Adaptive Immunity

Adaptive Immunity

Overview of Adaptive Immunity

  • Adaptive immunity is a complex immune response that specifically targets pathogens.

  • Humoral response is a key component of this system, characterized by antibody-mediated actions.

Humoral Immune Response

  • Definition: The humoral immune response is distinct for being mediated by antibodies against extracellular antigens.

  • Pathogen Interaction: The response is particularly involved with pathogens that remain outside of human cells (extracellular).

Key Players in Humoral Immunity
  • B cells: These are the primary cells that mediate the humoral response. They differentiate into plasma cells that produce antibodies.

  • Helper T cells: These cells assist in activating B cells and are crucial in the humoral response. They help by releasing cytokines.

Process of Humoral Response

Initial Interaction with Pathogens
  • Pathogens such as bacteria or spirochetes enter the body and trigger a response.

  • Trillions of B cells exist within the body, each capable of recognizing a specific antigen.

B Cell Activation
  1. B Cell Receptor Binding: Each B cell has a unique receptor that binds to its specific antigen on the pathogen.

  2. Internalization: The B cell internalizes the antigen after binding.

  3. Processing: The antigen is degraded into fragments within the B cell.

  4. MHC Class II Presentation: These fragments are presented on the B cell's surface via MHC class II molecules, indicating to helper T cells what is present.

Role of Helper T Cells
  • Recognition of Pathogenic Antigens: A helper T cell identifies an antigen presented by a B cell that is pathogenic.

  • Cytokine Release: The helper T cell secretes cytokines to activate the B cell.

  • Clonal Expansion: Activated B cells undergo proliferation, leading to the creation of numerous clones.

  • Differentiation into Plasma and Memory B Cells: Some B cells become plasma cells that produce antibodies, while others become memory B cells that remain for future responses.

Inactivation of B Cells
  • If a B cell presents a harmless antigen, the helper T cell will recognize it as non-threatening.

  • Cytokine Response: Instead of activating, the helper T cell will secrete cytokines that inactivate the B cell, known as anergy, preventing unnecessary immune reactions to benign substances.

B Cell Development

  • Origin: B cells are produced and mature in the bone marrow.

  • Naive B Cells: These immature B cells reside in lymph nodes awaiting activation.

  • Clonal Expansion and Differentiation: Upon activation, they undergo clonal expansion and differentiation into plasma or memory B cells.

Antibodies

Structure of Antibodies
  • Definition: Antibodies are proteins generated by plasma cells, commonly referred to as immunoglobulins (Ig).

  • Y-Shaped Structure: Consists of two heavy chains (green) and two light chains (gray) connected by disulfide bonds.

  • Regions of Antibodies:

    • Constant Region: Determines the class of immunoglobulin; type is critical for antibody function.

    • Variable Region: Unique for each antibody where antigen binding occurs, specifically at the arms of the Y.

  • Binding Sites: Two antigen binding sites per antibody, allowing for effective immune response against specific pathogens.

    • One is called the stem (Fc region). It serves as a red flag or a signal. This lets phagocytes know hey there is a problem here and I need your help.

    • The second is known as the fab region (antigen binding sites). The epitope is a segment of antigen where antibodies bind.

      • Epitopes (small protein subunit): The specific sites on antigens where antibodies bind, usually comprising a few amino acids (4-16).

Classes of Immunoglobulins
  1. IgM

    • Structure: Pentamer (five antibodies linked); large size limits its transfer across biological barriers. (10 antigen binding sites)

      • Too large to pass through most barriers.

      • First class of antibody made against a specific antigen. So if a plasma cell has been introduced to an antigen for the first time. IGM is the first class to be made against that antigen.

    • Function: First antibody to be produced against a specific antigen; plays a key role in initial immune response.

  2. IgG

    • Structure: Smaller than IgM, abundant in circulation; can cross the placenta to provide fetal immunity.

      • Abundant in the body and the second class to be made.

      • It’s smaller therefore it can be transported from the placenta to the fetuses blood stream.

    • Function: Produced during a secondary immune response; essential for long-term immunity.

  3. IgA

    • Structure: Dimeric form (two Y shapes linked); abundant in mucosal areas.

      • The MOST abundant class of all the immunogobulins.

      • IgA is so important for mucosal immunity. IgA is found on the lining of mucus membranes.

        • Remember mucus membranes is where most pathogens enter from.

      • IgA is very important for preventing pathogens in the mucous membrane area.

      • IgA is also secreted in breast milk, tears, saliva, and any bodily fluids like that.

  1. IgD

    • Function: Less than 1% of antibodies; thought to be involved in development of immune responses.

  2. IgE

    • Function: Involved in allergic reactions and defense against helminths diseases like a parasitic worm; barely detectable in blood.

Actions of Antibodies on Antigens

  • Neutralization: Antibodies block pathogen binding sites of the virus or the toxin.

    • Which results in viral spikes not being able to attach to the host receptor because antibodies are blocking them. Or a toxin can’t bind to the host because antibodies are blocking them.

      • Happens when an antibody binds to a virus. A bunch of antibodies have bound all over the virus or an antibody binds all over to an exotoxin that is secreted from a bacteria.

  • Opsonization (easier for phagocytosis): Antibodies coat pathogens, which make it easier for phagocytes to recognize and engulf.

    • The stem on the antibody will signal or flag the phagocytes to come in and engulf.

  • Complement Activation: If an antibody binds to a pathogen it can activate the complement activation system which is part of your innate immunity.

  • Immobilization and Prevention of Adherence: Antibodies could bind to the flagella of a bacteria and this prevents the flagella from working properly so the bacteria are immobilized they can’t move.

  • Cross-linking: Is where one antibody bind to two bacteria two epitopes from two different antigens at the same time.

    • This creates a giant antibody pathogen clump. This is going to make it easier for phagocytes to come in and engulf all of this clump at once instead of one pathogen at a time.

  • Antibody-dependent Cellular Cytotoxicity (ADCC): Antibodies coat all the way around an infected human host cell with a virus which signals for a natural killer cells to come in and signal the host cell to undergo apoptosis in order to prevent the spread of the virus.

    • Natural killer cells will secrete cytokines so the human host cell knows to kill itself by apoptosis.