Basic questions regarding adaptive immunity

[Ascot]

Hello,

 

there are major gaps in my understanding of immunology and I'd really need to find the right answers. Text book knowledge surely covers these questions, but once I started getting confused the text books were no use anymore.

 

I'd really appreciate it if some of you would be so kind to answer the following questions:

 

• Antigen specificity: an almost infinite number of possible antigens can be bound by T cell receptors. Is it possible though that a bacteria/virus doesn't get recognized because it's specific antigen-binding T cell receptor is not expressed?

 

• Memory T cells: how many are there of one kind? When a T cell is activated clonal expansion occurs. Are all of the clones converted into memory T cells? Or is just a small percentage converted? How long is the life of a memory T cell (months, years? how?). Assuming there are - for instance - 3 kind of memory T cells that respond each to a peptide that is produced by the same pathogen protein and all 3 kinds are destroyed/ undergo apoptotis - is the memory effect exhausted? Does the total number of lymphocytes increase throughout the life as memory T cells are constantly created?

 

• How do APCs ensure that only membran associated particles are presented in MHC 2? Antibodies targeting intracellular protein would have no effect.

• How many MHC 1 or MHC 2 receptors are expressed in normal cells or APCs? Is every expressed intracellular protein presented by a fragment in MHC 1? Is every pathogen protein presented in an infected cell? Lets say the intracellular bacterial protein "A" is cleaved into 3 peptides, A1, A2 and A3. Are all peptides somehow transported to different MHC 1s (ignoring the sequence length limit for this example)? If so, are there specific T cells for each epitope? If so, how high is the number of the specific T cells? One? If one is correct, how can the T cell make sure to check all MHC receptors on a single cell? What if it doesn't detect bacterial epitopes because they are presented on the other side of the cell? And again, what if these particular T cells are destroyed by ROS for instance? Is the body incapable to react to the pathogen?

 

I'm aware that these questions are rather long and cannot be explained easily, so for anyone who's willing to read or even respond to them I give my kind thanks in advance.

 

Thank you very much,

Ascot

[fiveworlds]

Antigen specificity: an almost infinite number of possible antigens can be bound by T cell receptors. Is it possible though that a bacteria/virus doesn't get recognized because it's specific antigen-binding T cell receptor is not expressed?

 

 

An antigen is a foreign substance (such as bacteria or toxins) that induces antibody formation. If the bacteria/virus doesn't get recognized then it isn't an antigen. Antigens not getting recognized for some people is commonplace for instance I didn't develop the immunity to hepatitis b when given the injection and had to get the hep a and hep b(twinrex) injection instead.

 

Memory T cells: how many are there of one kind? When a T cell is activated clonal expansion occurs. Are all of the clones converted into memory T cells? Or is just a small percentage converted? How long is the life of a memory T cell (months, years? how?). Assuming there are - for instance - 3 kind of memory T cells that respond each to a peptide that is produced by the same pathogen protein and all 3 kinds are destroyed/ undergo apoptotis - is the memory effect exhausted? Does the total number of lymphocytes increase throughout the life as memory T cells are constantly created?

 

That is the job of the phlebotomist but as far as I remember lifelong immunity depends on the levels of lymphocytes in the blood expressed as a percentage. When testing for Hepatitis B levels they are tested on electrical equipment on a scale and levels over 100 are required to ensure lifelong immunity. Levels do reduce over time but generally there are few that you need booster shots for and not all of them ever need booster shots. You are supposed to get blood tests throughout your life because different people tend to have different results.

 

 

 

How do APCs ensure that only membran associated particles are presented in MHC 2? Antibodies targeting intracellular protein would have no effect.

How many MHC 1 or MHC 2 receptors are expressed in normal cells or APCs? Is every expressed intracellular protein presented by a fragment in MHC 1? Is every pathogen protein presented in an infected cell? Lets say the intracellular bacterial protein "A" is cleaved into 3 peptides, A1, A2 and A3. Are all peptides somehow transported to different MHC 1s (ignoring the sequence length limit for this example)? If so, are there specific T cells for each epitope? If so, how high is the number of the specific T cells? One? If one is correct, how can the T cell make sure to check all MHC receptors on a single cell? What if it doesn't detect bacterial epitopes because they are presented on the other side of the cell? And again, what if these particular T cells are destroyed by ROS for instance? Is the body incapable to react to the pathogen?

Haven't a clue

Edited March 23, 2015 by fiveworlds

[Ascot]

Thank you for replying!

 

That is the job of the phlebotomist but as far as I remember lifelong immunity depends on the levels of lymphocytes in the blood expressed as a percentage. When testing for Hepatitis B levels they are tested on electrical equipment on a scale and levels over 100 are required to ensure lifelong immunity. Levels do reduce over time but generally there are few that you need booster shots for and not all of them ever need booster shots. You are supposed to get blood tests throughout your life because different people tend to have different results.

 

But how do these cells stay alive for years? I know that some cells like in the germ line or nerve cells stay dormant for decades but a highly differentiated lymphocyte always keeps me wondering. If these cells are "immortal" (as in only dying when specific changes in the environment occour) then I would assume that the overall weight of the "lymphocytom" increases throughout the aging process. Imagine two identical mice that are fed the same food (nutrition-wise) but one is held in germ-free environment while the litter mate is exposed to pathogens in an uncontrolled manner. At the end of their life, would there be a (small) difference in the weight, as the latter accumulated memory T cells? Would be hard to proove though as most weight changes will be associated with the microbiota.