Notes_on_Immune_System

The Immune System Overview

Definition

The immune system is a complex network of cells, tissues, and organs that provides resistance to disease by identifying and eliminating pathogens such as bacteria, viruses, fungi, and parasites. In addition, it plays a crucial role in recognizing and destroying abnormal cells, including cancer cells, thus maintaining overall health.

Intrinsic Systems

Innate (Nonspecific) Defense System

• First Line of Defense:

  • External Body Membranes: Skin serves as a physical barrier, while mucosal membranes line the respiratory, gastrointestinal, and urogenital tracts, providing additional protection.

• Second Line of Defense:

  • Internal Defenses: Involves various cells such as phagocytes, natural killer (NK) cells, and the inflammatory response.

  • Phagocytes: White blood cells that consume pathogens.

  • Inflammation: A critical response that develops to isolate and eliminate harmful agents.

Adaptive (Specific) Defense System

• Third Line of Defense:

  • Targets specific antigens presented by pathogens.

  • Activated upon exposure to foreign substances and involves a prolonged immune response that can take days to develop but leads to a robust defensive mechanism.

Functional Nature

The immune system operates more as a functional entity rather than a confined organ system, meaning that different components work together dynamically to provide protection against diseases.

Interconnection

The innate and adaptive immune systems are intricately interconnected. Both systems utilize similar molecules for detection and response, coordinating efforts during an immune challenge.

Innate Defenses

Surface Barriers

• Skin: Composed of multiple layers; keratinocytes produce keratin, which resists physical damage and microbial invasion.

• Mucous Membranes: Provide a mechanical barrier that secretes mucus to trap pathogens.

Protective Chemicals

• Acidity: The acid mantle of the skin and secretions of sebaceous glands inhibit microbial growth.

• Enzymes: Lysozymes in saliva and tears break down bacterial cell walls, contributing to pathogen destruction.

• Mucin: The sticky nature of mucus traps microorganisms effectively.

• Defensins: Antimicrobial peptides that inhibit growth and assist in microbial clearance.

Internal Defenses

• Phagocytes: Include neutrophils and macrophages, which are essential for engulfing pathogens and presenting antigens to activate adaptive immunity.

• Natural Killer Cells (NK): Provide an immediate response against viral infections and tumor formation by inducing apoptosis (programmed cell death) in infected or abnormal cells.

Phagocytosis Mechanism

1. Recognition: Phagocytes recognize pathogens through specific markers on their surfaces. Some pathogens evolve to evade such recognition.

2. Opsonization: Process by which pathogens are tagged by antibodies or complement proteins to enhance phagocytosis.

3. Engulfing: Formation of pseudopodia around the pathogen and internalization into a phagosome.

4. Digestion: Fusion of the phagosome with lysosomes leads to the formation of a phagolysosome, wherein enzymes digest the pathogen.

5. Exocytosis: Expulsion of undigested debris from the phagocyte into the extracellular environment, restoring homeostasis.

Inflammation

Definition

The inflammation process is a protective response initiated by cell injury, resulting from pathogens, heat, chemicals, or physical trauma.

Benefits

• Prevents the spread of pathogens.

• Disposes of cellular debris and pathogens effectively.

• Activates and alerts the adaptive immune system to involve specific defenses for prolonged infection.

Cardinal Signs

The classic signs of inflammation include redness, heat, swelling, pain, and occasionally loss of function at the affected site.

Phagocyte Mobilization Stages

1. Leukocytosis: Increased production of neutrophils in response to infection or injury.

2. Margination: Endothelial cells in blood vessels express cell adhesion molecules (CAMs) that help leukocytes to cling to them.

3. Diapedesis: Neutrophils squeeze through blood vessel walls into surrounding tissues.

4. Chemotaxis: Inflammatory mediators attract phagocytes to the site of injury or infection.

Clinical Imbalance

• Pus: A mixture of dead neutrophils, tissue debris, and live pathogens.

• Abscess: A localized collection of pus that may require surgical drainage if it does not resolve.

• Granulomas: Formed by macrophages that have absorbed pathogens; may remain inactive or reactivate under immune suppression.

Antimicrobial Proteins

Functions

Enhance innate immunity by attacking pathogens or inhibiting their reproduction and spread.

Key Proteins

• Interferons (IFNs): Proteins released by host cells in response to viral infections.

  • Types:

    • IFN-alpha & IFN-beta: Warn neighboring cells to boost defenses against viruses.

    • IFN-gamma: Activates macrophages and NK cells, promoting the immune response.

• Complement Proteins: Series of proteins that play a vital role in the immune response by targeting pathogens for destruction.

  • Activation Pathways:

    • Classical Pathway: Triggered by antibodies.

    • Lectin Pathway: Activated by binding of lectins to specific sugars on pathogens.

    • Alternative Pathway: Initiated by certain non-specific triggers.

  • Actions: In addition to promoting inflammation, they facilitate opsonization and direct cell lysis of pathogens.

Adaptive Defenses

Definition

Adaptive immunity tailors the immune response specifically to the pathogens encountered and is characterized by long-lasting protection.

Characteristics

• Specificity: Distinguishes between different pathogens, allowing for targeted actions.

• Systemic Effect: The response is comprehensive and affects the entire body, not just the site of infection.

• Memory: Immunological memory enables faster and more effective responses to previously encountered antigens.

Types of Adaptive Immunity

• Humoral Immunity: Mediated by B cells that produce antibodies targeting extracellular pathogens (bacteria and toxins).

• Cellular Immunity: Involves T cells that target and destroy infected or abnormal cells within the body.

Antigens

Definition

Antigens are molecules or molecular structures that trigger an immune response. They can be proteins, polysaccharides, or sometimes nucleic acids on the surface of pathogens.

Characteristics

• Complete Antigens: Possess full immunogenic properties, including the capacity to trigger antibody production.

• Haptens: Small molecules that only provoke an immune response when attached to a larger carrier, such as a protein.

Antigen-Presenting Cells (APCs)

Role

APCs, including dendritic cells, macrophages, and B cells, engulf pathogens and present their antigens on MHC molecules to T cells, facilitating the activation of the adaptive immune response.

Lymphocyte Development

Process

Lymphocytes originate in the red bone marrow and undergo maturation in primary lymphoid organs, specifically the thymus for T cells and the bone marrow for B cells.

Maturation

Cells are educated to differentiate between self and non-self components to develop immunocompetence and self-tolerance, ensuring that they can effectively respond to pathogens while avoiding the body’s own tissues.

Activation

Naïve lymphocytes, upon encountering their specific antigens, undergo clonal expansion, which leads to the production of effector and memory cells to facilitate a rapid immune response upon re-exposure.

Cytokines

Role

Cytokines are immune system signaling molecules that facilitate communication between cells, coordinating the immune response. Key types include interleukins and interferons that influence the behavior of immune cells and tailor the response to various immune challenges.

The Immune System Overview

Definition

The immune system is a complex network of cells, tissues, and organs that provides resistance to disease by identifying and eliminating pathogens such as bacteria, viruses, fungi, and parasites. In addition, it plays a crucial role in recognizing and destroying abnormal cells, including cancer cells, thus maintaining overall health.

Intrinsic Systems

Innate (Nonspecific) Defense System

• First Line of Defense:

  • External Body Membranes: Skin serves as a physical barrier, while mucosal membranes line the respiratory, gastrointestinal, and urogenital tracts, providing additional protection.

• Second Line of Defense:

  • Internal Defenses: Involves various cells such as phagocytes, natural killer (NK) cells, and the inflammatory response.

  • Phagocytes: White blood cells that consume pathogens.

  • Inflammation: A critical response that develops to isolate and eliminate harmful agents.

Adaptive (Specific) Defense System

• Third Line of Defense:

  • Targets specific antigens presented by pathogens.

  • Activated upon exposure to foreign substances and involves a prolonged immune response that can take days to develop but leads to a robust defensive mechanism.

Functional Nature

The immune system operates more as a functional entity rather than a confined organ system, meaning that different components work together dynamically to provide protection against diseases.

Interconnection

The innate and adaptive immune systems are intricately interconnected. Both systems utilize similar molecules for detection and response, coordinating efforts during an immune challenge.

Innate Defenses

Surface Barriers

• Skin: Composed of multiple layers; keratinocytes produce keratin, which resists physical damage and microbial invasion.

• Mucous Membranes: Provide a mechanical barrier that secretes mucus to trap pathogens.

Protective Chemicals

• Acidity: The acid mantle of the skin and secretions of sebaceous glands inhibit microbial growth.

• Enzymes: Lysozymes in saliva and tears break down bacterial cell walls, contributing to pathogen destruction.

• Mucin: The sticky nature of mucus traps microorganisms effectively.

• Defensins: Antimicrobial peptides that inhibit growth and assist in microbial clearance.

Internal Defenses

• Phagocytes: Include neutrophils and macrophages, which are essential for engulfing pathogens and presenting antigens to activate adaptive immunity.

• Natural Killer Cells (NK): Provide an immediate response against viral infections and tumor formation by inducing apoptosis (programmed cell death) in infected or abnormal cells.

Phagocytosis Mechanism

1. Recognition: Phagocytes recognize pathogens through specific markers on their surfaces. Some pathogens evolve to evade such recognition.

2. Opsonization: Process by which pathogens are tagged by antibodies or complement proteins to enhance phagocytosis.

3. Engulfing: Formation of pseudopodia around the pathogen and internalization into a phagosome.

4. Digestion: Fusion of the phagosome with lysosomes leads to the formation of a phagolysosome, wherein enzymes digest the pathogen.

5. Exocytosis: Expulsion of undigested debris from the phagocyte into the extracellular environment, restoring homeostasis.

Inflammation

Definition

The inflammation process is a protective response initiated by cell injury, resulting from pathogens, heat, chemicals, or physical trauma.

Benefits

• Prevents the spread of pathogens.

• Disposes of cellular debris and pathogens effectively.

• Activates and alerts the adaptive immune system to involve specific defenses for prolonged infection.

Cardinal Signs

The classic signs of inflammation include redness, heat, swelling, pain, and occasionally loss of function at the affected site.

Phagocyte Mobilization Stages

1. Leukocytosis: Increased production of neutrophils in response to infection or injury.

2. Margination: Endothelial cells in blood vessels express cell adhesion molecules (CAMs) that help leukocytes to cling to them.

3. Diapedesis: Neutrophils squeeze through blood vessel walls into surrounding tissues.

4. Chemotaxis: Inflammatory mediators attract phagocytes to the site of injury or infection.

Clinical Imbalance

• Pus: A mixture of dead neutrophils, tissue debris, and live pathogens.

• Abscess: A localized collection of pus that may require surgical drainage if it does not resolve.

• Granulomas: Formed by macrophages that have absorbed pathogens; may remain inactive or reactivate under immune suppression.

Antimicrobial Proteins

Functions

Enhance innate immunity by attacking pathogens or inhibiting their reproduction and spread.

Key Proteins

• Interferons (IFNs): Proteins released by host cells in response to viral infections.

  • Types:

    • IFN-alpha & IFN-beta: Warn neighboring cells to boost defenses against viruses.

    • IFN-gamma: Activates macrophages and NK cells, promoting the immune response.

• Complement Proteins: Series of proteins that play a vital role in the immune response by targeting pathogens for destruction.

  • Activation Pathways:

    • Classical Pathway: Triggered by antibodies.

    • Lectin Pathway: Activated by binding of lectins to specific sugars on pathogens.

    • Alternative Pathway: Initiated by certain non-specific triggers.

  • Actions: In addition to promoting inflammation, they facilitate opsonization and direct cell lysis of pathogens.

Adaptive Defenses

Definition

Adaptive immunity tailors the immune response specifically to the pathogens encountered and is characterized by long-lasting protection.

Characteristics

• Specificity: Distinguishes between different pathogens, allowing for targeted actions.

• Systemic Effect: The response is comprehensive and affects the entire body, not just the site of infection.

• Memory: Immunological memory enables faster and more effective responses to previously encountered antigens.

Types of Adaptive Immunity

• Humoral Immunity: Mediated by B cells that produce antibodies targeting extracellular pathogens (bacteria and toxins).

• Cellular Immunity: Involves T cells that target and destroy infected or abnormal cells within the body.

Antigens

Definition

Antigens are molecules or molecular structures that trigger an immune response. They can be proteins, polysaccharides, or sometimes nucleic acids on the surface of pathogens.

Characteristics

• Complete Antigens: Possess full immunogenic properties, including the capacity to trigger antibody production.

• Haptens: Small molecules that only provoke an immune response when attached to a larger carrier, such as a protein.

Antigen-Presenting Cells (APCs)

Role

APCs, including dendritic cells, macrophages, and B cells, engulf pathogens and present their antigens on MHC molecules to T cells, facilitating the activation of the adaptive immune response.

Lymphocyte Development

Process

Lymphocytes originate in the red bone marrow and undergo maturation in primary lymphoid organs, specifically the thymus for T cells and the bone marrow for B cells.

Maturation

Cells are educated to differentiate between self and non-self components to develop immunocompetence and self-tolerance, ensuring that they can effectively respond to pathogens while avoiding the body’s own tissues.

Activation

Naïve lymphocytes, upon encountering their specific antigens, undergo clonal expansion, which leads to the production of effector and memory cells to facilitate a rapid immune response upon re-exposure.

Cytokines

Role

Cytokines are immune system signaling molecules that facilitate communication between cells, coordinating the immune response. Key types include interleukins and interferons that influence the behavior of immune cells and tailor the response to various immune challenges.