3.1. B cells and Tuberculosis Antibody ResponsesBased on the concept of division of labor by the cell-mediated and the humoral arm of the immune response in controlling pathogens, protection against intracellular microbes is generally thought to be mediated exclusively by cell-mediated immunity (Casadevall, 2003). This has led to the use of highly T cell-centric strategies for the development of vaccines against intracellular pathogens including M. tuberculosis (Sender and Hill, 2000).Although antibodies are induced against a broad range of protein and non-protein antigens in active TB disease, they are not useful for diagnosis due to a lack of sensitivity and specificity. There is evidence for reduced antibody avidity in active TB disease and perturbation in Fc receptor expression, suggesting that phagocytosis and antibody-mediated cellular cytotoxicity could be dysregulated. Transcriptomic signatures for B cells are also depressed in TB, suggesting down-regulation or exhaustion of the B cell response (Scriba et al., 2017).
B cells and antibodies are involved in the immune response to TB, and the interaction of antibodies with phagocytic cells through Fc receptor engagement is emerging as a key area for research. The quantity of antibodies produced during M. tuberculosis infection is related to bacterial load, and higher antibody responses are observed in those at risk of disease and are correlated with the mycobacterial load during disease (Kunnath et al., 2012). This suggests that antibodies are important in the control of active TB disease and has also led to the development of antibody-based assays for TB diagnosis (Scriba et al., 2017).

                                                                      Figure 3: How do B cells modulate the immune responses to M. tuberculosis?

Production of M. tuberculosis-specific antibodies can mediate the formation of an immune complex that can modulate the functions of effector cells such as dendritic cells and macrophages. It remains to be demonstrated whether specific neutralizing antibodies exist. B cells can serve as antigen-presenting cells to influence T cell activation, polarization, and effector functions and the establishment of T cell memory. B cells can also modulate the functions of granulomatous immune cells. In concert, these antibody-dependent and independent functions of B cells play an important role in determining disease outcome in terms of the elimination of control of bacteria, as well as the development of immunopathology that could damage tissues and promote dissemination (L. kozakiewicz et al., 2013).

3.2. Antibody Quality
The primary purpose of antibody measurement has been the diagnosis of TB disease, and most studies focus on the number of antibodies detected and not antibody quality. Antibody avidity is variable in TB patients (Maes RF, 1991), and shortly following TB treatment, there is an increase in antibody quantity and a decrease in avidity, suggesting exhaustion of the B cell response (Aris-Bouda LM et al., 2003). A decrease in avidity of antibody specific for the live cell surface of mycobacteria in TB patients, suggesting conversion of antibodies to low avidity IgG or B cell exhaustion (Perley et al., 2014). Antibody avidity was also higher in those previously immunized with BCG, which raises the possibility of using vaccination to improve antibody avidity as a potential mechanism for protection against TB (Scriba et al., 2017). 3.3. Variation in Human Antibody Responses against Mycobacterium Tuberculosis

It has long been known that natural infection induces the formation of antibodies against MTB (Jacobs et al., 2016). Studies demonstrated that 90% of TB patients have raised titers of serum immunoglobulin against mycobacterial antigens at the time of clinical presentation (Lyashchenko et al., 1998). The correlation between antibody responses and active TB disease led to an investigation of antibodies as diagnostic markers rather than a therapeutic strategy, but these efforts were discouraged by the WHO in 2012, due to suboptimal sensitivity and specificity in studies (WHO, 2021). 3.4. Isotypes and Subclasses of Antibodies to Mycobacterium Tuberculosis Infection Within the broadest of strokes, antibody titers increment as Mycobacterium tuberculosis burden increments, apparently due to expanded antigen accessibility (De- Araujo et al.,
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2018). More particularly, a few but not all think about appearing that dynamic aspiratory TB inspires Mycobacterium tuberculosis particular IgG isotype reaction with the rise of both Mycobacterium tuberculosis -particular and add up to IgG1 and IgG3 subclasses in serum (De- Araujo et al., 2018). In vitro, IgG1 mediates TNF-α discharge from human monocytes but does not increment the anti-inflammatory cytokine IL 10 (Hussain et al., 2001). Reliable with these affiliations, complement C1q levels are higher in dynamic TB compared to inactive TB, and complement cascade particles are up-regulated 18 months sometime recently movement from Mycobacterium tuberculosis infection to TB disease (Lubbers et al., 2018). In addition, a few monoclonal Mycobacterium tuberculosis IgG1 can upgrade bacterial replication in vitro, illustrating the potential to worsen illness (Zimmermann et al., 2016). Notably, the defensive impact shows up to be revoked with the enzymatic evacuation of glycan buildups (Olivares et al., 2013). Hence, Mycobacterium tuberculosis receptive IgG with intact glycosylation in complex polyclonal reactions may take an interest in controlling bacterial burden (Milla et al., 2019). Beyond IgG, IgA has been a center of interest due to the significance of this isotype in mucosal immunity inside the aspiratory compartment, the most courses of TB infection, acquisition, and ensuing transmission (Milla et al., 2019). Monoclonal IgA was able to repress Mycobacterium tuberculosis development, whereas IgG antibodies to the same targets advanced disease (Zimmermann et al., 2016). Intriguingly, this isotype-mediated control of MTB appears to be modulated via FcαR/FcγR independent mechanisms (Milla et al., 2019).

3.5. Antibodies as Potential Biomarkers for Protective Immunity against Mtb Individuals with persistent negative TSTs, despite years of exposure to ATB patients, had elevated anti-Mtb IgG levels, and their serum was able to block proliferation of peripheral blood mononuclear cells in response to protein purified derivatives (PPD) (171). In concordance, highly exposed, but TST-negative, individuals displayed high anti-PPD Abs titers, which inhibited autologous T-cell proliferation after PPD stimulation (172). Abs specific for CFP-10 and ESAT-6 in Quantiferon TB Gold (QFT) supernatants independently separated LTBI from ATB (173). More recently, Lu et al. reported that highly exposed, but TST- and IFN-γ release assay (IGRA)-negative, individuals harbored Mtb-specific IgM and IgG, while diminished CD4-mediated IFN-γ responses directed toward Mtb early secreted Ag of 6 kDa (ESAT-6), 10 kDa culture filtrate protein (CFP-10), Ag85A and Ag85B were found (163). Taken together, these studies implicate that humoral immunity is detectable infrequently exposed individuals with persistently negative skin testing or QFN evaluation, which represent read-outs of effector T-cell responses. In such settings, Abs may be considered biomarkers of protective immunity.

4.1. Humoral Immunodeficiency and Risk of Tuberculosis
HIV is known to cause immune dysfunction, rendering HIV/TB-co-infected individuals more susceptible to progression to ATB (Esmail et al., 2018; Gupta et al., 2015). Specifically, progressive untreated HIV infection is associated with a loss of total (Esmail et al., 2018) and M. tuberculosis-specific CD4 T cells (Yao et al., 2014). Given the critical role of CD4 T cells in the control of TB in mice (Lin, 2012), depletion of T cells is likely to contribute to the development of ATB in HIV-infected individuals.
Genetic susceptibility to mycobacterial disease is well described and is typically seen in the loss of functionality in the IL-12, STAT1, and IFN-ℽ pathways (Cottle, 2011). IFN-γR1 deficiency resulting from homozygous or compound heterozygous null mutations in IFN-γR1 causes severe, often fatal infection (Newport et al., 1996; Jouanguy et al., 1997; Altare et al., 1998). A homozygous null mutation in IFN-γR2 also results in severe atypical mycobacterial infection (Dorman and Holland, 1998). In both deficiencies, granulomas fail to form in tissues. Both the binding (IFN-γR1) and signaling (IFN-γR2) chains of the IFN-γ receptor are essential for IFN-γ mediated signaling and control of mycobacterial infection. In partial IFN-γR1 deficiency, the IFN-γR1 is expressed on monocytes but has reduced ligand affinity (Jouanguy et al., 1997). In contrast, to complete IFN-γR1 deficiency, this reduced IFN-γ signaling is sufficient for the organization of granulomas, and the clinical course is milder.
4.2. Antibodies in Prevention of Infection with Mycobacterium Tuberculosis
Antibodies that have been obtained from persons with latent tuberculosis and those with active tuberculosis have functional differences in vitro. Antibodies from peripheral-blood cells of persons with the latent disease and active disease have the efficacy of inhibiting Mycobacterium tuberculosis infection in macrophages and epithelial cells (Lu et al., 2016 and Zimmermann et al., 2016). IgG from persons with the latent disease was more effective at inhibiting mycobacterial growth in macrophages than IgG from persons with active disease (Lu et al., 2016). IgA isotypes inhibited infection of an epithelial cell line and the IgG isotypes promoted infection (Zimmermann et al., 2016).
4.3. Monoclonal Antibody Studies during Mycobacterium Tuberculosis Infection in Mice

The defensive impact of monoclonal antibodies focuses on three well-known MTB antigens: heparin-binding hemagglutinin (HBHA), alpha-crystallin, and arabinomannan (AM), the sugar component of the glycolipid lipoarabinomannan (LAM) (Clemens, H, and Carolyn, G. King, 2021). Monoclonal antibodies decreased bacterial burden, improved control of microbes, or diminished lung pathology (Balu et al., 2021). HBHA is a surface-exposed protein that interacts with proteoglycans and can facilitate MTB entry into epithelial cells in vitro (Locht et al., 2006).
During infection, HBHA was shown to be required for extrapulmonary dissemination, as mucosal administration of MTB lacking HBHA expression impaired its ability to spread to other organs, such as the spleen (Pethe et al., 2001). Similar to HBHA, LAM is found within the bacterial cell envelope and constitutes a major component of the cell wall (Clemens, H, and Carolyn, G. K, 2021). Alpha-crystallin (too called 16-kDa antigen or HspX) may be a cytosolic protein that has moreover been recognized within the cell envelope of MTB (Hermann et al., 2021). Accordingly, alpha-crystallin is essential for bacterial survival during periods of disease latency when MTB also undergoes metabolic adaptation to survive under conditions of oxygen deprivation, nutrient depletion, and low pH (O’Toole et al., 2018).
4.4. Potential Mechanisms of Antibody-Mediated Immunity in Tuberculosis
Despite being a facultative intracellular pathogen, MTB is potentially susceptible to various mechanisms of antibody-mediated immunity. Opsonization through FcγR was shown to promote phagolysosomal fusion (Armstrong and Hart, 1975) and to increase macrophage Ca2+ signaling and intracellular killing (Malik et al., 2000). IgG bound to BCG increased the release of oxygen in the phagosomes of alveolar macrophages, suggesting the enhancement of antimycobacterial macrophage activity by antibody (Suga et al., 1996). Immune complexes that stimulate
FcεRII CD23 receptors trigger has been associated with antimycobacterial activity (Mossalayi et al., 2009).
Furthermore, the existence of potentially synergistic functions between humoral and cell-mediated immunity against TB is suggested by the observation that anti-mycobacterial antibodies in BCG-vaccinated persons enhance both innate and cell-mediated immune responses against mycobacteria (de Vallière et al., 2005) and that sera from TB contacts with high but not low IgG titers against tuberculin can block proliferation of PBMC cultures with tuberculin (Encinales et al., 2010). Moreover, a robust T cell response against mycobacteria is enhanced by specific antibody responses that can augment Th1 activation via FcR by facilitating rapid uptake, processing, and presentation of antigens (Igietseme et al., 2004).

The antibody can also contribute to the host defense against MTB by promoting the clearance of immunomodulatory antigens such as LAM (Glatman-Freedman et al., 2000). Finally, antibodies that mimic the action of fungal killer toxins are bactericidal to M.tb (Conti et al., 1998). Although such antibodies are unlikely to be present in MTB infection, the fact that mycobacteria can be killed directly by certain antibodies provides a precedent for such a mechanism of antibody-mediated protection.
In addition to these direct mechanisms, antibodies can influence the outcome of mycobacterial infection through their ability to modulate inflammation. Some antibodies, such as IgM, can demonstrate pro-inflammatory properties through their ability to activate complement (Ciurana et al., 2004), while other antibodies, such as IgG, can demonstrate pro- or anti-inflammatory properties depending on the antigen and FcR receptor engaged (Ballow, 2011; Lux et al., 2010).

                                                           Figure 4: Antibodies modulate MTB-macrophage interaction via FcR mediated phagocytosis

Antibodies are now also understood to augment CMI and reduce the survival of intracellular pathogens via effector functions of the Fcγ receptor (FcR) (Tameris et al., 2013).
4.6. Mucosal Protection against Tuberculosis
It is well known that the mucosa is the largest immune organ in the body, and it is generally believed that almost all infectious diseases are initiated at the mucosal surface (Ye et al., 2011). The respiratory tract is the natural route for Mtb infection, where Mtb infects the individual mainly through the mucosal tissue of the respiratory tract after inhalation of mycobacteria containing droplets from the external environment. Normally, the pathogen (Mtb) infection could be eliminated by the host’s immune system, but it is desirable to induce immunity before the infection through vaccination in most cases. To effectively prevent Mtb infection, the approach of mucosal immunization has recently received increasing attention in the field of tuberculosis vaccination owing to its potency in inducing mucosa-associated protection from mucosal infectious diseases (Ogra et al., 2001). Several lines of evidence have suggested that mucosal immunity can provide unique advantages for protection against mycobacterial infection, by which the immune cells, such as macrophages, dendritic cells, and leukocytes recognize the pathogen-associated molecular patterns (PAMPs), and sequentially activate the anti-mycobacterial immune responses including the activation of specific T-cell and antibody synthesis (Mogensen, 2009).

Mice missing the polymeric Ig receptor which transports IgA into the respiratory mucosa are more helpless to MTB infection than wild-type mice (Tjarnlund et al., 2006). In a novel try, polyclonal human secretory IgA (hsIgA) was decontaminated from colostrum given by healthy women and appeared to contain IgA able to tie entirety BCG and MTB lysate (Alvarez et al., 2013).
Prophylactic intra-tracheal incubation or pre-incubation of MTB with this hsIgA diminished bacillary stack and moved forward granuloma arrangement within the lungs of mice challenged with live MTB (Alvarez et al., 2013). This appeared that antibodies able of interacting with MTB within the mucosa may be passively passed on between mother and child, which human MB particular hsIgA can alter the course of disease (Alvarez et al., 2013).
4.7. Antibody Function in Mycobacterium tuberculosis
With differential glycosylation, isotypes, and subclasses, antibody Fc-domain engagement of Fc receptors on immune cells helps modulate pro- and anti-inflammatory signals, the balance of which, in TB, can contribute to outcome (Hogarth, 2012). Despite lower Mycobacterium tuberculosis particularly IgG titers in inactive compared to active TB, there is a higher affinity for the activating FcγRIIIa and no difference in the activating FcγRIIa or inhibitory FcγRIIb (Lu et al., 2016).
Studies in mice deficient of the inhibitory FcγRIIb have greater control of MTB bacterial burden, whereas complete knock out of the Fcγ chain region, which is essential for activating FcγR signaling, resulted in more severe disease in pulmonary pathology (Maglione et al., 2008). Furthermore, there are higher levels of FcγRI receptor quality expression in people with active TB compared to inactive TB (Sutherland et al., 2014), and these levels diminish throughout therapy (Cliff et al., 2013). FcγRI is an activating receptor, which is upregulated by cytokines such as IFN-γ and GM-CSF and binds with high affinity to IgG1, IgG3, and IgG4 in comparison to the low-affinity FcγRIIIa or IIa (Hogarth, 2012).
As such, high FcγRI levels in active TB may either be a marker of or contribute to the inflammation. At a cellular level, immune cells expressing Fc receptors have been implicated in both the enhancement of bacterial uptake, as well as the control of bacterial fate, in the context of antibodies (Milla et al., 2019). In studies with human cells and Mycobacterium tuberculosis, macrophages, NK cells, and alveolar epithelial cells have been illustrated to both possibly repress additionally upgrade bacterial development within the setting of antibodies (Milla et al., 2019).
Be that as it may, upon the expansion of filtered polyclonal IgG after Mycobacterium tuberculosis disease, the intracellular bacterial burden is diminished within the setting of antibodies from inactive compared to active TB people (Lu et al., 2016). Particularly, the classical antibody-inspired effector capacities of NK cell actuation and consequent generation of granulysin to interceded ADCC have been watched (Lu et al., 2016; Roy et al., 2018).
Additionally, phagolysosomal fusion, inflammasome activation, and IL-1β production could be elicited more with polyclonal IgG purified from individuals with latent compared to active TB (Lu et al., 2016). Typically steady with monoclonal antibodies upgrading BCG lysosomal colocalization (Joller et al., 2010). Pre-hatching with human serum containing mycobacterial particular IgG and IgM encourage upgrades to complement authoritative to mycobacteria (Carrol et al., 2009).
4.8. The Antibody Reaction after Immunization
Mucosal or intravenous BCG inoculation in macaques was too as of late appeared to actuate close sterilizing resistance to MTB infection challenge, connecting with an increment in MTB-specific IgG, IgA, and IgM antibodies within the blood and bronchoalveolar lavage liquid (BAL) liquid (Dijkman et al., 2021).
IgG and IgM antibodies separated from the BAL of BCG immunization macaques have in this way been appeared to opsonize MTB and upgrade bacterial take-up by macrophages in vitro (Dijkman et al., 2021). Notably, MTBVAC—a live weakened MTB inferred immunization that evokes more vigorous and fast versatile resistant reactions compared with BCG (Dijkman et al., 2021).
Interestingly, oral administration of BCG led to increased anti-LAM IgA titers in tears, underscoring its capacity to induce mucosal antibody responses (Brown et al., 2003). Another ponder on intradermal BCG inoculation of members detailed increased AM-specific IgG reactions within the serum, which correlated with opsonization and killing of BCG by human macrophages (Chen et al., 2016).
Here, elevated Ag85A-specific IgG within the serum is related to diminished hazard of illness after BCG inoculation (Fletcher et al, 2016). At long last, and comparative to MTB disease, BCG immunization was appeared to initiate high avidity IgG antibodies to bulk surface antigens, like tuberculosis glycolipid (Nabeshima et al., 2015).

4.9. Antigens Targeted by Humoral Immunity during Tuberculosis Infection
Nevertheless, the foremost regularly recognized antigens for serological think about incorporating alpha-crystallin, HBHA, AM/LAM, antigen 85 (Ag85), PstS1, LpqH, MPT32, and malate synthase G (Steingart et al., 2009). Most of these antigens are recognized within the cell envelope and are at the slightest somewhat included in bacterial interaction with macrophages. Most of these antigens are at the slightest incompletely found within the
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cell envelope of MTB, highlighting the significance of this layer in creating antibody reactions amid disease (Clemens Hermann and Carolyn G. King, 2021).
The Ag85 complex, consisting of the subunits Ag85A, Ag85B, and Ag85C, is a secreted protein that also exhibits cell wall glycosyltransferase activity and is required for the biosynthesis of cord factor, a virulent glycolipid that drives granuloma formation (Belisle et al., 1997). Ag85 has a high affinity for fibronectin and facilitates the attachment of MTB to murine alveolar macrophages. PstS1 is a surface-exposed lipoprotein involved in the uptake of inorganic phosphate, an essential but often limiting nutrient in the microenvironment. Like Ag85, PstS1 can also act as an adhesin for binding to human and mouse macrophages (Esparza et al., 2015).
LpqH, another cell surface-exposed antigen, is a glycoprotein that acts as a TLR2 agonist, inducing up-regulation of MHC II and cytokine secretion by macrophages (Greenway et al., 2005; Nossa et al., 2001). The antigen MPT32 is secreted by MTB early on during disease progression but has also been detected in the cell envelope fraction of MTB. MPT32 functions as an adhesin and is suggested to be involved in the invasion of epithelial cells (Abeba et al., 2007). Lastly, malate synthase G is a cytosolic protein that functions in glycolate metabolism and elicits strong antibody responses during active TB (Laal et al., 1997).
Most of these antigens are at least partly located in the cell envelope of MTB, highlighting the importance of this layer in generating antibody responses during infection. In general, antibodies that bind to cell-surface exposed antigens can lead to opsonization, thereby impacting bacterial uptake and intracellular trafficking by phagocytic cells (Clemens Hermann and Carolyn G. King, 2021).
4.10. Attempts to Connect Antibody Specificity and Tuberculosis Illness
MTB disease is clinically tested by two tests: the tuberculin skin test (TST) and the interferon-ℽ (IFN-ℽ) release assay (IGRA). The TST involves an injection of PPD into the skin, which results in a delayed-type hypersensitivity reaction in individuals with previous MTB exposure or infection. IGRA measures IFN-ℽ production by MTB-specific T cells following ex vivo stimulation with MTB peptides, ESAT6, and CFP10 (Clemens Hermann and Carolyn G. King, 2021).
Individuals who stay TST and IGRA despite high presentation to individuals with clinically analyzed MTB have been named ‘resisters’ or ‘long-term controllers’ (Simmons et al., 2018). Antibodies from the serum of resisters were responsive to PPD, Ag85, ESAT6/CFP10, alpha-crystallin, GroES, and LAM (Clemens Hermann and Carolyn G. King, 2021). Although the specificities of antibodies isolated from resisters and individuals with latent TB infection were largely overlapping, bulk PPD-specific antibody responses in resisters were qualitatively distinct from individuals with latent TB, with higher avidity IgG and higher titers of antibodies capable of eliciting IFN-ℽ secretion of NK cells (Lu et al., 2019).
Although glycosylation of the Fc antibody domain regulates IgG structure and effector function, the link between glycosylation and function reflects changes in antibody specificity. Increased galactosylation that correlates with reduced antibody efficacy during active TB could represent the expansion of nonspecific plasma cells, which poorly target MTB (Clemens Hermann and Carolyn G. King, 2021).
MTB-specific plasma blasts appeared a high recurrence of IgA+ B cells proposing their mucosal root. Importantly, IgA antibodies were able to prevent epithelial cell infection in vitro while IgG antibodies with identical specificity either promoted infection or had no effect (Clemens Hermann and Carolyn G. King, 2021). In MTB infection, the high plenitude of IgG and IgA plasma cells within the lung is connected with a high bacterial load (Gideon et al., 2020). IgG antibodies focusing on AM in latently infected patients were found to upgrade take-up of MTB and intracellular killing by human macrophages in vitro. This impact was subordinate to anti-AM-specific antibodies since consumption of AM particular antibodies repealed the impact (Chen et al., 2020).

Future applications of antibody formulations for the control of TB may include several possibilities including treatment, prevention, and diagnosis.
5.1. Treatment
Antibody-based therapy could potentially be useful in several scenarios. They could be used to shorten the standard treatment period of patients with uncomplicated TB when coupled with standard chemotherapy. However, they would be particularly important in the treatment of patients infected with Multi-drug Resistant (MDR) and Extensively Drug-Resistant (XDR) strains, in combination with the standard treatment (Armando et al., 2017).
Monoclonal antibodies against the surface of Methicillin-resistant Staphylococcus Aureus (MRSA) have very recently been used to deliver antibiotics directly to host cells, where MRSA appears to establish intracellular reservoirs to evade host immunity (Lehar et al., 2015). Utilizing comparable novel antibody-antibiotic conjugate innovation, Mabs seem possibly to be adjusted to provide drugs straightforwardly to TB-infected have cells (Ashley et al., 2016).5.2. Prophylactic use
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Prophylactic use of antibodies could be applied in recent contacts of TB patients, with special attention to risk groups (Norazmi et al., 2005). In this regard, successful prophylactic use of antibodies in exposed individuals has been shown in the case of several other pathogens such as varicella, tetanus, Respiratory Syncytial Virus (RSV), rabies, and Hepatitis B (Casadevall et al., 2004).
5.3. Vaccines
The induction of specific protective antibody responses by vaccination, either alone or as an addition to the stimulation of cell-mediated immunity could be a novel strategy for the development of the new generation of prophylactic and therapeutic vaccines against TB.
The prevailing past dogma that discounted the role of antibodies in host protection against TB has resulted in a limited study of B cell immunodominant epitopes as targets for protective immunity (DeGroot et al., 2005).
5.3.1. Polysaccharide conjugate vaccines
Polysaccharide conjugate vaccines are considered to elicit specific protective antibody responses against a variety of pathogens (Pollard et al., 2009). However, the polysaccharide conjugate vaccine against Salmonella typhi (Thiem et al., 2011) demonstrates the feasibility of this kind of vaccine for the prevention of infectious diseases caused by intracellular pathogens. In the case of M. tuberculosis, several authors reported the use of polysaccharide conjugated vaccine candidates (Glatman Freedman et al., 2004). Arabinomannan protein conjugate immunization initiated both antibody and T-cell reactions. Counteraction of LAM-induced T-cell suppression and inhibition of macrophage function by an antibody is another potential mechanism (Hamasur et al, 2003).
All these vaccine candidates induced the production of specific IgG (Schwebach et al., 2002) and some of them conferred variable levels of protection (Hamasur et al., 2003) which validate this strategy as one of the potential avenues for the development of a new generation of vaccines against tuberculosis.
5.3.2. Identifying other B-cell immunodominant epitopes
With the development of bioinformatics tools for bacterial genome analysis, it has been possible to predict in silico microbial regions that trigger immune responses relevant for protection and vaccine development. A candidate experimental vaccine based on proteoliposomes from M. smegmatis is currently in development (Rodriguez et al., 2011). In one study, a bibliographic search was used to identify highly expressed proteins inactive, latent, and reactivation phases of TB (LeThuy et al., 2010). The subcellular localization of the selected proteins was defined according to the report on the identification and localization of 1044 M. tuberculosis proteins using two-dimensional, capillary high-performance liquid chromatography coupled with mass spectrometry (2DLC/MS) method (Mawuenyega et al., 2005) and using prediction algorithms of a new generation of vaccines against tuberculosis.
In addition to cellular immune effectors recognizing antigens from M. tuberculosis, cross-reactive humoral immune responses of several IgG subclasses corresponding with a combined Th1 and Th2 pattern against antigenic components of M. tuberculosis were elicited. These findings were in concordance with the in silico predictions (LeThuy et al., 2010). It is interesting to note that differences in the pattern of humoral recognition of lipidic components were dependent on the characteristics of the adjuvant used, which could have relevance for the development of vaccines that includes lipidic components (Rodriguez et al., 2011).
Bioinformatics tools for the prediction of T and B epitopes were also employed for the design of multi-epitopic constructions, which were used to obtain recombinant BCG strains. Based on this prediction, B cell epitopes from ESAT-6, CFP-10, Ag87B, and MTP40 proteins were selected and combined with T cell epitopes of the 87B protein and fused to Mtb8.4 protein (Acosta et al., 2010).Next-generation sequencing has moreover contributed to the illustration of the Antibodies collection in reaction to infection and immunization (Georgiou et al., 2014). This progress may permit mapping of how the antibody reaction creates amid active TB infection, and how it is subverted by MTB to avoid the arrangement of any defensive antibodies as proposed by the antigenic variety in B-cell epitopes and the need for surface-binding antibodies (Ashley et al., 2016). The thinks about clinical populaces who show up to be safe to securing inactive disease with MTB are too of extraordinary intrigued in arrange to get it resistance against TB (Fletcher et al., 2016).

5.3.3. Diagnosis
Although no serological assays are currently recommended for the diagnosis of TB (Morris, 2011), largely due to the possibility of false results and thus incorrect treatments, for many other pathogens, serological diagnostic tests have been of great value, particularly in poor countries. In some cases, antibody responses can constitute useful correlates of protection (Edwards, 2001). In the specific case of TB, several studies of the antibody response have been reported (Velayudhan and Gennaro, 2010).
There is a substantial amount of variability in antibody response to TB (Navon et al., 2003). This variability has been attributed to several factors. Some of these factors are associated with the pathogen (strain variation, microenvironment, and growth state of bacteria) and others are related to the host, primarily previous exposure to related antigens and host genetics [99]. However, it is important to consider that only a small fraction of the genomic regions of M. tuberculosis encoding proteins have
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been explored. Currently, novel immunoassay platforms are being used to dissect the entire proteome of M. tuberculosis, including reacting protein microarrays with sera from TB patients and controls [101,102]. These studies could lead to the discovery of new antigens that may constitute suitable diagnostic markers and tools for the identification of protection correlates.

Infection and illness caused by MTB emphatically invigorate humoral resistance in people. Even though CMI remains the overwhelming relate of security, there's proof to recommend that antibodies may contribute, at the slightest in portion, to resistance. The nearness of antibodies against particular MTB antigens such as LAM shows up to vary in patients with pneumonic and dispersed TB.
This compares to mAbs against LAM and HBHA that can diminish the bacillary stack and avoid dispersal of mycobacterial disease. Antibodies are presently broadly caught on to tweak CMI through FcR official and especially surface-binding antibodies in cases of mycobacterial contamination in test models. It is hence of intrigued that such antibodies don't appear to be invigorated amid normal disease, and the trend in protective mAbs hence distant could be a proposal that surface official with focusing on to FcR for improvement of CMI can happen in vivo.
These discoveries point to the require for assist testing of whether antibodies may bestow predominant security in immunization by improving CMI, or can avoid contamination on the off chance that shows earlier to have experience with MTB. Numerous challenges stand in this way, such as a need for information concerning the presence of useful mAbs in people and which epitopes are likely to initiate their arrangement. Be that as it may, modern innovations presently exist to conclusively address the achievability of joining objectives to target AMI within the plan of the following generation of antibody candidates.
There's a recommendation that Antibody-based therapy could potentially be useful to shorten the standard treatment period of patients with uncomplicated TB when coupled with standard chemotherapy. The study of the antibodies application in tuberculosis opens new possibilities for future development of new vaccines, diagnostics tools, and therapies against mycobacterium tuberculosis. Discoveries will likely arise from the ongoing studies in this area that will expedite the introduction of new strategies in the fight against tuberculosis.

The author declare no conflicts of interest.