Immunological Principles of Activation and Response by T-Lymphocytes: A Concise Overview on T-Cytotoxic and T-Helper Cells

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Abstract:

Immunological principles deal with a varied spectrum of host defense system, incorporating subjects dealing with the introduction of xenobiotics/ allergen/pathogen, to the immune responses evoked in the host defense system by the former insulting agents. The basic aim of this review article is to highlight the basic principles of immunology including the major role players in the scenario, activation and the ultimate response shown by the same.

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1) Introduction

T-lymphocytes play a major and prior role in almost all the infectious diseases: both curable as well as non-curable. Besides this, some diseases are themselves caused due to hyperactivity of immune system, with T-lymphocytes playing the ultimate role. Rather, the recent trend of shifting the pharmacological agents from therapeutic and chemotherapeutic agents to immunological agents like monoclonal antibodies, is just enough to augment the priority of knowing the basic principles of immunology.
T-Lymphocytes primarily compose of T-Helper, T-Cytotoxic and T-Suppressor Cells. However, the first two are dealt with since they are the principal agents of activation of host’s immunity, which is else contradicted by T-suppressor cells [9].

2) T-helper cells

Though, the role played by T-helper cells is varied and wide, but the stimulus which makes T-helper cells to start acting is more or less the same. Actually, the domain of immunology is very complex to understand but the different types of lymphocytes start acting in their own unique ways.

2.1) Brief Description

It consists of a regular eukaryotic leukocyte cells; the difference being primarily in the cell membrane molecules.
It has 2 main receptors:

2.1.1) TCR- This abbreviates for T-Cell Receptor and is the receptor that is present in all the lymphocytes and functions to bind the MHC classes in the body and thereby getting evoked to play further actions.

2.1.2) CD4 – This is present only on T-helper cells and characterizes this sub-class of lymphocytes.
Further, 2 sub-sets of helper-T cells have been recognized-

Th1 cells, producing IL-2, IL-3, gamma-interferon and granulocyte/macrophage colony stimulating factor in response to antigent presenting cells (APC), and
Th2 cells,producing IL-3, B cell Stimulatory Factor 1, mast cell growth factor and T-cell growth factor [1].

Th1 cells inhibit development of Th2 cells, while Th2 cells inhibit Th1 cell development, macrophage activation and bactericidal activity [6].

2.2) The initial Stimulus

The initial impulse depends much upon the antigens against which the body has to act. These antigens may be bacterial antigen, xenobiotics (foreign substances) etc. These antigens are initially ingested by a special class of leucocytes named Antigen Presenting Cells (APC) or Dendritic cells [7] which constitute primarily of macrophages and monocytes.

Moreover, these APC have a special components which aid in their recognition by the lymphocytes. These ‘components’ are called as Major Histocompatibility Complex- II (MHC-II). These processed antigens are then bound over to MHC-II over APC surface. This plays as an initial actor to stimulate T-helper cells later in the play.

2.3) Response by T-Helper cells

Now, the APC is ready with the processed antigens. The only task that is remaining is to summon the T-Helper cells. The APC plays a role here by secreting various types of cytokines. These chemicals are chemo attractant in nature and allure the lymphocytes. But only T-Helper cells can bind because only it has the receptor to bind to MHC-II that is present over APC. Usually, Th1 type helper cells are activated by this process.On binding of T-helper cells, they further evoke the phagocyte cells (macrophages, monocytes and neutrophils) and B-cells (humoral immunity; might accompany activation of complement system further amplifying the protective response and even damage body’s own cells), by releasing lymphokines like IL2 and gamma-interferon [6]. These helper cells, however, have been found to undergo self-apoptosis upon irradiated by UVA radiation bu means of generation of singlet oxygen free radicals [5]. Neutrophils and monocytes play a role in first 24 hours of inflammatory response, while macrophages, being the activated form of monocytes (Monocytes converted macrophages), dominate the scenario of inflammatory response after 24 hours. These phagocytes, inturn, release cytokines like TNF-alpha, free radicals etc. The release IL-2 further summon cytotoxic T-cells to carry out further role in inflammatory process [2]. These helper T-cells have a well adapted ability to distinguish between self and non-self cells [11].

3) T-Cytotoxic cells
T-Helper cells just act to evoke the response by other cells which actually kill the microbe responsible for delivering their antigens; T-Helper cells aren’t cytotoxic themselves. This role is played by another sub-class of T-lymphocytes called as T-Cytotoxic cells.

3.1) Brief Introduction

A T-Cytotoxic cell consists of a regular eukaryotic leukocyte cells; the difference being primarily in the cell membrane molecules.
It has 2 main receptors:

3.1.1) TCR- T-Cell Receptor is common to both T-Helper cells and T-Cytotoxic cells and functions to bind the MHC classes in the body and thereby getting evoked to play a role lethal for microbial (and even body’s own cells, sometimes) cells.

3.1.2) CD8 – This is present only on T-Cytotoxic cells and characterizes this sub-class of lymphocytes.

3.2) The initial Stimulus

The initial impulse depends much upon the antigens against which the body has to act, as similarly shown for T-Helper cells. But in this case, these antigens are usually viral antigens (viral peptides). These peptides enter the eukaryotic cells (host’s cells), enter the Rough Endoplasmic Reticulum and get processed to act as an effective antigen. Later, it enters the Golgi Body gets processed further and integrate therein with MHC-I class of membrane proteins and are then expressed over cell membrane. A second way of introduction of viral peptide is the synthesis (by transcription and translation) of viral peptide itself by the viral DNA and from there on similar cascade follows.

Now, the eukaryotic cell is ready to evoke the T-Cytotoxic cells.

3.3) Response by T-Cytotoxic cells

Now, the eukaryotic cell is ready with the processed antigens. The next task that is performed is to summon the T-Cytotoxic cells. The host cell plays this role probably by secreting various types of cytokines and even interferons (gamma-interferon), which serve to inhibit the growth of virus. Now, T-Cytotoxic cells approach the infected host cell as well as tumour cells [8] and kill them after they bind to them because they possess a TCR and CD8 which is specific for MHC-I found over host cells. The cytotoxic activity of cytotoxic T-cells is supposed to be caused by either of the 2 pathways:

2.3.1) Perforin Pathway- The activated cytotoxic T-cells release perforins which punches holes in the cell membrane of target cell, resulting in its lysis and hence death [3].

2.3.2) Fas Pathway- The activation of cytotoxic T cells upregulates the expression of Fas ligand by the lymphocytes, which upon binding to Fas molecule on the target cell, induces apoptosis of the latter resulting in lethal consequences on the target [3, 4].

4) Conclusion

This was a very minor portion of role played by T-Helper cells and disabling these cells in AIDS, by means of activation induced death due to apoptosis [10] might explain well what causes the whole of body’s immune system to get dampened down. There is no activation of phagocyte cells and hence, no neutralization and killing of toxins and microbes, resulting in an increased susceptibility of the infected host to variety of pathogenic diseases.

5) References-

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