Defense Against Disease

The immune system acts as the body's defense mechanism against harmful organisms and altered cells. It can be classified into two major categories. The Innate Immunity functions as a quick response system without any prior exposure to the invader, meaning it doesn't retain memory of past infections. On the other hand, the Adaptive Immunity develops a tailored response based on specific pathogens encountered previously, allowing for a stronger and faster reaction during subsequent infections. This memory component is crucial for the effectiveness of vaccines.

Innate immunity provides the first defensive barrier against pathogenic invaders. It includes physical and chemical barriers, such as the skin and mucous membranes, which prevent entry. If pathogens breach these surfaces, various immune cells, like neutrophils and macrophages, work to engulf and destroy them. Neutrophils are the body's first responders to infection, acting quickly to consume bacteria and dead cells. Macrophages are larger cells that can engulf many pathogens and play a role in alerting the adaptive immune system by presenting antigens. Meanwhile, Natural Killer (NK) cells can directly kill infected or cancerous cells without needing prior exposure, enhancing the body's rapid response.

The inflammatory response is an immediate reaction to injury or infection aimed at protecting the body. When tissues are affected, chemical signals cause blood vessels to widen, increasing blood flow to the area, which leads to redness and heat. Increased vascular permeability allows plasma proteins and immune cells to exit the blood and enter the affected tissues, causing swelling and pain. Chemotaxis guides immune cells to the site of infection, where they combat invaders. After the threat is managed, immune cells like neutrophils die off, and macrophages clear debris to promote healing.

The complement system comprises a series of proteins that enhance (or 'complement') the ability of antibodies and phagocytic cells to eliminate pathogens. It can be activated through different pathways, including the classical pathway (involving antibodies), the lectin pathway (triggered by recognized sugars on microbes), and the alternative pathway, which can spontaneously activate in the presence of pathogens. Once activated, these proteins can lead to the formation of a membrane attack complex (MAC) that can directly lyse pathogens. The complement system enhances inflammation and facilitates the opsonization of pathogens, making them easier targets for immune cells.

Acute phase response is a rapid inflammatory response initiated by cytokines like IL-1, IL-6, and TNF-α, resulting in the liver producing acute phase proteins. One of these proteins, C-reactive protein (CRP), helps to mark pathogens for destruction and activate the complement system, enhancing the immune response. Fibrinogen is another acute phase protein that promotes clotting and can indicate the presence of inflammation through an increased erythrocyte sedimentation rate (ESR). This process ensures that the body quickly reacts to and contains infection or injury.

Pattern recognition receptors (PRRs) are crucial components of the innate immune system that identify common features on pathogens, known as pathogen-associated molecular patterns (PAMPs). TLRs are a prominent type of PRR found on immune cells that trigger responses upon detecting these patterns. For instance, TLR4 recognizes lipopolysaccharides (LPS) on bacteria, stimulating a cascade of immune responses that lead to the activation of inflammation and adaptive immunity. They act as the sentinels of the immune system, helping it understand the nature of the threat to tailor an appropriate response.

Interferons (IFNs) are vital proteins that allow cells to communicate about viral infections. Type I interferons, such as IFN-α and IFN-β, are produced by cells already infected by viruses. Once released, they bind to adjacent cells, warning them to prepare for a viral attack by inducing their own antiviral defenses like producing enzymes that can inhibit viral replication. This signaling mechanism is critical in containing viral spread within tissues and enhancing the overall antiviral response.

Adaptive immunity is characterized by its ability to recognize specific pathogens, remember past infections, and respond more effectively the next time a pathogen is encountered. It can be broadly divided into humoral and cell-mediated branches. Humoral immunity involves B cells that produce antibodies targeting specific antigens, while cell-mediated immunity primarily involves T cells that can directly kill infected cells or help coordinate the immune response through signaling. This system ensures that each pathogen is targeted with precision, leading to definitive removal from the body.

The major histocompatibility complex (MHC) plays a vital role in antigen presentation, which is essential for adaptive immune responses. MHC Class I molecules are found on almost all nucleated cells and present internal antigens (like those from viruses) to CD8+ cytotoxic T cells, which can destroy infected cells. On the other hand, MHC Class II molecules are found only on professional antigen-presenting cells (APCs). They present processed exogenous antigens to CD4+ helper T cells, initiating and regulating an immune response. This dual pathway allows the immune system to effectively recognize and respond to a variety of pathogens.

B cell development takes place primarily in the bone marrow, where they undergo genetic rearrangements (V(D)J recombination) to form a diverse set of B cell receptors (BCRs) that can bind various antigens. After maturation, naïve B cells circulate until they encounter their specific antigen. Activation requires help from T helper cells, including recognition and signaling. Once activated, B cells migrate to germinal centers in lymph nodes, where they undergo clonal expansion and affinities maturation to ensure strong and specific antibody production, while also switching their antibody class to better suit the immune response required by the pathogen.

Antibodies are specialized proteins produced by B cells, presenting a distinct Y-shaped structure made of two heavy and two light chains. The Fab region contains the variable portions that specifically bind to antigens, allowing for targeted responses to diverse pathogens. The Fc region interacts with other components of the immune system, such as phagocytes and complement proteins, making antibodies effective in opsonization, neutralization, and initiating immune responses. This intricate structure allows antibodies to both recognize and respond to pathogens efficiently.

T cell development occurs primarily in the thymus, where precursor thymocytes complete a rigorous training program. In positive selection, those T cells that can successfully recognize self-MHC molecules survive. In negative selection, T cells that show too much affinity toward self-antigens are eliminated to prevent autoimmunity. Upon successful maturation, CD4+ helper T cells can recognize antigens presented by MHC Class II molecules, enabling them to communicate with B cells and cytotoxic T cells, orchestrating a broader immune response against various types of invaders.

Immunological memory is a critical feature of the adaptive immune system, allowing the body to respond more efficiently upon re-exposure to previously encountered pathogens. After the initial immune response, a subset of B and T cells becomes memory cells that persist long after the infection has cleared. They provide an accelerated and more robust response upon second exposure to the same pathogen, thus preventing illness or significantly alleviating symptoms. This principle underlies the effectiveness of vaccinations, which introduce components of pathogens to stimulate this memory response without causing disease.

Immunological tolerance ensures that the immune system does not attack the body's own tissues, differentiating between self and non-self. Central tolerance involves the deletion of T and B cells that react strongly to self-antigens during their development in the thymus and bone marrow. Peripheral tolerance mechanisms help regulate immune activity in mature cells to prevent autoimmunity, such as T regulatory cells inhibiting excessive responses. A failure in these systems can lead to autoimmune diseases, where the immune system mistakenly attacks healthy tissues.

Vaccination is a method used to stimulate an immune response without causing disease by introducing either a weakened or inactive form of a pathogen (active immunization). This process leads to the creation of memory cells that provide long-term protection. Alternatively, passive immunization involves the direct administration of antibodies from another individual (such as anti-rabies immunoglobulin), providing immediate but short-term protection. This approach is particularly useful in cases where immediate immunity is critical, such as post-exposure to rabies.