11.01 Antibodies & Blood Groups

Antibody Basics

Antibodies (Immunoglobulins):

• Definition: Glycoproteins produced by B lymphocytes (a type of white blood cell) that specifically recognize and bind to antigens.
• Structure: Typically Y-shaped molecules composed of four polypeptide chains (two heavy and two light chains) with variable regions that determine antigen specificity.
• Function:
  • Recognition: Bind to specific epitopes on antigens, marking them for destruction.
  • Neutralization: Prevent pathogens or toxins from interacting with host cells.
  • Opsonization: Enhance phagocytosis by tagging antigens for immune cells.
  • Complement Activation: Initiate the complement cascade, leading to the lysis of pathogens.

Structure of Antibodies

• Specificity: The unique sequence of amino acids in the variable region creates a specific three-dimensional shape tailored to bind a particular antigen. This specificity is achieved through interactions between the antigen and the antibody’s R groups (side chains).

Basic Composition

• Globular Glycoproteins: Antibodies are globular (spherical) proteins with attached carbohydrate groups, making them glycoproteins.
• Quaternary Structure: They possess a quaternary structure, meaning they are composed of multiple polypeptide chains assembled together.

Polypeptide Chains

• Heavy Chains: Each antibody has two identical heavy chains.
• Light Chains: Each antibody also has two identical light chains.
• Disulfide Bridges: The heavy and light chains are interconnected by disulfide bonds, stabilizing the overall structure.

Y-Shaped Structure

• Overall Shape: The assembly of these chains forms a characteristic Y-shaped molecule.
• Regions of the Y-Shape:
  • Constant Region (Lower Part of the Y):
    • Uniformity: This region has a consistent amino acid sequence across all antibodies of the same class.
    • Function: It binds to receptors on immune cells like phagocytes, macrophages, and neutrophils.
    • Class Determination: The constant region defines the class of the antibody (e.g., IgM, IgG, IgA, IgE).
  • Variable Region (Upper Part of the Y):
    • Diversity: This region varies among different antibodies, allowing for the specific recognition of diverse antigens.
    • Binding Sites: Each antibody has two identical binding sites within the variable region, formed by both light and heavy chains.

Antibody Mechanisms

1. Viral Inhibition: Antibodies prevent viruses from binding to or damaging host cells.
2. Reduced Bacterial Mobility: Antibodies bind to bacterial flagella, limiting movement and aiding phagocytosis.
3. Agglutination: Causes clumping of bacteria, reducing their spread.
4. Bacterial Lysis: Some antibodies create pores in bacterial cell walls, leading to cell burst due to osmotic pressure.
5. Enhanced Phagocytosis: Antibodies coat pathogens, making them easier for phagocytes to ingest via receptor binding.
6. Antitoxin Action: Specialized antibodies (antitoxins) neutralize bacterial toxins.

Immune Responses and Immunological Memory

• Secondary Immune Response: Faster, stronger response due to memory B cells. Leads to rapid antibody production and higher antibody levels, often preventing symptoms.
• Primary Immune Response: Initial response to a specific antigen; slow due to low specific B cell count.

Cell Surface Antigens

Definition:

• Cell Surface Antigens: Molecules present on the surface of cells that are unique to each individual or organism. They include proteins and carbohydrates that serve as markers distinguishing self from non-self.

Role in Immunity:

• Self vs. Non-Self Recognition:
  • Self Antigens: Recognized by the immune system as part of the body, preventing an immune response.
  • Non-Self Antigens: Recognized as foreign, triggering an immune response.
• Immune Tolerance: The immune system does not typically produce antibodies against self antigens, avoiding autoimmunity.
• Cross-Reactivity: When antigens from another individual (e.g., in blood transfusion) are introduced, they can trigger an immune response.

Example: ABO Blood Group Antigens

• ABO System: Determines blood types based on the presence of specific carbohydrate antigens on red blood cells (RBCs).
  • Blood Group A: Possesses the A antigen (a specific carbohydrate structure) on RBCs.
  • Blood Group B: Possesses the B antigen.
  • Blood Group AB: Possesses both A and B antigens.
  • Blood Group O: Possesses neither A nor B antigens.

ABO Blood Group System

Blood Group A:

• Antigens: Contains A-specific carbohydrate chains attached to glycolipids and glycoproteins on RBC surfaces.
• Antibodies: Naturally occurring anti-B antibodies in the plasma.

Immune Reaction in Blood Transfusion:

• Incorrect Transfusion Example:
  • Scenario: Transfusing blood group A to a blood group B recipient.
  • Immune Response: The recipient’s anti-A antibodies recognize the A antigens on the transfused RBCs as foreign, leading to agglutination (clumping) and hemolysis (destruction) of RBCs.
• Correct Transfusion Example:
  • Scenario: Transfusing blood group B to a blood group B recipient.
  • Outcome: The recipient’s immune system recognizes the B antigens as self, preventing an immune reaction.

Why Type B Blood Isn’t Given to Type A Individuals:

• Reason: Blood group A individuals possess anti-B antibodies. Introducing type B blood would result in these antibodies attacking the foreign B antigens, causing an immune rejection.

Immune Response Overview

Lymphocytes’ Role:

• B Lymphocytes (B Cells):
  • Function: Produce antibodies specific to antigens encountered.
  • Activation: Require antigen binding and helper T cell signals for activation and differentiation into plasma cells.
• T Lymphocytes (T Cells):
  • Helper T Cells (CD4+): Assist in activating B cells and other immune cells.
  • Cytotoxic T Cells (CD8+): Directly kill infected or cancerous cells presenting foreign antigens.

Immune Mechanisms:

• Humoral Immunity: Mediated by antibodies produced by B cells, targeting extracellular pathogens and toxins.
• Cell-Mediated Immunity: Involves T cells targeting infected cells and coordinating the immune response.

Differences Between Antibodies and Antibiotics

Self vs. Non-Self Recognition in the ABO System

Mechanism:

• Self Recognition:
  • The immune system identifies its own cell surface antigens (e.g., A or B antigens) as self.
  • Prevents the production of antibodies against these antigens.
• Non-Self Recognition:
  • Introduction of foreign antigens (e.g., from a different blood type) is recognized as non-self.
  • Triggers the production of specific antibodies against these antigens.

Example:

• Blood Group A Individuals:
  • Self Antigen: A antigen on their RBCs.
  • Non-Self Antigen: B antigen from another blood type.
  • Immune Response: Presence of anti-B antibodies that react against B antigens.

Key Terms

• Antibody (Immunoglobulin): A glycoprotein produced by B lymphocytes that specifically binds to an antigen.
• Antigen: A molecule capable of inducing an immune response, typically a protein or polysaccharide on pathogens.
• Lymphocytes: White blood cells involved in the adaptive immune response, including B cells and T cells.
• Humoral Immunity: Immune response mediated by antibodies in body fluids.
• Cell-Mediated Immunity: Immune response involving T cells that target infected or abnormal cells.
• Phagocytes: Immune cells (e.g., macrophages, neutrophils) that engulf and digest pathogens and debris.
• Agglutination: Clumping of cells (e.g., RBCs) caused by antibodies binding to antigens.
• Hemolysis: Destruction of red blood cells, often resulting from an immune reaction.
• Opsonization: Process by which antibodies mark pathogens for ingestion and destruction by phagocytes.
• Complement System: A group of proteins that assists antibodies in clearing pathogens through lysis, opsonization, and inflammation.

Additional Notes:

Monoclonal vs. Polyclonal Antibodies:

• Monoclonal Antibodies: Identical antibodies produced by a single B cell clone, specific to one epitope.
• Polyclonal Antibodies: A mixture of antibodies produced by different B cell clones, targeting multiple epitopes on the same antigen.

Antibody Structure and Classes:

• IgG: Most abundant, provides long-term immunity, crosses the placenta.
• IgM: First antibody produced in response to an infection.
• IgA: Found in mucosal areas, such as the gut, respiratory tract, and saliva.
• IgE: Involved in allergic reactions and defense against parasites.
• IgD: Functions mainly as a receptor on B cells.

Blood Transfusion Compatibility:

• Importance of cross-matching blood before transfusion to ensure compatibility.
• Understanding of Rh factor (positive/negative) in addition to ABO blood group.

Immune System Disorders:

• Autoimmune Diseases: Result from the immune system mistakenly targeting self-antigens.
• Immunodeficiencies: Conditions where the immune system is less effective, increasing susceptibility to infections.