Understanding Cell-Mediated Immunity (it's simple and fun!)

Immunology is one of the most interesting and important branches of Pathology, yet it makes us go crazy with the various complications involved. My first many classes of immunology went by as if they were teaching it in Chinese. I thought that I was the stupid one but soon realized that, well I’m not the alone. But, hey! If studied with interest, Immunology can be absolutely amazing!

So to help others like me and even the non-medics who may be interested in this fascinating science to get through the basic concepts of immunology, I tried to put one of the aspects – The T-lymphocyte Immune Response - in a simpler, yet hopefully understandable version.

Our body is like the Gotham city. A regular city with normal people like you and me (read: cells) living in absolute harmony, going about their daily chores in sync without causing any inconvenience to each other.

Now the problem arises when Joker comes up with a super-evil plan and intends to create havoc. Whoa, but wait! Why worry when we have BATMAN!

The Joker is metaphorically the foreign substances (i.e. microbes) that cause infections in the body. On the other hand, Batman is our Immune cells.

However fantastic may he be but batman, or any other superhero for that matter, can in no world beat the heroic abilities of our Immune System. Our Gotham city has many Batmans with a variety of superpowers.

In this section, we’ll discuss the Adaptive Cell-mediated Immune Response of our body. This type of immunity is specific for intracellular microbes. For the purpose of understanding this phenomenon, we’ll have our own superhero – T-man (a T- lymphocyte or T-cell)!

As we know every superhero requires a side kick. Similarly to fight crime (read: infections) , our superhero has sidekicks too. These sidekicks catch the culprits and bring them to T-man. These cells are known as Antigen Presenting Cells (APCs).

Consider an incident.

Many terrorists of the same organisation, i.e. the disease causing microbes, enter the city. Now some of them were caught at the border itself by the one of the sidekick APCs -  Langerhans Cell or a Naive Dendritic Cell. Upon sighting the microbe, the sidekick is activated – i.e. it becomes an Active Dendritic cell after trapping the microbe. 

An active DC takes the microbe to the nearest police station – a Lymph node.

 Just like a criminal is stripped off of his disguise and beaten up in a Police station, the trapped microbe is processed and converted into small peptide antigens. These peptide antigens can be handcuffed and presented to our superhero, i.e the T-cell. The handcuffs are made up of what is known as the Major Histocompatibility Complex (MHC molecule).

Now unfortunately our superhero is blind but he has a special weapon. It’s a magic wand, with 4 beads on it, which he binds to the suspect to recognise it. The magic wand is a T-cell receptor (TCR). The beads are the four proteins bound with the TCR that help in signal transduction.

These four proteins are –

·         CD28 molecule

·         CD3 molecule

·         CD4 / CD8 molecule

·         ⱬ proteins

The "Magic Wand" of a CD4 T-cell : TCR complex

With the help of his magic wand our Superhero recognizes the culprit. But there’s a catch! The culprit can be recognized only if he is accompanied by T-man’s sidekick and is handcuffed, i.e. an Antigen can be recognized only if it is bound to an antigen presenting cell and is displayed by an MHC molecule (no Batman without Robin, eh!)

As soon as the culprit is identified the beads on the wand start their magic! They send signals to T-man’s brain to activate his various superpowers.

The first signal is transmitted by CD28 molecule.  

The T-cells in our body have specificity for different antigens. When the antigen is recognised, the CD28 molecule binds to B7 protein (CD80 or CD82 molecule) of the Antigen Presenting Cell and that particular lymphocyte which is specific for the antigens starts rapid multiplication. This phenomenon is known as Clonal Selection, i.e. out of a pool of many lymphocytes, the one with highest affinity to the antigen is selected for multiplication.

The second signal is transmitted by the CD3 proteins present in close proximity with the TCR. 

It transmits signals to the nucleus increasing the activity of various transcriptional factors.

The first transcriptional factor causes release of a cytokine known as Interluekin-2 (IL-2).

The second transcriptional factor caused increased activity of the Interleukin 2 receptors (ILRs) present on the T-cells surface. 

IL-2 interacts with ILR and it leads to the rapid multiplication of the selected T-cell. This phenomenon is called Clonal Expansion, i.e. expansion of the selected clones to combat infections.

Meanwhile the microbe also activates The APC to produce molecules called co-stimulators which send further signals to ensure that the immune response is not induced by any harmless substances.

So by now we are familiar with the following superpowers of T-man –

• Clonal Selection
• Clonal Expansion
• Ability to restrict the immune response to true culprits(harmful substances)

Upon countering an infection, the T-lymphocyte differentiates into Effector T-cell and memory T-cell.

Now that we have an entire army of T-men, we can fight the remaining terrorists! 

These cells are released in the circulation to fight rest of the microbes that entered along with the one caught by Dendritic Cell.

Now, to look further into the superpowers, we need to know that our Effector T-men army has two contingents – The helpers and the killers.

A T-lymphocyte exists in two forms  :   a) CD4+ lymphocyte (Helper T-cell)

                                                                b) CD8+ lymphocyte (Cytotoxic T-cell)

In normal individuals, they exist in a ratio of - CD4 : CD8 = 2 : 1

A helper T-cell recognises antigens expressed by MHC class II molecule whereas a Cytotoxic T-cell recognises antigens expressed by MHC class I molecule.

The CD4 form fights criminals in the following ways –

v  Calls in his microbe killing  friends - the macrophages (macrophage activation)

v  Inflammatory response

v  Stimulation of his superhero brother , B-man , or a B-lymphocyte ( We will discuss his “adventures” in another section)

The CD8 form is crueller, he is a slayer! The cytotoxic T-cell causes killing of the infected cell.

Summary of T-man's Adventures!

When the culprits are defeated, our very modest superhero T-cell kills himself (Neki kar aur dariya me daal, right?). The effector T-cell undergoes apoptosis after the immune response has achieved its aim.

The memory T-cell stays in the circulation, in case the terrorists return with more men.

And voila, the microbe is taken care of. T-man saves the day!