The Immune System: Innate and Adaptive Defenses

Introduction to the Immune System

The immune system is a functional system that provides resistance to disease by recognizing and eliminating pathogens and abnormal cells. It consists of two main branches: innate (nonspecific) defenses and adaptive (specific) defenses. These systems work together to protect the body from infection and disease.

Innate (Nonspecific) Defenses

Overview of Innate Defenses

Innate defenses are present at birth and provide the first and second lines of defense against pathogens. They respond quickly and non-specifically to a wide range of invaders.

• First line of defense: Surface barriers such as skin and mucous membranes.

• Second line of defense: Internal defenses including phagocytes, natural killer cells, inflammation, antimicrobial proteins, and fever.

First Line of Defense: Surface Barriers

The skin and mucous membranes, along with their secretions, form physical and chemical barriers to most microorganisms. These barriers are essential in preventing pathogen entry.

• Keratin: Provides resistance against acids, alkalis, and bacterial enzymes.

• Mucosae: Line body cavities open to the exterior and trap microorganisms.

Second Line of Defense: Internal Defenses

If pathogens breach surface barriers, the second line of defense is activated. This includes various cells and chemicals that inhibit the spread of invaders and initiate inflammation.

• Phagocytes: White blood cells that ingest and digest pathogens. Main types include neutrophils and macrophages.

• Natural Killer (NK) Cells: Nonphagocytic lymphocytes that kill virus-infected and cancer cells by inducing apoptosis.

• Inflammation: Local tissue response to injury or infection, characterized by redness, heat, swelling, pain, and loss of function.

• Antimicrobial Proteins: Interferons and complement proteins that attack microorganisms or hinder their reproduction.

• Fever: Systemic response that increases body temperature to inhibit pathogen growth and speed up tissue repair.

Phagocytes

Phagocytes are essential for engulfing and destroying pathogens. Neutrophils are the most abundant but short-lived, while macrophages are the main phagocytic cells and can be free or fixed in tissues.

Phagocytosis Process

1. Phagocyte recognizes and adheres to pathogen (often enhanced by opsonization).

2. Cytoplasmic extensions (pseudopods) engulf the particle, forming a phagosome.

3. Phagosome fuses with a lysosome, forming a phagolysosome.

4. Lysosomal enzymes digest the pathogen.

5. Indigestible material is expelled by exocytosis.

Natural Killer (NK) Cells

NK cells patrol the body, targeting cells that lack "self" markers, such as virus-infected or cancerous cells. They induce apoptosis and secrete chemicals that enhance inflammation.

Inflammation

Inflammation is triggered by tissue injury and serves to prevent the spread of damaging agents, dispose of debris, alert the adaptive immune system, and set the stage for repair. The five cardinal signs are redness, heat, swelling, pain, and loss of function.

Inflammatory Chemicals

Phagocyte Mobilization

1. Leukocytosis: Neutrophils enter blood from bone marrow.

2. Margination: Neutrophils cling to capillary walls.

3. Diapedesis: Neutrophils squeeze out of capillaries into tissues.

4. Chemotaxis: Neutrophils follow chemical signals to the injury site.

Pus and Granulomas

Pus is a mixture of dead neutrophils, tissue cells, and pathogens. Some bacteria resist digestion and can form granulomas—tumor-like masses of infected macrophages surrounded by other immune cells.

Antimicrobial Proteins

Antimicrobial proteins such as interferons and complement proteins enhance innate defenses by attacking microorganisms or hindering their ability to reproduce.

Fever

Fever is a systemic response to infection, mediated by pyrogens that reset the hypothalamic thermostat. Moderate fever helps by sequestering iron and zinc and increasing metabolic rate for repair.

Adaptive (Specific) Defenses

Overview of Adaptive Defenses

The adaptive immune system is specific, systemic, and has memory. It eliminates almost any pathogen or abnormal cell and amplifies the inflammatory response. It is divided into two main branches: humoral (antibody-mediated) and cellular (cell-mediated) immunity.

• Humoral immunity: Mediated by B cells and antibodies; targets extracellular pathogens.

• Cellular immunity: Mediated by T cells; targets intracellular pathogens and abnormal cells.

Antigens

Antigens are substances that provoke an immune response. They are usually large, complex molecules not normally found in the body. Antigens can be complete (immunogenic and reactive) or haptens (incomplete, only immunogenic when attached to body proteins).

• Antigenic determinants: Specific sites on antigens where antibodies or lymphocyte receptors bind.

• Self-antigens (MHC proteins): Unique to each individual; present self or foreign antigens to T cells.

Lymphocytes and Antigen-Presenting Cells (APCs)

Adaptive immunity involves three major cell types:

• B lymphocytes (B cells): Responsible for humoral immunity.

• T lymphocytes (T cells): Responsible for cellular immunity.

• Antigen-presenting cells (APCs): Engulf antigens and present fragments to T cells (e.g., dendritic cells, macrophages, B cells).

Lymphocyte Development, Maturation, and Activation

1. Origin: Both B and T cells originate in red bone marrow.

2. Maturation: B cells mature in bone marrow; T cells mature in thymus. They develop immunocompetence and self-tolerance.

3. Seeding secondary lymphoid organs: Immunocompetent but naïve lymphocytes circulate and colonize secondary lymphoid organs.

4. Antigen encounter and activation: Lymphocytes encounter antigens and become activated.

5. Proliferation and differentiation: Activated lymphocytes proliferate and differentiate into effector and memory cells.

Summary Table: Innate vs. Adaptive Defenses