SARS COV2 has by now engulfed the entire world and with recent information of the presence of dangerous mutants in parts of the world such as the UK and South Africa ,has threatened the confidence of the worried scientific community as never before in recent history .

So far no new drug has been found to be clearly useful except for a few repurposed drugs that too in very limited sense.

The only hope even today is on the availability of appropriate vaccines which can work against all such mutations of COVID 19 in near future and work on all such  viruses ,zoonotic or otherwise in future.

Vaccines have emerged as true panacea not just against dreadful viruses but against a long list of microbes also and in providing answer to poorly treatable ‘Autoimmune diseases  ‘ ( disease caused by self destruction due to own immune system )and even against Emperor of  all  Maladies - The cancer .

The scientific basis of vaccine use has been drawn by better understanding of the body's natural response in containing the viral disease and mimicking the same process by introducing only an innocuous part of the virus  .

Introduction of virus in the body leads first to generation of non specific immunity known as ‘Innate immunity which is a ‘general purpose protection irrespective of the nature and type of the attack .

There is yet another type of protection or immunity known as ‘Adaptive immunity ‘which is specific to each type or even sub type of micro organisms and therefore called upon every time that agent visits or attacks by using it’s memory stored in the lymphocytic cells .  The ever present memory cells revive the memory of the attack and threat is soon contained. Such a specific immunity is generally life long and is known as ‘Adaptive immunity ‘suggesting it’s ability to adapt to each new type of organism .

Landmark research on fundamentals of immunity leading to clearer understanding of the genetic control and involved molecular process regulating both Innate and Adaptive immunity brought huge attention to the scientific world and consequently

Nobel prize of physiology or medicine of 2011 was awarded ,one half jointly to Bruce A. Butler and Jules A .Hoffmann for their discoveries concerning genetic and molecular control of Innate Immunity and other half to Ralph M. Steinmann for his discovery of mechanism  leading to better understanding of Adaptive immunity

Jules A. Hoffmann studied a fruit fly, ‘Dorsiphila Melanogaster ‘ as a model to know how our innate immunity works as the first line of defence against infection. Dr Hoffmann procured mutant fruit  flies from the laboratory of Christiane Volgards who had prepared it for studying embryonic development and for which she herself got a Nobel prize in 1995 . 

Dr Hoffmann demonstrated that when such mutant fruit flies are attacked by a fungus a gene called’ Toll’ ( meaning Great or peculiar in Dutch ) and its protein product TLR( Toll Like Receptor) gets activated and  it was demonstrated without doubt that all flies with altered ‘Toll genes ‘died uniformly and those with intact Toll genes remained healthy suggesting that Toll genes and it’s product were responsible for sensing pathogenic microorganisms and triggering host defence actions.

Dr Bruce Beutler instead went a step ahead and studied the same phenomena of protection in mammals, the mouse , as a model to locate the gene  which gets activated when attacked by gram negative bacteria with LPS ( Lipopolysaccharides) intact receptor molecule leading to septic shock and death . The most important tool was to locate a C3H / HeJ  mouse strain with a mutated or absent LPS gene .

Dr  Beutler launched a search which lasted for long five years to find the genes regulating the LPS receptor and subsequently he could find out to his pleasant surprise by the process of DNA sequencing that LPS genes were homologous to the ‘Toll genes ‘of Drosophila,the fruit fly and thus confirmed a system of Innate Immunity run by Toll/TLR just as in  insects (which is preserved through evolution )  in mammals also with similar life saving innate immunity functions.

Needless to say that even Humans carry the same Toll like genes  . 

Dr Ralph Steinmann was interested to know what keeps the immune system prepared round the clock and adapt to the specific microbial challenges at a very short notice .

 It was known that viral or any foreign antigen on its own can not recruit  lymphocytes and it needed some accessory cells as antigen presenting cells.

Steinmann located a peculiar cell in the midst of lymphoid system which act as accessory cells named as  ‘Dendritic Cell ( Greek word dendron meaning Tree like) ‘because of its shape with several tentacle or branches like projections  ,whose  own maturation is also linked to activation of ‘ Lymphocytic T cells’.

Steinmann  found that the innate immunity system signalled  by ‘TLR ‘ also helps in maturation of ‘Dendritic cells ‘and help coordinate the lymphocytic T and also  B cells activity when attacked by foreign antigens .

Layers of defence -

Much like the way our country is protected in layers of defence forces, our body too has layers of protection.

There is a generalised physical barrier of skin ,mucous membranes with cilia and it’s secretions , sweat ,tears etc . Their contents such as lysozymes , commensal (friendly )bacteria etc and physical factors such as acidic pH and even maintenance of temperature range - all help in keeping the body intact and integrated .

The immune response is triggered when the body is alerted about the entrance of foreign material. Triggers in the form of chemicals released from damaged cells and pathogens subsequent to the initial interactions in the form of local inflammation get the ball rolling.

What happens when microbes such as Viruses attack?

The moment virus enter the cells it tries to let the neighbouring  cells know about such enemy attack by putting on it’s surface certain peptide molecule known as MHC 1( class 1 Major Histo- compatibility Complex ) in large numbers with a mix of attacking virus’s detached proteins so that ever circulating  and roaming ‘cytotoxic T cells ‘ which have receptors on their surface known as TCR ( T  Cell Receptor) locate the MHC 1 molecule  on the infected cell - surface and effect a cascade of reactions by pouring  a set of chemicals which destroy the virus or other enemy infected cells .

However ,sometimes viruses allow very little MHC 1 molecules on infected cell surfaces and in such situations a different set of cells known as N K ( Natural Killer) cells  , mount attacks and destroy such virus infected cells in no time.

These Cytotoxic T and NK cells have granules containing chemicals such as ‘Perforin ‘make holes in the  infected cells and release Granzymes containing granulysin  etc . It also releases a host of infected cell destroying chemicals such as Interferon G and Tumour Necrosis Factor am( TNF ) alpha which mediate inflammation  and doubly alert the neighbouring cells .

There are some other ways also by which immune  system neutralise the invading viruses

1. By releasing Interferons , which are proteins made out of virus - host cell interactions allowing increase of MHC1 molecules on cell surface and by prohibiting active replication of viruses within the cells .

Antibodies produced by circulating B lymphocyte and plasma cells specific for each virul antigens  and are capable to get rid of viruses by

1.  Mopping them the moment they are in the system

2.  Surround and neutralise the viral antigens by overwhelming them by a process called Agglutination

3. The virus bound antibody binds to the Fc receptor on the surface to phagocytic cells and triggers phagocytosis and engulf the virus.

4. It can also trigger the  ‘Complement system ‘ ( certain proteins to effect destruction of cells) by making a hole and leading to rupture the surface phospholipid bi- layer and activate the phagocytosis with the help of lysosomes present in the cell cytoplasm.

( Author is former Professor and Head of Medicine, RIMS, Ranchi)