11.09 Chapter Summary

Phagocytes are specialized white blood cells that protect the body by engulfing and digesting harmful particles, bacteria, and dead or dying cells. The two primary types of phagocytes are macrophages and neutrophils.

Macrophages

• Origin & Location: Derived from monocytes in the bloodstream; reside in tissues throughout the body.
• Function:
  • Phagocytosis: Engulf and digest pathogens and debris.
  • Antigen Presentation: Processed antigens are presented on their surface to T-lymphocytes, initiating the adaptive immune response.
  • Secretion of Cytokines: Release signaling molecules that modulate immune responses.

Neutrophils

• Origin & Location: Produced in the bone marrow; circulate in the bloodstream and migrate to sites of infection.
• Function:
  • Rapid Response: First responders to bacterial infections.
  • Phagocytosis: Engulf and destroy pathogens.
  • Degranulation: Release enzymes and antimicrobial substances to kill ingested microbes.

Phagocytosis Process

• Chemotaxis: Movement of phagocytes towards the site of infection in response to chemical signals.
• Recognition & Attachment: Phagocytes recognize pathogens through receptors that bind to antigens or opsonins (e.g., antibodies).
• Engulfing: The pathogen is enclosed within a phagosome.
• Digestion: The phagosome fuses with a lysosome, forming a phagolysosome where the pathogen is destroyed by enzymes and reactive oxygen species.
• Exocytosis: Indigestible debris is expelled from the phagocyte.

Definition of Antigen

• Antigen: Any substance that is recognized by the immune system as foreign and can trigger an immune response. Typically, proteins or polysaccharides found on the surface of pathogens like bacteria, viruses, or fungi.

Self Antigens vs. Non-Self Antigens

• Self Antigens:
  • Definition: Molecules present on the body’s own cells.
  • Recognition: Normally ignored by the immune system to prevent autoimmune reactions.
  • Role in Immune Tolerance: Ensures that immune responses are targeted only against foreign invaders.
• Non-Self Antigens:
  • Definition: Molecules found on pathogens or foreign cells.
  • Recognition: Identified by the immune system as targets for attack.
  • Examples: Bacterial surface proteins, viral coat proteins, pollen proteins.

Key Difference: Self antigens are part of the body’s own cells and tissues, whereas non-self antigens originate from outside the body and are recognized as foreign.

The primary immune response is the body’s initial reaction to encountering a pathogen. It involves several key players and a sequence of events leading to the elimination of the antigen.

Sequence of Events

• Antigen Entry: Pathogen enters the body and is recognized as foreign.

Phagocytosis by Macrophages:

• Role: Engulf pathogens and present antigens on their surface to activate lymphocytes.

Activation of B-Lymphocytes:

• B-Lymphocytes: Mature in bone marrow; responsible for antibody production.

Activation Process:

• Binding of antigens to B-cell receptors.
• Interaction with T-helper cells for full activation.
• Plasma Cells: Differentiated B-cells that produce and secrete large quantities of antibodies specific to the antigen.

Activation of T-Lymphocytes:

T-Helper Cells (CD4⁺):

• Role: Activate B-lymphocytes and other immune cells by secreting cytokines.
• Function: Enhance the immune response by aiding in the activation and proliferation of other immune cells.

T-Killer Cells (Cytotoxic T-Cells, CD8⁺):

• Role: Destroy infected host cells presenting the antigen.
• Function: Induce apoptosis (programmed cell death) in infected cells to prevent pathogen replication.

Clonal Expansion:

• Process: Activated B and T cells proliferate to increase the number of effector cells specific to the antigen.

Effector Phase:

• Antibodies: Neutralize pathogens, opsonize for enhanced phagocytosis, and activate the complement system.
• Cytotoxic T-Cells: Eliminate infected cells.

Contraction Phase:

• Apoptosis of Excess Cells: After the pathogen is cleared, most effector cells die off.
• Formation of Memory Cells: A small population remains for faster response upon re-exposure.

Memory Cells are long-lived B and T lymphocytes that are formed during the primary immune response. They play a crucial role in the secondary immune response and provide long-term immunity.

Secondary Immune Response

• Rapid and Robust: Upon re-exposure to the same antigen, memory cells are quickly activated, leading to a faster and more effective immune response.
• Higher Affinity Antibodies: Memory B-cells produce antibodies with greater specificity and affinity for the antigen.
• Greater Number of Effector Cells: More plasma cells and memory T-cells are generated, enhancing the response.

Long-Term Immunity

• Duration: Memory cells can persist for years or even decades, providing long-lasting protection against previously encountered pathogens.
• Mechanism:
  • Quick Activation: Memory B and T cells recognize the antigen immediately upon re-infection.
  • Efficient Clearance: Rapid production of antibodies and activation of cytotoxic cells swiftly eliminate the pathogen.
• Vaccination: Mimics natural infection by introducing antigens without causing disease, leading to the formation of memory cells and long-term immunity.

Importance of Memory Cells

• Prevention of Disease Recurrence: Ensures that the body can effectively combat pathogens upon subsequent exposures.
• Basis for Vaccines: Understanding memory cell formation is essential for developing effective vaccination strategies that provide long-term protection.

Key Terms to Remember

• Phagocytosis: The process by which phagocytes engulf and digest pathogens.
• Antigen: A substance that induces an immune response.
• Self Antigen: Molecules naturally present in the body, not targeted by the immune system.
• Non-Self Antigen: Foreign molecules recognized and targeted by the immune system.
• B-Lymphocytes (B-Cells): Cells responsible for producing antibodies.
• T-Lymphocytes (T-Cells): Cells that coordinate the immune response and kill infected cells.
• T-Helper Cells: Activate other immune cells.
• T-Killer Cells: Destroy infected host cells.
• Plasma Cells: Activated B-cells that secrete antibodies.
• Memory Cells: Long-lived cells that provide rapid and effective responses upon re-exposure to antigens.

Structure of Antibodies:

• Basic Unit: Y-shaped glycoprotein composed of four polypeptide chains:
  • 2 Heavy Chains: Longer chains with a constant region.
  • 2 Light Chains: Shorter chains with variable regions.
• Regions:
  • Variable Regions (Fab):
    • Located at the tips of the Y.
    • Responsible for antigen binding; highly specific.
  • Constant Region (Fc):
    • Determines the antibody’s class (e.g., IgG, IgM).
    • Interacts with cell receptors and complement proteins.

Functions of Antibodies:

• Antigen Binding: Specific binding to unique antigens on pathogens.
• Neutralization: Block pathogens from entering host cells.
• Opsonization: Mark pathogens for phagocytosis by immune cells.
• Activation of Complement System: Initiates a cascade that destroys pathogens.
• Antibody-Dependent Cellular Cytotoxicity (ADCC): Recruits natural killer cells to destroy infected cells.

Key Points:

• Each antibody is specific to a particular antigen.
• The structure allows flexibility and specificity in immune responses.

Overview:

• Purpose: To produce large quantities of identical (monoclonal) antibodies targeting a specific antigen.

Steps Involved:

1. Immunization:
   • Inject a mouse (or other suitable animal) with the desired antigen to elicit an immune response.
2. Cell Fusion:
   • Extract B-lymphocytes (antibody-producing cells) from the spleen.
   • Fuse these B-cells with myeloma (cancerous) cells using a fusion agent like polyethylene glycol.
3. Selection:
   • Grow the hybrid cells (hybridomas) in HAT medium (hypoxanthine, aminopterin, thymidine) to select fused cells.
   • Unfused myeloma and B-cells do not survive in HAT medium.
4. Cloning:
   • Isolate single hybridoma cells to grow into clonal cell lines, each producing one type of monoclonal antibody.
5. Harvesting Antibodies:
   • Cultivate hybridomas in culture or grow them in mice (ascites production) to collect monoclonal antibodies.

Advantages:

• Produces highly specific antibodies.
• Unlimited supply of identical antibodies.

Applications:

• Diagnostic tests, research, and therapeutic treatments.

Diagnosis:

• Diagnostic Tests:
  • ELISA (Enzyme-Linked Immunosorbent Assay): Uses monoclonal antibodies to detect the presence of antigens (e.g., HIV, COVID-19).
  • Western Blotting: Identifies specific proteins using monoclonal antibodies.
  • Immunohistochemistry: Locates antigens in tissue samples for cancer diagnosis.

Treatment:

• Therapeutic Agents:
  • Targeted Therapy: Monoclonal antibodies can target specific cancer cells (e.g., Rituximab for lymphoma).
  • Autoimmune Diseases: Treatments like infliximab target inflammatory cytokines.
  • Infectious Diseases: Monoclonal antibodies can neutralize pathogens (e.g., Ebola, COVID-19).

Mechanisms:

• Blocking Receptors: Prevents pathogen entry or cell signaling (e.g., Herceptin blocks HER2 receptors in breast cancer).
• Recruiting Immune Cells: Enhances destruction of target cells.
• Delivering Cytotoxic Agents: Attached toxins or radioactive substances kill target cells.

Advantages:

• High specificity reduces side effects.
• Can be engineered for improved efficacy and reduced immunogenicity.

Active vs. Passive Immunity

Active Immunity:

• Definition: Immunity developed through exposure to an antigen, leading to the body producing its own antibodies.
• Acquisition:
  • Natural Active Immunity: Resulting from infection with a pathogen (e.g., recovering from chickenpox).
  • Artificial Active Immunity: Resulting from vaccination (e.g., measles vaccine).
• Characteristics:
  • Long-lasting or permanent.
  • Involves memory cells for faster response upon re-exposure.

Passive Immunity:

• Definition: Immunity acquired by receiving antibodies from an external source.
• Acquisition:
  • Natural Passive Immunity: From mother to fetus via placenta or to infant via breast milk.
  • Artificial Passive Immunity: Through administration of antibody-containing serum (e.g., antivenom).
• Characteristics:
  • Immediate but short-lived (weeks to months).
  • No memory cell formation.

Natural vs. Artificial Immunity

Natural Immunity:

• Definition: Immunity gained through natural exposure to antigens.
• Includes:
  • Natural Active Immunity: From infection.
  • Natural Passive Immunity: From mother to child.

Artificial Immunity:

• Definition: Immunity gained through medical intervention.
• Includes:
  • Artificial Active Immunity: From vaccination.
  • Artificial Passive Immunity: From antibody therapy.

Key Differences:

• Source of Antigens/Antibodies: Natural involves exposure to the actual pathogen; artificial uses vaccines or administered antibodies.
• Duration and Onset: Active immunity takes time to develop but is long-lasting; passive immunity is immediate but temporary.

Components of Vaccines:

• Antigens:
  • Live Attenuated Vaccines: Weakened forms of the pathogen (e.g., MMR vaccine).
  • Inactivated Vaccines: Killed pathogens (e.g., polio vaccine).
  • Subunit Vaccines: Specific parts of the pathogen (e.g., Hepatitis B vaccine).
  • Toxoid Vaccines: Inactivated toxins produced by pathogens (e.g., tetanus vaccine).
  • mRNA Vaccines: Genetic instructions to produce antigens (e.g., some COVID-19 vaccines).

Mechanism of Action:

1. Introduction of Antigen:
   • Mimics natural infection without causing disease.
2. Immune System Activation:
   • B-cells: Recognize antigens and differentiate into plasma cells producing antibodies.
   • T-cells: Helper T-cells assist in activating B-cells; cytotoxic T-cells may be activated against infected cells.
3. Memory Cell Formation:
   • Long-lived B and T cells provide rapid and robust response upon future exposure to the same antigen.

Outcome:

• Long-Term Immunity: Protection against future infections by the same pathogen.
• Herd Immunity: High vaccination rates reduce the overall presence of the pathogen in the population.

Advantages of Vaccination:

• Prevents disease outbreaks.
• Reduces morbidity and mortality.
• Cost-effective public health measure.

Role of Vaccination Programmes:

• Public Health Strategy: Organized efforts to immunize populations.
• Targets High-Risk Groups: Infants, elderly, immunocompromised individuals.
• Scheduled Immunizations: Routine vaccination schedules (e.g., childhood vaccines).

Impact on Disease Control:

• Reduction in Transmission: Fewer susceptible hosts limit pathogen spread.
• Eradication of Diseases: Successful programmes can eliminate diseases (e.g., smallpox eradicated).
• Prevention of Epidemics: Maintained high immunity levels prevent outbreaks.

Examples of Successful Programmes:

• Polio Eradication: Global efforts have reduced cases by over 99%.
• Measles Control: High vaccination coverage has significantly lowered incidence.
• Influenza Vaccination: Annual programmes help control seasonal flu spread.

Challenges:

• Vaccine Hesitancy: Misinformation and fear reduce uptake.
• Logistical Issues: Ensuring vaccine availability and distribution.
• Mutation of Pathogens: May require updated vaccines (e.g., seasonal flu).

Strategies to Enhance Programmes:

• Public Education: Increase awareness of vaccine benefits.
• Accessibility: Make vaccines easily available and affordable.
• Monitoring and Surveillance: Track vaccination rates and disease incidence.

Benefits:

• Individual Protection: Prevents individuals from contracting diseases.
• Community Protection: Protects those who cannot be vaccinated through herd immunity.
• Economic Savings: Reduces healthcare costs associated with treating diseases.