Evolution of the immune system in humans from infancy to old age
These two processes will increase the baby immune system by thought that babies acquire innate immunity quickly with the help of colonization after . with bacteria has lead to a symbiotic relationship involving immunity. The adaptive immune system, also known as the acquired immune system or, more rarely, as Like the innate system, the acquired system includes both humoral immunity .. cells to activate them, and B cells are crippled without T cell help. . Immunity- involves a natural transfer of antibodies from a mother to her infant. to the Immune Innate and Adaptive Immunity Cells of the Immune System Myeloid from Mother to Infant Immune Response in the Elderly Innate and Adaptive Although the relationship between microbes and infectious diseases dates far.
Natural killer cells are a distinct lineage of lymphoid cells, lacking CD3, but expressing CD56 and NKp46 are part of innate immune system against viral infections and tumors.
During early stages of gestation, NK cells are highly regulated and very hypo-responsive to target cells as part of their protective role as fetus is developing 11 Later, throughout the gestation, NK cytolytic function increases compared with earlier phases. At birth NK cells are presented in high frequencies, but lower toxicity. However, they show a reduced level of threshold for activation which renders anti-viral protection.
Throughout the neonatal stages and even during the next few days after birth, NK frequencies decreases and reaching adult levels by 5 years of age 3 It is documented that expression of receptors in NK cells e. Both human and animal studies have indicated that the balance between stimulatory and inhibitory receptors plays a central role in susceptibility, function, interaction, and activation of of NK cells 13 Given their role in sowing of intestinal tissues and lymphoid system throughout the embryonic stages, it is clear that ILCs play fundamental functions during embryogenesis.
Their pivotal roles are more extended further after birth and through neonatal phase, particularly considering their capability of rapidly responding to environmental signals, containing infections, and maintaining tissue homeostasis. All these provides strong rationale not only to explore more about ILCs but also test the potential of targeting ILCs as therapeutic modality in the treatment of neonatal diseases.
Innate Lymphoid Cells Innate lymphoid cells, characterized and reported in three important publications, belong to a new class of lineage-negative Lin- lymphoid cells that mediate both pro-inflammatory and anti-inflammatory responses 6715 — Rather than specific antigens, they target conserved, shared components of the pathogens, and thus do not require recombination or expansion from memory cells.
The presence of ILCs in different tissues throughout the body is specified. They are implicated in the development of tissue microenvironment, structure, composition, and recovery from very early embryonic stages through the whole lifetime 718 — Like true sentinels, ILCs respond with rapidity, measured in minutes to hours.
Many ILCs do not possess cytotoxicity; rather, they release highly bioactive mediators in an auto- and paracrine manner. Based on their transcriptome and cytokine profiles, there are five subtypes of ILCs. ILC2 is similar to Th2 in that it can provide T-cell-independent B-cell help and is important in wound healing and tissue homeostasis. Because of these functions, group 2 ILCs are particularly adapted in defense against helminthic infections.
Since the neonatal gut is sterile and must cultivate its own microbial flora, ILCs are key to the co-evolution of the intestinal microbiome and adaptive immunity of the infant 7. At the intersection of innate and adaptive immune systems, ILCs occupy a central role in coordinating inflammation, immunity, wound healing, and tissue homeostasis, with a wide range of influence from metabolism to tumor defense to obesity They accomplish these varied tasks through intimate interactions with macrophage and classic adaptive immune cells: Based on the functional demands and the capabilities, maternal ILCs are ideally suited to assist the neonate.
Supporting this conjecture, a report documenting ILCs in human milk appeared very recently We have investigated the presence of ILCs in human infant oral epithelium, and have found their presence with a predominance of ILC2 ILC2s are also reported to contribute to the development of asthma during neonatal stages in mice by expression of IL throughout the early-life viral infection e. Therefore, it is plausible to suggest that ILC2s maybe considered as a therapeutic target in the treatment of neonatal respiratory disorders such as asthma 24 Further, ILC2s are reported to promote asthma at very early age of life through an ILdependent mechanism.
This is mainly attributed to the accumulation of ILC2s as well as mast cells, basophils, and eosinophils in the developing lungs during both perinatal and postnatal period.
Therefore, it is plausible to explore the potential of IL axis as an immunotherapeutic target in the initiation, progression, and treatment of asthma 26 — LIP is a condition associated with T cell activation, memory differentiation, tissue destruction, and a loss of TCR diversity. It is strongly suggested that T cell homeostasis in neonatal mice is regulated by mechanisms that are fundamentally different to adults.
This ILC-based inhibition of LIP ensures the generation of a diverse naive T cell pool in lymphopenic neonates that is mandatory for the maintenance of T cell homeostasis and immunological self-tolerance later in life. Moreover, this make it plausible to test the hypothesis that neonatal ILCs might lose their suppressive function in an age-dependent manner, remains to be more comprehensively interrogated. Further, a novel role for ILC3s, through an ILmediated mechanism has been reported which may attribute a biotherapeutic role to ILC3s in the treatment of neonatal intestinal inflammation.
Accordingly, any intervention e. This condition may lead to uncontrolled bacterial proliferation, cytokine storm, and death. This is specifically important because ILCs neither possess nor need rearranged-specific antigen receptors like regular lymphocytes, their response can be more rapid, usually within minutes. This sentry function is further enhanced by the fact that they reside near borders where heavy microbial contacts occur, such as skin and the lining of aero-digestive tracts Figure 3.
The mucosal and cutaneous barriers encounter both pathogenic and commensal microbes. It is possible that maternal ILCs present in the milk serve four important functions for the infants: In addition, from the maternal perspective, lactating mothers must guard against microbial infection of the breasts—one-third of the premature cessation of breastfeeding is due to mastitis. Milk leukocytes may well perform such a protective function In addition, it is clinically important to understand how milk shapes the intestinal microbiome of the infants, as well as the development of their T and B cell repertoires.
Altogether and whether ILCs involve other innate leukocytes e. The presence of immune components in mammary glands. The strategic location of SLT to the milk glands allows lymphocytes to defend the lactating breast as well as deployment to the infant through milk. B High magnification of the histology of lactating mouse mammary tissue, H and E stain, showing afferent and efferent lymphatic vessels, capillaries, and follicular formation with densely packed heterogeneous small lymphocytes in close proximity to active secretary units made up of cuboidal alveolar lactocytes.
This is not different from the aerial photograph of a military base with tens of thousands recruits undergoing training where inbound and outbound roads bring in supplies and remove wastes. The Transfer of Mediators and Cells by Milk: Human milk contains at least 32 non-cellular bioactive elements from carbohydrates to lipids, to proteins, and 5 cell types The presence of cells in fresh, unpasteurized human, and animal milk have been characterized since the late s; they include neutrophils, macrophages, lymphocytes, stem cells, epithelial cells, and microbe.
These bioactive molecular and cellular milk components protect the breast from infection while modulating the development and maturation of the neonatal immune system Among the non-cellular factors in the milk, many have antimicrobial properties. For example, lactoferrin B, formed from digestion of lactoferrin, is a potent agent against both Gram-positive and Gram-negative bacteria. That lysozymes and lactalbumin share similar amino acid sequences further supports the concept that milk is an antibiotic Together, these cellular and biochemical mediators cultivate and shape the developing gut microbiome of the infant.
Development of the Innate Immune Response: Role of the Maternal Microbiome
The luminal mucous layer has a particularly important reciprocal relationship, affecting and affected by, the epithelial barrier and the luminal microbiota Breast milk thus contains both prebiotics oligosaccharides and microbes that are critical in colonizing the infant gut as well as helping infants in the digestion of the nutrient components of milk. Innate lymphoid cells occupy the key intersection between adaptive and innate immunity, functioning like elite foreign troops sent into vulnerable regions to boost and train defenses, establishing a safe and sustainable local environment Figure 4.
ILCs of human milk may shape the infant or a land intestinal microbiomes by modulating neonatal immunity.
The immature immune system of the newborn must rapidly respond to the transition from a sterile intra-uterine environment to a microbe-laden external world and differentiate what is to be tolerated from microbes that need elimination through vigorous host responses.
Furthermore, lactating mothers must guard against microbial infection of the breasts; the milk leukocytes provide such defense Milk ILCs may impart innate immunity in newborns.
The next step is to investigate how they shape neonatal immunity and microbiome. The oral transfer of maternal cells through milk clearly occurs, and these cells e.
Although documented, however, how mammary glands sense and respond to the changes in the infant microbiome is largely remained unclear for now.
Components of innate and acquired immunity in infants and neonates. Heuristically, the immune system defends the neonate and infant against infections in similar manners as the military and the police keeping the country safe. The young immune system must develop de novo to respond to some foreign antigens pathogens and more rarely, abnormal autoantigens neoplastic and auto-reactive cellswhile accepting some other foreign antigens commensal microbes and normal autoantigens.
Multiple components from innate and adoptive immune system collaborate to accomplish the above tasks with multiple redundancies to ensure robustness.
The active defense against pathogens, like many joint operations in the military, requires coordination of multiple units from different branches of the armed forces.
Innate immunity is faster to respond seconds to minutes but the duration of action is shorter 3—5 days. In contrast, the adaptive immunity takes longer 4—7 days to activate but the response is much more specific and sustained weeks to years. At birth, the neonatal gut suddenly has two new tasks: The former involves digesting and absorbing nutrients, and the latter involves the five Ds with every microbial encounter, both are critical to survival. Maternal intestinal microbiome contains species while infants have far fewer.
Seventy-two percent of the specific operational taxonomic units OTU found in intestinal microbiome of vaginally delivered neonates are identical to maternal OTUs. The gastrointestinal tract faces an onslaught of pathogens while performing its digestive and absorptive duty For most infants, the gut carries out these functions efficiently and safely.
The more than unique milk glycans capable of binding specific microbes, and the high levels of lactoferrin, contributes to this great reduction in mortality. Some of the intestinal injury in NEC is due to inflammation, like cities destroyed by war.
The earliest exposure to maternal microbes occurs in utero Microbes have been detected in amniotic fluid, the umbilical cord, the placenta, and the meconium of healthy term babies 43 — In one study examining gut microbiome acquisition, pregnant mice were orally inoculated with a genetically labeled microbe.
Pups from these dams were obtained by cesarean section 1 day before predicted labor, and the labeled strain was isolated and identified in the meconium of these pups indicating vertical transmission of gut microbes in utero Delivery mode greatly impacts infant gut microbial composition: Infant diet immediately after birth breast milk, formula represents the next major factor that shapes the infant gut microbiome.
Breast milk, in addition to containing maternal immune cells and cytokines, also contains oligosaccharides and the microbes necessary to metabolize these oligosaccharides—an optimal inoculum for healthy infant gut development 3249 Clinical studies comparing maternal areolar skin and milk flora to the infant gut microbiome in healthy maternal-infant dyads showed definitively the seeding of the neonatal gut by the maternal sources. During the first month of life, milk and areolar skin flora accounted for Metagenomic function analyses predicted that maternal flora have significant influence on carbohydrate, amino acid, and energy metabolism.
Such maternal influence continued even after the introduction of solid foods These early exposures to microbes can have long-term effects on infant health and immune development.
These defects indicate that gut microbiota play a key role in normal immune development. Infant delivery mode and the associated microbial communities acquired with each mode have also been linked to long-term health effects including increased risk of immune-mediated diseases in infants born by Cesarean delivery This indicates that both microbial presence and microbial composition are essential to healthy immune development in infants.
Innate Immunity, an Army Inside: First, the invaders have some antigens that are different from host antigens, making it possible to differentiate them from self. Second, there is conservation among some of these non-host antigens so that specific individual identification is not necessary, reducing the magnitude of the surveillance required, and improving the efficiency of detection.
Third, these conserved, common antigens are essential for the invaders, such that they cannot mutate and do away with them From this evolved the concept of pattern recognition molecules and pathogen associated molecular pattern PAMP.
The receptors that bind pathogen-associated antigens have expanded greatly and now include eight major classes divided into three functional groups. The TLRs, or TOLL-like receptors, are evolutionarily conserved receptors, some on the cell surface TLR1, 2, 4, and 6 others are endolysosomally associated TLR3, 7, 8, and 9which when engaged by the specific target parts of the invaders, illicit rapid and escalating innate immune defense against the hostile agents.
The second group of pattern recognition receptors includes pentraxin, collectin, and ficolin. They mediate opsonization and complement activation. C-type lectin and scavenger receptors make the third group and they mediate phagocytosis. Together, these receptors form an intelligence surveillance network, constantly patrolling the integuments and internal domain for dangerous invaders.
Once they detect microbial presence, there are multiple feed-forward cycles which up-regulate the inflammatory and immune responses. The initial, rapid, and responses are the responsibility of the innate immune system. A more specific, sustained, but slower response is from the adaptive immunity. There are 10 TLRs in humans and 11 in mice.
The rapidity of the response comes, in part, from the readymade, stably coded nature of TLRs, without the need for any somatic recombination of genes, nor transcription or translation to produce novel receptors.
The adaptive immunity requires education of the T and B cells by prior antigenic exposure and formation of memory cells. Though slower to respond initially, these traditional lymphocytes have specific receptors through hypervariable recombination and, once expanded produce extremely effective antibodies and cytotoxic T cells. The defense by an organism against the ever-present threat of microbial invasions is exactly like national defense against hostile invaders.
There are five Ds that describe the stages of defense by the military across scales from a single soldier, or a fighter jet to a division or a carrier battle group: All of these specialized cells and parts of the immune system offer the body protection against disease.
This protection is called immunity. Immunity Humans have three types of immunity — innate, adaptive, and passive: Innate Immunity Everyone is born with innate or natural immunity, a type of general protection.
Many of the germs that affect other species don't harm us. For example, the viruses that cause leukemia in cats or distemper in dogs don't affect humans. Innate immunity also includes the external barriers of the body, like the skin and mucous membranes like those that line the nose, throat, and gastrointestinal tractwhich are the first line of defense in preventing diseases from entering the body.
Adaptive Immunity The second kind of protection is adaptive or active immunity, which develops throughout our lives. Adaptive immunity involves the lymphocytes and develops as people are exposed to diseases or immunized against diseases through vaccination.
Passive Immunity Passive immunity is "borrowed" from another source and it lasts for a short time. For example, antibodies in a mother's breast milk give a baby temporary immunity to diseases the mother has been exposed to.
This can help protect the baby against infection during the early years of childhood. Everyone's immune system is different.
Adaptive immune system
Some people never seem to get infections, whereas others seem to be sick all the time. As people get older, they usually become immune to more germs as the immune system comes into contact with more and more of them.
That's why adults and teens tend to get fewer colds than kids — their bodies have learned to recognize and immediately attack many of the viruses that cause colds. Immunodeficiencies also can be acquired through infection or produced by drugs these are sometimes called secondary immunodeficiencies. Immunodeficiencies can affect B lymphocytes, T lymphocytes, or phagocytes. Examples of primary immunodeficiencies that can affect kids and teens are: IgA deficiency is the most common immunodeficiency disorder.
IgA is an immunoglobulin that is found primarily in the saliva and other body fluids that help guard the entrances to the body. IgA deficiency is a disorder in which the body doesn't produce enough of the antibody IgA. People with IgA deficiency tend to have allergies or get more colds and other respiratory infections, but the condition is usually not severe. SCID is a serious immune system disorder that occurs because of a lack of both B and T lymphocytes, which makes it almost impossible to fight infections.
DiGeorge syndrome thymic dysplasiaa birth defect in which kids are born without a thymus gland, is an example of a primary T-lymphocyte disease. The thymus gland is where T lymphocytes normally mature. Acquired or secondary immunodeficiencies usually develop after someone has a disease, although they can also be the result of malnutrition, burns, or other medical problems. Certain medicines also can cause problems with the functioning of the immune system. Acquired secondary immunodeficiencies include: It is caused by HIV, a virus that wipes out certain types of lymphocytes called T-helper cells.
Without T-helper cells, the immune system is unable to defend the body against normally harmless organisms, which can cause life-threatening infections in people who have AIDS. Newborns can get HIV infection from their mothers while in the uterus, during the birth process, or during breastfeeding. People can get HIV infection by having unprotected sexual intercourse with an infected person or from sharing contaminated needles for drugs, steroids, or tattoos.
Immunodeficiencies caused by medications. Some medicines suppress the immune system. One of the drawbacks of chemotherapy treatment for cancer, for example, is that it not only attacks cancer cells, but other fast-growing, healthy cells, including those found in the bone marrow and other parts of the immune system. In addition, people with autoimmune disorders or who have had organ transplants may need to take immunosuppressant medications, which also can reduce the immune system's ability to fight infections and can cause secondary immunodeficiency.
Autoimmune Disorders In autoimmune disorders, the immune system mistakenly attacks the body's healthy organs and tissues as though they were foreign invaders. The substances that provoke such attacks are called allergens.
The immune response can cause symptoms such as swelling, watery eyes, and sneezing, and even a life-threatening reaction called anaphylaxis. Medicines called antihistamines can relieve most symptoms.