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The Art of Immune Warfare - The Arsenal

Updated: Jun 8, 2020

We looked at the key players of our immune system, now lets look at the arsenal at their disposal.


The Arsenal

Weapons

Most WBCs produce chemicals of many kinds that modulate the functional activities of many other cell types. Immune response involves a lot of cell-to-cell communication, and WBCs make and use proteins, enzymes, hormones, and neurotransmitters to facilitate the immune response. Some of these molecules share similar physiology to  other organ systems. Others are special creations of the immune system and have no other functions. Several different cell types coordinate their efforts as part of the immune system, including B and T cells, macrophages, mast cells, neutrophils, basophils and eosinophils. Each of these cell types has a distinct role in the immune system, and communicates with other immune cells via various chemical compounds and proteins. Lets look into the various weapons our immune system possess to engage in a warfare.


Chemical Warfare

The immune system produces numerous chemicals to destroy a pathogen or to communicate with other immune cells. Chemical mediators are molecules responsible for many aspects of innate immunity. Some chemical mediators on the surface of cells, such as lysozyme, sebum, and mucus, kill microorganisms or prevent them from entering the cells. Other chemical mediators, such as histamine, complement proteins, and cytokines etc, promote inflammation by causing vasodilation and increasing vascular permeability, attract white blood cells, and stimulate phagocytosis (Pakman). Lets look at the key chemical mediators in a bit detail.



Histamine

Histamine (a derivative of amino acid Histidine) is a nitrogen compound with several physiological functions but is best known for its role in local immune responses. Histamine is produced by basophils and by mast cells found in nearby connective tissues as part of the inflammatory response. It plays a major role in many allergic reactions because they get overstimulated. As part of the inflammation response, histamine dilates small blood vessels, activates the vascular endothelium, and increases blood vessel permeability to WBCs and inflammatory proteins. It also irritates nerve endings, leading to itching or pain.


For example, people who have hay fever inhale antigens (usually plant pollen), which are then absorbed through the respiratory mucous membrane. The combination of the antigens with antibodies stimulates mast cells to release inflammatory chemicals, such as histamine. The resulting localized inflammatory response produces swelling and increased mucus production in the respiratory tract.




The itchy bump on your skin after a mosquito bite is caused not by the bite but by the

histamine that’s released to initiate the process by which the antigens that the

mosquito introduced are destroyed. It’s also why scratching them makes the itch

worse. You damage the surrounding tissue, leading to more inflammation!


Cytokines

Cytokines are proteins secreted by one cell to regulate the function of another cell, thereby serving as intercellular chemical messengers. They are signalling molecules that allow cells to communicate with each other over short distances. They mediate and regulate immunity, inflammation and haematopoiesis (formation of blood cells). They regulate the intensity and duration of immune response and stimulate the proliferation and differentiation of cells. They are secreted by phagocytes and helper T Cells (Interleukins) and Infected Cells (Interferons).


Cytokine is just a general name and other names are defined based on their presumed function like cell of secretion or target of action. Once secreted, the cytokine binds to a specific molecule, called a receptor, on the surface of the target cell, an event that triggers a signaling cascade inside that cell.


Examples of cytokines are Interferons, Interleukins, and TNF-alpha.


Interferons are produced by the body’s cells as a defensive response to viruses, combat bacterial and parasitic infections. They are important modulators of the immune response by inhibiting the replication of the infected cells. Cells that have been infected with a virus produce interferon, which sends a signal to other cells of the body to resist viral growth. They are produced by various types of WBCs. They pretty much raise the alarm so the neighbouring cells can be more alert and prepared for an assault.


Interleukins induce fever and the acute-phase response. When the body is invaded by a pathogen, macrophages release the protein signals interleukin-1 (IL-1) and interleukin-6 (IL-6) to help fight the infection. One of their effects is to raise the temperature of the body, causing the fever that often accompanies infection. They are also key signalling molecules to activate Helper T Cells and B Cells.


TNF (tumour necrosis factor)-alpha, initiates the inflammatory response. TNF is produced by macrophages when they encounter the poisonous substance in bacteria that is known as an endotoxin (toxic substance bound to the bacterial cell walls). This one's a bit of a rebel and seems to perform both helpful and harmful functions within the body. The release of TNF in response to the presence of endotoxins appears to be responsible for most of the septic shock related issues in humans, however it seems to help the body defend itself against malarial parasites.


There are both pro-inflammatory cytokines and anti-inflammatory cytokines.



Antigens and Antibodies

Our immune system can recognize, respond to, and remember a particular pathogen. Components on these pathogens that stimulate the adaptive immunity are called Antigens (Remember the identity card?). Antigens can be further divided into two groups. Foreign and Self Antigens. Foreign antigens are not produced by our body but are rather introduced from outside. Components of bacteria, viruses, and other microorganisms are examples of foreign antigens. An antigen that induces an immune response is called an immunogen. Many of these trigger an allergic reaction, an overreaction of the immune system in some people.


If an adaptive immune system response is to occur, lymphocytes must recognize an antigen. However, lymphocytes do not interact with an entire antigen. Instead, lymphocytes interact with specific regions of the antigen called antigenic determinants (keys with different shapes), or epitopes. So an antigen has many different uniquely shaped keys on its surface. Our immune system produces antibodies with an identical antigen receptor which can bind to the keys on the antigen and thereby triggering an immune response. So each receptor (lock) can only bind to a specific, matching determinant (key). Binding between the receptor and epitope occurs only if their structures are complementary. This complementarity of shape allows the receptor and the foreign molecule to conform to each other and activate B-cell production of antibodies. A bit like a jigsaw puzzle!



Antigens, in fact, aren’t a bad thing at all — they’re actually essential. It’s like every living cell is always wearing its own, personalized hat, and that’s how we recognize them from non-self.


Antibodies are produced by specialized white blood cells called B Cells. Antibodies directly affect antigens by inactivating the antigens or binding the antigens together (clumping). They recognize and latch onto antigens in order to remove them from the body. Antibodies together provide one of the most important functions of immunity, which is to recognize an invading antigen and to produce a tremendous number of protective proteins that scour the body to remove all traces of that antigen. Antibodies can directly affect antigens in two ways:

  1. Antibodies can bind to the antigenic determinant (Key) and interfere with the antigen’s ability to function or

  2. The antibody can combine with an antigenic determinant on two different antigens, rendering the antigens ineffective.


The amount of antibody formed in response to stimulation depends on the kind and amount of antigen involved, the route of entry to the body, and individual characteristics of the host.


Antibodies are also known as Immunoglobulins and come in five classes. IgA, IgD, IgE, IgG, and IgM. Each class is designated by a letter attached to an abbreviation of the word immunoglobulin.

IgG antibodies are the most important class, accounting for about 80 percent of the antibodies. They’re the type most involved in the secondary (adaptive) immune response as they circulate in the blood and other body fluids.

  • IgAs are found in exocrine secretion (like tears and bile). They protect against infections of the mucous membranes lining.

  • IgDs are found on the surfaces of B cells (forming the receptors), they have been shown to activate basophils and mast cells to produce antimicrobial factors.

  • IgMs are specialized for blood compatibility. This large antibody molecule is particularly effective at attaching to antigenic determinants present on the outer coats of bacteria. When this IgM attachment occurs, it causes microorganisms to agglutinate, or clump together.

  • IgEs binds to allergens and triggers histamine release from mast cells and basophils. They are mostly involved in allergic reactions and promote inflammation.

  • IgGs are a major type of antibody found in the blood that can enter tissues and fight infection. In its four forms, provides the majority of antibody-based immunity against invading pathogens.

Memory B cells, which are specialized for responding to repeat infections by a given antigen,

make IgG or IgA immediately. The tail of the antibody determines the fate of the antigen

once it becomes bound to the antibody. They are responsible for the special

biological properties of immunoglobulins.


IgG is the only class of immunoglobulin capable of crossing the placenta thereby providing

some degree of immune protection to the developing foetus. These molecules also are

secreted into the mother’s milk and, once they have been ingested by an infant,

can be transported into the blood, where they confer immunity.



Complement system proteins – Prime the pathogens for the real killers (Antibodies)

The complement system is a complex system of more than 30 proteins that act in concert to help eliminate infectious microorganisms. These proteins are produced mainly by the liver and they just hang around in the blood waiting for a signal. Once they get a signal they get activated and sets off a chain reaction. They support the activity of antibodies to clear pathogens. This system is activated by either the innate or adaptive immune response, triggered by antibodies bound to the surfaces of a microorganism (classic pathway - adaptive response) or directly by molecules embedded in the surface membranes of invading microorganisms (alternate pathway - innate response)



The functions of complement proteins include:

  • Making bacteria more susceptible to phagocytosis (Pakman)

  • Directly lysing (breaking down) some bacteria and foreign cells

  • Producing chemotactic substances (signalling molecules)

  • Increasing vascular permeability

  • Causing smooth muscle contraction

  • Promoting mast cell degranulation (release the contents within)

Now that we are locked and loaded, lets get stuck into the act of war! That's coming up..

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