Acquired immune system

It takes the acquired immune system about 6 days to respond to an infection. A class of white blood cells called lymphocytes (i.e. B-lymphocytes and T-lymphocytes) mediates acquired immunity. B-lymphocytes produce soluble plasma proteins called antibodies. Each B-lymphocyte can only be activated by its specific antigen, and can only produce antibodies against one of the millions of foreign antigens that may infect the body. Also, each T-cell bears cell surface receptors that can only bind one type of foreign antigen among the vast number of foreign antigens that abound. The defining features of acquired immunity are “specificity” and “memory”.

Specificity

A B-lymphocyte bears immunoglobulin antigen receptors that can recognize and attack one foreign antigen, strongly enough. Reason being that one B-cell is specific for one antigen only. Nevertheless, the same B-cell can bind other antigens, but its interaction with other antigens will be very weak.

The same thing applies to T-cells; each T-cell has several identical receptors on its surface membrane. These receptors are unique for each T-cell, and can only bind one antigen with high specificity. This phenomenon is termed the specificity of acquired immunity

Memory

The first time a pathogen infects your body; B and T-lymphocytes, which are specific for the infecting pathogen, recognize the pathogen and become activated. Activated B and T-lymphocytes divide, multiply and differentiate into two cell types: effector cells and memory cells. Effector B and T-cells are responsible for killing the invading pathogen.

Cellular mediators of acquired immunity (T and B-lymphocytes)

Lymphocytes are the cellular mediators of acquired immunity. Lymphocytes are the only immune cells capable of recognizing specific antigens using a vast number of highly specific receptors: T-cell receptors for T-lymphocytes and immunoglobulin antigen receptors for B-lymphocytes.

T-lymphocytes: some of the lymphocytes migrate from bone marrow and populate the gland called thymus. In the thymus, these lymphocytes get transformed into T-lymphocytes under the influence of the hormone called thymosin.

B-lymphocytes: In humans, during fetal life, our lymphocytes travel to liver where they mature. However, after birth, our bone marrow no longer sends immature lymphocyte precursors to liver, instead, bone marrow produce mature B-lymphocytes. In order words, after birth, B-lymphocytes leave the bone marrow into circulation as mature B-lymphocytes.

The morphology of B and T-lymphocytes is identical but the two cell types can be distinguished based on glycoprotein markers they carry on their surface membrane.

Branches of acquired immunity

Acquired immunity has two branches: humoral and cell-mediated immunity. Cell-mediated immunity is mediated by special receptors found on the surface membranes of T-lymphocytes; these surface receptors are called T-cell receptors (TCR).

Humoral immunity

Soluble proteins called antibodies mediate humoral immunity; antibodies dissolve in blood, lymph and other body humors. This is the reason antibody-mediated immunity is called humoral immunity. Antibodies bind antigen to form antigen-antibody complexes. Each B-lymphocyte in the body is genetically determined to respond to, and produce antibodies against a particular foreign antigen. Humoral immunity essentially defends the body against extracellular pathogens (i.e. mainly bacterial pathogens).

If a clone of B-lymphocytes fails to encounter their specific antigen in circulation, the lymphocytes will never get activated. And they will remain viable and dormant in what is called resting state, B-lymphocytes that remain in resting state and circulate just for few days before they undergo apoptotic cell death. However, when resting B-lymphocytes come in contact with its specific antigen, the B-lymphocyte gets activated and begins to divide and multiply into two groups of daughter cells.

While all daughter cells of the activated B-lymphocytes share certain features, they actually represent two cell types with different effector functions.

  1. Effector B-cells also called plasma cells.
  2. Memory B-cells

Effector B-cells produce antibodies: most of the B-cells divide and differentiate into larger and more functional cells called plasma cells. Plasma cells flood the system with antibodies against the inducing antigen.

Plasma cells produce a variety of antibodies (immunoglobulins), which mediate humoral form of acquired immunity

Plasma cells produce a variety of antibodies (immunoglobulins), which mediate humoral form of acquired immunity

Understand that the antibodies produced are specific for the antigen that activated the B-cell. In other words, these antibodies will only bind and kill cells that bear antigens which induced the antibody generation, and will fail to bind any other class of antigens in the system. Effector B-cells can survive for few days to few weeks, during which they produce large amounts of antibodies.

Memory B-cells keep immunological memory of foreign antigens: interestingly enough, not all activated B-cells differentiate into plasma cells; some differentiate into memory B-cells. Moreover, after every immune response, most of the plasma cells (effector B-cells) will die by apoptosis leaving behind a handful of memory B-cells.

Capture11Memory cells do not produce antibodies, but they bear surface immunoglobulins on their membrane surfaces. These surface immunoglobulins are receptors that recognize the antigen that induced the immunoglobulin formation. Memory B-cells can remain viable (capable of reproduction) and dormant for decades.

The second time the same antigen infects the individual for a second time, the antigens bind to surface immunoglobulins on memory B-cells stimulating the memory cells to multiply, and differentiate immediately into plasma cells and produce antibodies in an explosive fashion. The second immune response is very potent and results in the quick elimination of the pathogen even before it can cause any harm to the host.

Cell-mediated immunity (cellular immunity)

Capture12T-cell receptors (TCR) mediate cellular immunity. Cytotoxic T-cells kill by inserting perforins and by initiating apoptosis. Helper T-cells secrete cytokines that activate B-cells to produce antibodies. Helper T-cells also secrete cytokines that activate macrophages, and enhance the ability of macrophage to kill engulfed intracellular pathogens. Thus as the name implies, Helper T-cells help other cells of the immune system to perform their roles.

It is important to note that if Helper T-cells fail to activate B-cells, B-cells will be unable to produce antibodies.

Cellular immunity is a major defense against infections due to intracellular pathogens such as viral particles, fungi, and a few bacterial cells. Cellular immunity is also defends against tumors.

Helper T-cells help macrophages in killing intracellular pathogens

A host of human pathogens avoid attack, by antibodies in blood and other ECF compartments, by invading body cells and taking up residence right inside host cells. Such pathogens are called intracellular pathogens. All viral particles (recall virus is not a cell, but a particle), few bacteria and handful of protozoa are intracellular pathogens to human.

Intracellular pathogens develop defensive measures that enable them to survive right inside host cells; sometimes phagocytes engulf intracellular pathogens, but are unable to kill them using the normal phagocytic intracellular killing mechanisms.

When macrophages engulf intracellular pathogens, which they are unable to kill usually, they recruit help from Helper T-lymphocytes. Macrophages recruit help from CD4+ T-cells by displaying fragments of the antigens derived from these pathogens on class-II MHC proteins. Helper T-lymphocytes which bear receptors for the displayed antigens bind the displayed antigen and becomes activated. Activated Helper T-cells release cytokines (lymphokines) that stimulate macrophages, sufficiently enough, to kill the engulfed pathogens. Thus Helper T-cells helps macrophages in killing intracellular pathogens.

Cytotoxic T-cells kill host cells, which are virus-infected or damaged

Viral particles can infect virtually any cell in our body. The saving grace is that all body cells express class-I MHC proteins on their surface. If any cell in our body is infected by viral particle, the cell displays antigen fragments derived from the viral particle on the class-I MHC protein.

Capture13

Cytotoxic (CD8+) T-cells, which bear receptors for the displayed antigens, bind and destroy the cell. Most times, this prevents the multiplication and spread of the virus within the body. Cytotoxic T-cells kill by inserting perforins and by initiating apoptosis.

Fell free to ask questions, and leave your comments.

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