Antibody dependent cell mediated cytotoxicity and anamnestic reactions: An insight on how the body handles infective cells.

in #stemng6 years ago (edited)

Antibodies are not capable of working independently to destroy antigens, there is always the need for an additional help from other systems which ensures the elimination of the antigens. The antibodies are in a way mere receptors as their primary function is to bind the antigen which may be an allergen, microbe, virus or even defective cells of the body through its antigen binding site and then activate other systems such as the complement system and effector cells of immune system.


Antibody-dependent Cellular Cytotoxicity. Image credit Wikimedia. Image by Satchmo2000. Creative Commons Attribution-Share Alike 3.0 Unported license.

The complement system is a system of extremely lytic proteins produced as zymogens by the liver hepatocytes and to an extent by the blood monocytes and macrophages. Synthesis of the complement proteins as zymogens ensures that they do not initiate any reaction until they are activated either by the binding of the antibody to an antigen or by immunogenic properties of microbes such as their cell walls.

When the complement system is activated, a series of cascading reaction ensues which eventually leads to the formation of a membrane attack complex, a series of activated proteins which destroys the cells by creating pores through which molecules and hydrolytic enzymes moves in and destroys the immunogenic cells.

However, the antibodies does not always go through this means, in some cases, antigenic cells which binds to the antibodies are lysed by another cells, these cells are the effector cells and this process is the antibody dependent cell mediated cytotoxicity. ‘Antibody dependent ’ in the sense that these effector cells will not function in the absence of an antibody-antigen complex, ‘cell-mediated cytotoxicity ’ in the sense that the destruction of these cells is by other cells.

Lets now discuss the Cells that are involved in Antibody dependent cell mediated cytotoxicity.

Natural killer cells


During the production of blood cells, the haemopoietic stem cells differentiates into lymphoid and myeloid progenitor cells; the myeloid progenitor cells further differentiates into blood cells such as the monocytes, megekaryocytes (platelets), polymorphornuclear cells (neutrophils), basophils, eosinophils and mast cells. The lymphoid progenitor cells differentiates into B-cells, T-cells and the natural killer cells. The B-cells produce plasma which is committed to the synthesis of antibodies; the T-cells are involved in cell mediated immunity.


hematopoiesis in human. Image credit Wikimedia. Image by Mikael Häggström Creative Commons Attribution-Share Alike 3.0 Unported license.

The natural killer cells are granular lymphocytes which lacks antigen receptors but are able to recognise the antigen-antibody complexes. The natural killer cells contains proteins known as perforins, when activated, they release these perforins and these proteins binds to the membrane of these immunogenic cells and allows the diffusion of serine proteases known as granzymes; granzymes induces the destruction of these cells through calcium ion (Ca2+) dependent reaction.


A colorized scanning electron micrograph of a natural killer cell from a human donor. Image credit Flickr. Image by NIAID. CC BY 2.0 licence.

The natural killer cell’s destruction mechanisms are non-specific, hence this reaction is similar in every cell it encounters, it also lacks the ability to keep memory of already encountered cells.

Amidst these short comings, the natural killer cells are effective enough to exert strong lytic effect in virus infected cells and also cancerous cells; they are a subject of Immunotherapy as it’s actions could be enhanced to destroy tumor cells and fight cancer, it’s reactions has lesser side effects than the already in use chemotherapy.

Eosinophils



Image credit Wikimedia. Image by BruceBlaus. Creative Commons Attribution 3.0 Unported license.

Eosinophils are bilobed granulocytes measuring about 12-17um in diameter, when stained, the granules in the cytoplasm of eosinophils appears orange in colour. Eosinophils are unprofessional phagocytes but are very active in the killing of parasites, they have receptors for the FC regions of immunoglobulins and the complement system.

Eosinophils store series of lytic proteins in their cytoplasm, these proteins includes the major basic protein located at the core of the cytoplasmic granules and three other proteins are located at the periphery of these granules namely, eosinophil peroxidase, eosinophil cationic protein and eosinophil derived neurotoxin. These proteins are released when the eosinophils are activated by binding to the antigen-antibody complex, when released, these proteins are capable of destroying parasites as large as helminthes.

Monocytes


myeloid progenitors differentiates into blood cells which includes monocytes, these monocytes circulates for few hours after which they mature into macrophages and enters the tissues; maturation into macrophages involves the enlargement of the monocytes, their organelles also enlarges and increases in size, there is also an increase in the phagocytic and cytotoxic abilities of the monocytes, the matures monocytes in the tissues are now known as macrophages.


monocytopoiesis; the process of production of monocytes. Image Wikimedia. Image by A. Rad, Mikael Häggström, Spacebirdy, RexxS and domdomegg. Creative Commons Attribution-Share Alike 4.0 International license.

The macrophages makes up the Reticuloendothelial system (RES) which is a system of macrophages in the tissues; macrophages of the Reticuloendothelial system has increased life span and are capable of lasting throughout an individual’s life time.


A macrophage. Image credit Wikimedia. Image by A. Rad, Mikael Häggström, Spacebirdy, RexxS and domdomegg. Creative Commons Attribution-Share Alike 4.0 International license.

Macrophages have affinity for the FC regions of immunoglobulins. When they detect the antigen-antibody complex, they are delivered to the site of infection, through normal phagocytic process, they engulf the antigenic cells and release hydrolytic enzymes or produces toxic oxidases which destroys these antigens, the macrophages are capable of presenting the processed antigens to the major Histocompatibility complex (MHC) of the T-cells, thus creating a link between the innate and acquired immune systems; when these digested antigens are removed from the macrophages, they are restored to normal and are ready for another phagocytosis, this ability is the major factor which accounts for the impressivemy long life span of marriages as a produced monocyte which matures into a macrophage can last for a long period of time ranging from couple of months to years, macrophages can last as long as an individual's lifetime.
Macrophages in different body tissues bears different names and performs basically similar functions of phagocytosis and antigen presentation. Liver macrophages are termed kupffer cells, these macrophages resides in the liver tissues where they are specialized in phagocytosizing immunogenic cells found in this organ. The human brain and kidney are immunologically previledged sites, this is because little immune system activity is experienced here as these organs will not tolerate immunogenic reactions such as inflammation, hence the immune system is aided by macrophages found in this region, they are known as microglia cell for the brain macrophages and mesangial cells for kidney macrophages. Macrophages are also found in the bones and the skin, but basically their actions in these regions are similar, being non-specific and geared towards immunogenic cells Cytotoxicity.

Neutrophils


A microscopic examination of a stained blood leukocyte shows neutrophils, characterized by purple-violet granules, the nucleus of the neutrophils consists of 2-5 lobes. Neutrophils matures in about 14days, during this maturation stage, neutrophils acquires specific granules. These granules are responsible for most actions of the neutrophils, they are primary and secondary granules.


Image credit Wikimedia. Image by BruceBlaus. Creative Commons Attribution 3.0 Unported license.

The primary granules of the neutrophils are larger and contains various hydrolytic enzymes and peroxidase, the much smaller secondary granules contains lysozymes, lactoferrin and collagenases. Neutrophils are professional phagocytes and cytototoxic cells. When activated, the neutrophils phagocytose antigenic cells in a way which is similar to that described for macrophages, only difference being that unlike macrophages which presents these digested antigens to the helper T-cells, the neutrophils are Incapable of antigen presentation and usually does with the antigens and this constitutes the pale white looking pus seen in many immune reactions such as inflammation.

Neutrophils are however more likely to kill ingested microorganisms than the macrophages as they contain more lytic proteins than the macrophages, they are also able to produce more oxidases than the macrophages and hence destroys the antigens with more ease and efficiency.

Through these cells, the antibodies are able to destroy a wide range of cells which binds to their antigen binding fragment. The destruction of these harmful cells ensure the continuity of the body cells as more cells are not harmed by the toxins produced by these cells. Antibody dependent cell mediated cytotoxicity is thus very important in cell sustenance. Antibody-antigen complexes may also prompt other effector cells such as basophils to function in allergic reactions, this has already been described in hypersensitivity.

Anamnestic reactions


The acquired immune system has the ability of keeping memory of antigens and immunogens it encounters. This is a characteristic property of this type of immune system as the innate immune system is unable to perform this action. When the humoral or cell-mediated branch of the acquired immune system is activated, there is a proliferation of the cells of immunity namely the B-cells and T-cells.


Anamnestic reactions kicks in during advanced exposure usually after primary response. Image credit Wikimedia. Image by OpenStax College. Creative Commons Attribution 3.0 Unported license.

However, not all these produced cells are involved in the immune reaction, and not all the time cells in loved in the reaction are destroyed. These surviving and non-reacting cells becomes the memory cells .these cells keep the memory of previous infection and when the body is exposed to similar antigens, they trigger a more intense response , this is known as Anamnestic reactions or secondary response; this is just like saying that soldiers who survived a war knows the best way to fight such wars should they occur again.

Immunoglobulins involved in secondary response is mainly the Immunoglobulin G; the Immunoglobulin G are the most abundant immunoglobulins produced during secondary response. The binding of phagocytes to the FC regions of Immunoglobulin G requires prior interaction of the antibody with the antigen, when this FC regions of the Immunoglobulin G is bound to by a phagocytes, there is an enhanced phagocytosis and activation of the metabolic activity of the phagocytes.

REFERENCES


  1. Antibody-dependent cell-mediated cytotoxicity -Wikipedia
  2. Natural killer cells ~sciencedaily
  3. Eosinophil ~Wikipedia
  4. Monocyte ~Wikipedia
  5. Immune response ~Wikipedia


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Hello @joelagbo,

Air-Clinic sends her greeting!
We are happy that you are creating amazing medical contents on Steemit using the #Air-Clinic tag.

This article was found as a result of #Air-Curie Initiative! We encourage you to keep it up!

Expect an upvote from @Air-Clinic soon!

If you haven't joined us on Discord​ please do so by clicking here

Cheers!


@drqamranbashir- Air-Clinic Curator!

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I found you! (see my comment on your previous blog, https://steemit.com/stemng/@joelagbo/cell-sustenance-6-innate-barriers-and-immunoglobulins-in-neonatal-development). Today's blog is a perfect follow-to the previous one. You paint such a clear picture of the immune system. My eagerness comes from the fact that I just finished writing a blog about SLE. This is, of course, the immune system unhinged. All those soldiers you describe as fighting a noble battle to protect, turn into evil predators in lupus. What I'm learning to understand (and your two posts have been helpful) is the role of the Ig family. Thanks for all the useful information. You've moved me further along on my quest for understanding.

It's my pleasure, the immune system is a complex one, I've read your comment on the previous post. Actually I feel happier that you're learning a lot from my blog than the upvote I'd get from you. Feel free to pose any question you wish about the immune system and I will take you through. Thanks for stopping by.

I will take you up on that. Am interested in the role IgG4 plays in certain autoimmune diseases. I came across a reference incidentally and then your blogs turned a few light bulbs on. Have read a couple of articles tonight already. I'm way over my head, but that never stops me. So, yes, I'm sure there will be questions. Thank you very much.

Alright, rare cases of autoimmune diseases associated with immunoglobulin G4 have been reported, this is mainly due to the body organs being infiltrated by plasma cells producing immunoglobulin G4, this results in chronic inflammation and the common symptoms associated with this medical condition, however, placing the individual on steroid medication have proven remedial, the condition is associated with symptoms ranging from mild to severe, with organ destruction reported in some cases.
Feel free to ask more questions.

Thank you! More coming as my research consolidates and direction of inquiry becomes more clear....I won't be a nag, I promise :)

It's my pleasure

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