Basic principles of the different immune cells

[Monique]

Immunology is not my best subject, anyone care to lay out the basic principles of the different immune cells?

 

[iansmith]

B-cell : lymphocytes that mature in the bone marrow and express membrane-bound antibody.

Plasma Cell : Differentiated B-cell after the interaction with antigen. Secrete antibody

Memory Cell : Differentiated B-cell after the interaction with antigen. Present specific antibody and play a role in acquired immunity

T-cell : Lymphocytes that mature in the thymus and expreces T-cell receptor (Thymus Cell Receptor; TCR). Recognize antigen when associate with self by gene encoded within the major histocompatibility complex (MHC).

Eosinophils : Motile phagocytic cell that migrate from blood to the tissue space. Play a role in immunity against parasite. Granulocytes.

Neutrophiles : Granulocytes. Short-live phagocytes. First cell on site of infection and phagocytic.

There more cell but I have to go the lab

 

[iansmith]

Dendritic cell: Covered with a mazed of long membrane processes resembling dendrite of nerve cells. Present antigen and express high level of MHC. After processing antigen, migrate to various lymphoid organs to present antigen to lymphocytes.

Basophiles: Not phagocytic, possesses granules that contained active substance and are release at site of infection to destroy the invader. Granulocytes

Monocyte and macrophage: Mononuclear phagocytes. Monocyte enlarge and circulate in the blood for 8 hours then migrate to tisses and differentiate into specific tissue macrophage. Phagocytoses microorganism, insoluble particle, injured and dead cells and cellular debris. Play a role in innate and acquire immunity.
Two type of macrophage elicited and resident. Resident are recruted in non-inflamated tissues ad become permanent resident. Elicited are wandering macrophage that are recruited to inflamated tissues. Arrive to site of infection after neutophiles. Macrophage clean the mess up and promote healing.

Mast Cell: First cell to respond to the presence of invaders. iniate and coordinate inflamatory and immune responce. Present in a wide variety of tissues (Skin, connective tissues. epithelial tissue and intestinal track). Play a role in acquired immunity and allergies.

Null Cellls Do not express cell memmbrane glycoprotein of B and T cell. Have no immunolical specificity or memeory. One function is to be a natural-killer cell. Circulate in the blood. Cytotoxic against tumor cell. Play a role in innate immunity. Some express CD-16, a receptor or immunoglobulin. therefore they bind antibodies. Can kill in the presence of antibodies and it is refer to antibody dependent cell-mediated cytotixicity (ADCC).

Natural killer cell: Non specific effector cell. Granular lymphocytes and lack marker of T- and B-cell. Release Tumor necrosis factor beta and perforin

 

[Monique]

Thank you Ian that gives me something to go from.

Could you explain to me how the immune cells know not to attack the organisms own cells? What I remember is that all kinds of antigen binding domains are made, after which the ones that recognize 'self' are iliminated?

What exactly is the role of MHC in immunity?

 

[iansmith]

Originally posted by Monique
Could you explain to me how the immune cells know not to attack the organisms own cells? What I remember is that all kinds of antigen binding domains are made, after which the ones that recognize 'self' are iliminated?

That is the principle. For T-cell there is two selection. positive selection is in the thymus and only the T-cell that recognize the self-MHC molecules are keep (self-MHC-restricted T-cell). Negative selection eliminates T-cells that recognize self-MHC too strongly (Self tolerant T-cell). Our prof use to call this the thymus school.

Originally posted by Monique
What exactly is the role of MHC in immunity?

1) To recognize self and reject non-self. MHC present antigen.

2) Participate in mounting humoral and cell mediated immune responce.

There 3 class of MHC

Class I: Glycoportien present on nearly all nucleated cells. Recognize by Cytotoxic T-cell (Tc). CD8+ T-cell receptor. Present on cells that have process antigen of intracellular invader (ex: virus).
Class II: Glycoprotein primarily on antigen presenting cell (Macrophage, dendricic cells and B-cell). Recognize by Helper T-cell (Th). CD4+ T-cell receptor. Present on cells that have process antigen of phagocytosed invaders.
Class III: Gene product associated with immune responce such as complements, and tumor necrosis factors.

 

[Monique]

Originally posted by iansmith
That is the principle. For T-cell there is two selection. positive selection is in the thymus and only the T-cell that recognize the self-MHC molecules are keep (self-MHC-restricted T-cell). Negative selection eliminates T-cells that recognize self-MHC too strongly (Self tolerant T-cell). Our prof use to call this the thymus school.

I appreciate that :)

You know, that is what I don't understand. T-cells that recognize the self-MHC are kept. What does that mean? What is this recognition and what then keeps them from tagging 'self' cells?

I really had a very bad immunology course, we were basically given a book and told: finish that, it was the last course of the year too so pretty much everyone failed, I was one of the three out of thirty who actually passed :P I rather would have failed, having to redo it..

 

[iansmith]

Originally posted by Monique

T-cells that recognize the self-MHC are kept. What does that mean? What is this recognition

MHC is required for presenting Antigen to T-cell. T-cell only recognize self-MHC. Also for graft rejection, T-cell will recognize the MHC on the graft material as foreign i.e. as non self-MHC. The T cell receptor (TCR) with CD4+ or CD8+ binds to class II or class I MHC complex, respectively.

Originally posted by Monique
what then keeps them from tagging 'self' cells?

Originally posted by iansmith
Negative selection eliminates T-cells that recognize self-MHC too strongly (Self tolerant T-cell).

 

[Monique]

Originally posted by iansmith
MHC is required for presenting Antigen to T-cell. T-cell only recognize self-MHC. Also for graft rejection, T-cell will recognize the MHC on the graft material as foreign i.e. as non self-MHC.

Only a cell that has self MHC is able to present antigens to the T-cell, but who says the antigens are not self?? Why can't foreign MHCs present antigens? Why not?

Basically I am asking about the mechanism of the workings.. I guess I'll just have to pick up the book when I get a chance and read the whole thing from start

I am not quite sure about the negative selection either.. how does the cell in the thymus know it recognizes the self MHC too strongly?

 

[iansmith]

Originally posted by Monique
Only a cell that has self MHC is able to present antigens to the T-cell, but who says the antigens are not self??

Invaders such as bateria have specific structure that are recognize but the immune system and cells in general. When it is encounter, then the cell process these structure and expose then as antigen. I'll have to look more carefully in my notes.

Originally posted by Monique
Why can't foreign MHCs present antigens? Why not?

Non-self MHC can present antigen but T-cell will not recognize the MHC complex because it has been selected to only recognize self MHC. There actually an experiment that demontrated that. I'll to go through my notes.

Originally posted by Monique
I am not quite sure about the negative selection either.. how does the cell in the thymus know it recognizes the self MHC too strongly?

As far as I remember, the prof never explained this in details and my notes do not explain this either but I have look in the more detail sections. I must be something about interraction between TCR and MHC and how T-cell responce.

 

[Monique]

Originally posted by iansmith
Non-self MHC can present antigen but T-cell will not recognize the MHC complex because it has been selected to only recognize self MHC. There actually an experiment that demontrated that. I'll to go through my notes.

I really don't see why immunity has selected that T-cells only react to antigens presented by innate cells.. and why these cells don't present antigens that are infact innate.. probably because the antigen binding structures are in fact the things which are selected for in thymus, that would make sense! ha!

The answer still then needs to be answered HOW this selection of MHC AND antigen binding domains takes place in the thymus.. I mean, how many proteins are there in the human body? All are potential antigens..

Can auto-immunity reset itself? Probably we don't know about it.. auto-immunity is still a new branch of research I guess..

 

[iansmith]

Originally posted by Monique
I really don't see why immunity has selected that T-cells only react to antigens presented by innate cells.. and why these cells don't present antigens that are infact innate..

T-cell only react to self HMC because a pathogen could mimic the MHC and present non-specific antigen and create confusion. Also cancer cell could then be view as self. Because self antigen would not be process by the immune system and presented to T-cell on the MHC.

Originally posted by Monique
probably because the antigen binding structures are in fact the things which are selected for in thymus, that would make sense! ha!

What do you mean? Antigen binding structure are usually antibodies. MHC are antigen poresenting structure.

Originally posted by Monique
The answer still then needs to be answered HOW this selection of MHC AND antigen binding domains takes place in the thymus..

MHC gene can go rearrangement. So there a region that do not rearange and probably represent self whereas other region (the antigen binding domain) go through rearrangement. So the TCR, CD4+ and CD8+ receptor recognize the non-rearranging region. If the binding is unspecific (i.e. does not recognize self) then the cell go into apoptosis. Imagine if the imunne system did not recognize self then everybody would have some auto-immune disease because the immune system could not make the difference between invader and self. During negative selection, if the binding is too strong (too much specific) it probably illicit some reaction and then the cell goes into apoptosis.

Problem is that the book does not into detail and my notes either. People probably don't know what is really happening.

Originally posted by Monique
I mean, how many proteins are there in the human body? All are potential antigens..

It is why the MHC class I is there for. MHC tell the immune system that it is self and not an invader or cancer cell.

 

[Another God]

the second I don't have assesments looming, I promise i will read all of this!
thanks for posting this monique, and thanks for knowing the answers ian!

 

[iansmith]

Originally posted by iansmith
If the binding is unspecific (i.e. does not recognize self) then the cell go into apoptosis. Imagine if the imunne system did not recognize self then everybody would have some auto-immune disease because the immune system could not make the difference between invader and self. During negative selection, if the binding is too strong (too much specific) it probably illicit some reaction and then the cell goes into apoptosis.

I screw up, the explanation is not appropriate.

Positive selection is needed to recognize self otherwise there would beT-cell would not diffenciate between self and non-self. Pathogens and cancer could go inside without being notice. Plus T-cell could attack self by mistake

Negative selection is needed because strong binding would create hypersensitivity reaction such as allergies. If the binding is not specific enough, then the antigen would be recognize as non-self but it could be self.

 

[None]

Try and think of it from a biochemical perspective! But first, some clarifying...

Iansmith has been talking about negative and positive selection in the thymus. First off, TCRs (T-Cell receptors) have two different binding sites, one for antigen/MHC and one for the MHC itself (this is how CD8 and CD4 interact with MHC I and MHC II respectively).

Positive selection is undergone first, with the T-cells being exposed to MHC of cortical epithelial cells in the thymus. Most of these MHC contain self-antigen. Only those T-cells which recognize the MHC/antigen complex or at least the MHC will be allowed to live.

Negative selection occurs with the pool of T-cells remaining being exposed to dendritic cells. Here's where the biochem comes in. Of these T-cells remaining, all sorts of different conformations will be present (due to the high variability of TCRs and antibodies in general). Some conformations have really high affinity for self-MHC/self-antigen complex or even just self-MHC itself. These cells with high affinity are potentially dangerous, possibly causing autoimmune responses in the host. Anything with an interaction over a certain threshold is selected against and apoptosized.

Monique, your question about the enormous number of proteins in the body and all the possible self-Ags they could make is a good one... I don't see how all these possibilities could be accounted for through negative selection in the thymus alone. I'll ask a professor and get back to you.

None.

 

[Jikx]

I'll take a pot shot (no proof, except it makes sense) -

Maybe not all cellular proteins are ever expressed on the cell surface, nor fished out by MHC to the surface. As a consequence, there is no need to select against immune cells that target them, as only disfunctional cells would have them.

 

[None]

Good assumption Jikx, but MHC presents small fragments of peptide, not the entire protein - around 10 amino acids.(Though it differs depending on the class of MHC)

For cytoplasmic proteins, think about what happens if that cell lyses, all its contents are open to the extracellular environment. Sure the proteins may even be degraded by proteases, but what's to stop one of those fragments from being picked up by a circulating APC? (antigen presenting cell)

 

[Monique]

Originally posted by None
but what's to stop one of those fragments from being picked up by a circulating APC? (antigen presenting cell)

Does that really happen like that? I know that cell death not by apoptosis can give a nasty inflammation on site..

 

[None]

The processing mechanism is a little bit more complex, and it differs depending on what type of antigen you're talking about (ie. extracellular vs. intracellular). For example there is a multisubunit protein called the proteosome that cleaves peptide in MHCII presentation.

The main idea remains, however, that peptide is picked up from outside the cell (or is already present inside the cell) and is processed to be in the proper form for MHC presentation. There are APCs circulating through all tissues in the body looking for Ag to present.

Inflammatory response in necrosis is due to the release of cellular breakdown products which stimulate the innate response. This doesn't happen in apoptosis because the cells are neatly packaged into apoptotic bodies and these products are not released.

 

[Monique]

Since I am brushing up on my immunology, I ran into the following cool table:

http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/immunol_F.01/graphics/figure19-02b.gif

http://www.blc.arizona.edu/courses/181gh/Lectures_WJG.01/immunol_F.01/graphics/cell.gif

the pictures don't show..

 

[brainyman89]

How can T cytotoxic (T8L) be responsible of graft rejection (graft material of foreign MHC i.e non self-MHC ), though it can recognize only foreign antigen associated with self MHC.

 

[sameeralord]

This is strange. I remember asking some immunology questions few months back, maybe one year and you gave some very good explanations (@monique). Now you seems to have gone to the stage I was when I was asking those questions. Did you forget everything?

https://www.physicsforums.com/showthread.php?t=345617

EDIT: I didn't read the topic fully, so you probably might be asking some advanced questions. Just ignore the post if it is so.

 

[brainyman89]

What i meant to ask is if T cells are normally restricted to recognizing foreign peptides displayed by self-MHC molecules, why should these T cells recognize foreign MHC?

 

[madcat8000]

What i meant to ask is if T cells are normally restricted to recognizing foreign peptides displayed by self-MHC molecules, why should these T cells recognize foreign MHC?

Positive selection (MHC Restriction) - acording to Lauren Sompayrac's lecture book titled How the Immune System Works third edition the reason for positive selection is to ensure that only antigens presented by MHC's are recognized by mature T-cells. This ensures that unpresented antigens cannot trigger a responce as they do in B-cells. The problem is that T-cell receptors are pollymorphic as they are created by mixing genes and so must be tested to ensure that they do actually work. The selectivity for "self MHC" selection is a byproduct and not an intent.

 

[madcat8000]

Does that really happen like that? I know that cell death not by apoptosis can give a nasty inflammation on site..

The T-cells that could be triggered by APC's that incidentialy pick up self antigens and present them as forigen will be working alone. They need other signals to proliferate and remain energized. Working alone they will become anergized(they cease to function) from lack of co-stimulation and eventually commit aptosis.

 

[nismaratwork]

This should be distilled and added to the library or a sticky.