The Immune System Overview

I. Biological Immunity

• Definition: Structures and processes that defend the body against pathogens, including bacteria, viruses, parasites, and fungi. The immune system plays a crucial role in identifying, neutralizing, and eliminating foreign invaders while distinguishing them from the body’s own tissues.

II. Recognition of Self and Non-Self

• Histocompatibility Antigens:

  • Markers present on the cell membrane that are critical for self-recognition, primarily coded by major histocompatibility complex (MHC) genes.

  • MHC Class I molecules are found on nearly all nucleated cells and present endogenous antigens (from inside the cell) to cytotoxic T cells, while MHC Class II molecules are found primarily on professional antigen-presenting cells (APCs), such as dendritic cells and macrophages, presenting exogenous antigens (from outside the cell) to helper T cells.

  • The variation in these proteins among individuals increases with genetic differences, making MHC a key factor in tissue compatibility for organ transplantation.

III. Types of Immunity

1. Innate/Non-specific Immunity:

   • The body’s immediate and non-specific first line of defense against pathogens.

   • Physical Barriers: Skin and mucous membranes prevent pathogen entry. Secretions (such as lysozyme in tears) contain antimicrobial properties.

   • Cellular Defenses: White blood cells (leukocytes) such as macrophages, neutrophils, and natural killer (NK) cells act quickly upon infection.

2. Specific/Adaptive Immunity:

   • A slower, highly specific response tailored to specific pathogens, relies on the activation of lymphocytes (B and T cells).

3. Active Immunity:

   • Immunity generated through exposure to pathogens or vaccination, leading to the development of memory cells that allow for a rapid response upon re-exposure to the same pathogen.

4. Passive Immunity:

   • Temporary immunity gained through the transfer of antibodies from another individual, such as maternal antibodies transferred through breast milk or immunoglobulin injections.

IV. Innate Immunity Mechanisms

A. PAMPs:

• Pathogen-associated molecular patterns recognized by pattern recognition receptors (PRRs) on immune cells, initiating innate immune responses through inflammation and phagocytosis. These include components like lipopolysaccharides (LPS) from bacterial cell walls and viral RNA.

B. Fever and Inflammatory Response:

• Fever enhances immune function by inhibiting pathogen growth and fostering an environment conducive to recovery. The inflammatory response increases blood flow and attracts immune cells to sites of injury or infection, promoting tissue healing.

C. Interferons:

• Cytokines produced by infected cells that signal neighboring cells to enhance their antiviral defenses. Interferons also activate immune cells such as macrophages and NK cells.

D. Phagocytes:

• Key players in the immune response. Types include:

  • Neutrophils: Rapid responders that ingest and destroy pathogens through phagocytosis and release reactive oxygen species (ROS).

  • Monocytes: Differentiate into macrophages and dendritic cells that process and present antigens to T cells and clean up dead cells.

  • Organ-Specific Phagocytes: Fixed phagocytic cells like Kupffer cells in the liver and microglia in the brain that continuously monitor their respective tissues.

E. Cytokines Activation:

• Cytokines released by activated phagocytes and other immune cells regulate immune responses, mediating communication between cells, and recruiting additional immune cells to sites of infection.

F. Phagocytosis:

• The process involves the engulfing of pathogens, formation of phagosomes, and fusion with lysosomes, resulting in pathogen destruction by enzymes and toxic substances within the immune cells.

V. Inflammation

• Symptoms: Swelling, pus, redness, warmth, and pain are responses that result from the influx of immune cells and increased blood flow to a site of infection or injury. This process also involves the release of inflammatory mediators (like histamines and prostaglandins) and is vital for healing.

VI. Specific Immunity: B and T Lymphocytes

A. B Cells:

• Develop in the bone marrow and are responsible for producing antibodies to neutralize specific antigens. They also develop into memory B cells that provide lasting immunity.

• Antigen Characteristics:

  • Antigenic determinant sites (epitopes) define how an antigen is recognized by antibodies.

B. T Cells:

• Developed in the thymus, they include:

  • Cytotoxic T Cells: Target and kill infected cells directly.

  • Helper T Cells: Stimulate and coordinate the immune response, activating B cells and other immune cells.

  • Regulatory T Cells: Maintain immune tolerance and prevent autoimmunity.

VII. Complement System

A. Overview:

• Comprises a series of serum proteins that enhance ("complement") the ability of antibodies and phagocytic cells to clear pathogens. There are three pathways for activation: classical (antibody-mediated), lectin, and alternative pathways.

B. Functions:

• Includes opsonization (marking pathogens for destruction), recruitment of inflammatory cells, and direct killing of pathogens through the formation of the membrane attack complex.

VIII. T Lymphocyte Activation

A. Development: Mature in the thymus, then travel to peripheral lymphoid organs, such as lymph nodes and spleen, to encounter antigens.B. Memory Cell Formation:

• After primary activation, T cells proliferate and differentiate into effector cells and long-lived memory cells that expedite future responses to the same antigen.

C. Apoptosis:

• A critical regulatory mechanism to terminate the immune response after the pathogen is cleared, preventing tissue damage and autoimmunity through a programmed cell death mechanism.

IX. Immunologically Privileged Sites

• Certain areas, such as the eyes, brain, and testes, are shielded from immune responses to prevent autoimmunity and maintain the function of sensitive tissues. These sites have specialized barriers and mechanisms that control immune access and activity.