Chapter 21: The Immune System
Chapter 21: The Immune System
BIOL 206: Human Anatomy and Physiology
Adam Franssen, Ph.D.
Overview of the Immune System
Humans and other animals possess complex defense mechanisms against invaders (pathogens).
The immune system can be categorized into two main types:
Nonspecific (Innate) Defense: Provides immediate response to all pathogens.
Adaptive (Acquired) Defense: Specific responses to particular pathogens.
Part 1: Innate Defenses
Surface Barriers
External (First Line) Defense
Pathogens: Types include bacteria, viruses, fungi, etc.
The first line of defense consists of:
Mechanical (Nonspecific): Physical barriers that include skin and mucous membranes.
Chemical: Includes protective substances such as sweat and antimicrobial proteins.
The second line of defense consists of:
Fever: A systemic response to pathogens.
Chemical responses: Such as reflexes and protective proteins (cytokines).
Natural Killer (NK) Cells: Non-phagocytic cells that destroy abnormal cells.
Inflammation: A response to tissue damage that includes several physiological changes.
The third line of defense involves:
Phagocytosis: The process by which certain cells engulf and digest pathogens.
Nonspecific Defense - Mechanical Protection
Surface Barriers: Skin
Skin: Serves as a physical barrier composed of keratinized epidermal cells that are impenetrable to most bacteria and viruses.
Acids present in sweat and oils inhibit microbial growth.
Net flow of sweat, saliva, and tears provides mechanical protection.
Surface Barriers: Mucous Membranes
Mucous Membranes:
Line body cavities and secrete mucus which lubricates and moisturizes surfaces.
Mucus traps pathogens, hairs in the nose and cilia help clear these pathogens.
Nonspecific Defense - Chemical Protection
Sebaceous Glands: Secrete substances that maintain an acidic environment on the skin, inhibiting microbial growth.
Perspiration: Contains lysozyme which flushes pathogens from the skin surface.
Tears, Saliva, Nasal Secretions: Also contain lysozyme to destroy pathogen cell walls.
Hyaluronic Acid: Found in connective tissue; slows the spread of pathogens.
Gastric Juice: Strongly acidic, destroys most ingested bacteria.
Vaginal Secretions: Slightly acidic, helps slow bacterial growth.
Part 2: Specific Defenses
Second Line Defense - Phagocytes
Role:
Remove cellular debris and attack pathogens that breach the first line of defense.
Types of Phagocytes:
Microphages: Small phagocytic cells that respond quickly.
Macrophages: Larger phagocytic cells that engulf pathogens and dead tissue.
Mechanism of Phagocytosis
Chemotaxis: Movement of phagocytes towards a site of infection.
Adherence: Attachment to the pathogen.
Ingestion: Engulfing the pathogen.
Digestion: Breaking down the pathogen using enzymes.
Killing: Destruction of the pathogen post-digestion.
Second Line Defense - Natural Killer (NK) Cells
Function:
A subpopulation of lymphocytes that are not phagocytic.
They destroy abnormal cells (such as cancerous or virus-infected cells).
NK cells are generally not very selective in targeting cells for destruction.
Recognition and Action:
Upon recognition of an abnormal cell, NK cells relocalize their Golgi apparatus to release perforin and granzymes to induce lysis of the target cell.
Second Line Defense - Inflammation
Inflammation: The body’s response to tissue stress or damage from injury, pathogens, or chemical agents.
Cardinal Signs:
Redness, Pain, Heat, Swelling.
Functions:
Prevents the spread of damaging agents.
Disposes of cell debris and pathogens.
Prepares tissue for repair.
Stages of Inflammation
Vasodilation and Increased Permeability: Blood vessels dilate and become more permeable, allowing fluid to reach the injured area.
Phagocyte Migration: Phagocytes such as neutrophils and monocytes attracted to the area.
Tissue Repair: Regeneration or replacement occurs after clearance of pathogens and debris.
Vasodilation and Increased Permeability of Blood Vessels
Histamine: Released in response to injury, promoting vasodilation and permeability.
Kinins: Induce pain and further increase vascular permeability.
Prostaglandins: Enhance the effects of histamine and kinins; attract phagocytes.
Leukotrienes: Attract phagocytes and increase adhesion to damaged areas.
Complement Proteins: Assist in phagocytosis, attract phagocytes, and can directly destroy bacteria.
Second Line Defense - Phagocyte Migration
Neutrophils:
First responders to an inflammation site, attracted by microbial products and signaling molecules.
Monocytes:
Arrive after neutrophils, transforming into macrophages to support debris clearance and kill pathogens.
Pus Formation: A mass of dead phagocytes and damaged tissue results from ongoing infection until controlled.
Phagocyte Mobilization Mechanisms
Leukocytosis: Increased production of white blood cells in response to inflammation.
Margination: White blood cells adhere to the endothelial walls of blood vessels.
Diapedesis: White blood cells exit the bloodstream and migrate to tissue.
Chemotaxis: Phagocytes move toward the chemical signals emitted from the site of damage.
Fever
Definition: Fever is an abnormally high body temperature, a systemic response to infection.
Causes:
Triggered by pyrogens, which are chemicals secreted by activated leukocytes and macrophages during exposure to pathogens.
Function of Fever:
Sequesters iron and zinc necessary for bacterial growth, enhancing host defenses.
Tissue Repair
Process:
Blood vessels transport nutrients and proteins necessary for tissue regeneration and repair.
Types of Repair:
Regeneration: Replacement with the same type of tissue.
Replacement: Involves the formation of scar tissue with connective tissue.
Part 3: Acquired Immunity
Third Line of Defense - Specific Immunity
Overview: The third line of defense is activated after innate defenses fail, recognizing and attacking specific pathogens more efficiently.
Immunity:
Defined as resistance to specific invaders through defense against specific pathogens, referred to as antigens (Ag). Antigens provoke an immune response by being recognized as foreign entities by the immune system.
Acquisition of Immunity
Innate Immunity: Immunity present at birth.
Acquired Immunity: Can be active or passive.
A. Naturally acquired passive immunity: Antibodies passed from mother to baby through breastfeeding or placenta.
B. Induced passive immunity: Antibodies injected to combat disease (e.g., rabies treatment).
C. Naturally acquired active immunity: Resulting from natural infection.
D. Induced active immunity: Immunity formed after vaccination (exposure to an antigen that does not cause disease).
Types of Immunity
Specific Resistance (Immunity): Responds to threats individually.
Innate Immunity: Genetically determined, no prior exposure or antibody production.
Active Immunity: Generated via immune response to antigens.
Passive Immunity: Involves transfer of antibodies from another organism.
Properties of Immunity
Specificity: The immune response targets a specific antigen; effector T cells and B cells respond to distinct molecular configurations of the antigen.
Versatility: The immune system adapts to various invaders, developing many unique populations of lymphocytes during development.
Memory: Memory cells are generated that respond swiftly to previously encountered antigens, allowing for rapid reactions upon re-exposure and preventing pathogens from causing disease.
Tolerance: Lymphocytes learn not to attack the body’s own tissues, developing an understanding of “self” vs. “non-self.”
Mechanisms of Specific Immunity
B Cell Activation:
Primary exposure to an antigen leads to phagocytosis by macrophages, initiating helper T cells.
Memory helper T cells and activated B cells subsequently produce antibodies in response to re-exposure.
Cell-Mediated Immunity - T Cells
Types of T Cells:
Cytotoxic T Cells (TC): Recognize and destroy foreign antigens displayed with MHC-1 molecules.
Helper T Cells (TH): Stimulate the activation of other T and B cells, crucial for overall immune activation.
Suppressor T Cells (TS): Regulate and suppress immune responses.
Memory T Cells: Enable rapid and robust responses upon subsequent exposure to the same antigen.
T Cells Activation Process
Activation Steps:
T cells recognize antigens bound to MHC proteins on infected cells.
Activated T cells proliferate and differentiate into various functional subpopulations.
Activated T cells either attack directly or stimulate other immune cells to respond to the pathogen.
Antibody-Mediated Immunity - B Cells
B Cell Differentiation: Upon activation, B cells divide into:
Memory B Cells: Remain for future encounters.
Plasma Cells: Produce and secrete antibodies, circulating in the bloodstream to target pathogens.
Part 4: Homeostatic Imbalances of Immunity
Immunodeficiency Disorders
Severe Combined Immunodeficiency (SCID): Genetic disorder leading to absence or inactivity of both T and B cells, resulting in a dysfunctional immune response.
Acquired Immunodeficiency Syndrome (AIDS): Caused by the human immunodeficiency virus (HIV), which infects T cells, particularly those with CD4 receptors, diminishing the immune response.
Autoimmune Disorders
Autoimmunity: When the immune system attacks its own tissues, failing to distinguish between self and non-self antigens, leading to the production of autoantibodies.
Conditions include:
Multiple Sclerosis, Myasthenia Gravis, Grave’s Disease, Type I Diabetes, Systemic Lupus Erythematosus, Glomerulonephritis, Rheumatoid Arthritis.
Allergic Reactions
Allergy: Hypersensitivity to environmental antigens (allergens).
IgE antibodies bind to mast cells, triggering histamine release, which contributes to allergic symptoms like mucus production and bronchoconstriction.
Types of Hypersensitivity
Immediate Hypersensitivity: Symptoms occur rapidly upon re-exposure to an allergen, can lead to anaphylactic shock.
Delayed Hypersensitivity: Slower response regulated by T cells, manifesting after a few days. Typically seen in contact dermatitis reactions.