Immunology concept driving me crazy, cd8+ killing

[aspiringmd1015]

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as well all know, Cell mediated Immunity is directed towards intracellular pathogens, viruses, oncogenically transformed cells etc, and we know th1 helper t cells assist in cell mediated immunity and cytotoxic killing by secreting cytokines(il-2, ifn) I understand this well, what i dont understand is, with these intracellular pathogens, where does the antigen presenting cell come to play? i understand if its a macrophage(which is an APC) it can present the antigen on mhc2 and present to helper 2 cells, but if its aany other cell thats infected, how do the antigen presenting cells process and present an antigen that is intracellular, and then on top of that take that antigen and present this antigen to helper t cells, which then will form th1 cells?

 

[MD22412]

intracellular processing from the inside of the cell presents it to the CD8 guys==>

extracellular processing by APCs (eg macrophage, dendritic cells--B cells (different b/c B cells are specific to the extracelllular component) present to CD4 cells generally; ==>

 

[MD22412]

To clarify, any cell can present via intracellular pathway and thus an infected cell doesn't need an APC to present, as the NK cell or CD8 cell will pick up on that infected cell.

Classically we're talking about virally infected or cancer cells. NK cells pick up on decreased MIC expression due to the intracellular pathogen (accounts for cases when viruses decrease MHC2 and thus will be missed by CD8 cells), whereas CD8 cells can detect via this route of seeing the MHC2 w/antigen being presented to it.

Hope that makes sense! Let me know if you hav emore questions

 

[Jabbed]

OP I think that you're just confuzzled about CD4+ cell activation altogether. APCs like dendritic cells, macrophages, and B cells can present antigen via MHC II receptors to activate it, BUT each APC has a different pattern of activation. i.e. dendritic cells activate CD4+ in the lymph nodes, macrophages re-stimulate them in the tissue, and B cells activate them during the chronic phase or subsequent acute infection (typically in the lymph nodes). Just to clarify, when you say "intracellular antigen presentation," you're referring to MHC I presentation and the associated CD8+ recognition, right?

 

[aspiringmd1015]

by intracellular antigen presentation i mean, those antigens which require killing via cell mediated immunity as they are not extracellular, and usually are falcutative intracelular pathogens or cancer cells/virus infected cels which express neo antigens on their mhc 1. i know an infected cell doesnt need an apc to present, but if they dont present them to cd4+ helper t cells, then how will th1 cells interact with the immune response if theres no apc presenting an antigen to them first?

 

[aspiringmd1015]

th1 cells by secreting il-2 active and cause clonal proliferation of cd8+ t cells increase the activity of cell mediated immunity, otherwise cd8+ t cells by binding the target cell without th1 assitance is a much weaker response.

 

[Jabbed]

by intracellular antigen presentation i mean, those antigens which require killing via cell mediated immunity as they are not extracellular, and usually are falcutative intracelular pathogens or cancer cells/virus infected cels which express neo antigens on their mhc 1. i know an infected cell doesnt need an apc to present, but if they dont present them to cd4+ helper t cells, then how will th1 cells interact with the immune response if theres no apc presenting an antigen to them first?

They won't. An APC must present antigen via MHC II (MHC II presentation is the defining feature of APCs) to the CD 4+ cells before the helper T cells can become activated. Without MHC II presentation > no active helper T cell > no Il-2 secretion > no CD8+ cytotoxicity.

The reason why I asked about your meaning of "intracellular antigen presentation" is because MHC II presentation is considered to be the presentation of antigen that is in the extracellular environment of the APC. Just wanted to be sure that we were referring to the same thing.

 

[4-cyclohexene]

HELP!!!

 

[4-cyclohexene]

Elizabeth is a 19 year old girl with severe chrons disease. In the course of this disease is characterized by diarrhea, loss of appetite, and weight loss, the associted inglammatory processes led to bowel obstruction that necessitated the resection of a portion of intestine. unfortunately so much of the samll intestine was removed that the remaining part could no longer absorb nutrients. Elizabeth was given IV nutrition and became a candidate for a pilot intestinal transplant program and recieved a small intestinal transplant one month earlier. In this procedure, the surgeon transplants a segment of cadaver's small intestine into the patient. She was prescribed immunosuppresive drugs to overcome rejection but this also increases the risk of infection.

After 27 days, Elizabeth returned to the hospital showing evidence of weight gain but a diffuse weeping rash covering her body, abdominal cramps, and a fever of 5 days duration. What is a possible explanation???

 

[4-cyclohexene]

Elizabeth is a 19 year old girl with severe chrons disease. In the course of this disease is characterized by diarrhea, loss of appetite, and weight loss, the associted inglammatory processes led to bowel obstruction that necessitated the resection of a portion of intestine. unfortunately so much of the samll intestine was removed that the remaining part could no longer absorb nutrients. Elizabeth was given IV nutrition and became a candidate for a pilot intestinal transplant program and recieved a small intestinal transplant one month earlier. In this procedure, the surgeon transplants a segment of cadaver's small intestine into the patient. She was prescribed immunosuppresive drugs to overcome rejection but this also increases the risk of infection.

After 27 days, Elizabeth returned to the hospital showing evidence of weight gain but a diffuse weeping rash covering her body, abdominal cramps, and a fever of 5 days duration. What is a possible explanation???

I am between two explanations: the immunosupprressive drug regime she is on resulted in an opportunistic infection or this is some type of first set rejection of the allograft. I think that if it is a rejection, it's a minor histocompatability rejection because it happened almost 30 days after the surgery took place, where a first set rejetion would normally create T-cells and provoke an immune response and symptoms in 10-14 days. That being said, I think there might be some surface protein on the cadaver's small intestine that was not an MHC that is causing Elizabeth to have a response. However, the thing that is confusing me and I am unable to explain is the weeping rash. What causes this? And why the abd cramping????

Thanks!!

 

[Transposony]

I am between two explanations: the immunosupprressive drug regime she is on resulted in an opportunistic infection or this is some type of first set rejection of the allograft. I think that if it is a rejection, it's a minor histocompatability rejection because it happened almost 30 days after the surgery took place, where a first set rejetion would normally create T-cells and provoke an immune response and symptoms in 10-14 days. That being said, I think there might be some surface protein on the cadaver's small intestine that was not an MHC that is causing Elizabeth to have a response. However, the thing that is confusing me and I am unable to explain is the weeping rash. What causes this? And why the abd cramping????

Thanks!!

Most likely Graft Versus Host Disease since MALT is the very rich in lymphocytes.