2775_2025_IMMUNE GZ

The Kiss of Death | Christina Trambas & Eric Vivier

THE IMMUNE SYSTEM

The Three Lines of Defense

1. Physical Barriers

2. Innate Immune Response

   • Mediated by:

     • Granulocytes

     • Macrophages and Dendritic Cells (DCs)

       • Cytokine secretion

       • Phagocytosis

     • Natural Killer (NK) cells

       • Killing of virus-infected cells and cancer cells

     • Complement

     • Interferon

3. Adaptive Immune Response

   • Mediated by:

     • B cells

       • Antibody production

       • Immunity acquisition

     • T cells

       • Killing of virus-infected cells and cancer cells

       • Regulation of immune response

     • Antibodies

     • Complement

1. Physical Barriers

• Types of Barriers:

  • Physical: Intact skin

  • Mechanical: Mucus and cilia in trachea and lung; mucus and cilia in nasopharynx

  • Chemical: Stomach acidity, Fatty acids from skin glands

• Commensals:

  • Symbiotic (beneficial) bacteria

  • Live in a mutually beneficial relationship with the host, tolerated by our immune system

  • Outnumber human cells tenfold, contribute to gut microbiome stability

  • Commensals in females contribute through an acidic microenvironment

2. The Microbiome

• Composed of ~100 trillion symbiotic microbes (bacteria, fungi, viruses)

• First Colonization:

  • Begins at birth, stabilizes by age three

  • Leads to T cell training for tolerance of friendly microbes

  • Failure of tolerance may lead to Inflammatory Bowel Disease and Atopic Dermatitis

• Functions:

  • Compete with pathogens for resources

  • Produce antimicrobial agents

  • Mediate nutrient and drug metabolism

  • Promote immune tolerance

• Hygiene Hypothesis:

  • Suggests reduced childhood exposure to infections may lead to increased allergies and autoimmune diseases

3. The Innate Immune Response

• Characteristics:

  • Immediate, non-specific response

  • Not remembered by the immune system

• Mechanism:

  • Recognition of pathogen-associated molecular patterns (PAMPs) by leukocyte pattern recognition receptors (PRRs)

  • PAMP/PRR binding activates leukocyte responses

4. Tissue and Pathogen Recognition

• Damage-Associated Molecular Patterns (DAMPs):

  • Indicate tissue damage (e.g., fibrin, collagen)

• PAMPs:

  • Indicate bacterial invasion (e.g., bacterial toxins, cell wall components)

• Chemotaxins:

  • Attract leukocytes to the infection site

  • Secrete chemotaxic cytokines

5. Chemicals of the Innate Immune Response

Functional Classes of Chemicals

• Chemotaxins: Molecules attracting phagocytes

• Opsonins: Coat pathogens for recognition by phagocytes

• Pyrogens: Fever-inducing substances

Specific Chemicals and Their Functions

• Acute Phase Proteins: Enhance inflammatory response

• Bradykinin: Stimulates pain, induces vasodilation

• Complement: Acts as opsonins, cytolytic agents, mediators of inflammation

• C-reactive Protein: Activates complement cascade

• Granzymes and Perforin: Induce apoptosis in infected cells

6. Phagocytosis and NK Cell Activation

A. Phagocytosis

• Mediated by neutrophils, macrophages, and DCs

• Involves ingestion of foreign particles

• Some bacteria can evade recognition through surface masking

B. NK Cell-Induced Apoptosis

• Mediated by NK cells

• Recognize cells with low MHC-I levels, signaling viral infection

• Trigger apoptosis via cytotoxic granules

7. Major Histocompatibility Complex (MHC)

• Encoded by genes of MHC; highly polymorphic

• MHC proteins display fragments of foreign proteins for T cell recognition

• MHC-I: present on all cells; MHC-II: present on antigen-presenting cells (APCs)

8. Bacteria vs. Viruses

Bacteria

• Cells, surrounded by cell wall, can survive indepedently

• Single circular DNA chromosome, susceptible to antibiotics

Viruses

• Not cells, require host to reproduce

• Nucleic acid core in protein capsid; treated with antiviral drugs only

9. Activation of T Cells

• Naive T lymphocytes and their activation

• Produce cytotoxic, helper, and regulatory T cells after antigen exposure

10. Antibody Function and Immunity

• Antibodies produced by activated B cell clones

• Distinction between active immunity (own antibodies) and passive immunity (transferred antibodies)

11. Vaccination and Immune Memory

• Primary vs. Secondary Immune Response

  • Memory cells created via vaccination lead to quicker and stronger responses to pathogens

12. Conclusion

• Importance of adaptive immunity and functions of MHC, cytotoxic T cells, and antibodies in fighting infections.