Understanding the Immune System: Barriers, Cells, and Responses
EXTERIOR BARRIERS: Their Importance in Preventing Pathogen Entry
Primary Barriers
2.1. Anatomical or Mechanical Barrier
The skin acts as a physical barrier, containing fatty acids and commensal microorganisms that help prevent pathogen entry. Mucous membranes, with their wet epithelium, serve as the body’s first line of defense against microorganisms.
2.2. Chemical Barrier
Various substances, such as sweat (acidic pH of 3.5), gastric acid (pH 1 to 2), and basic duodenal fluid (pH 8), inhibit bacterial growth.
2.3. Biochemical Barrier
Fluids like tears, nasal mucosa, and saliva contain antibacterial enzymes, such as lysozyme, which breaks down the bacterial cell wall.
2.4. Biological Barrier
Commensal microorganisms residing in the skin, digestive tract, and urogenital tract release antibiotics that prevent the proliferation of foreign microorganisms.
CELLS OF THE IMMUNE SYSTEM
3.1. Phagocytes (Phagocytic Cells)
Monocytes: These cells have a kidney-shaped nucleus and differentiate into macrophages or dendritic cells upon reaching infected tissue, where they phagocytize foreign substances. Macrophages are larger than other phagocytes and possess high phagocytic capacity and chemotactic activity.
Neutrophils: Characterized by a nucleus with three or four lobes, neutrophils contain numerous lysosomes in their cytoplasm. They are the first phagocytes to respond to bacterial infections and form abscesses with the remains of dead bacteria.
Eosinophils: Eosinophils have a two-lobed, sausage-shaped nucleus and are phagocytes that act against infections caused by worm parasites and pathogens.
3.2. Auxiliary Cells
Basophils: With an S-shaped nucleus and granules in their cytoplasm, basophils release substances that trigger inflammation, indicating an immune response. They are involved in allergic and inflammatory reactions, along with mast cells.
Mast Cells: These resident cells of connective tissue contain granules rich in histamine and heparin. They play a role in immune and neuroimmune responses, particularly in allergic and inflammatory reactions.
3.3. Blood and White Cell Origin and Maturation
All blood and white cells of the immune system originate and mature in the red bone marrow, with T cells also maturing in the thymus. They arise from multipotential hematopoietic stem cells that can divide and differentiate into various blood cell types. Monocytes mature into dendritic cells or macrophages, while B cells mature into plasma cells.
NATURAL (INNATE) AND SPECIFIC (ADAPTIVE) IMMUNITY
4.1. Innate Immune System
The innate immune system serves as a secondary barrier and is characterized by its non-specific response, regardless of the pathogen. It involves phagocytes, which cause a non-specific cellular response, and molecules like histamine, prostaglandins, and eicosanoids, which trigger a local inflammatory response. The innate immune response is rapid but lacks immunological memory for the invading pathogen.
4.2. Adaptive Immune System
The adaptive immune system, found only in vertebrates, provides tertiary defense and is specific to the pathogen. It identifies and eliminates pathogens based on their surface antigens. Lymphocytes are responsible for the cellular immune response, while antibodies mediate the humoral immune response. The adaptive immune response is slower but develops immunological memory against the invading pathogen, allowing for a faster and more effective response upon subsequent encounters. Immune tolerance prevents the system from attacking the body’s own cells and tissues.
INNATE IMMUNE SYSTEM: THE LOCAL INFLAMMATORY RESPONSE
The innate immune system employs non-specific defenses, primarily phagocytes, to combat pathogens that breach the body’s barriers. Phagocytes engulf and destroy pathogens through lysosomal digestion and can penetrate capillary walls to enter infected tissues via diapedesis. Damaged tissues release soluble mediators like histamines, eicosanoids, cytokines, and interferons, while mast cells, platelets, and basophils also contribute to the inflammatory response. Histamine causes vasodilation and increased permeability, leading to redness and swelling. Eicosanoids raise local temperatures, while cytokines and interferons attract phagocytes and activate lymphocytes. The inflammatory response often manifests as redness, swelling, and pain, with fever potentially aiding in pathogen destruction. Once the pathogen is eliminated, fibrocytes and macrophages clean and repair the affected area.
ADAPTATIVE IMMUNE SYSTEM
The adaptive immune system comprises lymphocytes, organs (and tissues), and molecules.
6.1. Molecules
6.1.1. Antigens
Antigens are substances, typically foreign molecules, that induce a specific immune response. They are often macromolecules on the surface of pathogenic cells or viruses. Examples include proteins, glycoproteins, and complex polysaccharides. An epitope, or antigenic determinant, is a small region of the antigen that binds to the paratope of an antibody molecule.
6.1.2. Immunoglobulins (Antibodies)
Antibodies are proteins synthesized by B lymphocytes in response to foreign particles. They identify and bind to specific molecules on pathogens, facilitating their destruction. Antibodies have a Y-shaped structure with variable regions for antigen recognition. The basic unit of an antibody is a monomer, which can exist as a single molecule or combine to form dimers or pentamers.
6.1.3. Major Histocompatibility Complex (MHC)
The MHC is a set of cell surface proteins crucial for adaptive immunity. These proteins distinguish between self and foreign molecules and play a vital role in antigen presentation and transplant rejection.
MHC Class I Proteins: These proteins recognize molecules produced within cells, such as viral or tumor antigens, and present them to cytotoxic T cells (killer T cells). They are present in all normal cells and trigger immune responses by T8 and natural killer cells when bound to antigens in infected cells.
MHC Class II Proteins: Found in phagocytes (antigen-presenting cells), MHC Class II proteins recognize and present antigens derived from extracellular pathogens to helper T cells, triggering T4 responses and immune activation.
6.1.4. Complement Immune System
The complement system consists of about 20 proteins secreted by monocytes and produced in the liver. It is activated in local and general bacterial infections and facilitates capillary dilation and complements the action of antibodies by attacking the bacterial cell wall.
Cytokines: These protein hormones are produced by leukocytes upon encountering a pathogen and activate other cells, triggering an inflammatory reaction. Excessive cytokine secretion, known as a cytokine storm, can cause severe inflammation, as seen in respiratory tract infections like SARS, MERS, and COVID-19.
Interferons: Interferons (IFNs) are signaling proteins released by host cells in response to viral infections. They induce nearby cells to heighten their antiviral defenses, activate immune cells like natural killer cells and macrophages, and increase host defenses by upregulating antigen presentation.
Immune Responses
Agglutination: Antibodies link multiple cells with surface antigens, forming aggregates that are destroyed by macrophages and NK cells.
Precipitation: Antibodies bind to soluble macromolecules with epitopes, forming three-dimensional complexes that are easily expelled.
Neutralization: Antibodies bind to epitopes on viruses or toxins, preventing them from associating with target cells and blocking their ability to infect.
Opsonization: Phagocytes readily phagocytose pathogens coated with antibody molecules.
T LYMPHOCYTES
T lymphocytes are generated in the red bone marrow and mature in the thymus before entering the bloodstream.
T Helper Lymphocytes (T4 Lymphocytes, TH): These cells initiate the immune response by activating and enhancing the response of other immune cells, such as macrophages, B lymphocytes, and cytotoxic T lymphocytes, using cytokines.
Cytotoxic T Lymphocytes (T8 Lymphocytes, CTL or Killers): These cells directly destroy cancer cells and cells infected by intracellular pathogens.
Regulatory T Lymphocytes (TS): These cells suppress the immune response, inhibiting antibody synthesis and T lymphocyte activity.
Natural Killers (NK): Differentiated from immature T lymphocytes without thymus maturation, NK cells lack specific antigen receptors and exhibit a non-specific immune response, attacking infected and tumor cells.
B LYMPHOCYTES AND PLASMA CELLS
B lymphocytes are generated and mature in the red bone marrow. During maturation, they produce membrane-bound antibodies. Upon activation by T4 lymphocytes, B lymphocytes differentiate into plasma cells, which synthesize and release specific antibodies against a particular antigen, mediating the humoral immune response.
Primary and Secondary Immune Responses
Primary Immune Response: This initial response is slower, with lower antibody levels, primarily IgM, and a shorter duration. It is initiated by TH lymphocytes, which activate TC lymphocytes and B lymphocytes.
Secondary Immune Response: This subsequent response is faster, with higher antibody levels, primarily IgG, and a longer duration. It is mediated by memory T and B lymphocytes, which differentiate into TC lymphocytes and plasma cells, respectively.
Active and Passive Immunization
Active Immunization: This involves the synthesis of antibodies against a specific antigen.
Natural Active Immunization: The body acquires immunity after overcoming an infectious disease.
Artificial Active Immunization: Vaccination triggers a humoral immune response, leading to the production of antibodies and memory lymphocytes.
Passive Immunization: Antibodies produced in one individual are transferred to another.
Natural Passive Immunization: Newborns receive maternal antibodies (IgG) through the placenta or colostrum.
Artificial Passive Immunization: Serotherapy involves administering a serum containing antibodies to provide immediate protection against a disease.
Vaccination and Serotherapy
Vaccination: Vaccination is a prophylactic measure that induces active acquired artificial immunity against a specific infectious disease. Vaccines typically contain weakened or killed forms of the microbe, its toxins, or surface proteins, stimulating the body’s immune system to recognize and combat the pathogen in the future. Vaccination contributes to herd immunity.
Serotherapy: Serotherapy involves administering specific antibodies against an antigen to individuals who are ill or at risk of illness, providing passive immunity. However, it should be used judiciously due to the risk of an immune response against the serum. Serums are safe, have a short duration of action, and are primarily used for therapeutic purposes.