies. These antibodies bind to mast cells and basophils, which are then primed to release histamine and other mediators upon subsequent exposure to the same allergen.
- Clinical Examples: Common allergic conditions such as asthma, hay fever, urticaria, and anaphylaxis.
- Type II Hypersensitivity (Antibody-Mediated Cytotoxicity):
- Mechanism: This reaction is characterized by the production of IgG or IgM antibodies against cell surface antigens, leading to complement activation and cell lysis. It can also involve antibody-dependent cellular cytotoxicity (ADCC).
- Clinical Examples: Hemolytic anemia, Goodpasture syndrome, and Rhesus incompatibility.
- Type III Hypersensitivity (Immune Complex-Mediated Reactions):
- Mechanism: In Type III reactions, immune complexes formed between antigens and antibodies deposit in various tissues (kidneys, joints, skin), leading to inflammation and tissue damage through the activation of the complement system.
- Clinical Examples: Systemic lupus erythematosus (SLE), rheumatoid arthritis, and serum sickness.
- Type IV Hypersensitivity (Cell-Mediated or Delayed-Type Hypersensitivity):
- Mechanism: Type IV hypersensitivity is T-cell mediated, and the response is delayed compared to other types. It involves the activation of CD4+ T-cells, which release cytokines that recruit and activate macrophages. This leads to inflammation and tissue destruction.
- Clinical Examples: Contact dermatitis, tuberculin skin test, and chronic transplant rejection.
Conclusion
In conclusion, Unit-IV of immunology focuses on understanding the immune effector mechanisms, the role of cytokines, the complement system, and various forms of allergic reactions and hypersensitivity responses. These mechanisms form the foundation of both protective immune responses and immune disorders. The intricate interactions between the components of the immune system underscore the complexity of immune defense, while the study of allergies and hypersensitivity highlights the delicate balance the immune system must maintain to avoid damaging healthy tissues. Through a comprehensive understanding of these topics, one can appreciate how the immune system maintains health and the challenges it faces in response to infections, allergens, and diseases.
Q1: What are the key components of the immune system and their functions?
Answer: The immune system is a complex network of cells, tissues, and organs that work together to defend the body against harmful invaders, including pathogens, toxins, and foreign substances. The immune system can be categorized into two main types: the innate immune system and the adaptive immune system.
- Cells of the Immune System:
- B-lymphocytes (B-cells): These cells are primarily responsible for humoral immunity by producing antibodies that neutralize pathogens.
- T-lymphocytes (T-cells): These play a central role in cell-mediated immunity, with subsets such as helper T-cells (Th1, Th2, Th17) and cytotoxic T-cells (CD8+ T-cells) involved in activating other immune cells and directly killing infected cells.
- Natural Killer (NK) cells: These innate immune cells target and kill virally infected or cancerous cells.
- Dendritic cells and macrophages: Serve as antigen-presenting cells (APCs) that process and present antigens to T-cells to initiate the adaptive immune response.
- Organs of the Immune System:
- Primary lymphoid organs: Bone marrow and thymus are involved in the formation and maturation of immune cells.
- Secondary lymphoid organs: Lymph nodes, spleen, and mucosal-associated lymphoid tissues (MALT) serve as sites for immune cell activation and interaction with pathogens.
Key Terms: Immune system components, T-cells, B-cells, NK cells, antigen-presenting cells, lymphoid organs, innate immunity, adaptive immunity.
Q2: How do antibodies interact with antigens, and what are the key types of antibody-antigen interactions?
Answer: Antibodies, also known as immunoglobulins, are proteins produced by B-cells in response to antigens. These antibodies specifically bind to antigens, neutralizing them and marking them for destruction by other immune cells.
- Antibody Structure:
- Antibodies have a Y-shaped structure consisting of two heavy chains and two light chains. The variable region binds to antigens, while the constant region mediates immune responses like complement activation.
- Antibody-Antigen Interactions:
- Affinity: The strength of the binding between an antibody and its specific antigen.
- Avidity: The overall strength of the binding between multivalent antibodies and antigens.
- Cross-reactivity: The ability of an antibody to bind to similar antigens, even if they are not identical.
- Precipitation reactions: Occur when soluble antigens react with antibodies to form insoluble complexes.
- Agglutination: The aggregation of particulate antigens (such as bacteria) by antibodies, aiding in their elimination.
Key Terms: Antibodies, immunoglobulins, antigen-antibody interactions, affinity, avidity, precipitation, agglutination.
Q3: What is the role of cytokines in immune response, and how do they regulate immune cell function?
Answer: Cytokines are small proteins that play a critical role in cell signaling within the immune system, regulating immune responses, inflammation, and hematopoiesis. They are produced by various immune cells such as T-cells, B-cells, and macrophages.
- Cytokine Types:
- Interleukins (IL): These cytokines promote the growth and differentiation of immune cells. For example, IL-2 stimulates T-cell proliferation, while IL-4 aids in B-cell activation.
- Interferons (IFNs): Primarily involved in viral defense, they inhibit viral replication and activate NK cells.
- Tumor necrosis factor (TNF): Involved in inflammation and the destruction of tumor cells, particularly TNF-α.
- Growth factors: Such as colony-stimulating factors (CSFs), these stimulate the production of hematopoietic cells from bone marrow.
- Cytokine Receptors and Signaling: Cytokines exert their effects by binding to specific cytokine receptors on the surface of target cells, activating intracellular signaling pathways like JAK-STAT, which influence gene expression and cell behavior, including proliferation, differentiation, and apoptosis.
Key Terms: Cytokines, immune cell signaling, interleukins, interferons, TNF, colony-stimulating factors, cytokine receptors, JAK-STAT signaling.
Q4: What are the major types of hypersensitivity reactions, and how do they differ from each other?
Answer: Hypersensitivity reactions are exaggerated immune responses to harmless substances, resulting in tissue damage. These reactions are classified into four types based on their mechanisms and the immune components involved:
- Type I Hypersensitivity (IgE-mediated):
- Mechanism: Involves IgE antibodies, which bind to mast cells and basophils, leading to the release of histamine and other inflammatory mediators upon subsequent exposure to the allergen.
- Clinical Examples: Allergic rhinitis, asthma, anaphylaxis.
- Type II Hypersensitivity (Antibody-mediated Cytotoxicity):
- Mechanism: Involves IgG or IgM antibodies targeting cells or tissues, leading to complement activation and cell lysis.
- Clinical Examples: Hemolytic anemia, Rhesus incompatibility.
- Type III Hypersensitivity (Immune Complex-mediated):
- Mechanism: Immune complexes formed between antibodies and antigens deposit in tissues, triggering inflammation and tissue damage via complement activation.
- Clinical Examples: Systemic lupus erythematosus (SLE), rheumatoid arthritis.
- Type IV Hypersensitivity (Cell-mediated/Delayed-type):
- Mechanism: T-cells, particularly CD4+ Th1 cells, mediate delayed inflammation by recruiting and activating macrophages.
- Clinical Examples: Contact dermatitis, tuberculin skin test.
Key Terms: Hypersensitivity, IgE, antibody-mediated, immune complexes, T-cell mediated, inflammation, anaphylaxis, autoimmune diseases.
Q5: How does the complement system contribute to the immune defense, and what are the mechanisms of its activation?
Answer: The complement system is a crucial part of the innate immune system and consists of a series of proteins that help eliminate pathogens, promote inflammation, and clear dead cells. It works by activating a cascade of events that leads to the formation of the membrane attack complex (MAC), which lyses pathogens.
- Activation Pathways:
- Classical pathway: Triggered by antigen-antibody complexes binding to the C1 complex.
- Alternative pathway: Activated by pathogen surfaces without the need for antibodies, with C3b binding directly to the pathogen.
- Lectin pathway: Initiated by the binding of mannose-binding lectin (MBL) to carbohydrates on pathogens, leading to complement activation.
- Functions of the Complement System:
- Opsonization: Complement proteins coat pathogens, marking them for phagocytosis by immune cells.
- Chemotaxis: Complement components like C5a recruit immune cells to the site of infection.
- Lysis of pathogens: The formation of the MAC results in pathogen membrane disruption.
- Inflammation: Complement proteins like C3a and C5a increase blood vessel permeability and attract immune cells to infection sites.
- Regulation of Complement Activation: Complement activity is tightly regulated by proteins such as C1 inhibitor, factor H, and CD59 to prevent unwanted damage to host tissues.
Key Terms: Complement system, C1 complex, membrane attack complex (MAC), C3b, opsonization, chemotaxis, C5a, C1 inhibitor, complement regulation.
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Q6: What is the difference between innate and acquired immunity, and how do they work together?
Answer: The immune system has two primary defense mechanisms: innate immunity and acquired immunity (also known as adaptive immunity). These systems work together to provide a robust defense against pathogens, with innate immunity acting as the first line of defense and acquired immunity providing a more specific, targeted response.
- Innate Immunity (Non-specific Immunity):
- First line of defense: Innate immunity includes physical barriers (skin, mucous membranes), physiological barriers (fever, pH), and inflammatory responses.
- Key cells involved:
- Phagocytic cells like macrophages, neutrophils, and dendritic cells recognize and engulf pathogens.
- Natural killer (NK) cells target infected or cancerous cells.
- Complement system aids in pathogen destruction by lysis and enhancing phagocytosis (opsonization).
- Non-specific response: Innate immunity does not recognize specific pathogens but responds in a generic manner to threats.
- Acquired Immunity (Specific Immunity):
- Second line of defense: Acquired immunity is characterized by the ability to recognize specific antigens and generate a tailored immune response.
- Key cells involved:
- B-cells produce antibodies that neutralize specific antigens.
- T-cells (including helper T-cells and cytotoxic T-cells) coordinate the immune response and directly kill infected cells.
- Immunological memory: Acquired immunity generates immune memory, ensuring a faster and stronger response to subsequent exposures to the same pathogen.
- Types of acquired immunity:
- Humoral immunity (mediated by B-cells and antibodies).
- Cell-mediated immunity (mediated by T-cells and cytokines).
- Collaboration Between Innate and Acquired Immunity:
- The innate immune system activates the acquired immune system by presenting antigens to T-cells via dendritic cells.
- Cytokines secreted by innate immune cells influence the activation of specific T-cells, guiding the adaptive immune response.
Key Terms: Innate immunity, acquired immunity, phagocytic cells, NK cells, antibodies, T-cells, cytokines, immunological memory, complement system.
Q7: What are the types of immunoglobulins (antibodies), and how do they function in immune responses?
Answer: Immunoglobulins (Ig), or antibodies, are specialized proteins produced by B-cells to recognize and neutralize foreign antigens. There are five major classes of immunoglobulins, each with unique structures and functions that contribute to different aspects of the immune response.
- IgG (Gamma Globulin):
- Structure: The most abundant antibody in blood and tissue fluid, with a long half-life.
- Function: Provides long-term immunity and is the main antibody in secondary immune responses. It can cross the placenta to provide passive immunity to the fetus and activate the complement system.
- Subclasses: IgG is further divided into four subclasses (IgG1, IgG2, IgG3, and IgG4), each with distinct functions.
- IgA:
- Structure: Found in mucosal secretions (saliva, tears, breast milk, and respiratory and gastrointestinal secretions).
- Function: Plays a crucial role in mucosal immunity, preventing pathogen attachment to epithelial cells in mucosal surfaces.
- Secretory IgA (sIgA): The form of IgA present in mucosal secretions, composed of two IgA molecules and a secretory component.
- IgM:
- Structure: The first antibody produced during the primary immune response, existing as a pentamer (five IgM molecules joined together).
- Function: Highly effective in activating the complement system and agglutinating pathogens. It is the largest antibody and is predominantly found in the blood.
- IgE:
- Structure: Present in very low concentrations in the blood but plays a critical role in allergic reactions.
- Function: Binds to mast cells and basophils, leading to the release of histamine and other inflammatory mediators upon re-exposure to allergens. IgE is key in Type I hypersensitivity reactions, such as asthma and anaphylaxis.
- IgD:
- Structure: A membrane-bound antibody found on the surface of immature B-cells.
- Function: Primarily acts as a receptor for antigens on B-cells, helping to activate the B-cell during the immune response.
Key Terms: Immunoglobulins, IgG, IgA, IgM, IgE, IgD, complement activation, primary immune response, secondary immune response, allergic reactions.
Q8: How do T-cells contribute to the adaptive immune response, and what are the key subsets of T-cells involved?
Answer: T-cells are central players in adaptive immunity, responsible for recognizing specific antigens presented by other cells and mounting a targeted immune response. T-cells originate in the bone marrow and mature in the thymus before being released into the bloodstream.
- Helper T-cells (Th cells):
- Function: Th cells coordinate the immune response by releasing cytokines that activate other immune cells, including B-cells, macrophages, and cytotoxic T-cells. There are different subsets of helper T-cells based on their cytokine profiles:
- Th1 cells: Activate macrophages and enhance cell-mediated immunity.
- Th2 cells: Stimulate B-cell differentiation and antibody production, especially in allergic responses.
- Th17 cells: Involved in inflammatory responses and the defense against extracellular pathogens.
- Function: Th cells coordinate the immune response by releasing cytokines that activate other immune cells, including B-cells, macrophages, and cytotoxic T-cells. There are different subsets of helper T-cells based on their cytokine profiles:
- Cytotoxic T-cells (CD8+ T-cells):
- Function: These cells directly recognize and kill infected cells by inducing apoptosis. They recognize antigens presented on MHC class I molecules and play a crucial role in viral defense and tumor surveillance.
- Regulatory T-cells (Tregs):
- Function: Tregs suppress the immune response to maintain immune tolerance and prevent autoimmune diseases. They prevent excessive immune activation and protect the body from attacking its own tissues.
- Memory T-cells:
- Function: Memory T-cells persist long after an infection has been cleared, allowing for a faster and more robust response upon re-exposure to the same antigen.
Key Terms: T-cells, helper T-cells, cytotoxic T-cells, regulatory T-cells, memory T-cells, Th1 cells, Th2 cells, Th17 cells, cytokines, autoimmunity.
Q9: What are the mechanisms of antigen presentation in the immune system, and how does antigen processing occur?
Answer: Antigen presentation is a critical step in the immune response, where antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B-cells, process and present antigens to T-cells, initiating the adaptive immune response.
- Antigen Processing:
- Exogenous antigens (e.g., pathogens): These antigens are internalized by APCs through phagocytosis or endocytosis. Once inside the cell, they are broken down into peptides by lysosomal enzymes.
- Endogenous antigens (e.g., viral proteins): These are proteins produced within infected cells. Proteasomes break down these proteins into peptides, which are transported into the endoplasmic reticulum.
- Antigen Presentation on MHC Molecules:
- MHC Class I molecules: Present on the surface of all nucleated cells, these molecules display endogenous peptides to cytotoxic T-cells (CD8+ T-cells).
- MHC Class II molecules: Present on APCs, these molecules display exogenous peptides to helper T-cells (CD4+ T-cells).
- Peptide-MHC complex: The antigen is presented as a complex with the MHC molecule, which is recognized by specific T-cell receptors (TCRs) on T-cells.
- T-cell Activation:
- The interaction between the TCR and the peptide-MHC complex triggers the activation of T-cells, leading to either the activation of cytotoxic T-cells or the activation of helper T-cells, depending on the antigen presented.
Key Terms: Antigen processing, antigen presentation, MHC molecules, T-cells, cytotoxic T-cells, helper T-cells, APCs, TCR, peptide-MHC complex.
Q10: How do monoclonal antibodies work, and what are their applications in medical research and therapy?
Answer: Monoclonal antibodies (mAbs) are laboratory-made antibodies designed to target specific antigens. These antibodies are produced by creating a hybridoma—a fusion of a single B-cell and a myeloma cell—which allows for the production of large quantities of a single type of antibody (monoclonal).
- Mechanism of Action:
- Target specificity: Monoclonal antibodies are engineered to recognize and bind to a specific antigen, typically a protein or glycoprotein on the surface of cancer cells, viruses, or bacteria.
- Immune system activation: Upon binding to the target, mAbs can activate the complement system, trigger antibody-dependent cellular cytotoxicity (ADCC), or block the activity of the target antigen (e.g., neutralizing viruses).
- Applications in Medical Research:
- Diagnostic tools: mAbs are widely used in diagnostic tests to detect the presence of specific biomarkers (e.g., ELISA, Western blotting).
- Therapeutic uses: mAbs are used in the treatment of diseases such as cancer (e.g., rituximab, trastuzumab), autoimmune disorders (e.g., adalimumab for rheumatoid arthritis), and infectious diseases (e.g., monoclonal antibody cocktails for COVID-19).
- Types of Monoclonal Antibodies:
- Murine: Derived entirely from mice (e.g., OKT3).
- Chimeric: A mixture of murine and human components (e.g., rituximab).
- Humanized: Primarily human, with a small portion of murine antibodies (e.g., trastuzumab).
- Fully human: Entirely human (e.g., adalimumab).
Key Terms: Monoclonal antibodies, hybridoma, target specificity, diagnostic tools, therapeutic uses, cancer treatment, immune response, chimeric antibodies, humanized antibodies.
Q11: What is the role of hematopoiesis in immune system development, and how are B and T lymphocytes formed?
Answer: Hematopoiesis is the process through which blood cells, including immune cells, are produced. It occurs primarily in the bone marrow and is crucial for the development of B-cells and T-cells, which are essential components of the immune system.
- Hematopoiesis Process:
- Hematopoiesis begins with the differentiation of hematopoietic stem cells (HSCs) into various progenitor cells that give rise to all blood cell lineages.
- The differentiation of these stem cells into immune cells occurs through multiple stages:
- Common lymphoid progenitors (CLPs) are responsible for the production of B-cells, T-cells, and natural killer (NK) cells.
- Common myeloid progenitors (CMPs) give rise to cells like macrophages, neutrophils, and dendritic cells.
- B-Cell Formation and Maturation:
- B-cells are produced in the bone marrow, where they undergo several stages of differentiation and maturation. These include the development of the pre-B-cell and immature B-cell stages.
- Once matured, B-cells express a specific B-cell receptor (BCR) on their surface, which is a membrane-bound immunoglobulin that recognizes specific antigens.
- Negative selection occurs in the bone marrow to eliminate self-reactive B-cells, ensuring immune tolerance.
- T-Cell Formation and Maturation:
- T-cells originate in the bone marrow but mature in the thymus. In the thymus, immature T-cells undergo several selection processes:
- Positive selection: T-cells that recognize MHC molecules on thymic epithelial cells are selected for further maturation.
- Negative selection: T-cells that strongly react with self-antigens presented by dendritic cells are eliminated to prevent autoimmune responses.
- The final mature T-cells express either CD4+ (helper T-cells) or CD8+ (cytotoxic T-cells) receptors, depending on the selection process in the thymus.
- T-cells originate in the bone marrow but mature in the thymus. In the thymus, immature T-cells undergo several selection processes:
Key Terms: Hematopoiesis, hematopoietic stem cells, B-cells, T-cells, bone marrow, thymus, B-cell receptor, positive selection, negative selection, immune tolerance.
Q12: What is the Major Histocompatibility Complex (MHC), and how does it contribute to immune response?
Answer: The Major Histocompatibility Complex (MHC) is a group of molecules found on the surface of cells that play a crucial role in the immune system by presenting antigens to T-cells. MHC molecules are essential for distinguishing self from non-self, helping to initiate an immune response against foreign pathogens while avoiding attacks on the body’s own cells.
- Types of MHC Molecules:
- MHC Class I molecules are expressed on the surface of all nucleated cells and present endogenous antigens (e.g., from viruses or intracellular bacteria) to cytotoxic T-cells (CD8+). This activates cytotoxic T-cells to kill infected cells.
- MHC Class II molecules are found on antigen-presenting cells (APCs), including dendritic cells, macrophages, and B-cells, and present exogenous antigens (e.g., from extracellular pathogens) to helper T-cells (CD4+). This initiates a series of immune responses, including B-cell activation and the production of antibodies.
- Antigen Presentation Process:
- Antigen processing involves breaking down pathogens into smaller peptide fragments inside the APC. These peptides are loaded onto MHC molecules, which then migrate to the cell surface to be presented to T-cells.
- In MHC Class I, endogenous antigens are processed by the proteasome, while in MHC Class II, exogenous antigens are processed in endosomes and loaded onto MHC molecules.
- MHC and Immune Response:
- The interaction between the T-cell receptor (TCR) on T-cells and the peptide-MHC complex on the surface of APCs is critical for activating T-cells.
- MHC molecules are highly polymorphic, meaning they vary greatly between individuals. This genetic diversity plays a key role in determining tissue compatibility during organ transplantation and influences an individual’s immune response to pathogens.
Key Terms: Major Histocompatibility Complex (MHC), MHC Class I, MHC Class II, antigen presentation, cytotoxic T-cells (CD8+), helper T-cells (CD4+), antigen-presenting cells (APCs), T-cell receptor (TCR), proteasome, tissue compatibility.
Q13: What are the mechanisms of antigen-antibody interactions, and how do they contribute to immune defense?
Answer: Antigen-antibody interactions are fundamental to the immune system’s ability to identify and neutralize pathogens. The specific binding of an antibody to its corresponding antigen triggers a variety of immune responses that help eliminate the threat.
- Antigen-Antibody Binding:
- Affinity refers to the strength of the binding between an antibody and a single antigenic determinant (epitope). A high affinity ensures that the antibody effectively binds to the antigen.
- Avidity is the overall strength of the antigen-antibody interaction, taking into account the binding sites on the antibody and the multivalent nature of antigens.
- Types of Antigen-Antibody Interactions:
- Neutralization: Antibodies can neutralize toxins or prevent pathogens from binding to host cells, thereby stopping infection. For example, IgG antibodies can neutralize viruses.
- Opsonization: Antibodies can bind to antigens and enhance their recognition by phagocytes, such as macrophages and neutrophils, facilitating pathogen elimination. This is mediated by IgG antibodies.
- Complement activation: The binding of IgG or IgM antibodies to antigens can activate the complement system, leading to the formation of the membrane attack complex (MAC), which induces lysis of the pathogen.
- Agglutination and Precipitation: Antibodies can cross-link multiple antigens, forming visible aggregates (agglutination) or precipitates, facilitating their removal by phagocytes.
- Clinical Applications of Antigen-Antibody Interactions:
- Diagnostic tests such as ELISA (enzyme-linked immunosorbent assay) and Western blot rely on the specificity of antigen-antibody binding to detect pathogens or antibodies.
- Monoclonal antibodies are engineered to bind to specific antigens and are used for therapies in cancer, autoimmune diseases, and infections.
Key Terms: Antigen-antibody interactions, affinity, avidity, neutralization, opsonization, complement activation, agglutination, precipitation, monoclonal antibodies, ELISA, Western blot.
Q14: How does the complement system function in immune defense, and what are its activation pathways?
Answer: The complement system is a crucial part of the innate immune system that enhances the body’s ability to fight infections. It consists of a series of plasma proteins that, when activated, work together to destroy pathogens, promote inflammation, and assist in the removal of dead cells.
- Complement Activation Pathways:
- Classical Pathway: Initiated by the formation of an antigen-antibody complex. The C1 complex binds to the antigen-antibody complex, leading to the activation of downstream complement proteins.
- Alternative Pathway: Activated directly by the surface of pathogens, particularly gram-negative bacteria, independent of antibodies. This pathway involves C3b binding to the pathogen surface and initiating a cascade of complement activation.
- Lectin Pathway: Triggered by mannose-binding lectin (MBL), which binds to specific sugars on the surface of pathogens, activating the complement cascade.
- Functions of the Complement System:
- Opsonization: Complement proteins like C3b bind to pathogens, marking them for phagocytosis by immune cells such as macrophages and neutrophils.
- Lysis of Pathogens: The formation of the membrane attack complex (MAC) (composed of C5b, C6, C7, C8, and C9) forms pores in the pathogen membrane, leading to its rupture and death.
- Inflammation: Complement proteins such as C3a and C5a act as chemotactic factors, recruiting immune cells to the site of infection and promoting inflammation.
- Regulation of Complement Activation:
- The complement system is tightly regulated to prevent damage to host tissues. Proteins such as C1 inhibitor, factor H, and CD59 prevent excessive complement activation and protect host cells from unintended damage.
Key Terms: Complement system, classical pathway, alternative pathway, lectin pathway, C3b, opsonization, membrane attack complex (MAC), chemotactic factors, C1 inhibitor, factor H, CD59.
Q15: What are the types of hypersensitivity reactions, and how are they classified based on immune mechanisms?
Answer: Hypersensitivity refers to exaggerated or inappropriate immune responses that lead to tissue damage. These reactions can be classified into four types based on the immune mechanisms involved.
- Type I Hypersensitivity (Immediate Hypersensitivity/Allergic Reactions):
- Mechanism: Mediated by IgE antibodies, which bind to mast cells and basophils. Upon re-exposure to the allergen, these cells release histamine and other inflammatory mediators, causing symptoms of allergy.
- Clinical Examples: Asthma, hay fever, urticaria, anaphylaxis.
- Type II Hypersensitivity (Antibody-Mediated Cytotoxicity):
- Mechanism: Involves IgG or IgM antibodies binding to antigens on the surface of host cells, leading to complement activation and cell lysis.
- Clinical Examples: Hemolytic anemia, Goodpasture syndrome, Rhesus incompatibility.
- Type III Hypersensitivity (Immune Complex-Mediated Reactions):
- Mechanism: Immune complexes (antigen-antibody complexes) form and deposit in tissues, leading to inflammation and tissue damage via complement activation.
- Clinical Examples: Systemic lupus erythematosus (SLE), rheumatoid arthritis, serum sickness.
- Type IV Hypersensitivity (Cell-Mediated/Delayed-Type Hypersensitivity):
- Mechanism: Mediated by T-cells, especially CD4+ T-helper cells, which recruit macrophages and initiate an inflammatory response.
- Clinical Examples: Contact dermatitis, tuberculin skin test, chronic transplant rejection.
Key Terms: Hypersensitivity, IgE, antibody-mediated, immune complexes, T-cells, inflammation, anaphylaxis, autoimmune diseases.