Immunome Research
Open Access

Complement System and Secondary Responses of the Immune Response

James Mehrtens^{* *}Correspondence: James Mehrtens, Department of Clinical Immunology, University of Auckland, Auckland, New Zealand, Email:

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About the Study

The immune system is a marvel of biological engineering, safeguarding the body against a myriad of pathogens and foreign invaders. Comprising a complex network of cells, tissues, and organs, the immune system orchestrates a highly coordinated response to threats, maintaining homeostasis and ensuring survival.

Immune system

The immune system can be broadly categorized into two interconnected branches: The innate immune system and the adaptive immune system. The innate immune system serves as the body's first line of defense, providing rapid, nonspecific responses to a wide range of pathogens. Key components of the innate immune system include physical barriers like the skin and mucous membranes, as well as cellular and molecular defenses such as phagocytes, natural killer cells, and antimicrobial proteins.

The adaptive immune system mounts a more targeted and specific response to pathogens encountered by the body. This branch of immunity relies on the recognition of specific antigens and the generation of immunological memory, allowing for a faster and more effective response upon subsequent exposure to the same pathogen. T lymphocytes (T cells) and B lymphocytes (B cells) are the primary cellular mediators of the adaptive immune response, orchestrating the elimination of pathogens through various mechanisms, including antibody production and cell-mediated cytotoxicity.

Initiation of the immune response

The immune response is initiated when the body's surveillance mechanisms detect the presence of foreign antigens, signaling the need for immune activation. Antigens can be derived from pathogens such as bacteria, viruses, fungi, and parasites, as well as non-pathogenic substances like allergens and environmental toxins. Upon recognition of antigens, immune cells undergo activation and proliferation, leading to the deployment of effector mechanisms aimed at neutralizing and eliminating the threat.

The process of antigen recognition and immune activation is mediated by a diverse array of receptors expressed on the surface of immune cells. Pattern recognition receptors (PRRs), such as Toll-Like Receptors (TLRs) and Nucleotide-binding Oligomerization Domain (NOD)-like receptors, recognize conserved molecular patterns associated with pathogens, triggering intracellular signaling cascades that promote immune activation.

Innate immune response

Upon encountering pathogens, the innate immune system mounts a rapid and nonspecific response aimed at containing and eliminating the threat. Phagocytes, including neutrophils, macrophages, and dendritic cells, play a central role in innate immunity by engulfing and digesting invading microorganisms through a process known as phagocytosis. Additionally, Natural Killer (NK) cells contribute to innate immunity by recognizing and destroying virus-infected or cancerous cells through the release of cytotoxic granules.

Inflammatory responses are another hallmark of innate immunity, serving to recruit immune cells to sites of infection or tissue damage. Proinflammatory cytokines, such as Interleukin-1 (IL-1), Tumor Necrosis Factor-Alpha (TNF-α), and interleukin-6 (IL-6), are secreted by activated immune cells and promote the recruitment and activation of additional immune effector cells. While inflammation is essential for combating infection and promoting tissue repair, dysregulated or excessive inflammation can contribute to the pathogenesis of inflammatory diseases.

Complement system

The complement system represents a crucial component of the innate immune response, consisting of a cascade of soluble proteins that interact to opsonize pathogens, promote inflammation, and facilitate their destruction. Complement activation can occur through three main pathways: The classical pathway, the lectin pathway, and the alternative pathway. Each pathway is initiated by distinct triggers but converges on the generation of C3 convertase, which cleaves C3 into C3a and C3b, leading to further amplification of the complement cascade and the formation of the Membrane Attack Complex (MAC), capable of lysing target cells.

Adaptive immune response

While the innate immune response provides immediate defense against pathogens, the adaptive immune response offers a more tailored and specific mechanism of protection. Central to adaptive immunity are T cells and B cells, which undergo clonal selection and expansion upon encountering specific antigens. T cells recognize antigenic peptides presented by Major Histocompatibility Complex (MHC) molecules on the surface of Antigen-Presenting Cells (APCs), whereas B cells recognize intact antigens through their B cell receptors.

T cell activation requires two signals: Antigen recognition by the T Cell Receptor (TCR) and co-stimulatory signals provided by interactions between co-stimulatory molecules on APCs and their corresponding receptors on T cells. Following activation, T cells differentiate into effector subsets, such as cytotoxic T cells (CD8⁺ T cells) and helper T cells (CD4⁺ T cells), which mediate cell-mediated immunity and provide help to B cells, respectively.

B cells, on the other hand, differentiate into plasma cells, which secrete antibodies specific to the encountered antigen. Antibodies, also known as Immunoglobulins (Igs), are glycoproteins that recognize and neutralize pathogens through various mechanisms, including opsonization, complement activation, and neutralization of toxins and viruses.

Memory and secondary responses

One of the hallmark features of the adaptive immune system is its ability to generate immunological memory, conferring long- lasting protection against previously encountered pathogens. Memory T cells and memory B cells, formed during the primary immune response, remain quiescent but can rapidly proliferate and differentiate into effector cells upon re-exposure to the same antigen. This phenomenon enables the immune system to mount a more rapid and robust response during secondary encounters with pathogens, often preventing symptomatic infection and promoting faster recovery.

Regulation of the immune response

The immune response is tightly regulated to maintain a delicate balance between protective immunity and immunopathology. Various mechanisms ensure the resolution of immune responses once the threat has been eliminated, preventing excessive tissue damage and chronic inflammation. Regulatory T cells (Tregs) play a critical role in immune tolerance and suppression of aberrant immune responses by inhibiting the activation and effector functions of other immune cells.

Dysregulation of the immune response can lead to the development of autoimmune diseases, hypersensitivity reactions, and immunodeficiency disorders. Autoimmune diseases arise from the loss of self-tolerance, resulting in immune-mediated destruction of host tissues and organs. Hypersensitivity reactions encompass a spectrum of immune-mediated responses to innocuous antigens, ranging from mild allergic reactions to lifethreatening anaphylaxis.