IMMUNE RESPONSE

Introduction to the Immune System

  • The immune system is a set of specialized cells that works with the lymphatic system to fight off foreign substances that enter the body.

  • These foreign substances are known as pathogens.

Major Categories of Immune Defenses

  1. Innate (Non-specific) Defenses

    • Work quickly, but are not specialized for individual pathogens.

      • Examples:

      • Skin

      • Mucous Membranes

  2. Acquired (Adaptive) Defenses

    • Work slowly, but provide specialized and long-lasting defense against pathogens.

      • Subcategories:

      • Humoral Immunity

      • Cell-mediated Immunity

Innate Resistance Mechanisms

  • Innate resistance starts with barriers.

1. External Barriers: Prevent Pathogens from Entering the Body

a. Skin

  • Keratinized cells create a physical barrier.

  • Skin produces oil and sweat which inhibit the growth of bacteria.

    b. Mucous Membranes

  • Mechanical Elimination: Mucus physically traps pathogens; cilia of the respiratory tract can sweep them towards the mouth for removal.

  • Secretions: Gastric juice from the stomach, saliva, and tears contain enzymes that kill pathogens.

    • Example: Tears contain lysozyme, an enzyme that kills bacteria by destroying their cell walls.

2. Internal Barriers: Activated Once Pathogen Passes into Body Tissues

a. Phagocytes: “Eat” foreign invaders.

  • Neutrophils: Kill bacteria then die, creating pus.

  • Macrophages: Move with cytoplasmic extensions to ingest pathogens.

    b. Natural Killer Cells

  • Lyse (explode) infected or abnormal body cells based on a lack of “self” surface receptors.

    c. Inflammation

  • Basophils & Mast Cells stimulate blood vessels to dilate/widen.

  • Swelling (edema) allows macrophages to quickly arrive through vessels.

  • Pyrogenic chemicals cause fever, which increases cell metabolism to speed up repair.

    d. Antimicrobial Proteins

  • Complement Proteins: Work with other defenses by lysing pathogenic bacteria or marking pathogens for easier phagocytosis (a process known as opsonization).

  • Interferons: Warning signal proteins secreted by virally-infected cells and are a type of cytokine (chemical signals used for cell communication during an immune response).

Responses When Innate Defenses Fail

  • If the non-specific defenses don’t stop the infection, the body creates an immune response specific to that pathogen.

  • Substances that trigger this response are called antigens.

  • The cells responsible for this specific response are lymphocytes, which produce antibodies that match certain antigens.

Features of Acquired Immunity

  • The acquired immunity portion of the immune response must be able to:

    1. Discriminate between self and non-self antigens.

    2. Recognize a specific antigen among trillions of possible substances.

    3. Generate a large diversity of antibodies so any possible substance can be recognized and eliminated.

    4. Provide memory of antigens for a swift response upon re-exposure.

    • A second exposure to an antigen is immediately recognized, and the infection is barely noticed.

Types of Responses in Acquired Immunity

  1. Humoral Response

    • Involves B-cells.

    • Responds to antigens before they infect body cells.

  2. Cell-mediated Response

    • Involves T-cells.

    • Responds to body cells that have already been infected with foreign pathogens.

Humoral Immunity

  • B Cells: Pathogens are attacked in bodily fluids such as blood and lymph.

  • T Cells: Cells that are infected by a pathogen are attacked. This is a specific part of the acquired immune response.

Mechanism of Acquired Immunity

  • Acquired immunity is triggered by specific antigens.

  • Lymphocytes (B and T cells) recognize the antigen, produce a large number of antibodies, and remember the antigen for future infections.

B-Cell Functionality

  • Name: B-cell

  • Superpowers: Ability to recognize invading antigens and clone itself.

  • Mature in: Bone Marrow

B-Cell Activation Process

  1. B-lymphocytes (B cells) recognize a foreign antigen.

  2. B cells rapidly divide, creating cloned plasma B cells and memory B cells.

    • Plasma B cells can secrete antibodies at a rate of 2,000 per SECOND!

  3. Memory B cells are long-lived and produce a swift and strong response if the same antigen is encountered in the future (this is called the “secondary response”).

  4. The antibodies produced by plasma B cells can:

    • Neutralize the antigen by physically surrounding it.

    • Immobilize the antigen by agglutination (clumping).

    • Activate macrophages to destroy the antigen.

Visualization of B-Cell Activation

  • Antigen → Virus → B-cell activation → Antibody → Memory B-cell → Plasma cell → Activation of B-cell → Lymphoblast.

Types of Immunity

  • Immunity can be earned or borrowed:

    • Active Immunity: Earned through the creation of our own antibodies.

      • Natural Active Immunity: Occurs when we contract an infection.

      • Artificial Active Immunity: Occurs when we are given a vaccine.

    • Passive Immunity: When we borrow the immunity that another individual has already created.

      • Natural Passive Immunity: Occurs when antibodies are passed from mother to child through breastmilk or the placenta.

      • Artificial Passive Immunity: Occurs when we are injected with antibodies from the blood serum of an individual that has already been infected.

Recruitment of Immune Cells

  • Humoral immunity involves the activation of B-cells. Once activated by a foreign antigen, B-cells produce both cloned plasma B-cells and memory B-cells for future infections.

  • Immunity can be earned through active immunity or borrowed from another through passive immunity.

Antigen-Presenting Cells (APCs)

  • To amplify the immune response, B-cells can also act as antigen-presenting cells.

  • Antigen-presenting cells engulf antigens and present pieces of the antigen to other immune cells, thus sounding the alarm for an infection to recruit more immune defenders.

    • APC Examples: B-cells, macrophages, dendritic cells.

  • The antigen fragment is presented on a receptor known as MHC-II (major histocompatibility complex-2).

  • T-cells will bind to this MHC-II and mount a stronger response against the antigen.

T-Cell Functionality

  • Name: T-cell

  • Superpowers: Detect and kill infected body cells.

  • Mature in: Thymus.

T-Cell Activation and Action Process

  1. After the antigen-presenting cells display the foreign antigen to a helper T-cell, the T-cell is activated.

  2. A signaling cascade begins, creating more helper T-cells and memory T-cells.

  3. Some cytokine signals activate cytotoxic T-cells, which bind to infected body cells and cause apoptosis.

  4. Regulatory T-cells release chemicals to slow the immune response after the antigen is destroyed.

Types of T-Cells and Their Functions

  • Cytotoxic T Cells: Produce toxic agents to kill target cells.

  • Helper T Cells: Stimulate B cells to produce antibodies and stimulate T cells to become active.

  • Regulatory T Cells: Suppress immune responses (STOP function).

Secondary Immune Response

  • During a secondary infection (re-infection with a previous pathogen), the body uses Memory B and Memory T cells to respond more quickly.

    • Often, a person with a secondary infection will not even show symptoms.

    • Symptoms may appear but recede more quickly than during the first infection.

    • Examples: Cold viruses, flu.

    • Importance of Vaccines: Vaccines can help the body mimic the first infection, thus preparing Memory B and T cells to fight it upon actual exposure.

Summary of Antigen-Presenting Cells

  • Antigen-presenting cells provide fragments of the infecting antigen to helper T-cells.

  • After activation, helper T-cells signal for the formation of memory T-cells, cytotoxic T-cells, and regulatory T-cells.

  • If the same antigen is encountered again, the memory T-cells will mount a prompt and effective response.