Unit 9

UNIT 9: IMMUNOLOGY - INNATE AND NONSPECIFIC

Authors

• Dr. Hemangi Patil, Ph.D.

• Dr. Yasser Saad, Ph.D.

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LEARNING OBJECTIVES

• Define Immunology: The study of the immune system, including its structure, function, and processes that defend against disease.

• List the Three Lines of Host Defenses: 1) First line: physical and chemical barriers; 2) Second line: innate immune responses; 3) Third line: adaptive immunity.

• Explain Role of Normal Microbiota: Normal microbiota help shape immune responses and limit pathogen colonization by occupying niches, competing for nutrients, and producing antimicrobial substances.

• Identify Components of the First Line of Defense: Includes skin, mucosal membranes, and secretions such as saliva and tears.

• List Physical Barriers: Skin, mucous membranes, and other anatomical structures.

• List Nonspecific Chemical Defenses: Antimicrobial peptides, enzymes in saliva, lysozyme, stomach acid.

• Explain Genetics in Susceptibility: Genetic factors can influence the effectiveness of immune responses, leading to varying susceptibility to infections.

• Factors Affecting the First Line of Defense: Age, nutritional status, and overall health can impact the efficacy of the barrier defenses.

• Identify and Explain Systems Involved in Immune Defenses: Involves the lymphatic system, blood components, and cellular responses.

• Explain the Lymphatic System and Organs: Includes lymph nodes, spleen, thymus, and the network of lymphatic vessels.

INNATE DEFENSES

• Innate Defenses (Nonspecific): General defense mechanisms that respond to pathogens in a generic manner, lacking specificity.

• Adaptive/Acquired Defenses (Specific): Tailored immune response with memory for specific pathogens.

Three Lines of Defense

1. First Line of Defense:
      - Barrier Defenses: Prevent microbes from entering sterile body compartments.

2. Second Line of Defense:
      - Cellular and Molecular Defenses: Activated when microbes bypass the first line.

3. Third Line of Defense:
      - Specific Immune Responses: B and T lymphocytes target specific pathogens.

First Line of Defense Components

• Tears, Saliva, Mucus, and Breast Milk:
    - Contain lysozyme which kills bacteria.

• Antimicrobial Peptides:
    - Found in earwax, mucus, and saliva; disrupt pathogen membranes.

• Stomach Acid and Intestinal Enzymes:
    - Limit pathogens in the gastrointestinal tract.

• Physical Actions:
    - Tears rinse microbes.
    - Saliva limits microbial attachment.
    - Mucus in the respiratory tract traps invaders, moved by cilia.

• Skin Defenses:
    - Low pH and sweat deter many pathogens.
    - Structural barriers include intact skin and epithelial cells with keratin.

SECOND LINE OF DEFENSE - THE LYMPHATIC SYSTEM

Primary Lymphoid Organs

• Thymus: Site of T-cell maturation.

• Bone Marrow: Site of B-cell maturation.

Secondary Lymphoid Organs

• Lymph Nodes: Concentrated areas of immune cells.

• Spleen: Filters blood and mounts immune responses.

• Mucosa-Associated Lymphoid Tissue (MALT): Includes Payer's patches and appendix.

SECOND LINE OF DEFENSE - THE BLOOD

Blood Cell Types

• Erythrocytes (Red Blood Cells): Carry oxygen and carbon dioxide, no immune function.

• Leukocytes (White Blood Cells): Key in immune defense; various types with specific functions.
    - Granulocytes:
      - Neutrophils: Multilobed nucleus, major role in inflammation and phagocytosis.
      - Eosinophils: Bi-lobed nucleus, toxic to parasites.
      - Basophils: Contains histamine and heparin, involved in allergic responses.
    - Agranulocytes:
      - Monocytes: Largest WBCs, mature into macrophages and dendritic cells.
      - Lymphocytes: Include B-cells, T-cells, and Null cells (natural killer).
        - B Lymphocytes: Produce antibodies, involved in humoral immunity.
        - T Lymphocytes: Involved in cell-mediated immunity.
        - Null Cells: Attack and destroy defective host cells.

SECOND LINE OF DEFENSE - INFLAMMATION

Key Components

• Involvement of Neutrophils and Macrophages:
    - Neutrophils initially respond to infection, while macrophages clean up and process antigens.

Characteristics and Causes of Inflammation

• Signs of Inflammation: Tumor (swelling), Calor (heat), Rubor (redness), Dolor (pain).

• Early Events: When tissue is damaged, inflammatory mediators are released (e.g., histamine, bradykinin).

Functions of Inflammatory Components

• Cytokines: Regulate immune responses and facilitate communication among immune cells.

• Fibrin: Localizes pathogens and aids in clot formation.

• Complement Proteins: Enhance inflammation, opsonization, and phagocytosis.

• Neutrophils and Macrophages: Critical for destroying pathogens and facilitating healing.

• Fever-Inducing Pyrogens: Elicit systemic responses.

SECOND LINE OF DEFENSE - PHAGOCYTOSIS

Phagocytosis Steps

1. Diapedesis: Movement of phagocytes to the site of infection.

2. Attachment and Ingestion: Phagocytes bind and ingest pathogens.

3. Phagosome Formation: Enclosing pathogen in vesicles.

4. Phagolysosome Formation: Fusion with lysosomes for digestion.

5. Destruction and Antigen Presentation: Pathogen parts are presented to T-cells.

SECOND LINE OF DEFENSE - FEVER

Fever Ranges

• Low-Grade Fever: $37.7°C ext{ to } 38.3°C ext{ (100°F to 101°F)}$

• Moderate Fever: $38.8°C ext{ to } 39.4°C ext{ (102°F to 103°F)}$

• High Fever: $40.0°C ext{ to } 41.1°C ext{ (104°F to 106°F)}$

• Fatal Fever: >43.0°C ext{ (>109.4°F)}

SECOND LINE OF DEFENSE - ANTIMICROBIAL PROTEINS

Overview of Antimicrobial Substances

• Lysozyme: Causes lysis of bacterial cell walls.

• Complement Proteins: Induce cell lysis and inflammation.

• Lactoferrin and Transferrin: Bind iron to inhibit microbial growth.

• Interferons: Defense against viral infections; trigger apoptotic mechanisms in infected cells.

Complement System Pathways

• Classical Pathway: Activated by antigen-antibody complexes to form C3 convertase.

• Alternative Pathway: Initiates without antibodies, stabilizing factors on microbial surfaces.

SECOND LINE OF DEFENSE - ANTIMICROBIAL PEPTIDES

• Mechanism of Action: Binds to microbial cell walls, causing membrane lysis and inhibiting intracellular function.

• Effect on Immune Responses: Internalized peptides activate immune cells and regulate inflammation.

Learning Objectives

• What is Immunology?
  The study of the immune system that defends against diseases.

• Three Lines of Host Defenses:

  1. First Line: Physical and chemical barriers (like skin and saliva).

  2. Second Line: Innate immune responses (body's immediate reaction).

  3. Third Line: Adaptive immunity (targeted attack with memory).

• Role of Normal Microbiota:
  Good bacteria protect us by limiting harmful germs.

• First Line of Defense Components:
  Includes skin, mucous membranes, and secretions (like tears).

• Physical Barriers:
  Skin and mucous membranes block germs.

• Chemical Defenses:
  Antimicrobial substances in saliva and stomach acid fight germs.

• Genetic Factors:
  Your genes affect how well you fight infections.

• Factors Affecting Defense:
  Age and health influence how strong your defenses are.

• Immune Defense Systems:
  Involves the lymphatic system and blood cells.

• Lymphatic System Organs:
  Includes lymph nodes, spleen, and thymus.

Innate Defenses

• Innate Defenses (Nonspecific):
  General reactions to germs without targeting specific ones.

• Adaptive/Acquired Defenses (Specific):
  Customized responses with a memory for specific germs.

First Line of Defense Components

• Tears and Saliva:
  Contain lysozyme to kill bacteria.

• Antimicrobial Peptides:
  Found in earwax and mucus; they disrupt germs.

• Stomach Acid:
  Helps kill pathogens in food.

• Physical Actions:

  • Tears wash away germs.

  • Saliva prevents bacteria from sticking.

  • Mucus traps invaders in the lungs.

• Skin Defenses:
  Skin's low pH and sweat repel many germs.

Second Line of Defense - Lymphatic System

Primary Organs

• Thymus: Where T-cells mature.

• Bone Marrow: Where B-cells mature.

Secondary Organs

• Lymph Nodes: Collect immune cells.

• Spleen: Filters blood and helps the body fight germs.

• MALT: Includes areas like the appendix that help with immunity.

Second Line of Defense - Blood

Blood Cell Types

• Erythrocytes: Red blood cells, no immune function.

• Leukocytes: White blood cells, crucial for fighting infections.

  • Granulocytes:

  • Neutrophils: Major players in inflammation.

  • Eosinophils: Attack parasites.

  • Basophils: Involved in allergies.

  • Agranulocytes:

  • Monocytes: Become macrophages to clean up germs.

  • Lymphocytes: Include B-cells (make antibodies) and T-cells (attack infected cells).

Second Line of Defense - Inflammation

Key Components

Neutrophils and macrophages are first responders to infection.

Signs of Inflammation

• Tumor (swelling)

• Calor (heat)

• Rubor (redness)

• Dolor (pain)

Functions of Inflammation

• Cytokines: Help immune cells communicate.

• Complement Proteins: Assist in the immune response.

Second Line of Defense - Fever

• Fever Levels:

  • Low: $37.7°C ext{ to } 38.3°C$

  • Moderate: $38.8°C ext{ to } 39.4°C$

  • High: $40.0°C ext{ to } 41.1°C$

  • Fatal: >43.0°C

Antimicrobial Proteins

• Overview:

  • Lysozyme: Destroys bacterial walls.

  • Complement Proteins: Cause cell lysis.

  • Lactoferrin: Binds iron to stop bacteria.

  • Interferons: Protect against viruses.