1570lec9

Human Immune System Lecture Notes

Introduction

  • The human body provides a nutrient-rich environment for microbes,
    • However, the interior of the body is generally sterile or has very few microbes.
    • Microbes are kept in check by the immune system.
  • The immune system has two major parts:
    1. Innate immunity
    2. Adaptive immunity

Immune System

Innate Immunity
  • Routine protection that is present at birth.
  • Characteristics:
    • Does not remember previous encounters.
    • Not specific to certain microbes.
    • Begins protecting immediately.
  • Divided into:
    1. 1st line of defense
    2. 2nd line of defense
Adaptive Immunity
  • Develops throughout life as the body is exposed to microbes or foreign materials.
  • Characteristics:
    • Remembers previous encounters.
    • Specific to certain microbes.
    • Exhibits a time lag (3rd line of defense).

Innate Immunity

1st Line Defenses
  • Prevent microbial entry:
    • Skin:
    • Dry, salty environment that sheds dead skin (along with attached microbes).
    • Intact skin prevents penetration of pathogens.
    • Mucus Membranes:
    • Line digestive, urinary, and respiratory tracts.
    • Mucus coat is thick and sticky, preventing the entry and attachment of bacteria.
    • Cilia push mucus up from lungs to mouth for expulsion.
    • Sensor Systems:
    • Detect cell damage and microbial invasion using pattern recognition receptors (PRRs).
    • Complement System:
    • A series of proteins that assist immune reactions.
2nd Line Defenses
  • Eliminate invaders when the first line is breached.
    • Interferon Response:
    • Cellular response to viral infections and enhances immune actions.
    • Phagocytosis:
    • Process by which phagocytes ingest and destroy pathogens.
    • Complement Activation:
    • Enhances the immune response.
    • Inflammatory Response:
    • Attracts immune cells to the site of infection.
    • Fever:
    • A systemic response to infection.

Details on Immune Components

Skin
  • Lacks microbes due to dryness and desquamation.
  • Very few pathogens can breach intact skin.
Mucus Membranes
  • Found in various body tracts:
    • Moist and permeable, with mucus impeding bacterial attachment.
    • Cilia aid in clearing mucus from the respiratory tract.
Pattern Recognition Receptors (PRRs)
  • Located on cell surfaces and within immune cells.
  • Recognize various microbial components and signs of host damage.
  • Example: Toll-like receptors (TLR) detect flagellin and lipopolysaccharide (LPS).
Cytokines
  • Chemical messengers produced by cells with activated PRRs.
  • Induce changes in target cells that enhance immune responses.
  • Examples include interferons, interleukins, and tumor necrosis factors.

Second Line of Defense

  • Activated when pathogens breach the first line.
  • Components:
    • Specialized cells in the bloodstream and lymph.
    • Lymphatic system collects and manages escaped fluid from blood circulation.
White Blood Cells (WBCs)
  • Move throughout the body searching for pathogens.
  • Always present in normal blood; numbers increase during infections.
  • Two major types:
    1. Granulocytes
    2. Agranulocytes
Granulocytes
  • Contain granules that release antimicrobial and cytotoxic molecules.
  • Three types:
    1. Neutrophils: Engulf and destroy bacteria.
    2. Basophils: Involved in allergic reactions and inflammation; contain histamine.
    3. Eosinophils: Combat parasitic infections.
Agranulocytes
  • Monocytes: Differentiate into macrophages or dendritic cells.
    • Macrophages: Major phagocyte; located in tissues to digest foreign material.
    • Dendritic Cells: Focus on antigen presentation to activate adaptive immunity.
    • Lymphocytes: Focus on adaptive immunity.

Second Line of Defense Components

  1. Phagocytosis
  2. Complement Activation
  3. Interferon
  4. Inflammation
  5. Fever
Phagocytosis
  • Macrophages: Long-lived, present in tissues, phagocytize debris and invaders.
  • Neutrophils: First responders, phagocytize microbes; have a short lifespan of 1–2 days.
The Complement System
  • Activated by binding of complement molecules to foreign cells or by antibodies.
  • Outcomes of Activation:
    1. Opsonization: Promotes phagocytosis via binding to foreign particles.
    2. Inflammation: Increases blood vessel permeability to recruit immune cells.
    3. Lysis of Foreign Cells: Forms membrane attack complexes (MACs) that lead to cell lysis.
Interferon
  • Regulates immune responses by altering genetic expression upon binding to cell surfaces.
  • Particularly effective against viral infections.
Inflammation
  • Triggered by cytokines, microbial invasion, and tissue damage.
  • Goal: Limit damage and restore function, though it can also cause tissue damage.
  • Compared to a fire sprinkler system for damage limitation.

Classic Signs and Symptoms of Inflammation

  1. Rubor: Redness from increased circulation and vasodilation.
  2. Tumor: Swelling from increased fluid in tissues.
  3. Dolor: Pain from nerve-ending stimulation.
  4. Calor: Warmth from increased blood flow.
Fever
  • Defined as an abnormally elevated body temperature.
  • Reset hypothalamus raises body temperature, prompting heat production.
  • Benefits:
    • Inhibits multiplication of temperature-sensitive pathogens.
    • Stimulates immune reactions and metabolic processes.
Treatment of Fever
  • Opposing views on whether to suppress fever.
  • Consensus:
    • Allow slight to moderate fevers.
    • Treat high/prolonged fevers and in patients with specific health conditions (e.g., cardiovascular disease).
Endotoxin
  • Lipid A portion of LPS from bacterial cell walls.
  • Triggers cytokine release from macrophages, leading to an overshoot of the immune response and septic shock.

Adaptive Immunity

  • Ability to adapt to different antigens encountered over a lifetime.
  • Antigen (Ag): Stands for antibody generator; a molecule that elicits an adaptive immune response.
  • Antigens can be diverse, e.g., microbes or pollen, with specific regions stimulating antibody generation.
  • Three Key Characteristics:
    1. Self/non-self recognition
    2. Diversity and specificity
    3. Memory
Self/Non-self Recognition
  • MHC markers on plasma membranes differentiate between self and non-self.
  • Facilitates the recognition of immune cells.
Diversity and Specificity
  • Billions of adaptive immune cells exist, each with unique receptors.
  • Upon exposure to an antigen, only matching receptors will activate and proliferate.
Memory
  • The first exposure to an antigen generates a primary immune response, while subsequent exposures result in a quicker secondary response.

Branches of Adaptive Immunity

  1. Humoral Immunity
  2. Cell-Mediated Immunity
  • Immature immune cells that differentiate upon encountering an antigen into:
    • Effector cells: Actively combat antigens.
    • Memory cells: Long-lived cells for future protection.
B Cells
  • Develop and mature in the bone marrow.
  • Activated in response to extracellular antigens.
  • Produces two types of cells:
    1. Memory B cells: Respond quickly to later encounters.
    2. Plasma cells: Produce Y-shaped proteins called antibodies (immunoglobulins).
    • Antibody Structure:
    • Two identical arms (variable region) bind specific antigens.
    • The stem (constant region) determines the antibody class.
Classes of Antibodies
  • IgD: Unknown function
  • IgE: Allergy response and parasitic infections
  • IgG: Dominant in antibody-mediated immunity and can cross the placenta.
  • IgA: Present in mucosal tissues and body fluids.
  • IgM: First produced upon infection as a pentamer.
Outcomes of Antibody-Antigen Binding
  1. Neutralization: Prevents binding of toxins and viruses.
  2. Immobilization: Interferes with bacterial flagella.
  3. Cross-linking: Antibodies bind separate antigens.
  4. Opsonization: Enhances phagocytosis.
  5. Complement Activation: Triggers the complement system for pathogen destruction.
  6. Antibody-dependent Cellular Cytotoxicity (ADCC): Targets cells for destruction by Natural Killer (NK) cells.
T Cells
  • Develop in the bone marrow and mature in the thymus.
  • Activated to respond to intracellular antigens presented by other cells.
  • Types of T Cells:
    1. Cytotoxic T cells (TC): Directly kill infected cells.
    2. Helper T cells (TH): Release signals that activate other immune cells.
    3. Memory T cells: Rapid response to future encounters.
Antigen Presentation
  • Essential for T cell activation.
    • Antigens presented on MHC complexes enable T cell recognition and response.
  • MHC Classes:
    1. MHC I: Present on all human cells, indicating infection.
    2. MHC II: Present only on professional phagocytes.
Cytotoxic T Cells
  • Recognize antigens on MHC I markers and induce apoptosis in infected cells.
Helper T Cells
  • Recognize antigens on MHC II markers and release cytokines to activate B cells and cytotoxic T cells.
Natural Killer (NK) Cells
  • Target and kill cancerous and virus-infected cells.
  • Recognize cells lacking MHC markers.
Superantigens
  • Induce enormous overstimulation of the immune system, activating a high percentage of T cells.
  • Associated with severe consequences, such as Toxic Shock Syndrome.

Applications of the Immune System

  • Immunological Testing:
    • Tuberculin Skin Test: Involves injecting tuberculin protein to check for immune response.
    • Enzyme-Linked Immunosorbent Assay (ELISA): Detects antibodies in serum, useful in determining infections like HIV.

Adaptive Immune System

Active vs. Passive Immunity