Innate and Adaptive Immunity
Learning Outcomes
Define immune system, innate immunity, and adaptive immunity.
Explain the types and importance of physical barriers in defense against pathogens.
Enumerate the defensive functions of each kind of white blood cell.
Explain the process of inflammation.
Discuss the mechanism, benefits, and drawbacks of fever.
Immune System Overview
Definition of Key Concepts
Immune System: A complex network of cells, tissues, and organs that work together to defend the body against harmful invaders, such as bacteria, viruses, and parasites.
Innate Immunity: The first line of defense against pathogens; it is non-specific and does not provide long-lasting immunity. This form of immunity is present from birth and includes physical barriers and immune responses that occur immediately or within hours of an antigen's appearance in the body.
Adaptive Immunity: The second line of defense that is specific to particular pathogens and involves the creation of memory cells to recognize and combat previously encountered invaders. This immunity develops over time as the immune system adapts to specific pathogens.
Lines of Defense Against Pathogens
Overview of Pathogen Defense
A Pathogen is any organism capable of causing an infection.
Three Lines of Defense
First Line - Non-specific Immunity:
External Barriers: Skin and mucous membranes that serve as physical barriers against microbial entry.
Second Line - Innate Immunity:
Elicits several nonspecific defense mechanisms, including various cells, chemicals, and processes that are effective against a broad range of pathogens.
Third Line - Specific Immunity:
The adaptive immune response which is specific to pathogens and results in immunological memory for faster response to future infections.
First Lines of Defense: Physical Barriers
Key Physical Barriers
Skin:
Acts as a primary barrier to block the entry of microorganisms. Composed of layers that are keratinized, dry, salty, acidic, and nutrient-poor, reducing the ability of pathogens to survive and multiply.
Mucous Membranes:
Lining present in the respiratory, gastrointestinal, and urogenital tracts. Mucus traps pathogens and the presence of tears and saliva contains lysozyme—an enzyme that destroys bacterial cell walls.
Second Line of Defense: Innate Immunity (Non-Specific)
Cells of Innate Immunity
Neutrophils:
The first responders to infection (1-2 hours after). These white blood cells phagocytize pathogens and release chemicals that destroy them.
Eosinophils:
Primarily active against parasitic infections.
Basophils/Mast Cells:
Release pro-inflammatory chemicals that promote inflammation.
Monocytes:
Differentiate into macrophages after 8-12 hours post-infection, acting as phagocytes and antigen-presenting cells (APCs).
Natural Killer (NK) Cells:
Continuous surveillance for pathogens and diseased cells; kill infected cells using perforins and granzymes.
Chemicals of Innate Immunity
Interferons:
Secreted by cells infected by viruses; they activate NK cells and macrophages to kill infected hosts.
Antimicrobial Proteins:
Small proteins produced by the body that activate mechanisms of defense including the Complement System, which consists of small blood proteins that can lead to cell lysis via the Membrane Attack Complex (MAC). The MAC creates holes in pathogen membranes, leading to their destruction.
Fever
Description of Fever
Fever: An abnormal rise in body temperature often due to infection or illness.
Benefits of Fever
Enhances the immune response by increasing levels of interferons, metabolism, and tissue repair.
Inhibits microbial reproduction.
Role of Pyrogens
Pyrogens: Substances that induce fever through blood vessel dilation leading to increased blood flow and elevated body temperature. Pyrogens can be further classified into:
Endogenous Pyrogens: Originating from within the body due to immune activity.
Exogenous Pyrogens: Originate from microbial sources.
The increase in blood flow is referred to as Hyperemia.
Antipyretic Agents
Medications that reduce fever.
Inflammation
Definition and Purpose
Inflammation: A non-specific local response to tissue injury. Terminologies related to inflammation end in “-itis.”
Cardinal Signs of Inflammation
Redness
Swelling (Edema)
Local Heat
Pain
Loss of Function (Fifth sign)
Process of Inflammation
Mobilization:
Release of cytokines, pro-inflammatory chemicals, causes blood vessel dilation, and increased permeability leading to the movement of white blood cells (WBCs) and nutrients to the site of injury. This includes:
Margination: Movement of WBCs through the bloodstream.
Diapedesis: Movement of WBCs through blood vessel walls into tissues.
Chemotaxis: Attraction of WBCs to the site of infection.
Phagocytosis: Process by which WBCs engulf and digest debris or invaders.
Containment:
Formation of a fibrin scar that acts as a barrier to prevent pathogens from spreading; neutrophils swarm the area to eliminate bacteria and recruit macrophages.
Clean-Up and Tissue Repair:
Arrival of monocytes 8-12 hours post-injury for phagocytizing debris; lymphatic system aids in debris removal. Growth factors secreted by platelets and vascular endothelial cells foster tissue repair.
Adaptive or Specific Immunity
Properties of Specific Immunity
Specificity: T/B cells respond uniquely to 1 antigen.
Versatility: A diverse range of WBCs/antibodies that can recognize millions of antigens.
Immunologic Memory: Previous encounters with pathogens allow for a more rapid response upon re-exposure.
Tolerance: The immune system differentiates between self-antigens and foreign antigens.
Antigens
Antigen: Any substance that triggers an immune response. The specific region on the antigen recognized by antibodies is called an Epitope.
Antigen-Presenting Cells (APCs)
APCs present foreign antigens to T cells via receptors known as the Major Histocompatibility Complex (MHC).
MHC Type I: Present on all nucleated cells; recognized by CD8+ T cells.
MHC Type II: Present on specialized APCs; recognized by CD4+ T cells.
Arms of Adaptive Immunity
Humoral Immunity (B cells):
Mediated by antibodies which bind to antigens; effective against extracellular pathogens.
Cellular Immunity (T cells):
Direct destruction of infected or diseased cells by T cells that attack directly.
T cells and Their Functions
Development and Types of T Cells
T cells originate in the bone marrow and mature in the thymus. They can differentiate into various types:
Naïve T Cell: Has not encountered an antigen.
Helper T Cells (CD4+): Assist B and T cell activation and stimulate immune responses through the release of interleukins.
Regulatory T Cells (CD4+): Help prevent overactivation of the immune response.
Cytotoxic T Cells (CD8+): Directly kill infected cells.
Mechanism of Cytotoxic T Cells (CD8+)
CD8+ T cells respond to MHC I on infected cells. Their activation leads them to release Perforin and Granzymes, which induce cell death and inhibit viral replication. Tumor Necrosis Factor (TNF) can also activate macrophages and destroy cancer cells.
Helper T Cells (TH)
TH cells recognize MHC II on APCs and recruit other immune cells. After facilitating the immune response, they can become memory T cells to ensure quicker responses in future infections.
B Cells and Humoral Immunity
Development of B Cells
B cells develop and mature in the red bone marrow. Upon activation and recognition of antigens via T helper cells, they differentiate into:
Plasma Cells: Produce antibodies.
Memory B Cells: Retain information for future encounters with the same antigen.
Structure and Function of Antibodies
Antibodies (Immunoglobulins): Y-shaped proteins that can bind two antigens each. They have:
Variable Region: Specifically binds to the antigen.
Constant Region: Remains the same across different antibody classes.
Five Classes of Antibodies:
IgG: Most common, crosses the placenta, combats viruses, bacteria, and toxins.
IgE: Binds to mast cells, involved in allergic responses.
IgD: Present on B cell surfaces, participates in B cell activation.
IgA: Located in secretions, plays a role in mucosal immunity.
IgM: First antibody produced during an immune response, important for blood typing.
Mechanisms of Antibody Action
Neutralization: Antibodies cover antigens, preventing pathogen attachment.
Complement Fixation: Activates the complement system to enhance pathogen destruction.
Agglutination: Clumping of pathogens for easier elimination.
Precipitation: Antigens bind to antibodies, resulting in precipitate that is removed from circulation.
Integration of Innate and Adaptive Immunity
Both innate and adaptive immune responses work together. Exposure to antigens initiates actions from both branches, enhancing the overall immune defense mechanisms.
Categories of Immunity
Active Immunity: When an individual produces their own antibodies and T cells.
Passive Immunity: Acquiring antibodies from another source.
Natural Active Immunity: Through natural exposure, e.g., recovering from illness.
Natural Passive Immunity: Acquired through maternal antibodies during breastfeeding or placental transfer.
Artificial Active Immunity: Through vaccines that stimulate the production of antibodies.
Artificial Passive Immunity: Via injections of antibodies, for example in treatments against diseases like COVID using immune serum or antivenoms.
Review and Study Resources
To aid your understanding and memory of the immune system's functions and processes, utilize available resources such as online flashcards, educational videos, and interactive learning games. Recommended video resources:
Crash Course videos on innate immunity and T cells/adaptive immunity.