Chatbox

Showing posts with label immunity. Show all posts
Showing posts with label immunity. Show all posts

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



                                                                                                     

Saturday, 2 July 2016

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