Adaptive immunity: T cells, B cells, and immune responses

Adaptive immunity is a vital part of our immune system that helps us fight off infections specifically and persistently. While our body’s first line of defense works immediately and generally, adaptive immunity takes a little longer to work but is much more precise. Adaptive immunity involves two main types of immune cells: T cells and B cells. These cells not only remember past infections but also respond more effectively if the same pathogen invades again. In this guide, we’ll take a closer look at how adaptive immunity works, focusing on how T cells and B cells develop and contribute to the immune response. Whether you’re interested in how your body fights disease or just want to learn more, this article will give you a clear understanding of how adaptive immunity protects you.

Introduction to Adaptive Immunity

Adaptive immunity, also called acquired immunity, is a sophisticated defense system designed to recognize and eliminate specific pathogens or antigens. Unlike innate immunity, which provides broad, general defense against a variety of invaders, adaptive immunity provides a targeted response and retains a memory of previous encounters with specific antigens. This memory allows the immune system to respond more quickly and effectively when exposed to the same pathogen again.

Characteristics of adaptive immunity

Adaptive immunity is distinguished by several important features.

• SpecificityThe system is highly specific for individual microorganisms and pathogens, and achieves this specificity through a diverse repertoire of antigen receptors on lymphocytes, enabling the immune system to precisely target a vast array of antigens.
• MemoryOne of the most defining features of adaptive immunity is its ability to remember previous exposure to an antigen. When the immune system encounters a pathogen, it generates long-lasting memory cells. When reexposed to the same antigen, these memory cells promote a faster and stronger immune response.
• Enhanced Response: After initial exposure to a pathogen, the immune response is faster and more effective during subsequent encounters. This enhancement is due to a memory component, allowing for more efficient elimination of the pathogen.

Adaptive immunity typically takes longer to activate than innate immunity, but it offers more durable protection. To achieve this, the immune system utilizes two main arms: cell-mediated immunity and humoral immunity.

T cell differentiation and function

T cell development

T cells arise from hematopoietic stem cells in the bone marrow and mature in the thymus. Their development is a multistep process.

• Double Negative (DN) StageAt this early stage, thymocytes lack both CD4 and CD8 surface markers.
• Double Positive (DP) StageThymocytes express both CD4 and CD8 markers when they undergo genetic rearrangement of the T cell receptor (TCR).
• Single positive (SP) stageThymocytes that have successfully rearranged their TCR genes and passed the selection process will express either CD4 or CD8, but not both.

Thymocytes undergo several important processes within the thymus.

• Gene rearrangementsThymocytes undergo rearrangement of the genes encoding the beta chain of the TCR, resulting in the formation of a unique antigen-binding site.
• Positive SelectionThymocytes are selected based on their ability to moderately recognize MHC molecules on stromal cells of the thymic cortex. Successful thymocytes proceed to the next stage.
• Negative choicesThymocytes that are unable to bind MHC molecules or that bind too strongly to self-antigens undergo apoptosis, ensuring self-tolerance and preventing autoimmunity.

T cell subsets and functions

T cells can be divided into several subsets based on surface markers and function.

• Helper T cells (CD4+)These cells secrete cytokines to help other immune cells and can be further classified as follows:
  • Th1 cellsThey produce cytokines such as IFN-γ, IL-2, and TNF-β, which are essential for activating cytotoxic T cells (Tc) and macrophages to fight intracellular pathogens.
  • Th2 cells: They secrete interleukins IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13. Th2 cells help B cells produce antibodies and are involved in the elimination of extracellular parasites and allergic reactions.
  • Th17 cells: Produces IL-17 and IL-22, recruits granulocytes to fight bacterial infections, and may contribute to autoimmune diseases.
• Regulatory T cells (Treg, CD4+CD25+)These cells help maintain immune tolerance by suppressing immune responses to self- or harmless antigens, and they secrete inhibitory cytokines to modulate the activity of other T cell populations.
• Cytotoxic T cells (CD8+)These cells are specialized to kill cells infected with intracellular pathogens by releasing cytotoxic granules containing perforin and granzymes, which can induce apoptosis in target cells through binding to death receptors.

B cell differentiation and function

B cell development

B cells also arise from hematopoietic stem cells but mature in the bone marrow. Their development goes through several stages.

• Antigen-independent stageIt begins in the bone marrow and progresses through the following steps:
  • Pro-B cells: Initiates rearrangement of immunoglobulin genes.
  • Pre-B cells: Expresses the pre-B cell receptor (pre-BCR) with heavy chains and surrogate light chains.
  • Immature B cells: Complete rearrangement of light chain genes results in the expression of a functional B cell receptor (BCR) on its surface.
  • Mature B cells: They have functional BCRs and are ready to migrate to secondary lymphoid organs.

During development, B cells undergo genetic rearrangement to generate diverse antibody specificities, a process that includes the creation of variable regions by somatic recombination that are essential for recognizing a broad range of antigens.

Antigen-dependent phase

Upon encountering an antigen, B cells enter the antigen-dependent phase.

• Activation and proliferationB cells become activated when they bind to a specific antigen, which often requires the help of Th cells, especially for T-dependent antigens, and then proliferate and differentiate.
• DifferentiationActivated B cells undergo differentiation as follows:
  • Plasma cells: Specialized in producing and secreting large amounts of antibodies. Found in bone marrow and peripheral lymphoid organs, they are rich in cytoplasmic immunoglobulin (Ig) but have very little surface Ig.
  • Memory B cells: It lasts for a long time and allows you to respond more quickly and effectively to subsequent exposure to the same antigen.

The role of T cells in adaptive immune responses

T cells play a key role in adaptive immune responses through their interaction with antigen-presenting cells (APCs) and differentiation into different subsets.

• Armored personnel carrierThese include dendritic cells, macrophages, and B cells. APCs process antigen fragments and present them via MHC molecules to T cells, which is essential for initiating adaptive immune responses.
• T cell activationT cells circulate through the bloodstream, lymph nodes, and secondary lymphoid tissues in search of APCs presenting specific antigen-MHC complexes. Interaction of the TCR with the antigen-MHC complex, plus additional costimulatory signals, leads to T cell activation and proliferation.

The role of B cells in the adaptive immune response

B cells are central to the humoral immune response.

• Antigen Recognition and BindingB cells have membrane-bound immunoglobulins that act as antigen receptors. Upon encountering an antigen, B cells become activated and differentiate.
• Antibody productionActivated B cells differentiate into plasma cells that secrete antibodies that neutralize pathogens, promote phagocytosis, and activate the complement system.

T-dependent and T-independent antigens

• T-dependent antigensThese antigens require the help of T helper cells to activate B cells. B cells respond by producing different antibody classes (e.g., IgG) and generating memory cells. The antigen specificity of the BCR is improved during the immune response through a process called affinity maturation.
• T-independent antigensThese antigens can activate B cells without the help of T cells, and usually have repeat structures that cross-link the BCR, leading to the production of IgM antibodies, but T-independent responses usually do not generate memory cells.

Clinical Significance and Advances

Autoimmune disorders

Failure of adaptive immunity can lead to autoimmune diseases, in which the immune system mistakenly targets self-tissues. For example:

• Rheumatoid arthritisIt is characterized by chronic inflammation of the joints.
• Type 1 diabetes: It involves the destruction of insulin-producing cells in the pancreas.

Immunodeficiency

Immunodeficiencies result from defects in adaptive immunity and lead to increased susceptibility to infections, including:

• Severe Combined Immunodeficiency (SCID)A genetic disorder that leads to a severe deficiency of both B and T cells.
• HIV/AIDSHuman immunodeficiency virus targets CD4+ T cells, causing acquired immune deficiency.

Advances in immunotherapy

Recent advances in immunology have led to innovative treatments, including:

• CAR-T cell therapyThe patient’s T cells are modified to express a chimeric antigen receptor (CAR) that targets cancer cells.
• mRNA vaccinesThey use messenger RNA to instruct cells to produce antigens to trigger an immune response, a technology notably applied to COVID-19 vaccines.

Conclusion

Adaptive immunity is a complex, highly specialized system that provides targeted and long-lasting defense against specific pathogens. Through the complex processes of T and B cell development, activation, and differentiation, the adaptive immune system ensures a precise response to infection and the ability to remember previous encounters. Understanding these mechanisms not only advances our knowledge of immune function but also aids in the development of new treatments and vaccines, highlighting the essential role of adaptive immunity in maintaining health and fighting disease.

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