Ebola - all what you need to know about Ebola

Family: filoviridae

Viral hemorrhagic fevers

Introduction

Filoviridae means viral hemorrhagic fevers, a very high level of internal bleeding, family consists of two viruses: Marburg & Ebola viruses, Ebola has sub-types: Tai Forest, Sudan, Reston, Zaire & Bundibugyo, the virus concerned with the current outbreaks, is the Zaire species.

Mortality rate is high ranges between 30%sometimes 50% to 90%, depending on the virus, Ebola Reston is considered to be the one with low pathogenicity for humans

History

The virus first recorded in 1976 in ''Yambuku''  democratic republic of Congo it was then known as Zaire & Nzara, South Sudan, it first appeared in Ebola river for which the Ebola virus was named, It presents itself like the flu or malaria, symptoms resulted due to Ebola are severe headaches, diarrhea, vomiting, fever, muscle pain, weakness, stomach pain and bleeding among other things symptoms can appear from 2 to 21 days but the average time is between 8 to 10 days.

In December 2013 in west African countries of Guinea it was later confirmed in March 2014 then emerged to Liberia & Sierra Leone, they became the center of infection and some of these areas 90% of the patients died.

Then the disease prevailed to Europe and USA such as in Texas due to the travels between the cities, by far the cases has been growing more than 21,000 since January 2015.

Due to the several cases happened since 1976, we concluded that most of the countries and regions that have had this epidemic is usually countries of poor infrastructure, low economic level and very bad medical care.

Mortality rates of Ebola virus

Structure & Function

-Diameter: 80nm

-Length: 970nm

-Shape: filamentous, cylindrical or tubular-like, resembles a U-shape or takes the shape of number ''6'', pleomorphism '' as definition is the presence of more than one distinct shape'' (biological feature)

-Lipid( fatty) membrane, with glycoproteins on the surface of the virus as antigens for binding, glycoproteins are any class of proteins with carbohydrate group attached to the polypeptide chain then a viral capsid, ''capsid: a protein shell usually made to surround the viral genetic material'' in our case it is a negative-sense RNA strand '' negative-sense RNAs their genome has to be transcribed as soon as the virus enters the host cell in order to carry out replication''

Ebola virus has of approximately 19,000 base pairs, the 3' terminus is not polyadenylated & the virus encodes seven structural proteins: nucleoproteins (NP) '' are proteins structurally associated or presented with nucleic acids DNA and RNA  such as histone proteins, VP35 (polymerase cofactor) in the transcription & replication complex in RNA polymerase also blocks phosphorylation and activation of interferon regulatory factor 3 (IRF3) '' IRF3 briefly is a critical transcriptional factor for the induction of interferons alpha & beta.

VP40 it is the primary viral matrix protein means it organizes, covers and maintains the the virion structure, attached directly to the cell's membrane and provides budding function, in some RNA viruses it acts as a bridge between the membrane and nucleocapsid

GP, glycoproteins we mentioned that before saying they are found on the surface of the Ebola virus, acting as antigens for binding sites. Recall GP as definition? '' proteins attached with it any class of carbohydrate functional groups''

VP30 ''transcription activator'' phosphoprotein (any protein other than nucleic acid & phospholipid attached with it phosphorous) essential for the initiation of the Ebola virus transcription also an RNA binding protein.

VP24 is the secondary viral matrix protein attached beside VP40 '' the primary viral matrix protein'' minor component of the virion, it has a role in the formation of nucleocapsid & effect on transcription and replication of the viral genome, Last but not least, RNA polymerase (l).

Ebola virus anatomy

C.section of close view of Ebola virus

Signs & symptoms of the Ebola virus disease

Symptoms and signs of Ebola virus disease shows up from 2 to 21 days after the exposure to Ebola virus but the average ranges from 8 to 10 days, Ebola virus can kill its own patient within 7 to 14 days after developing symptoms, a person contracted with Ebola virus can be found hidden in his semen up to 7 weeks.

According to the world health organization (WHO), humans aren't infectious until they develop symptoms so whenever you find yourself or someone else developing symptoms of Ebola virus, seek medical care as soon as possible and avoid contact with anyone.

The symptoms developed by a person contract with Ebola are the following:

• Headache
• Aches in muscles & joints 
• Hiccups
• Abdominal pains
• High fever, usually more than 38.5 C*
• Sore throat
• Weakness
• Swelling
• Diarrhea 
• Stomach pains
• Internal & external hemorrhage (bleeding)
• Fatigue
• Chilling
• Vomiting 
• Nausea
• Red eyes & bleeding coming out of the eyes
• Chest pain and cough
• Rash
• Kidney and liver failures
• Severe weight loss

As we notice, it is very severe, the fatal range of such disease is between 50% -  90%,  seeking medical care immediately, obeying the precautions and the good medical care & the will of surviving and the status of the patient's immune response can develop a good recovery from Ebola, developing the suitable antibodies against such disease will help you get over it also such antibodies are said to be at least surviving in your body for 10 years or so.

Two crucial things we are going to talk about next, first the mechanism of prevalence in our body & the steps of replication of Ebola virus.

First: Mechanism of prevalence in our body 

Ebola virus directly attacks our immune system, it mainly goes onto one of your important immune antigen presenting cells ''Dendritic cells'' or Langerhan cells & macrophages (guard cells) both are type of your innate immune system cells, these cells have type two major histocompatibility complexes, once it penetrate through the dendritic cell releasing its components inside it starts taking control of it and uses its machinery to build more of itself once not only it infects the dendritic cells but it also trick the anti-viral cells and some specialized cells by sending them messenger proteins that end these cells life prematurely( meaning when they are still in their inactive states), there are cells such as Natural killer cells are present just to hunt down any virus-infected cells by sending enzymes ''granzymes'' which causes holes named ''perforins'' in the infected cell membrane in what we call ''Apoptosis'' (=program cell death).Unfortunately, these cells also gets infected by Ebola virus.

The guard cells such as macrophages and monocytes which are infected are ordered to send messenger chemical proteins ''cytokines'' to the blood vessels to releases its fluids inside our body causing internal bleeding, another areas such as liver, spleen and kidneys which are kind of the organs that maintains and balance our bodily fluids also gets infected by the Ebola virus leading to organ failure but in this case we can call it a massive or huge multiple organs failure besides the lungs which also gets shutdown due to the unstoppable attack of the virus on our immune system, the immune cells launches a cytokine storm at which each immune cell releases a massive secretion of chemical messengers called ''cytokines'' that at such case it affects our organ tissues and blood vessels,Paradoxically, the healthier the immune system, the more damage it can do to itself, so the copious amount of fluids spread all over the body leads to what this family is described by ''hemorrhagic fevers'' the body becomes seriously dehydrated and at this time, the chance of dying is very high.

Luckily, Ebola virus isn't high contagious, the only ways you can contract Ebola is to come in contact with bodily fluids of an infected person such as urine, semen, saliva, mucous, blood, feces or vomit and from fruit bats said to be '' natural reservoirs'' of Ebola virus so a conclusion is that Ebola virus is a type of zoonotic disease '' diseases that can be spread between animals and humans'' such as Dengue, yellow fever, HIV, malaria, Marburg, rabies, swine flu and much more, so other animals can be infected with Ebola since animals feed on each other and one day or another it will come to a fruit bat eaten by any other wild-type animals which people usually hunt down and uses its meat ''bush meat'' and that is one of the reasons why some people contracted Ebola in USA.

Replication of Ebola virus

As we know Ebola virus infects firstly your guard cells & antigen-presenting cells of your body macrophages and dendritic cells, these immune cells surface antigens has something called DC-SIGN (dendritic cells special intracellular ''means inside the cell'' adhesion molecule 3-grabbing non-integrin) also known as CD209 encoded by CD209 gene,adding that it is a C-type lectin receptor (lectins are type of proteins that can bind to the cell membranes, they recognize and bind specific carbohydrates found on the surfaces of cells also plays a role in interaction and communication between cells for recognition) , Glycoproteins surface antigens and receptors of the Ebola virus attaches to the target cell's receptors and eventually binds to it.

The virus then starts penetrating the cell's surface ( endocytosed) later enters an early endosome ''endosomes are membrane-bounded vesicles'' by macropinocytosis also known as clathrin-mediated endocytoses   ( cytosis means cell action, pinocytosis is an action the cells do to take up some nutrients by making a folds of its own membrane surrounding the nutrients or whatever molecules it is taking in a vesicle and receptors for binding)Ultimately, the virus glycoproteins receptors binds to the cell's receptors inwardly making an invagination taking the virus inside.

(Clathrin is a protein found on the surface of these cells that has a role in the formation of these vesicles)

Also NP-C1 Niemann-Pick C1 is a hydrophobic (hates water) lysosomal integral membrane that plays an essential role in cholesterol regulation, transport and storage facilitates the entrance of Ebola virus into your cell endosomes and lysosomes, without it the virus cannot leave the vesicles in order to start the infection.

http://www.microbiologyinfo.com/tag/ebola/

The fusion happens when the pH ( concentration of hydrogen ion in any solution) is low or with NPC1 binding.

Once the virus penetrate through the endosomes, it dissolves its outer hull, leaves its genetic material, nucleoproteins and enzymes, transcription phase starts now, RNA polymerase found on the RNA strand of the virus transcribes the RNA strand into seven monocistronic  mRNAs ( monocistronic mRNA means an mRNA that codes only for one protein) the cell's machinery now is taken control via the virus which makes it produce the required nucleoproteins, tRNA molecules, etc..

The polymerase slides over the RNA strand 3' to 5' order transcribing the genes into particular proteins.

After translation, replication phase starts at which the negative-sense ssRNA strand acts as template to synthesize a complementary +ssRNA  which is then used to synthesize a -ssRNA which is encapsidated with its proteins forming a new virus.

Now the virus is capsidated having its genetic material, nucleoproteins and enzymes inside, it is about time it leaves the cell to continue infecting other cells. Budding phase initiates.

The virus uses the cellular ESCRT (endosomal sorting complex required for ''transport'' ) system  '' it is machinery used to control the key cellular processes, the ESCRT proteins functions by binding membrane, generating curvatures and presence of some enzymes to complete the process'' ESCRT has various functions such as its enrollment in cytokineses, the ESCRT family consists of ESCRT -0, ESCRT- 1, ESCRT-ll & ESCRT-lll

ESCRT-0, ESCRT-l & ESCRT-ll functions in deformation of membranes & primarily involved in cargo sorting while ESCRT-lll cleaves (breaks down) the buds' neck from its cytosolic face.Last but not least, the VPS4 disassembles the complex and the virion is free from the cell now.

http://www.microbiologyinfo.com/tag/ebola/

 (Cytosolic face is the surface of a bio-membrane ''structure bounding a cell membrane or cell organelle it contains lipids, proteins, glycolipids, steroids and much more'' directed towards the cytoplasm)

Ebola virus replication

Are there any cures found for Ebola virus disease?Vaccines?

Currently no, by far no cures discovered but there are few ways that contribute in controlling and decreasing the infection rate of the Ebola virus in our body such as Intravenous fluids (IV), balancing electrolytes ( body salts), maintaining oxygen status and blood pressure until the body generates a powerful immune response,

Intravenous fluids regulation is carefully made to achieve and maintain an isotonic environment in the body ( used for cases of dehydration) usually when a person's body is dehydrated, fluid containing water and dissolved salts known as electrolytes such as Na & K, there are two types in which intravenous fluids are used: 1) Acute fluid resuscitation 2) Maintenance fluids

-Acute fluid resuscitation, which is important for our case, is used in the cases of hypovolaemia (hypo=low - vol=volume - aemia=anemia or loss) a loss in blood volume e.g. hemorrhage, severe diarrhea & vomiting, burns and much more symptoms like those mentioned in our case (Ebola)

There are three main types of fluids crystalloids which contains small molecules that can easily pass through the membranes of the cell e.g. Normal saline 0.9% sodium chloride, Hartmann's solution and 5% glucose or dextrose.

Hartmann's solution IV

Just a very small example of what some of these crystalloids contain, normal saline 0.9% sodium chloride has sodium 154mmol/L & chloride 154mmol/L.

Other treatments that help you get over Ebola virus which has saved many doctors who unfortunately contracted the Ebola virus from their patients, is a serum made from the blood plasma of other patients or doctors who had contracted and survived from the virus and, then injected into their bodies, which with the proper care later helped them get over the virus and develop an immune response but such thing is considered to be a type of passive humoral immunity since remember? the blood plasma contains immunoglobulins ( antibodies) produced by those whom survived the ebolavirus  but still yet researches are ongoing for such type of antibodies and a way to develop a vaccine through this.

Throughout the medicine and this incredible field of science, not only medicine-ways are the ones needed to help one survive any disease but also resistance to fatal disease like this requires the will and your believe in yourself that you can do, thrive and get over such disease beside taking, seeking and obeying medical care sharply will definitely let you defeat such disgusting fatal viruses.
(read this story about one of Ebola virus survivors and how it is inspiring, Dr. Melvin Korkor: http://archive.eboladeeply.org/articles/2014/09/6124/survivor-story-dr-melvin-korkor/)

The following link provides various medical equipment used for Ebola care according to WHO:  http://www.who.int/medical_devices/meddev_list_ebola_25nov_en.pdf?ua=1

Last but not least, no matter what happen, the humans has always had and still has an infinite potential of evolution which will succeed in eliminating such disease and consign it in its rightful place..... the history books.

References used:

• http://groups.molbiosci.northwestern.edu/holmgren/Glossary/Definitions/Def-M/monocistronic_mRNA.html
• http://archive.eboladeeply.org/background/basics/    <-there you can find various journals about ebola
• https://deepblue.lib.umich.edu/handle/2027.42/110318
• http://www.who.int/mediacentre/factsheets/fs103/en/
• http://www.ncbi.nlm.nih.gov/pubmed/10721995
• http://www.microbiologyinfo.com/tag/ebola/         (special thanks)
• https://micro.magnet.fsu.edu/cells/endosomes/endosomes.html
• http://ed.ted.com/lessons/what-we-know-and-don-t-know-about-ebola-alex-gendler
• https://www.youtube.com/channel/UCH4BNI0-FOK2dMXoFtViWHw
• https://www.youtube.com/channel/UCsXVk37bltHxD1rDPwtNM8Q
• https://www.youtube.com/channel/UCPY9IKSkr2GfFW5jbgA5Qbw
• http://geekymedics.com/
• http://www.washingtonpost.com/wp-srv/special/health/how-ebola-spreads/#b10g15t20w14 <-- check out this simulation showing how deadly Ebola virus is comparing to other viruses
• http://www.uniprot.org/uniprot/Q05127
• https://collab.itc.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/P/Ch24_Coleman_G_Niemann-Pick_C1/Coleman-NiemannPickC1_NPC1.html
•  http://www.ncbi.nlm.nih.gov/pubmed/12223058

Videos

1)Discusses the mechanism of infection

2)Facts about Ebola virus
3)Introduction to IV fluids (very informative)
4)Mechanism of spreading ( in a nutshell )
5)What we know and don't know about Ebola
6) Another video to help you mechanism of infection

    

Overview of immune system Part 4

Immune system

Continue adaptive immune defenses

Cellular defenses - T lymphocytes

Your immune system last efforts deploys when the  invaders made it to the cells, penetrated its membrane and started dividing, now it comes to a cell to cell combat.

T lymphocytes are one of your adaptive immune cells which originates in your bone marrow but matures in thymus gland, a lymphoid organ situated in your neck and becomes small by the time, puberty approaches, it secretes thymosin hormone stimulates the maturation & production of disease-fighting lymphocytes which are T-lymphocytes, there are kind of varieties of T-lymphocytes:

• Cytotoxic (killer) T cells, mainly kill/attack viruses, bacteria and infected host cells
• Helper T cells, they have a major role on your immune system, these cells are more likely to be the corner stone of the immune system, because of its presence, our immune system wouldn't have been able to identify & respond to any foreign antigens, these immune cells releases chemicals called ''Cytokines'' their secretions stimulates various things that contributes to your immune response: 

1. Activates macrophages from your innate immune system
2. Causes inflammation 
3. Helps in the maturation and activation of other immune cells such as B-lymphocytes to become plasma cells & present to it the specific antigen of the foreign invader from macrophages in order to produce the specific antibody for it.
4. Their chemical secretions induces other white blood cells to come to the                                     site of infection and increase the rate of white blood cells.    

                                                                                                                                                   

• Suppressor or Regulatory T cells, they have an important function in our immunity, they stop the immune processes when the infection is over in order to avoid any further production of immune cells or continuous immune responses which may lead to autoimmune diseases such as Multiple sclerosis where the white blood cells attack the myelin sheath surrounding the nerve cells or type one diabetes where the white blood cells attack pancreatic cells leading to the dysfunction in production of insulin also suppressor T cells induces plasma cells to save some cells having the information of the foreign invader ''Memory B cells'
• Memory T cells, which mainly has memories of the antigens of the specific invaders in case they made a comeback.
• Natural killer cell, these are of both types innate & acquired (adaptive) immune cells, they primarily attack infected-host cells by secreting messenger proteins containing ''Granzyme'' they are serine proteases ''enzymes that cleaves peptide bonds in proteins'' released by cytoplasmic granules within the cytotoxic T cells & natural killer cells they induces ''apoptosis'' (program cell death) that produces holes named perforins.

So this is how it goes, your macrophages from your innate immune system after engulfing a bacterium or virus they tend to present parts of these invaders on their outer layer on proteins found on the cell surface named major histocompatibility complexes of class (ll) these are professional antigen-presenting cells of class two such as macrophages, dendritic cells (=langerhans cells containing large organelles called Birbeck granules) and B-cells, dendritic cells, a major antigen-presenting cells binds to the antigens present on the macrophages they then travel to the nearest lymph node in about a day to bind with specific helper T cell which has a particular receptor for the specific antigen, once it binds it matures and start producing chemicals ''cytokines'' which calls for more white blood cells to get to the site of infection and divides producing memory T cells, regulatory T cells and killer T cells.

Thanks to the following websites and youtube channels for making this possible, if you find anything difficult send me your question in either my e-mail ahmed.maxi.93@gmail.com or just in the comments below I will be awaiting your feedback and we are finally done with Immune system episodes.

References used:
http://www.endocrineweb.com/endocrinology/overview-thymus
http://www.ebioscience.com/knowledge-center/cell-type/natural-killer-t-cells/granzymes.htm
https://en.wikipedia.org/wiki/Langerhans_cell
https://en.wikipedia.org/wiki/Phagocyte#/media/File:Dendritic_cell.JPG
https://www.youtube.com/channel/UCX6b17PVsYBQ0ip5gyeme-Q
https://www.youtube.com/channel/UCsXVk37bltHxD1rDPwtNM8Q

Dendritic cell under m

Diagram showing the binding of helper T cell with dendritic cell

This video explains  what is mentioned the above in a very simple way just in case you find something difficult to understand. 

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

                                                                                                     

Overview of Immune system Part 2

Immune system

Innate immune defenses 

The immune system isn't like the other systems in their description. In other words, the immune system is not a full/specific organ like the other systems for example when we recall the digestive system we know we are talking about the stomach, small intestines, esophagus and so on, when we say the respiratory system we know we are talking about the lungs, alveoli sacs and etc..

The immune system is the lymph nodes, vessels, tracts & trunks, also lymphocytes and bone marrow, the immune system's job is a prerequisite in order to live, the immune system helps our body keep foreign invaders outside of our bodies such as bacteria, virus, and fungi that are waiting for any chance to use you and your body's resources to divide, so our body needs to develop special soldiers in order to avoid these bad guys, for example, our first line of defense like our external barricades is our skin, the skin is made of three layers 1)epidermis *the outermost layer* 2) dermis *the inner layer* 3) Hypodermis *the deeper layer*

1)Epidermis,  several layers of epithelial cells, Stratum(corneum, lucidum, granulosm& germinativum) at the surface of this layer where the exterior cells exists are dead keratinocytes cells exists which makes up the substance of skin called Keratin, at the base of its inner layer, there are pigment cells which secrete granules responsible for the color of the skin through cells called melanocytes, the darker is your skin the more active melanin you have and vice versa.

2)Dermis, lies beneath the epidermis, consisting of connective tissues, also is crucial since it contains blood capillaries, nerve endings, lymphatics, sweat glands, fat glands, fatty cells and hair follicles, the sweat gland is one of the various points we will talk about as something related to our immune system, these sweat glands through coiled tubes that reaches the skin surface through a pore secretes sweat which mainly consists of NaCl + water, some bacteria cannot bear the acidity of such secretions our skin releases, therefore our skin has sort type of immunity to our body so we categorize it in our innate immune defenses, also the presences of some peptides called defensins 
( antimicrobial polypeptides, they invade microbes )that also provides an immunity function by attacking any bacteria or fungi by binding to their membrane and increases their membrane permeability.

The presence of mucous membranes in our body that covers all the tracts that lead to the outside world such as digestive, respiratory, urinary & reproductive systems also have an immune function, mucous mainly composed of Mucin( mucin is a family of large heavily glycosylated proteins, ''glycosylation'' as a definition means the reaction in which a carbohydrate molecules ( glycosyl donor) is attached to any functional group of another molecule ( glycosyl acceptor) it is more likely a type of covalent bonding, these molecules or membranes tends to protect you from the outside world.

For example, your nasal passages containing mucous protect you from any harmful foreign invaders (airborne vectors) that you may inhale frankly as well as the presence of cilia which work on kicking out any tiny objects such as dust.

The saliva which your salivary glands secrete mucin, salts, and lysozymes among other things help protect you from anything you may take in while eating or through a mouth breath, lysozymes also known as bacteria-fighting enzymes destroys the bacteria's cell wall.

Your lacrimal eye fluid(tears) also has an immune function, it consists of water, electrolytes such as sodium & potassium, proteins such as lysozymes, immunoglobulins ( antibodies), mucin, defensins, and lipids among other things.

Your stomach which is a main digestive organ, any type of vector that somehow made it to your stomach can be eliminated due to the presence of acids secreted by the stomach in order to digest food such as HCl, pepsin, and enzymes secreted by the pancreas that tends to break down lipids, carbohydrates and proteins also tend to help in immunity.

In case any successful vector such as Staphylococcus bacteria( gram +ve bacteria) made it to through any cut you have made accidentally while peeling an orange, this induces your internal innate immune defenses where your body tends to activate a sort of weapons that work against these foreign objects such as fever, chemical signals, and inflammation,

What happens in the case of an infection?

It is a beautiful day until you accidentally cut your skin, nearby bacteria seize the opportunity and enters through your wound starting to divide, your body's first line of defense that arrive to the scene are phagocytes such as neutrophils which are the most abundant type of your innate immune cells they range in percentage of 40 to 70% they mainly destroy the bacteria and any toxins secreted by them their nucleus has two to six lobes also they tend to commit a suicide right after destroying any foreign invaders.

Another type of phagocytes which are bigger are Macrophages meaning big eaters, they have two types, mobile and fixed, the fixed ones such as those found in the liver where they are fixed on the liver cells tissues and others are mobile which has the ability to move around, they kill bacteria by engulfing them through cytoplasmic extensions through a process called phagocytosis, where the bacteria is eaten and digested due to the presence of various and more lysosomes ( lysosome is a cell organelle found in eukaryotic cells functions in digestion and waste removal so it has enzymes) these lysosomes tends to surround the bacteria and releases its enzymes, what characterizes the macrophages unlike the neutrophils they can devour many bacteria, fungi or viruses up to 100, macrophages are derived from immune phagocytic immune cells known as monocytes comprises about 3 to 8%, these cells that has left the bloodstream.

Natural killer cells, these cells aren't phagocytic, these immune cells patrol all your body cells looking up for any infected cells that has been infected by any sort of a vector, through cell signaling by sending messenger proteins which tends to activates a process known as apoptosis '' program cell death'' induces the cell to kill itself, the way the natural killer cells identify the infected or cancerous cells is that each normal cell has a special antigen called MHC1 '' Major histocompatibility complex'' also known as human leukocyte antigen ( are group of genes that expresses proteins found on the surface of cells that help the immune cells to identify any foreign invaders) but when any normal healthy cell gets infected they lose this antigen.

So back to the cut you had when you were peeling the orange, bacteria nearby embrace the opportunity and gets through, your body innately tends to protect you from any loss or any breach from foreign invaders into your body, so your damaged skin cells that have been affected by the cut releases chemicals known as chemokines ( small protein molecules, chemo>>chemical, kines>>kinetic*movable*) which tends to inform your body that something has gone wrong then this launches inflammatory response through chemicals, redness, swelling, heat, and pain for example in your dermis skin layer exactly in the connective tissue of this layer has specialized cells called mast cells ( are cells filled with basophils granules that releases histamine molecules & other substances during allergic reactions and inflammatory responses) mast cells basically fight worms, communicate with other cells, activate cells and causes inflammation as well among other things, histamine molecules one of the main factors of causing the inflammatory response, it goes to the capillaries feeding the skin cells with oxygen & nutrients  deeper into the endothelial cells layer stimulating them to widen & separate between each other to make the capillaries larger leading to what we call vasodilation which makes you feel with enlargement or swelling, this is helpful and are actual signs of healing since it helps increase the blood flow to the damaged tissue, platelets start to clot the wound in order to prevent more blood loss, fibroblasts found in the connective tissues secrete collagen( main structural protein found in the connective tissues of animals) towards the cut to take the shape of the original worn out tissue.
Since the capillaries are vasodilated and capillaries contain blood which in our case has lymphocytes and white blood cells that pass by, they will squeeze through the separated/widened capillaries moving towards the site of infection through a process called leukocytosis it is also a sign of inflammatory response where the number of white blood cells increases in number during an infection but when the foreign invaders are overwhelming the macrophages and neutrophils releases fever-inducing substances called pyrogen ( low molecular weight protein, endogenous since it is produced from the leucocytes) in response to the exogenous pyrogen released from the bacteria (foreign invaders) released into the blood circulation which stimulates the hypothalamus.
The hypothalamus is a section of the brain responsible for the production of many essential hormones that control different organs and cells, in our case the hypothalamus among other things is responsible for temperature regulation, thirst, and hunger, so when the pyrogen chemicals are released they stimulate the hypothalamus to increase the body temperature resulting in a higher metabolism of your cells making them consume more oxygen& nutrients leading to a faster healing, also this induces the liver and spleen to hold their iron and zinc in order to prevent the contribution of these materials to the growth of these foreign invaders that's why the person infected with any bacteria or virus tends to breathe heavily, lose appetite and feels sleepy among other things.

Thanks to the following websites and youtube channels for making this overview possible and I really hope you get educated and I am hoping you give me your feedback in the comments section, Thanks a lot.
References used:
http://www.healthline.com/human-body-maps/hypothalamus
http://medical-dictionary.thefreedictionary.com/pyrogen
https://www.britannica.com/science/major-histocompatibility-complex
https://www.boundless.com/physiology/textbooks/boundless-anatomy-and-physiology-textbook/integumentary-system-5/accessory-structures-of-the-skin-65/sweat-sudoriferous-glands-397-4497/
http://www.nature.com/eye/journal/v17/n8/fig_tab/6700566t1.html#figure-title
http://www.medicinenet.com/script/main/art.asp?articlekey=26300
https://www.youtube.com/channel/UC4a-Gbdw7vOaccHmFo40b9g  (Khan Academy)
https://www.youtube.com/channel/UCX6b17PVsYBQ0ip5gyeme-Q (CrashCourse)

Stay tuned for the next part, we will talk about some adaptive immune defenses!!

Diagram showing the existence percentage of some white blood cells in the blood

Capillary tube contents after centrifuge, discussing the presence of platelets that clots the damaged tissues, lymphocytes and white blood cells 

Capillary beds and the exchange of gases and nutrients to the damaged tissues