Adaptive Immunity and Immunology Vocabulary

Comparison of Innate and Adaptive Immunity

• Innate (Inborn) Immunity: This involves nonspecific resistance to a wide variety of different pathogens. It is a system humans are born with.

• Adaptive (Acquired) Immunity: This is characterized by specific resistance to a specific pathogen. Pathogens are identified by particular antigens, which stimulate an immune response.

• Immune Response Stimulation: In adaptive immunity, the host creates a variety of different B and T cells. These cells respond specifically to one single antigen.

Active vs. Passive Acquired Immunity

• Active Immunity:

  • Mechanism: The host is exposed to the antigen in some way.

  • Immune Response: Exposure stimulates an immune response in the host.

  • Timing: It is not immediate; the body requires time to respond.

  • Duration: It is long-term because it stimulates the production of memory cells.

• Passive Immunity:

  • Mechanism: The host is exposed to antibodies rather than the antigen.

  • Immune Response: There is no stimulation of an immune response.

  • Timing: Provides immediate protection.

  • Duration: It is short-term because no memory cells are produced.

Natural vs. Artificial Acquisition

• Naturally Acquired Immunity: Exposure occurs through natural events without human intervention.

  • Natural Active: Exposure to an antigen through normal daily events, such as contracting chickenpox or COVID-$19$. The body produces its own antibodies and memory cells.

  • Natural Passive: Antibodies are passed from mother to fetus via the placenta or to the newborn via colostrum (initial mother's milk high in antibodies). This provides the newborn with an immediate boost while their immune system is still developing.

• Artificially Acquired Immunity: Exposure occurs as a result of a medical injection, requiring direct human intervention.

  • Artificial Active: Exposure to an antigen via a vaccine. Vaccines take time (approximately $2$ weeks) to become effective but provide long-term protection through memory cells.

  • Artificial Passive: An injection of preformed antibodies (e.g., antivenom or convalescent serum). This provides immediate protection, but resistance is lost once the antibodies are removed from the body.

Antigens and Epitopes

• Definition: An antigen is a substance that causes the body to produce specific antibodies or sensitize T cells. They stimulate the production of specific B and T cells.

• Epitopes (Antigenic Determinants): These are specific parts of the antigen that are recognized by leukocytes. An antibody or T cell binds to the epitope. An antigen may have multiple different epitopes, each stimulating a different B or T cell strain, leading to a more robust response.

• Haptens: Molecules that are too small on their own to act as antigens. They must combine with a carrier molecule to be recognized and initiate an immune response.

• Chemical Composition:

  • Best Antigens: Proteins and polysaccharides (e.g., capsules, cell wall components, flagella, fimbriae, exotoxins, viral capsids).

  • Poor Antigens: Lipids and nucleic acids (e.g., endotoxins).

Categories of Antigens

• Autoantigens: Self-cells that trigger an immune response, potentially leading to autoimmune disorders.

• Alloantigens: Cell surface markers (like MHC) of one individual that are recognized as foreign by another individual of the same species (e.g., organ transplant rejection).

• Heterophilic Antigens: Molecules from unrelated species that share similar antigenic determinants (e.g., cowpox and smallpox).

• Super Antigens: Exotoxins that stimulate an overwhelming, potentially harmful immune response.

• Allergens: A special group of antigens that provoke an allergic response (e.g., pollen, egg albumin in vaccines).

Antibodies (Immunoglobulins)

• Structure:

  • Constant Region: Structurally identical across different antibodies; this region holds the molecule together but does not bind to epitopes.

  • Variable Region: Unique to each antibody; this forms the antigen-binding site.

• Genetics: Humans have genes on $3$ different chromosomes that code for antibodies. There are over $150$ genes for one portion of the variable region and $250$ plus genes for the other. These genes recombine to create millions of different antigen-binding sites.

• Classes of Antibodies:

  • IgG: Monomer ($2$ binding sites). Most common in serum. Crosses the placenta. Enhances phagocytosis and neutralizes toxins. High titers of IgG indicate a late-stage infection or recovery.

  • IgM: Pentamer ($10$ binding sites). First antibody produced in response to infection. High titers indicate an early-stage infection. Effective at agglutination.

  • IgA: Dimer ($4$ binding sites). Most common antibody in secretions and outside of the serum. Protects portals of entry (e.g., lungs, gut). Some pathogens produce IgA protease to break it down.

  • IgD: Monomer. Found on B cells; helps initiate the immune response.

  • IgE: Monomer. Found on mast cells and basophils. Involved in allergic reactions and the destruction of large parasites.

Major Histocompatibility Complex (MHC)

• Role: A molecular fingerprint used for self-recognition. It allows the immune system to differentiate between self-cells and foreign cells.

• Genetics: MHC is a multi-gene complex located on chromosome $6$.

• MHC Class I: Found on all nucleated cells in the body (every cell except erythrocytes). When paired with a processed antigen, it targets a cell for destruction by cytotoxic T cells.

• MHC Class II: Found only on antigen-presenting cells (APCs) such as macrophages, B cells, and dendritic cells. It is necessary for activating helper T cells.

B Cells and Humoral Immunity

• Maturation: B cells mature in the bone marrow.

• Clonal Deletion: During development, B cells that recognize self-antigens are deleted to prevent autoimmune disease.

• Clonal Selection and Activation:

  • Selection: A B cell is selected only when it binds with its specific antigen.

  • Division: The activated B cell clones itself into genetically identical daughter cells.

  • Plasma Cells: Short-lived cells that produce and secrete antibodies.

  • Memory B Cells: Long-lived cells that recall the antigen for future exposures.

• Antigen Presentation: B cells can act as APCs. They ingest an antigen, process it, and express it on the surface with MHC Class II to bind with a helper T cell.

T Cells and Cell-Mediated Immunity

• Maturation: T cells mature in the thymus.

• Helper T Cells (CD4): Recognize antigens processed and presented by APCs on MHC Class II. They coordinate the immune response via cytokines.

  • Type $1$ ($T_H1$): Activate B cells, cytotoxic T cells, and innate cells like macrophages and Natural Killer (NK) cells.

  • Type $2$ ($T_H2$): Specifically stimulate humoral immunity by activating B cells to become plasma cells.

  • Memory Helper T Cells: Play a role in rapid response during future exposures.

• Cytotoxic T Cells (CD8): Recognize antigens on MHC Class I. They destroy infected or compromised self-cells by releasing perforins and granzymes, which cause lysis and apoptosis.

• Regulatory T Cells (CD4/CD25): Suppress T cells that recognize self, protect normal gut microbiota, and help terminate the immune response.

Functions of the Immune Response

• Agglutination: Clumping pathogens together, reducing motility and making them easier to find and destroy through phagocytosis.

• Opsonization: Coating a pathogen with antibodies to make it more visible and easier for phagocytes to ingest.

• Complement Activation: Antibodies aigger the complement protein cascade, leading to the membrane attack complex and lysis.

• Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Antibodies attach to large parasites (e.g., flukes) and attract eosinophils or NK cells to release lytic enzymes.

• Neutralization: Blocking the attachment of viruses or bacteria to host cells, or blocking the active component of a toxin (e.g., AB toxins).

Cytokines and Signaling

• Interleukin-$1$ ($IL-1$): Produced by APCs; stimulates helper T cells and attracts phagocytes.

• Interleukin-$2$ ($IL-2$): Produced by activated helper T cells; stimulates the proliferation of T cells, B cells, and NK cells.

• Tumor Necrosis Factor (TNF): Promotes inflammation and vasodilation.

• Interferons: Protect against viral infections and help target infected cells for destruction.

• Cytokine Storm: An overwhelming, harmful overproduction of cytokines, leading to excessive inflammation and fluid in the lungs, as seen in severe COVID-$19$ cases.

Laboratory and Clinical Applications

• Serology: The study of interactions between antibodies and antigens.

• Monoclonal Antibodies (Hybridomas): Created by fusing a mouse B cell with a cancer cell (myeloma). This results in a long-lived cell that produces large quantities of specific antibodies used for diagnosis and treatment (e.g., COVID-$19$, Ebola).

• Diagnostic Tests:

  • Drug Tests: Detect drug metabolites (antigens) using specific antibodies on a test strip.

  • Pregnancy Tests: Detect Human Chorionic Gonadotropin (HCG) using antibodies.

  • Antibody Titer: Measures the amount of antibodies in the serum. It helps determine if a patient has currently active infection (IgM) or historical immunity/recovery (IgG via memory cells).

• Convalescent Plasma: Transferring antibodies from a recovered patient to a sick patient, a technique used since the Spanish Flu of $1919$.