Immunity: Innate & Adaptive Immune Responses

Introduction to Immunology

Immunology is the study of the physiological defenses by which the body recognizes 'self' from 'non-self' (foreign elements). Its primary functions include destroying or neutralizing foreign matter, whether living or non-living.

Primary Functions of Immune Defenses

1. Protection Against Infectious Agents: This includes microbes, viruses, bacteria, fungi, and parasites.

2. Isolation or Removal of Toxic Substances: Clearing debris after injury.

3. Destruction of Cancer Cells: Eliminating aberrant cells that arise in the body.

Immune cells recognize antigens, which are molecules that trigger an immune response.

Categories of Immune Defenses

Immune defenses are broadly divided into two major categories:

1. Innate Immune Response:

   • Non-specific response: Defends against foreign substances or cells without having to recognize specific antigens.

2. Adaptive Immune Response:

   • Specific response: Depends on specific recognition by lymphocytes (a type of white blood cell) of the substance or cell to be attacked. This response is highly targeted against a particular antigen.

Microorganism/Human Relationship Terminology

• Host: Any organism capable of supporting the growth of another organism. In human physiology, we are the host.

• Colonization: The act of establishing a presence, a necessary step for infection. For example, foreign invaders like viruses or bacteria.

• Infection: The presence and multiplication within a host of another organism, which subsequently causes injury to the host.

• Virulence: The disease-producing potential of a microorganism. High virulence indicates a strong ability to cause harm and disease.

• Microorganisms: Cells like bacteria can have counts similar to the host. They maintain multiple relationships with our microbiome.

• Microbiome: The collection of microorganisms that live in our bodies.

Relationships within the Microbiome

• Commensalism: One species benefits, while the other is unaffected.

• Mutualism: Both species benefit from the relationship. An example is Vitamin-K producing bacteria in the gut.

These relationships can be breached by injury, allowing microorganisms to leave their normal sites and cause infection elsewhere.

Infectious Disease and Opportunistic Pathogens

• Infectious Disease: Occurs when the host sustains injury or pathological damage in response to the infecting organism.

• Opportunistic Pathogen: A microorganism capable of producing an infectious disease when the host's health and immunity are compromised by illness, malnutrition, or medical therapy.

  • Examples:

    • Staphylococcus aureus: A normal flora on human skin that can cause infections if the skin barrier is broken or immunity is low.

    • Herpes simplex virus (HSV): In most individuals with a healthy immune system, HSV remains in an inactive (latent) state.

Innate Immunity: First Line of Defense

This involves physical, mechanical, and biochemical barriers, along with molecular and cellular components.

Physical & Mechanical Barriers

• Skin: A primary physical barrier.

• Linings of Organ Systems: Gastrointestinal, genitourinary, and respiratory tracts.

  • Sloughing off cells: A process of barrier maintenance.

  • Mucus & cilia: Aid in separation and removal of foreign particles.

  • Coughing & sneezing: Protective reflexes in the respiratory system.

Biochemical Barriers

• Secretions: Saliva, tears, earwax, sweat, and sebum, which contain protective substances.

• Antimicrobial Peptides: Directly destroy or inhibit microbial growth.

• Normal Bacterial Flora: Competitively inhibit the growth of pathogenic microorganisms.

Molecular & Cellular Defenses

• Molecular Defenses: Such as the complement system (a cascade of proteins).

• Cellular Defenses: Include phagocytic cells and Natural Killer (NK) cells.

Innate Immunity: Second Line = Innate Inflammatory Response

Inflammation is a local response to injury or infection, serving key functions to destroy foreign invaders and facilitate tissue repair.

Causes of Innate Inflammatory Response

It can be caused by a variety of agents, including infection, mechanical damage, ischemia, nutrient deprivation, temperature extremes, and radiation.

Local Manifestations (The $5$ Cardinal Signs of Inflammation)

1. Redness (rubor)

2. Heat (calor)

3. Swelling (tumor)

4. Pain (dolor)

5. Loss of Function (functio laesa)

Inflammatory conditions are commonly named by adding the suffix –itis to the affected organ or system (e.g., Appendicitis, Pericarditis).

Inflammation is associated with numerous diseases, including atherosclerosis, obesity, diabetes, cancer, stroke, and asthma.

Goals of Inflammation

• Increase blood flow: To the site of injury.

• Alert products of healing: To attend to the site of injury.

• Remove injured tissue: And prepare the site for healing.

• Establish a physical barrier: Against the spread of infection and further damage.

• Interact with components of the adaptive immune system.

Stages of Inflammation

Inflammation proceeds in two main stages:

1. Vascular Stage:

   • Increased blood flow (vasodilation).

   • Structural changes, including increased vascular permeability, allowing cells to leave the blood vessel.

2. Cellular Stage:

   • Migration of leukocytes (white blood cells) from the microcirculation.

   • Accumulation of leukocytes at the site of injury or infection.

The process ends with leukocyte activation and resolution.

Innate Immunity Cells

Phagocytic Leukocytes (Antigen-Presenting Cells - APCs)

These cells engulf and digest foreign particles and present antigens.

• Neutrophils:

  • A granulocyte, containing specific cytoplasmic granules and a multi-lobed nucleus.

  • Constitute up to $80 \%$ of white blood cells (WBC).

  • The first responders to infection or injury.

• Monocytes/Macrophages:

  • Monocytes circulate in the blood (constituting $3 - 8 \%$ of WBC).

  • They differentiate into Macrophages once they migrate into tissues.

• Dendritic Cells:

  • Constitute $0.2 - 0.7 \%$ of WBC.

  • Present in tissues and are highly efficient at antigen presentation.

Other Innate Immune Cells

• Natural Killer (NK) Cells:

  • Recognize altered host molecules (e.g., stress proteins on infected or cancerous cells).

  • Kill virally-infected or cancer cells without prior sensitization.

• Mast Cells:

  • A granulocyte.

  • Secrete histamine, which enhances the inflammatory response.

  • Histamine produces vascular vasodilation and increases permeability, promoting leukocyte exit into tissues.

Innate Immunity: Role of Cytokines

Cytokines are protein messengers primarily secreted by immune cells. They are crucial for communication within the immune system.

• Links Immune Components: They link different components of the immune system together.

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