Priming is the first contact that antigen-specific T helper cell precursors have with an antigen. It is essential to the T helper cells' subsequent interaction with B cells to produce antibodies. [1] Priming of antigen-specific naive lymphocytes occurs when antigen is presented to them in immunogenic form (capable of inducing an immune response). Subsequently, the primed cells will differentiate either into effector cells or into memory cells that can mount stronger and faster response to second and upcoming immune challenges. [2] T and B cell priming occurs in the secondary lymphoid organs (lymph nodes and spleen).
Priming of naïve T cells requires dendritic cell antigen presentation. Priming of naive CD8 T cells generates cytotoxic T cells capable of directly killing pathogen-infected cells. CD4 cells develop into a diverse array of effector cell types depending on the nature of the signals they receive during priming. CD4 effector activity can include cytotoxicity, but more frequently it involves the secretion of a set of cytokines that directs the target cell to make a particular response. This activation of naive T cell is controlled by a variety of signals: recognition of antigen in the form of a peptide: MHC complex on the surface of a specialized antigen-presenting cell delivers signal 1; interaction of co-stimulatory molecules on antigen-presenting cells with receptors on T cells delivers signal 2 (one notable example includes a B7 ligand complex on antigen-presenting cells binding to the CD28 receptor on T cells); and cytokines that control differentiation into different types of effector cells deliver signal 3. [2]
Cross-priming refers to the stimulation of antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) by dendritic cell presenting an antigen acquired from the outside of the cell. Cross-priming is also called immunogenic cross-presentation. This mechanism is vital for priming of CTLs against viruses and tumours. [3]
Immune priming is a memory-like phenomenon described in invertebrate taxa of animals. It is evolutionarily advantageous for an organism to develop a better and faster secondary immune response to pathogen, which is harmful and which it is likely to be exposed again. In vertebrates immune memory is based on adaptive immune cells called B and T lymphocytes, which provide an enhanced and faster immune response, when challenged with the same pathogen for a second time. It was assumed that invertebrates do not have memory-like immune functions, because of their lack of adaptive immunity. But in recent years evidence supporting innate memory-like functions were found. In invertebrate immunology the common model organisms are different species of insect. The experiments focusing on immune priming are based on exposing the insect to dead or sublethal dose of bacteria or microbes to elicit the initial innate immune response. Afterwards the researchers compare subsequent infections in primed and non-primed individuals to see if they mount a stronger or modified response. [5]
It seems that the results of immune priming research are showing that the mechanism differs and is dependent on the kind of insect species and microbe used for given experiment. That could be due to host-pathogen coevolution. For every species is convenient to develop a specialised defense against a pathogen (e.g. bacterial strain) that it encounters the most. [6] In arthropod model, the red flour beetle Tribolium castaneum , it has been shown that the route of infection (cuticular, septic or oral) is important for the defence mechanism generation. [7] Innate immunity in insects is based on non-cellular mechanisms, including production of antimicrobial peptides (AMPs), reactive oxygen species (ROS) or activation of the prophenol oxidase cascade. Cellular parts of insect innate immunity are hemocytes, which can eliminate pathogens by nodulation, encapsulation or phagocytosis. [8] The innate response during immune priming differs based on the experimental setup, but generally it involves enhancement of humoral innate immune mechanisms and increased levels of hemocytes. There are two hypothetical scenarios of immune induction, on which immune priming mechanism could be based. [7] [9] The first mechanism is induction of long-lasting defences, such as circulating immune molecules, by the priming antigens in the host body, which remain until the secondary encounter. The second mechanism describes a drop after the initial priming response, but a stronger defence upon a secondary challenge. The most probable scenario is the combination of these two mechanisms. [7]
Trans-generational immune priming (TGIP) describes the transfer of parental immunological experience to its progeny, which may help the survival of the offspring when challenged with the same pathogen. Similar mechanism of offspring protection against pathogens has been studied for a very long time in vertebrates, where the transfer of maternal antibodies helps the newborns immune system fight an infection before its immune system can function properly on its own. In the last two decades TGIP in invertebrates was heavily studied. Evidence supporting TGIP were found in all colleopteran, crustacean, hymenopteran, orthopteran and mollusk species, but in some other species the results still remain contradictory. [10] The experimental outcome could be influenced by the procedure used for particular investigation. Some of these parameters include the infection procedure, the sex of the offspring and the parent and the developmental stage. [10]
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.
T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.
Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Typically, immune cells detect the antigen presented on major histocompatibility complex (MHC) on infected cell surfaces, triggering cytokine release, causing the death of the infected cell by lysis or apoptosis. NK cells are unique, however, as they have the ability to recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class 1. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells, B cells, and Innate lymphoid cells (ILCs), of which natural killer cells are an important subtype. They are the main type of cell found in lymph, which prompted the name "lymphocyte". Lymphocytes make up between 18% and 42% of circulating white blood cells.
Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.
The adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.
An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T-cells.
Cross-presentation is the ability of certain professional antigen-presenting cells (mostly dendritic cells) to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells (cytotoxic T cells). Cross-priming, the result of this process, describes the stimulation of naive cytotoxic CD8+ T cells into activated cytotoxic CD8+ T cells. This process is necessary for immunity against most tumors and against viruses that infect dendritic cells and sabotage their presentation of virus antigens. Cross presentation is also required for the induction of cytotoxic immunity by vaccination with protein antigens, for example, tumour vaccination.
Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.
Co-stimulation is a secondary signal which immune cells rely on to activate an immune response in the presence of an antigen-presenting cell. In the case of T cells, two stimuli are required to fully activate their immune response. During the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors.
Memory T cells are a subset of T lymphocytes that might have some of the same functions as memory B cells. Their lineage is unclear.
Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, now bound to the major histocompatibility complex (MHC), is transported to the surface of the cell, a process known as presentation, where it can be recognized by a T-cell receptor. If there has been an infection with viruses or bacteria, the cell will present an endogenous or exogenous peptide fragment derived from the antigen by MHC molecules. There are two types of MHC molecules which differ in the behaviour of the antigens: MHC class I molecules (MHC-I) bind peptides from the cell cytosol, while peptides generated in the endocytic vesicles after internalisation are bound to MHC class II (MHC-II). Cellular membranes separate these two cellular environments - intracellular and extracellular. Each T cell can only recognize tens to hundreds of copies of a unique sequence of a single peptide among thousands of other peptides presented on the same cell, because an MHC molecule in one cell can bind to quite a large range of peptides. Predicting which antigens will be presented to the immune system by a certain MHC/HLA type is difficult, but the technology involved is improving.
In immunology, a naive T cell (Th0 cell) is a T cell that has differentiated in the thymus, and successfully undergone the positive and negative processes of central selection in the thymus. Among these are the naive forms of helper T cells (CD4+) and cytotoxic T cells (CD8+). Any naive T cell is considered immature and, unlike activated or memory T cells, has not encountered its cognate antigen within the periphery. After this encounter, the naive T cell is considered a mature T cell.
In immunology, peripheral tolerance is the second branch of immunological tolerance, after central tolerance. It takes place in the immune periphery. Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease. Peripheral tolerance prevents immune response to harmless food antigens and allergens, too.
Gamma delta T cells are T cells that have a γδ T-cell receptor (TCR) on their surface. Most T cells are αβ T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, γδ T cells have a TCR that is made up of one γ (gamma) chain and one δ (delta) chain. This group of T cells is usually less common than αβ T cells, but are at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs).
Marginal zone B cells are noncirculating mature B cells that in humans segregate anatomically into the marginal zone (MZ) of the spleen and certain other types of lymphoid tissue. The MZ B cells within this region typically express low-affinity polyreactive B-cell receptors (BCR), high levels of IgM, Toll-like receptors (TLRs), CD21, CD1, CD9, CD27 with low to negligible levels of secreted-IgD, CD23, CD5, and CD11b that help to distinguish them phenotypically from follicular (FO) B cells and B1 B cells.
Tissue-resident memory T cells or TRM cells represent a subset of a long-lived memory T cells that occupies epithelial and mucosal tissues without recirculating. TRM cells are transcriptionally, phenotypically and functionally distinct from central memory (TCM) and effector memory (TEM) T cells which recirculate between blood, the T cell zones of secondary lymphoid organ, lymph and nonlymphoid tissues. Moreover, TRM cells themself represent a diverse populations because of the specializations for the resident tissues. The main role of TRM cells is to provide superior protection against infection in extralymphoid tissues.
Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, these are secondary, tertiary and other subsequent immune responses to the same antigen. The adaptive immune system and antigen-specific receptor generation are responsible for adaptive immune memory. After the inflammatory immune response to danger-associated antigen, some of the antigen-specific T cells and B cells persist in the body and become long-living memory T and B cells. After the second encounter with the same antigen, they recognize the antigen and mount a faster and more robust response. Immunological memory is the basis of vaccination. Emerging resources show that even the innate immune system can initiate a more efficient immune response and pathogen elimination after the previous stimulation with a pathogen, respectively with PAMPs or DAMPs. Innate immune memory is neither antigen-specific nor dependent on gene rearrangement, but the different response is caused by changes in epigenetic programming and shifts in cellular metabolism. Innate immune memory was observed in invertebrates as well as in vertebrates.
Memory T cell inflation phenomenon is the formation and maintenance of a large population of specific CD8+ T cells in reaction to cytomegalovirus (CMV) infection.