The secretory piece helps IgA to be transported across mucosa and also protects it from degradation in the secretions. It is the second most common serum Ig and the major class of Ig in secretions - tears, saliva, colostrum, and mucus.
Since it is found in secretions secretory IgA is important in local mucosal immunity but does not fix complement [ 5 ]. IgD immunoglobulin: is a monomer and found in low levels in serum; found on B cell surfaces where it functions as a receptor for antigen also does not bind complement [ 5 ].
IgE immunoglobulin : is a monomer and rare on serum. It has role in allergic reactions and does not fix complement [ 5 ]. This response occurs against cells, which are called Target cells. Target cell is the infected cell with parasite and Types 4 hypersensitivity Delayed type of hypersensitivity [ 5 ].
This activation will increase these cells ability for killing and became more effecter. After T-cytotoxic cells and NK cells activation by Th cells, T-cytotoxic cells come into close contact with target cell; they will bind to the Ag by their specific Ag receptors. T-cytotoxic cells and NK cells will kill target cells by the following mechanisms [ 1 , 2 , 3 , 4 , 5 ]: Direct contact killing: Production of perforin, which is a protein able to form pores in target cell membrane at the point of contact between Tc cell and target cell, lead to osmotic lysis of target cell.
Indirect killing: By secretion of a toxin protein in the space between the two cells, which causes fragmentation of target cell nuclear DNA, then the death of target cell by Apoptosis: the programmed cell death. Antibody-dependent cellular cytotoxicity ADCC killing: it is specific mode of killing occurs when the parasites Ags have ability to induce both HMI and CMI, target cells will be coated with specific Abs formed after HMI against some parts of intracellular parasite like virus.
These Abs will bring Tc and NK cells very close to the target cell by acting like a bridge because Tc and NK have receptors to the constant region of Ab.
Then Tc and NK cells will be activated and kill the target cell by extracellular products toxins and enzymes. This type of CMI occurs when the foreign Ag persist for long time e. Mycobacterium tuberculosis infection is long standing intracellular infection , also, against some kinds of cancer cells [ 2 , 5 ]. It is the first exposure to the Ag resulting of forming specific Abs and memory B-cells for HMI or T-cells and memory T-cells for CMI, the phases are, Figure 2 [ 1 , 2 , 3 , 4 , 5 ]: Latent Phase: start after first time exposure to an Immunogen or after induction, include the followings.
Duration of this phase period is variable depending on many factors Ag immunogenicity, Ag dose, Ag solubility, Ag route of immunization or exposure. Logarithmic phase: starts when Ab titer begin to increase active biosynthesis of Ab , last for days till reach peak. Steady phase: starts when the rates of both formation synthesis and catabolism are equal, then serum concentration of Ab is constant. Decline phase: starts when the Ab titer starts to fall down due to increase Ab catabolism rate than synthesis.
Primary and secondary immune response. Note: during early primary response, IgM class antibodies is predominant and first rise than IgG appears later [ 2 , 5 ].
It is the second exposure to the same immunogen that induced the first immune response after booster dose of vaccination may be after weeks, months, or even years later, includes [ 1 , 2 , 3 , 4 , 5 ]: Accelerated or fast appearance of Abs. Salmonella is a Gram-negative facultative rod-shaped bacterium in the same family as Escherichia coli, Enterobacteriaceae.
Salmonella live in the intestinal tracts of warm and cold blooded animals. Most common species related to human infections are Salmonella Typhi and Salmonella Paratyphi cause host-specific infections, being human the host. But other serotypes as S. Typhimurium and S. Enteritidis , mainly related to food products are also important serotypes that cause human diseases [ 5 , 6 ]. Salmonella are found in the natural environment water, soil, sometimes plants used as food.
These bacteria are zoonotic, human or animal can excrete Salmonella either when they are infected with disease Salmonellosis and when they remain carriers.
Also this disease is called food handling born disease due to the infected or carrier food handling workers [ 7 ]. Salmonella is intracellular parasite pathogen, do not multiply significantly in the natural environment out of digestive tracts , but they can survive several weeks in water and several years in soil if conditions of temperature, humidity, and pH are favorable [ 5 ].
The bacterial antigens are the components or products of pathogens that are able to induce the immune defenses of the host to defend against, and to eliminate, the pathogen or disease.
As with all Enterobacteriaceae , the genus Salmonella has three kinds of major antigens with diagnostic or identifying applications: somatic, surface, and flagellar [ 8 , 9 , 10 ]. Somatic antigens are the O side chain of LPS; they are heat stable and alcohol resistant. Cross-absorption studies individualize a large number of antigenic factors, 67 of which are used for serological identification. O factors labeled with the same number are closely related.
Surface antigens, commonly in enteric bacteria e. Surface antigens in Salmonella may mask O antigens, and the bacteria will not be agglutinated with O antisera. One specific surface antigen is well known: the Vi antigen.
Flagellar antigens are heat-labile proteins. Mixing Salmonella cells with flagella-specific antisera gives agglutination. Also, anti-flagellar antibodies can immobilize bacteria H antigens. Antigenic changes of the flagella known as the phase variation of H1 and H2 occurs in Salmonella Typhimurium. Salmonella strains may produce a thermos-labile enterotoxin that which has a limited relatedness to cholera toxin and E.
Additionally, a cytotoxin that inhibits protein synthesis. Both of these toxins play a role in the diarrheal symptoms of Salmonellosis. Innate immunity barriers play a good role in defense against Salmonella adhesion and colonization. But, upon infection specific immunity come to act; both humoral and cellular specific immune response will be activated to control this infection. Primary infections with S. Typhi or Salmonella ParaTyphi usually induce a degree of immunity.
Reinfection may occur but is often milder than the first infection. Circulating antibodies to O and Vi are related to resistance to infection and disease [ 11 , 12 ]. Salmonella infections in humans vary with the bacterial species, the infectious dose upon ingested contaminated food, and the host health. Typhimurium cells oral dose are needed to cause symptoms of a toxic infection.
Infants, immunosuppressed patients, and those affected with blood disease are more susceptible to Salmonella infection than healthy adults [ 12 ].
In the pathogenesis of typhoid the bacteria enter the human digestive tract, penetrate the intestinal mucosa causing no lesion , and stope in the mesenteric lymph nodes. Enteric Fever, Salmonellosis or Enterocolitis occurs after attachment to enterocytes of the ileum and colon. About hours following ingestion of contaminated food containing a sufficient number of Salmonella , the ingested Salmonella reach the small intestine, from which they enter the lymphatics and then the bloodstream.
They are carried by the blood to many organs, including the intestine. Then Salmonella cells will attach to Microfold cells M cells and dendric cells of the jejunum. Invasion can occur in this stage via the means of endocytosis, transfer, and exocytosis. Phagocytosis in the subserosa by macrophages and translocation into the mesenteric lymph nodes.
Lymphogenous and hematogenous dissemination combined by immune cells proliferation and specific immune response is integrated. Of course the complement system upon these events is already activated, since LPS layer can activate the alternative pathway as soon as this endotoxin liberated from bacterial cells due to destruction leading to more inflammatory reactions at the site of invasion as described in the complement system roles.
Moreover, the mannose residues that are found on the surface of Salmonella undergo lectin pathway activation of the complement system [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. The organisms usually multiply in intestinal lymphoid tissue and are excreted in stools. Some people infected experience no symptoms at all. The symptoms generally appear several hours to three days after contact with Salmonella bacteria.
Salmonellosis usually goes away in five to seven days and often does not require treatment unless the infected person becomes severely dehydrated loss of water in the body causing weakness or dizziness or the infection spreads from the intestines to other parts of the body. Antibiotics are usually not necessary unless the infection spreads from the intestines.
Food workers, health care personnel, and children in daycare must obtain approval from local or state health department before returning to their routine activities.
An infected person can carry the bacteria for a few days or several months. People who have been treated with oral antibiotics and younger people tend to carry the bacteria longer than others. Navigation menu. Salmonellosis Reviewed: September What is salmonellosis? Who gets salmonellosis? How is salmonellosis spread? What are the symptoms of salmonellosis and when do they appear? In contrast, infection with S. Typhi can be prevented by vaccination with attenuated strains, e.
However, effective vaccines preventing iNTS disease are likely to differ from those protecting against S. Typhi infections. Furthermore, it is known that Salmonella generates chronic carriers; a chronic carrier state has been identified in 2. Although Salmonella invades myeloid cells and escapes phagocytosis, it is unclear why humoral immunity does not contribute to the clearance of Salmonella which continuously transfers among short-lived myeloid cells. Overall, the lack of a vaccine and the presence of chronic carriers suggests that NTS suppresses long-lasting humoral immunity, i.
Typhimurium provides a murine model for typhoid fever which bears many similarities to human S. Typhi infection. This S. Typhi model is ultimately fatal due to the inability of such mice to restrict bacterial growth in vivo. Administration of attenuated strains of S. Typhimurium as a model of vaccination resulted in the generation of immune memory against Salmonella and protection against death from challenge with a virulent strain of the bacteria 16 , The murine model infected with virulent S.
Typhimurium showed similar pathogenesis on the early growth of bacteria. However, it seems unclear whether the model with attenuated S. Typhimurium really mimics the clearance of Salmonella , i. Typhimurium are excluded from their hosts in a similar way.
Many studies have discussed typhoidal disease using NTS strains based on the assumption that S. Typhimurium utilize the same invasion system in the hosts. However, it is impossible to compare the mechanism on the clearance of Salmonella in vivo , because S. Typhi is not infectious in mice. Typhimurium are excluded by distinct bacterial clearances, the difference may affect the ability to generate vaccines against S.
Innate cells can have several roles to play during the early stage of an infection, including controlling bacterial replication and producing cytokines and chemokines that activate and recruit inflammatory cells to the site of infection. All three phagocytic cell types also harbor bacteria during infection. In addition to innate cells, the clearance of bacteria from the tissues also requires functional CD4 T cells 19 , resulting in long-lasting specific immunity to re-challenge infection In contrast, mice lacking B cells resolve primary infection with attenuated bacterial strains with similar kinetics to wildtype mice 24 , 25 , indicating that B-cell responses do not participate in the primary clearance of the bacteria.
However, recent experiments in mice lacking classical MHC class Ia genes, perforin, or granzyme, show that CD8 T cells make a modest contribution to Salmonella clearance during the later stages of the primary response However, the roles of adaptive immunity were considered from the viewpoint of how the lymphocytes respond to the infection, without any consideration of how Salmonella may purposefully subvert the immune response for its own advantage.
Salmonella is known to activate myelopoiesis and suppress B lymphopoiesis Interestingly, the disruption of B lymphopoiesis has been also reported on Plasmodium infection in mice 31 , suggesting the similar mechanism to Salmonella. Expanded myeloid cells are able to kill a lot of Salmonella , but some become the host cells for Salmonella without phagocytosis.
Furthermore, the provision of B cells to the periphery is impaired due to death of B cell precursors in the bone marrow BM , resulting in an indirect advantage to Salmonella for their long-term persistence. In general, antibodies can protect against bacteria mainly by facilitating the uptake of the pathogen by phagocytic cells, which then destroy the ingested bacteria.
Antibodies do this in two ways: one is to coat the pathogen to be recognized by Fc receptors on phagocytic cells, which is called opsonization. Alternatively, antibodies binding to the surface of a pathogen can activate the proteins of the complement system.
Complement activation results in opsonization of the pathogen by binding complement receptors on phagocytes. Other complement components recruit phagocytic cells to the site of infection, and the terminal components of complement can lyse certain microorganisms directly by forming pores in their membranes.
Most intracellular pathogens spread by moving from cell to cell through the extracellular fluids. The extracellular spaces are protected by humoral immunity. Antibodies produced by plasma cells cause the destruction of extracellular microorganisms and therefore prevent the spread of intracellular infections.
Phagocytes, Salmonella 's hosts, are short-lived and survive for 0. Therefore, in order to survive, Salmonella has to transfer into new host cells every 1—7 days passing through extracellular fluids containing antibodies. It is unknown how and why Salmonella can escape from antibodies in extracellular spaces when transferring into new host cells. In secondary immune responses, anti-S almonella IgG are critical for the enhancement of phagocytosis.
However, anti- Salmonella IgG in the late phase of the primary immune response does not contribute to the clearance of the bacteria This raises the following questions: what is the difference of anti- Salmonella antibodies in the primary and secondary immune responses? What other functions of Salmonella have to be also considered in the subversion of the immune response?
The activation of B cells and their differentiation into long-lived plasma cells is triggered by antigen and usually requires CD4 T cell help, presenting antigen on MHC class II. A subset of effector CD4 T cells, known as T follicular helper cells, also control isotype switching and have a role in initiating somatic hypermutation of antibody variable V-region genes for affinity maturation mainly in germinal centers GCs of the spleen.
Cunningham et al. This prevents the immune system's second wave of defence — the SAS cells - being activated. The scientists also found that the Salmonella protein works ingeniously - by hijacking machinery inside the immune cell and forcing it to destroy the fragments of bacteria, rather than taking them to the cell surface.
Professor David Holden , senior author of the study and Director of the MRC Centre for Molecular Bacteriology and Infection at Imperial said: "This is a very small protein but it packs a big punch — accounting in part for the ability of Salmonella to cause infections. Now we have this knowledge, we might be able to use it to enhance the effectiveness of vaccines against Salmonella and possibly other harmful bacteria and viruses.
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