Immune system
Overview.
Entry level barriers.
White blood cells.
Antigens.
Macrophages.
Specific immune system.
Cell mediated response.
Antibodies.
Long term immunity.
Vaccination.
Overview.
Our body has a very complex, and elegant defence system.
The defence is essential against pathogens.
Micro organisms, like bacteria and viruses, which are harmful to our body,
are called pathogens.
If the pathogens manage to enter our body, they are capable of dividing and multiplying rapidly.
The pathogens infect our healthy body cells and tissues.
This causes us to be unwell or sick.
Each pathogen is unique.
Different pathogens, can cause different illnesses.
The illnesses could range from a mild one, which causes discomfort, like a common cold,
to a lethal one like small pox.
The defence system, literally has to protect itself from thousands of possible pathogens.
The defence system, has many layers.
If the pathogen, manages to cross the first line of defence,
then a second line of defence, comes into action.
The skin is an example, of a first line of defence.
White blood cells, are an example, of an inner layer of defence.
They are like an army, constantly vigilant, to guard our body against infections.
When our body is infected, not only there are pathogens present in the body,
there are also body cells which are infected.
Both the pathogens and the infected cells are required to be addressed by the immune system.
The defence system is fairly complex.
There are many alternate ways, in which the pathogen will be attacked by the defence system.
Many of these work together, to defend against a foreign invasion.
Some of the immune system functionality, is transferred from mother to baby,
and we are born with a immune system.
Some immune systems are developed due to a previous infection.
Even if we are attacked, by a totally new pathogen,
the immune system has a mechanism to adapt and fight this unknown pathogen.
It even goes one step further, and remembers the new pathogen,
so as to prevent future infections.
This is called as the adaptive or acquired immune system.
Pathogens are continuously evolving living organisms.
This gives rise to new pathogens, which we have not encountered before.
Having a healthy acquired immune system, is critical to defend our body,
against new pathogens.
It is only in the late nineteenth century, that we became aware,
that germs are pathogens, are a cause for many illnesses.
Many scientists contributed to this discovery.
One of the prominent scientists, is Louis Pasteur, formulated the germ theory of diseases.
Louis Pasteur is best known, for his discovery of germ theory,
and development of vaccination.
Thanks to vaccination, hundreds of millions of lives have been saved,
and continue to be saved.
Scientist now have a more in-depth understanding of how the immune system works.
Many scientist are involved in further research of this fascinating system.
Hopefully this will lead to more and better ways, to prevent and cure illnesses.
Entry level barriers.
The skin is the most prominent entry level barrier for pathogens.
The skin covers most of our body, and protects it from environmental hazardous pathogens.
Apart from being a physical barrier, the skin has other mechanisms, to prevent pathogen entry.
The skin has a low pH, and some chemicals which disrupt pathogens.
The skin is a natural host to a flora of bacteria, which live harmlessly on our skin.
These bacteria crowd out any foreign pathogens.
There are some natural openings in the body, like the lungs and the digestive system,
through which pathogens could potentially enter.
The immune system has another layer, of protection in these areas.
In the lungs, coughing and sneezing mechanically eject pathogens or irritants.
The mucus which coats the respiratory tract, and the gastrointestinal tract,
trap any micro organisms, that enter the lungs and the digestive system.
Enzymes are present in saliva, tears, and breast milk, which are antibacterial.
In the stomach gastric acid and other chemicals kill ingested pathogens.
A complex community of micro organisms, called gut flora, exists in the digestive tract.
They exist in a non harmful, even beneficial way to humans.
These bacteria compete with pathogenic bacteria, and act as a biological barrier.
In this module, we will discuss a few of the important ways,
by which the immune system works.
White blood cells.
Most of the blood in our body comprises of red blood cells.
They are called erythrocytes.
Red blood cells do not have nucleus.
Their main function is to transport oxygen, to all the cells in the body.
Less than 1% of the blood, is composed of white blood cells.
They are called leukocytes.
White blood cells have a nucleus, and DNA.
They play a crucial role, in the immune system of the body.
White blood cells comprise of,
monocytes, neutrophils, eosinophils, basophils, and lymphocytes.
Phagocytes protect the body, by ingesting the harmful and dead cells.
Monocytes and neutrophils are macrophages.
Phagocytes include macrophages, neutrophils and dendritic cells.
Macrophages literally eat the pathogen cells.
Macrophages play an important role, in general immunity.
General immunity or innate response,
provides a defence against many types of pathogens.
Lymphocytes play an important role, in specific immunity.
Specific immunity is a defence mechanism against a specific pathogen.
For example, pathogen which causes, the chicken pox illness.
Specific lymphocytes, target specific pathogens.
For every known illness, the immune system has specific lymphocytes,
to defend against them.
Lymphocytes are also capable of adapting to unknown new pathogen,
and fighting it.
This is called as adaptive immunity or acquired immunity.
Lymphocytes broadly comprises of B cells and T cells.
Adaptive immune system relies on B cells and T cells.
B cells are made in the bone marrow.
T cells are made in the Thymus.
B and T cells can be found in the lymph nodes.
They could also be found in the blood stream and tissues.
Antigens.
All cells have surface proteins, which mark and identify as cell.
The body is able to identify a cell, as a "self cell", or a "foreign cell",
based on these markers.
Every cell in our body has surface proteins called MHC.
MHC stands for Major Histamine Complex.
There are two types of MHC proteins.
They are called class one MHC and class two MHC.
Pathogens also have their own unique marker.
This identification of the markers, is crucial for the immune system to work.
Identifying a cell as a "foreign cell" is the starting point for the immune system,
to get into action.
A pathogen is a bacteria cell or a virus.
A pathogen also has markers, which identify it as "foreign".
These identifiers of the pathogen, are called antigens.
Antigens are protein fragments, that bind to specific immune receptors,
in immune cells, and elicit an immune response.
The immune system identifies the antigen, of a pathogen.
There are many ways that the immune system works, to eliminate pathogens.
In some cases, pathogens are eaten by some white blood cells.
In some cases, pathogens are killed by toxic cells.
In some cases it generates antibodies, to fight the pathogen.
Macrophages.
Macrophages can recognise foreign cells.
They are capable of engulfing or eating a foreign cell.
Macrophages secretes enzymes and lysosomes.
The macrophages digest the pathogen, and effectively kills it.
This by itself acts as a immune response,
for certain types of foreign pathogen invasion.
Macrophages are part of what is called, as the innate immune system.
The innate immune system will fight against any foreign cell or pathogen.
The innate response is usually triggered, when microbes are identified,
by pattern recognition receptors.
These receptors can recognise patterns, which are broadly the same across,
groups of micro organisms.
The innate immune system, is not specific to a particular pathogen.
They respond to pathogens in a generic way.
The innate immune system, cannot remember the pathogen, it is fighting.
It does not contribute to long term immunity.
It acts like a first line of defence, against a foreign cell, or pathogen.
Immune system responses, which are specific to a particular pathogen,
is called as the adaptive immune system.
Macrophages play a role in both the innate immune system and the adaptive immune system.
When the macrophages digest the pathogen,
they break it up into small fragments.
These fragments could be any part of the pathogen.
They present these fragments on their surface, along with the class two MHC protein.
This is called as the MHC antigen complex.
The macrophages presenting these antigens, are called APC or antigen presenting cells.
Other immune cells like T cells or B cells could recognise and identify the pathogen,
by identifying the antigen presenting macrophages.
This is crucial for triggering the specific immune system.
Specific immune system.
The specific immune system has many pathways.
We will discuss some main representative pathways.
We will first discuss the case of a first time infection.
A special type of T cells, is called as the helper T cell.
These T cells have receptors which can recognise and bind to specific proteins.
Helper T cells ignore the MHC marker, of the body's "self" cell.
They ignore the antigen itself.
They only recognise the MHC antigen complex presented by the macrophage.
The macrophage which engulfed the pathogen, presence the antigen, to the helper T cell.
The helper T cells can recognise the antigen, with the help of a protein called CD4.
When an antigen is recognised, the helper T cells becomes, activated helper T cells.
The activated helper T cells presents the antigen, on its surface,
in the class 2 MHC complex.
Once the helper T cells gets activated.
Activated helper T cells, can trigger different responses of the immune system:
it can trigger the cell mediated, or T cell response.
it can trigger the anti body, or B cell response.
it can trigger macrophages.
Cell mediated response.
When pathogens invade the body, our body cells get infected.
To slow down, and halt the spread of the infection,
the infected body cells have to be destroyed.
The cell mediated immune pathway is primarily effected through T cells.
There are some cells called cytotoxic T cells.
Under normal conditions they are dormant.
When triggered by an activated helper T cell,
the cytotoxic T cell gets primed to recognise the specific antigen,
originally detected by the macrophage.
The primed or effecter cytotoxic T cell is now ready for action.
It first divides and multiplies itself.
This creates a larger army of cells, looking for a specific pathogen infected cell.
This army spreads out to carry out a search and destroy operation.
It is interesting to know, that this army, is specially designed,
to recognise cells infected by a specific pathogen.
The effective cytotoxic T cells ignore healthy body cells.
They ignore the actual pathogens itself.
They only look for cells infected by the pathogens.
When a healthy body cell is infected by a pathogen, a change takes place.
The infected cell presents the antigen, in the class one MHC antigen complex.
Recognition of this MHC antigen complex, is also aided by a protein called CD8.
The effecter cytotoxic T cell, recognises the MHC antigen complex and binds with it.
Cytotoxic T cells contain granules, filled with destructive enzymes.
For example, It can release a chemical, called perforin.
This chemical punches holes in the infected cell, and effectively kills the cell.
Some body cells, which are infected are sacrificed, to protect the other healthy cells.
Once after the cell has been killed, the cytotoxic T cells move on to search for other infected cells.
This process continues till all the infected cells are destroyed.
Some cytotoxic T cells are also called killer T cells.
The description clearly fits their role of killing infected cells.
Antibody immune response.
The antibody immune system directly attacks the pathogen.
B cells are involved in the antibody response of the immune system.
Cytotoxic T cells attack only the infected cells.
Antibodies generated by B cells attack the pathogen itself.
B cells are made in the bone marrow.
The starting point of the immune pathway, for the antibody response,
is similar to the starting point, for the cell mediated response.
Macrophages engulf pathogens.
They present their antigens in the class two MHC complex.
Helper T cells recognise this complex.
Helper T cells get activated.
The present the antigen in the class two MHC marker.
Helper T cells regulate both the cell mediated, and antibody immune response.
They determine which immune response, is required for each pathogen.
These cells by itself do not kill any pathogens directly.
They direct other cells, like killer T cells, or B cells, into action.
The antibody immune response, is mediated by B cells.
The activated helper T cells, prime the B cells, to get into action.
When a B cell is primed,
it becomes an effector B cell.
An effector B cell can recognise a specific pathogen.
The B cell divides and multiplies into many plasma cells.
Plasma B cells produce proteins called antibodies.
Antibodies belong to a family of large protein molecules called immunoglobulins.
These antibodies circulate in the blood and lymph system.
Antibodies attach to the antigen carrying pathogen, and neutralise them.
B cells can produce millions of free floating antibodies at a astonishing pace.
It is capable of making millions of copies of the same antibody in an hour.
This is understandable because invading pathogens also divide and multiple rapidly.
The antibody response tries to overtake the pathogens, in a race to overcome the infection.
Antibodies are specific to a pathogen.
They are compliment proteins to the antigen.
Antigens are so named, because they generate antibodies.
Antigens can be viewed as antibody generator.
Antibodies bind to the antigen of the pathogen.
Many antibodies can bind to the same pathogen.
This itself could make the pathogen ineffective.
It can also mark the pathogen, to enable macrophages,
or other phagocytic cells, to kill the pathogen.
Both B cells and T cells are involved in the adaptive immune system.
The adapting immune system responds to a specific pathogen.
The innate immune system is a generic response to any foreign cell or pathogen.
The adaptive immune system is specific to a particular pathogen.
Every type of infection involves a specific pathogen.
Even a minor illness, like a common cold,
could be due to hundred different types of rhinovirus.
Many other infections like chicken pox, flu, malaria, polio, jaundice,
are each caused by their specific pathogen.
The adaptive immune system responds to every specific antigen,
in a specific way.
It recognises each type of pathogen, by the antigen.
It generates specific antibodies, for each type of pathogen.
Antibodies.
The B cells in the immune system, produce specific antibodies for each type of pathogen.
We could be infected by a large number of pathogens.
How does the immune system generate these specific antibodies?
Antibodies belong to a family of large protein molecules, called immunoglobulins.
Some of the major kinds of immunoglobulins,
are called IgG, IgD, IgE, IgM, etc..
Ig stands for immunoglobulin.
The characters G,D etc., stand for the different types of heavy protein chain,
which is part of the antibody protein.
Antibodies can be visualised as a Y shaped protein structure.
It has a constant region, a heavy chain and a light chain.
Heavy chain is where the binding of the antigen takes place.
Antibodies generation takes place from gene slices of widely located genes,
in different chromosomes.
The genetic codes from these different genes, are combined together,
to generate a specific antibody.
A typical antibody would have:
A variable segment or a V segment,
A diversity segment or a D segment,
A joining segment or a J segment,
A constant segment or a C segment.
One of 400 possible variable gene segments,
combine with one of fifteen possible diversity segments,
which can combine with one of four joining segments.
This itself can create 24000 possible combinations for the heavy chain alone.
In this manner the immune system is able to generate a large variety of antibodies.
This variety is what makes it possible to generate specific antibodies for specific antigens.
B cells rapidly produce millions of antigens, in specific response to a given pathogen.
It will continue to produce this response, till all invading pathogens are neutralised.
Once the infection is controlled, it will stop producing antibodies.
In many cases antibody which binds to the pathogen, and marks the pathogen.
The marked pathogen is engulfed, by macrophages.
The immune system work together, as a system to fight infections.
Many cells work together, to generate an effective response.
The cells communicate with each other, with chemical signalling.
There are multiple pathways, which the immune system,
will invoke to generate the best possible response.
We have discussed a simplified version, of the immune system.
It serves to illustrate the basic concepts of the working of the immune system.
Long term immunity.
A very powerful feature of the adaptive immune system is the capability,
to remember the type of pathogen, that caused the infection.
The immune system encodes the antigen structure, and stores it in memory cells.
If the same pathogen attacks again, the memory cells directly get into action,
to provide a response to the known pathogen.
This provides a long term immunity for known infections.
When a first time infection takes place,
helper T cells activate B cells and cytotoxic T cells.
These cells then divide rapidly.
Most of these cells would be involved in the battle with the pathogens.
Some of the dividing cells differentiate, and become specialised memory cells.
Our immune system , has a ready stock of memory cells. specific to infections ,
that it was subjected to.
Memory immune cells are also passed on from mother to baby.
Both B cells and T cells have the capability to develop memory cells.
These memory cells could be retained by the immune system, for a life time.
When the same pathogen attacks again, these memory cells directly gets into action.
The response for a second time attack would be more immediate and faster.
This powerful defence system provides us protection from the repeated infections,
from the same pathogen.
Vaccination.
Vaccination is a powerful method, developed by Louis Pasteur.
By vaccinating children, they can be provided with life term immunity,
against potentially life threatening illnesses.
Many such illness have been eradicated, are almost eradicated using vaccination.
Small pox and polio, are some examples of illnesses, which have been mostly eradicated,
using vaccination.
Typically in vaccination, the virulent component of the pathogen, is inactivated,
and a small portion, is injected to people, usually children.
The antigens in the pathogen, however trigger the adaptive immune system.
This causes the immune system to respond in several ways.
Most importantly the immune system develops memory cells for the specific pathogen,
which it can typically remember for life.
This provides us immunity from many dangerous illness.
Vaccinations are now available for about 25 known illness.
It is a simple, cost effective way of health care,
where we harness the capabilities of our natural immune system.