**2. Specific antibodies: Players in the defense against TB**

In order to develop improved vaccines and new methods for controlling TB, an important element is the discovery of markers to measure the effectors' mechanisms of the protective immune response against *M. tuberculosis*.

**4. Experimental studies**

infection as it occurs in humans [19].

An important criterion for the evaluation of the role of specific antibodies in the protection against TB is the use of animal models. Currently, there is no optimal model to re-produce the

The Role of Antibodies in the Defense Against Tuberculosis

http://dx.doi.org/10.5772/53950

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The geographical location, genetic factors of the host, the presence of environmental myco‐ bacteria and other concomitant infections like helminthiasis, are factors that have to be considered when designing animal experiments [20]. Several animal models have been used to evaluate different aspects of mycobacterial infection and disease. A crucial aspect is the delivery of mycobacterial inoculum. In this regard, several routes of inoculation have been employed experimentally, including intravenous, intraperitoneal, intranasal, intratracheal

The study of the distribution of monoclonal and polyclonal antibody formulations in different organs and tissues of mice after administration by different routes, including the use of backpack models have been reported [23-27]. Each model has its advantages and drawbacks. For example, the backpack model is very useful for the evaluation of the protective role of IgA, but poses ethical problems in long term experiments due to the increase in tumour size over time produced by the inoculated hybridoma [28]. In prophylactic and therapeutic models, antibody formulations have been administered via the intranasal [29], intravenous [30] and intraperitoneal [26] routes and combined with cytokines and antibiotics [31, 32] before and/or after the infectious challenge. The administration of *M. tuberculosis* pre-coated with antibodies [27, 33] in different models of infection has also contributed to understanding the interactions

Another approach has been the use of knockout mice models for IgA [34] polymeric immu‐

A substantial number of studies utilizing anti mycobacterial antibodies have been conducted as far back as the end of the 19th century. These experiments can be grouped into several categories: serum therapies, mouse polyclonal antibodies, human polyclonal antibodies (including commercial human gamma globulins), secretory human IgA (hsIgA) and studies

Serum therapy experiments were conducted from the second half of the 19th century (reviewed in [39,40]). Immune sera was generated by immunizing animals with different mycobacterial fractions and administered either to animals or humans [39,40] The results obtained were either beneficiary, variable, inconclusive or contradictory, [39,40]. These variable results led to the

perceived minor role of antibodies in the defense against *M. tuberculosis*.

noglobulin receptor (pIgR) [34] and B cells [35,36,37,38], as will be discussed later.

**4.1. Animal models**

and aerosol [21, 22].

between host and microbe.

with monoclonal antibodies.

*4.2.1. Serum therapies*

**4.2. Experimental studies with antibodies**

For many years Cell-Mediated Immunity (CMI) was viewed as the exclusive defense mecha‐ nism against intracellular pathogens. The Th1/Th2 classical paradigm prevailed for a long time and the development of vaccines followed this theory [6]. Based on this theory, only intracel‐ lular pathogens could be effectively controlled by granulomatous inflammation induced by a Th1 response, whereas a Th2 response induces antibody production that controls extracellular pathogens and parasites. However, the question of what constitutes a true demarcation between "extracellular and intracellular" pathogens is important in this regard. During their infectious cycle, intracellular pathogens could be found in the extracellular space and *vice versa*. In the specific case of *M. tuberculosis*, it can be localized extracellularly at the beginning of the infection in the upper respiratory tract as well as during advanced stages of the disease, after rupture of granulomatous lesions occur [7]. This facultative intracellular pathogen was shown to have an extracellular phase [7] [8] that may include replication [7] which in turn could potentially be targeted by specific antibodies.

There are several prokaryotic and eukaryotic intracellular pathogens for which antibody have been shown to modify the course of infection by different mechanisms, as reviewed extensively by Casadevall and colleagues [9, 10, 11]. In the case of *Erhlichia* spp., specific antibodies were shown to mediate protection [12], possibly by blocking cellular entry or promoting the expression of proinflammatory cytokines. [13,14]. A combination of both humoral and cellular immune mechanisms could be the optimal choice controlling certain intracellular patho‐ gens,.In this regard, de Valliere and colleagues reported that human antimycobacterial antibodies enhanced Cell-Mediated Immune responses to mycobacteria that are beneficial to the host [15].
