Immunological memory

. Development of adaptive immune memory Immunological memory occurs after a primary immune response against the antigen. Immunological memory is thus created by each individual after a previous initial exposure to a potentially dangerous agent. The course of secondary immune response is similar to the primary immune response. After the memory B cell recognizes the antigen, it presents the peptide in the MHC class II complex to nearby effector T cells. That leads to activation of these cells and rapid proliferation of cells. After the primary immune response has disappeared, the effector cells of the immune response are eliminated. However, antibodies that were previously produced in the body persist and represent the humoral component of immunological memory and serve as an important defense against subsequent infections. In addition to the formed antibodies in the body, there remains a small number of memory T and B cells that make up the cellular component of the immunological memory. They stay in blood circulation in a resting state, and at the subsequent encounter with the same antigen, these cells are able to respond immediately and eliminate the antigen. Memory cells have a long life and last up to several decades in the body. As of 2019, researchers are still trying to find out why some vaccines produce lifelong immunity, while the effectiveness of other vaccines drops to zero in less than 30 years (for mumps) or less than six months (for H3N2 influenza). Evolution of adaptive immune memory The evolutionary invention of memory T and B cells is widespread; however, the conditions required to develop this costly adaptation are specific. First, to evolve immune memory, the initial molecular machinery cost must be high and will entail losses in other host characteristics. Second, middling- or long-lived organisms are more likely to evolve such an apparatus. The cost of this adaptation increases if the host has a middling lifespan, as the immune memory must be effective earlier in life. Furthermore, research models show that the environment plays an essential role in the diversity of memory cells in a population. Comparing the influence of multiple infections to a specific disease as opposed to disease diversity of an environment provides evidence that memory cell pools accrue diversity based on the number of individual pathogens exposed, even at the cost of efficiency when encountering more common pathogens. Individuals living in isolated environments, such as islands, have a less diverse population of memory cells, which are, however, present with sturdier immune responses. That indicates that the environment plays a large role in the evolution of memory cell populations. Memory B cells Memory B cells are plasma cells that are able to produce antibodies for a long time. Unlike the naive B cells involved in the primary immune response, the memory B cell response is slightly different. The memory B cell has already undergone clonal expansion, differentiation and affinity maturation, so it is able to divide multiple times faster and produce antibodies with much higher affinity (especially IgG). Memory T cells Memory T cells can be both CD4+ and CD8+. These memory T cells do not require further antigen stimulation to proliferate; therefore, they do not need a signal via MHC. Memory T cells can be divided into two functionally distinct groups based on the expression of the CCR7 chemokine receptor. This chemokine indicates the direction of migration into secondary lymphatic organs. Those memory T cells that do not express CCR7 (these are CCR7-) have receptors to migrate to the site of inflammation in the tissue and represent an immediate effector cell population. These cells were named memory effector T cells (TEM). After repeated stimulation they produce large amounts of IFN-γ, IL-4 and IL-5. In contrast, CCR7+ memory T cells lack proinflammatory and cytotoxic functions but express receptors for lymph node migration. These cells were named central memory T cells (TCM). They effectively stimulate dendritic cells, and after repeated stimulation, they are able to differentiate into CCR7- effector memory T cells. Both populations of these memory cells originate from naive T cells and remain in the body for several years after initial immunization. Experimental techniques used to study these cells include measuring antigen-stimulated cell proliferation and cytokine release, staining with peptide-MHC multimers, or using an activation-induced marker (AIM) assay. ==Innate immune memory==

Many invertebrates such as species of freshwater snails, copepod crustaceans, and tapeworms have been observed activating innate immune memory to instigate a more efficient immune response to second encounter with specific pathogens, despite missing an adaptive branch of the immune system. When innate immune cells receive an activation signal, for example, through recognition of PAMPs with pattern recognition receptors (PRRs), they start the expression of proinflammatory genes, initiate an inflammatory response, and undergo epigenetic reprogramming. After the second stimulation, the transcription activation is faster and more robust. Immunological memory was reported in monocytes, macrophages, natural killer cells, and innate lymphoid cells 1, 2, and 3 cells. Mechanism of innate immune memory At the steady state, unstimulated cells have reduced biosynthetic activities and more condensed chromatin with reduced gene transcription. The interaction of exogenous PAMPs (β-glucan, muramyl peptide) or endogenous DAMPs (oxidized LDL, uric acid) with PRR initiates a cellular response. Triggered Intracellular signaling cascades lead to the upregulation of metabolic pathways such as glycolysis, the Krebs cycle, and fatty acid metabolism. An increase in metabolic activity provides cells with energy and building blocks, which are needed for the production of signaling molecules such as cytokines and chemokines. It has been proposed that immune memory in innate and adaptive immunity represents an evolutionary continuum in which a more robust immune response evolved first, mediated by epigenetic reprogramming. In contrast, specificity through antigen-specific receptors evolved later in some vertebrates. ==Evolutionary mechanisms leading to the development of immunological memory==

The emergence of the adaptive immune system is rooted in the deep history of evolution dating back roughly 500 million years. Investigations and recent studies found that two major events led to the emergence of the same. These two macroevolutionary events were the origin of RAG and two whole rounds of genome duplication (WGD).The early origins and evidence for emergence of features resembling AIS dates to the era where jawed and jawless vertebrates diverged phylogenetically. Early investigations around the 1970s led to the discovery of unique inverted repeat flanking signal sequences while groups studied the RAG genome. Culmination of several works and review suggests that these disruptions could have been selected for a rearrangement to maintain genomic integrity which ultimately led to mechanisms like RAG diversifications in AIS. This discovery led to the hypothesis that there was an invasion event of a regulatory element-like region because these repeats resembled a remnant transposable element. == Measles and immune amnesia ==

The measles virus can deplete previously acquired immune memory by killing cells that make antibodies, thus weakening the immune system and increasing the risk of death from other diseases. Although the measles vaccine contains an attenuated strain, it does not deplete immune memory. Population studies from prior to the introduction of the measles vaccine suggest that immune amnesia typically lasts 2–3 years. Primate studies suggest that immune amnesia in measles is effected by replacement of memory lymphocytes with ones that are specific to measles virus, since they are destroyed after being infected by the virus. This creates lasting immunity to measles re-infection, but decreases immunity to other pathogens. corneal ulceration (leading to corneal scarring); and subacute sclerosing panencephalitis, a progressive and fatal inflammation of the brain that occurs in about 1 in 600 unvaccinated infants under 15 months. Common secondary infections include infectious diarrhea, bacterial pneumonia, and otitis media. ==See also==