Module 17: Immune Response Part II Adaptive Defenses

Characteristics of Adaptive Defenses

• Definition: The adaptive immune system is highly specific and provides a long-term defense against pathogens.

• Specificity: The immune system recognizes and responds to a specific antigen, differentiating it from all other substances.

• Systemic Nature: The adaptive response is not limited to the site of the initial infection; it is a system-wide response that occurs throughout the body.

• Memory: The system has the capacity to "remember" a specific antigen. This allows the body to mount a significantly stronger and faster response upon subsequent exposures to the same pathogen.

Antigens and Major Histocompatibility Complex (MHC)

• Antigen: Any substance that possesses the capability to induce an immune response.

• Immunogenicity: A quantitative or qualitative measure of the ability of an antigen to induce an immune response.

• Antigenic Determinants (Epitopes): These are specific sites on the surface of an antigen where an antibody or a lymphocyte receptor actually binds.

• Self Antigens: These are antigens that the immune system recognizes as part of the host body, preventing an attack on the host's own cells.

• Major Histocompatibility Complex (MHC): These are surface proteins encoded by MHC genes that serve as the primary markers for "self."

  • MHC Class I: These markers are found on the plasma membranes of all nucleated cells in the body; they are notably absent from Red Blood Cells ($RBC's$).

  • MHC Class II: These markers are found specifically on the surfaces of activated immune system cells. These include B cells, dendritic cells, macrophages, and thymic epithelial cells (the latter uses them to test T cells during maturation).

Cells of the Adaptive Immune System

• B Lymphocytes (B Cells):

  • Origin: These cells originate in the bone marrow.

  • Maturation: These cells complete their maturation process within the bone marrow.

• T Lymphocytes (T Cells):

  • Origin: These cells originate in the bone marrow.

  • Maturation: These cells migrate to and mature in the thymus.

  • Positive Selection: A screening process that identifies and preserves T cells that are capable of recognizing self $MHC$ proteins.

  • Negative Selection: A process that eliminates T cells that react too strongly to a combination of self $MHC$ and self antigens. Cells that fail this test undergo apoptosis.

  • Self Tolerance: The resulting state where the immune system does not attack the body’s own healthy cells unless those cells have become abnormal (e.g., infected or cancerous).

  • Apoptosis: The process of programmed cell death.

• Antigen Presenting Cells (APCs): Cells that process and present antigens in conjunction with $MHC\,II$ to the immune system. This group includes dendritic cells, macrophages, and B cells.

The Humoral Immune Response

• Clonal Selection: The process of selecting a specific B cell that matches a particular antigen and stimulating it to multiply rapidly through mitosis.

• B Lymphocyte Mechanism:

  • A B lymphocyte recognizes a specific antigen ($Ag$).

  • It possesses $IgD$ and $MHC\,II$ on its surface that are specific for that antigen.

  • The B cell processes the antigen and presents it on its surface via $MHC\,II$.

• Antigen Presenting Cell (APC) Role: Processes and presents the antigen on $MHC\,II$ to initiate the response.

• T Helper Lymphocyte Role:

  • Possesses a T cell receptor ($TCR$) that binds specifically to the $MHC\,II$ + antigen complex.

  • MHC Class II Restricted: The T Helper cell binds to the macrophage/APC and becomes activated.

  • Once activated, the T Helper cell differentiates and secretes $Interleukin\,4$ ($IL-4$).

  • $Interleukin\,4$ stimulates the B cell to proliferate (multiply) and differentiate into effector cells.

• Differentiation Pathways:

  • Plasma Cells: These function as "antibody factories." They secrete massive amounts of antibodies but do not have $BCR's$ (B cell receptors) on their surface.

  • Memory Cells: These cells remain in circulation for long periods. They do not actively fight the current infection but provide a faster and stronger response if the same antigen is encountered again.

Immunological Memory and Antibody Structure

• Primary Immune Response:

  • The initial exposure to an antigen.

  • It takes approximately $3-5$ days for the antibody titer (concentration) to increase.

  • The response lasts about $3$ weeks.

  • The sequence of antibody production is typically $IgM$ followed by $IgG$.

• Secondary Immune Response:

  • Occurs upon re-exposure to the same antigen.

  • Features a much shorter lag phase.

  • $IgM$ and $IgG$ are produced more or less simultaneously.

  • Produces a significantly higher titer of antibodies with a longer duration of protection.

• Basic Antibody Structure:

  • Heavy Chains: Large polypeptide chains that form the core of the Y-shaped antibody.

  • Light Chains: Smaller polypeptide chains attached to the heavy chains.

  • Variable Region: The tips of the Y-shape that form the antigen-binding site specific to a particular epitope.

  • Constant Region: The stem of the Y-shape; this part binds to complement proteins and host cells.

• Antibody Classes:

  • IgA: Found as a monomer in the serum, but as a dimer in body secretions such as mucus, milk, and tears.

  • IgM: Exists as a pentamer; its large size generally keeps it within the blood circulation.

  • IgD: Functions primarily as membrane-bound antigen receptors on B cells.

  • IgG: The most abundant antibody, representing approximately $85\%$ of all serum antibodies. It is a typical Y-shaped antibody involved in opsonization, neutralization, and complement activation.

  • IgE: Y-shaped antibodies that attach to receptors on eosinophils, mast cells, and basophils; they are involved in allergic responses.

• Antibody Diversity and Monoclonal Antibodies:Identical antibodies produced in a laboratory. They are widely used in diagnostics and medical test kits.

Cell-Mediated Immune Response

• T Lymphocytes (Cytotoxic T Cells / CD8): These cells are responsible for destroying infected or abnormal host cells.

• MHC Class I Restricted: The T cell receptor ($TCR$) on a $CD8$ cell is specific for the combination of $MHC\,I$ and an endogenous antigen (an antigen produced inside the cell).

• Activation: Requires two steps:

  1. Antigen binding.

  2. Co-stimulation.

• Co-stimulation: The use of cytokines to stimulate the T cell to continue its response. Examples include $IL-1$ and $IL-2$.

• Cytokines: These are chemical messengers that act as intercellular signals to coordinate the immune response.

• Mechanisms of the "Lethal Hit": Once activated, the Cytotoxic T cell destroys the target cell using several methods:

  • Perforin: Proteins that create transmembrane pores in the target cell's membrane, which is a mechanism similar to the complement Membrane Attack Complex ($MAC$).

  • Lymphotoxin: A substance that fragments the target cell's $DNA$.

  • Gamma (\gamma) Interferon: A cytokine that stimulates macrophages to reach "killer status," enhancing their phagocytic and destructive capabilities.

Immunity to Disease and Vaccination

• Active Immunity: The body produces its own antibodies and memory cells.

  • Naturally Acquired Active Immunity: Resulting from an actual infection.

  • Artificially Acquired Active Immunity: Resulting from vaccination.

• Vaccine Types:

  • Killed or Inactivated Whole: Contains the entire microorganism that has been killed.

  • Live Attenuated: Contains a weakened version of the live microorganism.

  • Subunit (Second Generation): Contains only pieces or specific components of the microorganism rather than the entire organism.

  • Synthetic (Third Generation): Genetically engineered vaccines where another organism is used to produce the subunit. An example is the $HBV$ (Hepatitis B Virus) vaccine.

  • DNA Vaccines: Use plasmids containing genetic information for antigens.

  • Toxoids: Inactivated toxins produced by pathogens.

• Adjuvants: Substances added to vaccines to increase their efficacy. Examples include aluminum sulfate (alum), aluminum hydroxide, mineral oil, and peanut oil.

• Herd Immunity: A phenomenon where if the majority of a population (e.g., >90\%) is immunized against a disease, susceptible (unprotected) individuals are unlikely to encounter an infected person, thereby protecting the whole community.

• Vaccine Components and Side Effects:

  • Thimerosal: An ethylmercury-containing preservative used in some vaccines to prevent bacterial and fungal growth.

• Passive Immunity: The body receives antibodies from an external source.

  • Naturally Acquired Passive Immunity: The transfer of maternal antibodies to a fetus via the placenta or to an infant via breast milk.

  • Artificially Acquired Passive Immunity: The administration of antiserum or gamma globulins (pre-formed antibodies) to a patient.