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Wednesday 6 July 2016

Overview of immune system Part 3

Immune system

Adaptive immune defenses

B lymphocytes & production of antibodies

B lymphocytes
Last episode we covered the innate immune defenses and how they truly use their all power and their innate property of killing and protecting you from outer invaders, we talked about phagocytes (Neutrophils & Macrophages) how they gobble them up through phagocytosis also natural killer cells and their ability to stimulate defected and cancerous cells to initiate apoptosis ''program cell death''

Today our second defenses ''adaptive immune defenses'' these defenses show up only on one condition when the innate defenses fail to take control of your body when there is an infection. In other words, when the outer invaders are overwhelming, any antigens such as bacterium, fungus, toxins, cancerous or defected cells, what characterizes your adaptive immune defenses is that they have the ability to remember the specific antigen which invaded your body also the adaptive immune defenses are more likely to be slow to progress in your body ''adaptive'' means it needs first to identify the antigen's characteristics and properties in order to initiate its attack so it is more ''specific'' than innate immune defenses also known as acquired immune defenses.

What are the defenses of the adaptive immunity?
It has two ways of defenses:
                                             1)Humoral immunity
                                             2)Cellular defenses ( we will discuss that in the next part)
Humoral immunity means protection of the body through something called ''Antibodies'' antibody-mediated immunity existing in extracellular fluids(ECF) '' all body fluids found outside the cell'' such as blood & lymph, antibodies(=immunoglobulins)  are Y shaped little protein molecules that has the ability to block the binding sites of a particular antigen of the foreign invader, consists of heavy and light chains''

-These antibodies are produced from special immune cells named B lymphocytes, these immune cells originate in bone marrow and mature in it by learning how to recognize a foreign antigen, avoid attacking your own body's antigens ( auto-immune disease) and by dispatching more than 10,000 protein receptors (antibodies) membrane-bounded antibodies.

-Once the B lymphocytes mature they start patrolling the body's fluids such as lymph, blood and the interstitial fluids between your cells searching for any pathogens and in case it finds one which matches a particular antibody on its surface it will bind to it and they start dividing producing and differentiating into Memory cells & plasma cells ''they are special type of differentiation of B lymphocytes that preserve the threshold antibody for that specific antigen whom invaded your body'' this process is considered to be your primary immune response which will take sometime to respond and act but any further attacks that may invade your body of the same antigen will initiate the secondary immune response due to the presence of your memory cells that has the particular antibody for that antigen so it occurs much faster.

-Plasma cells are packed up with rough endoplasmic reticulum ( cell organelle studded by ribosomes molecules on its surface that's why we term it by ''rough'' functions in assembling proteins for your cells and in our case antibodies) which acts as an antibody factory, it produces the particular antibody spreading it out through your whole body fluids 2000 antibody/second for like 4 or 5 days, so we conclude that they are free-floating meaning they will be just like cells moving around till they find and bind to the foreign invader's antigen blocking them from binding to any of your cells, antibodies can fully block the sites of binding of the foreign invaders in a process called Neutralization or another way since antibody's structure have several binding sites they have the ability to bind to more than antigen of a foreign invader resulting in clumps/groups/antigen-antibody clumps in a process called Agglutination, these clumps makes it an easy target for phagocytes like macrophages to phagocytose them, this process is termed as Opsonization '' means marking or identifying the foreign invader to phagocytes, the identification is by the antibodies''

How do the phagocytes respond?
It happens that the antibodies have the ability to produce substances that attract other immune cells like phagocytes and other cells from the adaptive immune system to get to the site of infection where these bad guys are blocked to bind anything.

All that we have been discussing can be called ''Active humoral immunity'' as a definition it is when B lymphocytes mature and start to produce antibodies for the specific antigen invader, this is so important to your immunity since it increases your body's immune system efficiency and strength, the more specific antibodies for specific foreign antigens you have, the more immune you are.

Vaccination
-This is more likely to be active humoral immunity but it happens artificially without the body's own cells, a vaccine is usually a sample of the specific pathogen extremely weakened or has lost the ability to reproduce or it can't invade cells anymore which are then injected to your body, this will initiate your body's immune response to eliminate the pathogen quickly and save a copy of its characteristics & properties .e.g. the needed antibody for that specific antigen,

-Cell culture adaptation, they allow the virus to reproduce in a weak medium meaning, not human cells.e.g. they inject the virus in chicken embryos in a petri dish making the virus adapt to this type of infection (chicken embryo cells) they are then adapted to infect chicken cells since viruses reproduce a lot they then take some of the reproduced viruses and inject them into human, the virus isn't acquainted or having enough strength to reproduce and invade human cells allowing the activation of immune response to identify and get rid of the invaders while saving some other cells for any further comebacks.

Passive humoral immunity
From its name we can conclude that it is not obtained from the body's own cells, for example, babies, while they are in their development stages in their mother's womb, receives ready-made antibodies from the mother's placenta '' placenta is a sac-like organ develops from the mother's uterine wall which connects the baby to the mother through the umbilical cord, it is where the exchange of nutrients, oxygen, carbon dioxide and wastes occurs between the mother and the baby'', later on from breast milk.Unfortunately, passive humoral immunity is a temporary immunity which means the baby's own immune system won't remember any antigen it has cured of it before if it gets infected again.

Passive humoral immunity can be also obtained artificially which is usually done when the person is infected with a very serious disease which has not yet cured but some others somehow survived by receiving exogenous ( means developing or originating from outside of the organism) proteins '' antibodies'' from the plasma of other persons.

No matter what happens, somehow pathogens will find a way to get into your cells and start reproducing, this is what we are going to discuss in the next part of our overview of the immune system!


Production of antibodies


The antibodies also known as immunoglobulins are small Y shaped protein molecules that are membrane-bounded to B lymphocytes and produced from special derivatives of B lymphocytes known as plasma cells to bind to the receptors (antigens) of foreign invaders and they mainly consists of heavy & light chains connected to each other by a disulphide bridge, on the edges of these two chains there can be found the variable regions of the antibody, it is what makes each antibody different than the others while the rest are constant regions.

-Antibodies has various forms/types, the isotypes of antibodies are:
                                                                                                            1)IgM                   3)IgA
                                                                                                            2)IgD                    4)IgE
                                                                                                            5)IgG
First of all, a progenitor B cell which is a biological cell more likely to be a stem cell differentiates to B cell which has the DNA containing genes responsible for the production of these antibodies which then later produces and put them onto its membranes making it bound to it, B cells when they are later differentiated into plasma cells which produce one specific antibody.

How heavy chains forms?

-The germline DNA(=constitutional DNA, is the source of DNA for all other cells in the body) with its long strand carrying various genes on it, the first is the ''V'' region which stands for variable, this region from its name we can say it is changeable, then the ''D'' region stands for diversity, making it the remarkable region which specializes antibodies meaning that they have variation, after that the ''J'' region stands for joining, which later on join the chains with each other, last regions are M, D, G, E & A and they are the constant regions of the antibody's structure.

The V, D & J region mainly consists of 40, 25 & 6 parts respectively, pretty much,  right? That's what makes the very long number of a variety of antibodies and the big amount of them which can be produced.

The mechanism of how the heavy chains forms start by the following:

One part of each D & J region are chosen making a part of D connected to J region labeling them as DJ recombination while the V region & the constant regions connected together with the DJ recombination, after that one part of the V region leaves its friends and connect with the DJ recombination forming VDJ recombination yet the constant regions still connected to the VDJ recombination labeling this as Recombined DNA, due to the many parts present of these genes we can create many antibodies, after that the whole strand of DNA gets transcribed into mRNA strand now to the important stage which is what constant regions are made up of, the constant regions gets spliced away leaving only one of them in our example let's say it is the ''A'' region so our new piece is a VDJ regions connected with an A region naming it spliced mRNA, later on, this spliced mRNA will be translated into the proteins forming what we know as ''Antibody'' Y-shaped protein structure, the same thing happens to the formation of light chains except that there isn't a D region in its structure just directly V connected to J region.
               
                                                                      *****

References used:
http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=561402
http://medical-dictionary.thefreedictionary.com/opsonization
http://www.healthline.com/health/placenta-previa#Overview1
https://meducation.net/
https://www.youtube.com/channel/UCX6b17PVsYBQ0ip5gyeme-Q



Antibody's isotypes
Opsonization simple explanation 
Antibody structure


Diagram showing various movements of antibodies blocking the sites of binding



                                                                                                     

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