The Immune response is the body's response caused by its immune system being activated by antigens. The immune response can include immunity to pathogenic microorganisms and its products, allergies, graft rejections, as well as autoimmunity to self-antigens. In this process the main cells involved are T cells and B cells (sub-types of lymphocytes), and macrophages (a type of leucocyte or white blood cell). These cells produce lymphokines that influence the other host cells' activities. B cells, when activated by helper T cells undergo clonal expansion. B cells differentiate into plasma cells, which are short lived and secrete antibodies, and memory B cells, which are long lived and produce a fast, remembered response when exposed to the same infection in the future. B cells mature to produce immunoglobulins (also known as antibodies), that react with antigens. At the same time, macrophages process the antigens into immunogenic units which stimulate B lymphocytes to differentiate into antibody-secreting plasma cells, stimulating the T cells to release lymphokines.
Complement is a group of normal serum proteins that enhance the immune response by becoming activated as the result of antigen-antibody interaction. The first contact with any antigen sensitizes individual affected and promotes the primary immune response. Next contact of the sensitized individuals with same antigen results in a more rapid and massive reaction, called the secondary immune response ("booster response" or the "anamnestic reaction"). It is most expressed in the level of circulating serum antibodies.
An anamnestic response in medicine is a delayed immunologic response. The term is frequently used in transfusion medicine and refers to a re-exposure incident where antibody is formed on initial exposure to an antigen in a transfused unit, but the specific memory B cell population fades over time, with antibody becoming undetectable over years. If a patient is re-exposed to the same offending antigen in a future transfusion (which might happen because the antibody screen would in fact be negative), there would still be a massive, rapid production of IgG antibody against the antigen, which will predictably lyse the transfused red cells, a delayed hemolytic transfusion reaction.
The immune response can be transferred via serum antibodies introduction from sensitized to desensitized individuals. It is highly specific for given antigen, and it is normally directed against foreign protein substances.
- 1 Innate
- 2 Adaptive
- 3 Natural killer cells
- 4 Natural killer T cells (NKT)
- 5 Regulation of immune response
- 6 References
- 7 External links
Innate response is evolutionary more conserved than adaptive immune response. It is the first line of defense when it comes to defending an organism from an foreign invader. Foreign invaders include bacteria, viruses, and parasites. Innate immunity responses are not specific to particular pathogen. They are rather limited to conserved features amongst pathogens. They depend on a group of proteins (complement, interferons, lectins) and phagocytic cells. The protection an innate response offers is beneficial because it attacks all foreign invaders that are not part of the cell's self. Innate response is very quick - the pathogen is eliminated within minutes. Moreover, the innate immune responses in vertebrates are required to activate adaptive immune responses.
An immune response can usually be described generally as "The reaction of the host's immune system to antigen in an invading (infecting) pathogenic organism, or to foreign protein, as in transplanted organs or tissues. The response is humoral and local; antibod[ies] produced by B cells combine... with antigen in an antigen-antibody complex to inactivate or neutralize antigen. This defensive mechanism often effectively controls infection." An immune response is divided into 2 parts; innate and adaptive.
The innate immune response is "the response by the host that comprises the cells and mechanisms that defend the host from infection by other organisms or is activated by endogenous molecules, in a nonspecific manner." The innate immune response is quick and is the body's initial response to unwanted invaders. It consists of the body's non-specific external and internal defense mechanisms. An example of the body's external defense mechanisms are mucus and skin. Skin consists of epithelial and endothelial cells which acts a sort of barrier against infection, invading antigens would have to pass through the initial skin barrier in order to actually get inside the host. Mucous acts similarly to skin, in that it is a barrier of sorts. Mucus traps invading pathogens and sometimes degrades them, preventing them from going any further into the body. Non-specific internal defense mechanisms are put in place in case the invading pathogens gets past the external defenses and actually makes it inside the body. Things such as phagocytes, and Natural Killer (NK) cells attack the pathogen and destroys it before further infection takes place.
Adaptive immunity relies on the capacity of immune cells to distinguish between the body's own cells and unwanted invaders. The host's cells express "self" antigens, that differ from those on the surface of bacteria or on the surface of virus-infected host cells ("non-self" or "foreign" antigens). The adaptive immune response is triggered by recognizing foreign antigen in the cellular context of an activated dendritic cell.
Almost all cells in our body are capable of presenting antigen through the function of major histocompatibility complex molecules. Moreover, some cells are specially equipped to present antigen, and to prime naive T cells. Dendritic cells, B-cells, and macrophages are termed professional antigen-presenting cells (APCs). Plus they are equipped with special "co-stimulatory" ligands recognized by co-stimulatory receptors on T cells. Adaptive immune response would be inefficient without those costimulatory signals as the T cells would become anergic. Several T cells subgroups can be activated by professional APCs, and each type of T cell is specially equipped to deal with each unique toxin or microbial pathogen. The type of T cell activated, and the type of response generated, depends, in part, on the context in which the APC first encountered the antigen.
The adaptive immune response is the body's second line of defense."Adaptive immunity has evolved to provide a broader and more finely tuned repertoire of recognition for both self- and nonself-antigens. Adaptive immunity involves a tightly regulated interplay between antigen-presenting cells and T and B lymphocytes, which facilitate pathogen-specific immunologic effector pathways, generation of immunologic memory, and regulation of host immune homeostasis." The cells of the adaptive immune system are extremely specific, because during early developmental stages the B and T cells develop antigen receptors that are specific to only certain antigens. This is extremely important for B and T-cell activation. B and T cells are extremely dangerous cells, if they are able to attack without going through a rigorous process of activation, a faulty B or T cell can begin exterminating the host's own healthy cells. Every B and T-cell is different, making way for a diverse community of cells ready to recognize and attack a full range of invaders. This response is much slower than the body's innate response because its cells are so specific and require to be activated before it is able to actually act. "In addition to specificity, another principal feature of adaptive immunity is the generation of immunologic memory. During the first encounter with an antigen (pathogen), sets of long-lived memory T and B cells are established. In subsequent encounters with the same pathogen, the memory cells are quickly activated to yield a more rapid and robust protective response". This feature of the adaptive immune response is responsible for the development of vaccines as well as other modern day medicines targeted at disease prevention. Immunologic memory is the basic concept behind the modern day flu shot. The flu shot basically is giving the recipient a dormant flu virus. This activates the recipient's immune response. After the immune response, immunologic memory is activated, so if the individual ever comes into contact with the flu virus again the body will be prepared to deal with it accordingly, this time faster, and more efficiently.
NK cells attack self cells that have become infected or more specifically compromised host cells (such as tumor cells or virus-infected cells) rather than attack foreign invaders. They distinguish cells with abnormally low levels of a cell-surface marker called MHC I (major histocompatibility complex). They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self." NK cells have cytotoxic chemicals which recognize a broad spectrum of foreign invaders in a non-specific manner. NK cells are bound to foreign substances and insert their cytotoxic chemical which results in the death of foreign cells. NK cells are a type of lymphocyte. In an organism, B and T lymphocytes are present. They grow in the bone marrow and in the liver and produce hematopoetic stem cells.
Natural killer T cells are a branch of T cells and a lymphocyte that is involved in the innate response. NKT cells can pinpoint nonpeptide antigens using MHC molecules from CD1 on the cell surface. NKT constantly express T-cell and NK cell antigens. Invariant NKT cells express a unique TCRa rearrangement, Va24-Ja18 with Vb11 that is expressed that characterizes many NKT cells. When NKT cells are activated, cytokines are rapidly produced. IL-4 is associated in allergy pathogenesis. Ulcerative colitis, UC, is a form of inflammatory bowel disease. It has recently been found that natural killer T cells can play a key role in the disease. According to a recent study, by manipulating natural killer T cells, it may be possible to modify the abnormal immunoresponse activity characteristic within UC.
Immune system must always be in balance. There must be balance between activated state and non-activated state - balance between tolerance and response to antigen. If this balance is disrupted it can have severe consequences - either autoimmune diseases or total immunosuppression which might lead to death. Therefore, the immune response must be regulated. It can be regulated via several mechanisms on several levels.
Antigen is the main regulator of immune response. Its presence in body starts the immune response and once the antigen is gone the response ends. Antigens are also important for affinity maturation of B cells (they compete for a limited amount of the antigen).
Soluble antibodies compete with B cell receptors for antigens. Thus they negatively regulate activation of additional B cells. Immunocomplexes with antibodies IgG are also negative regulators. They bind to the surface of B cells and inhibit their activation via agglomerating B cell receptors with inhibiting Fc receptor.
One of the most important regulatory mechanisms. Cytokines influence for example the development and differentiation of various T cell subpopulations. The influence of cytokines can be inhibit by endocytosis of receptors able to bind them or by inhibitors binding directly to the receptor instead. Intercellular synapse is a key part of immune responses. The immune response wont be activated without proper communication between cells. Moreover, effector cells need costimulation in order to be actually activated nad to avoid anergy.
The way of regulation via T lymfocytes is very complex. It can be illustrated in the relationship between Th1 cells and Th2 cells. There is mutual negative regulation via cytokines. Th2 cells produce cytokines like interleukin 4 and interleukin 10, that suppress Th1 induced immune response. Moreover, there is a huge population of regulatory T cells, that play the key role in suppressing autoreactive cytotoxic T cells.
There is also regulation via the neuroendocrine system. However it is not well studied yet. There are few things that illustrate the mutual relationship between the immune system and the neuroendocrine system. For example, some neurotransmitters effect leukocytes, and leukocytes have receptors for them on their surface (noradrenalin can be a good example). Leukocytes produce a lot of hormones (endorfines, ACTH, TSH, growth hormon, vitamin D3). Some cytokines important in immune system are also components of nervous system (interleukin 1, interleukin 6, LIF, TNF alpha).
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