Both MHC class I and II are involved in MHC restriction.
Both MHC class I and II are antigens targeted by the immune response in transplant rejection.
Some terms before we proceed:
Graft rejection refers to the recipients immune response rejecting the donor organ.
GVHD (graft versus host disease) refers to the transplanted organ mounting an immune response to the host's antigens. Sounds strange but GVHD is potentially fatal. That is why identification of Ag and Ab in both the recipient and donor is important.
HLA-A, HLA-B and HLA-DR are the main antigens targeted by the recipient, in graft rejection. If there are incompatibilities with these antigens, the feasibility of a successful transplant is low.
All MHC class II antigens are targets in GVHD.
Histocompatibility testing ideally should identify incompatibilities for both class I and class II. This will reduce the likelihood of both graft rejection and GVHD.
Wednesday, October 19, 2011
HLA and MHC
MHC is located on the short arm of chromosome 6. This locus codes for the HLA antigens that are found on various cells in the body. There are 3 classes of MHC.
MHC class I are found on platelets and all nucleated cells. examples of MHC class I are HLA-A, HLA-B and HLA-C.
MHC class II are found on macrophages, monocytes and lymphocytes. Examples are HLA-D, HLA-DP, HLA-DQ and HLA-DR.
Examples of MHC class III are C2, C4 and Factor B. (remember complement?)
We need to know the actual structures of MHC class I and II.
For each structure you need to know where antigen binds, and where CD4 or CD8 interacts. Remember that CD4 or CD8 are cell markers and are attached to cells, viz. TH and TC respectively. So do not draw just the cell marker; ensure that you draw the cell as well.
You need to know the names of each domain; these are not interchangeable and you will lose marks if they are labelled incorrectly.
Ag binds between alpha 1 and alpha 2, and CD8 interacts with alpha 3. (MHC class I)
Ag binds between alpha 1 and beta 1, and CD4 interacts with beta 2 (MHC class II)
MHC class I are found on platelets and all nucleated cells. examples of MHC class I are HLA-A, HLA-B and HLA-C.
MHC class II are found on macrophages, monocytes and lymphocytes. Examples are HLA-D, HLA-DP, HLA-DQ and HLA-DR.
Examples of MHC class III are C2, C4 and Factor B. (remember complement?)
We need to know the actual structures of MHC class I and II.
For each structure you need to know where antigen binds, and where CD4 or CD8 interacts. Remember that CD4 or CD8 are cell markers and are attached to cells, viz. TH and TC respectively. So do not draw just the cell marker; ensure that you draw the cell as well.
You need to know the names of each domain; these are not interchangeable and you will lose marks if they are labelled incorrectly.
Ag binds between alpha 1 and alpha 2, and CD8 interacts with alpha 3. (MHC class I)
Ag binds between alpha 1 and beta 1, and CD4 interacts with beta 2 (MHC class II)
Tuesday, October 18, 2011
TERMS in Ag Ab reactions
Titre refers to the concentration of a particular substance in a test tube.It is expressed by inverting the concentration of that substance. If the concentration of glucose is 1/16 in test tube no 4, the titre of test tube no 4 is 16.
A serial dilution is any dilution where the concentration decreases by the same quantity in each successive step.
double dilutions are a series of ½ dilutions. Each successive tube will ½ the amount of the original concentrated solution.
In any serological test done in the lab, we are looking for an unknown using a known. The known are the reagents that we use, usually commercialy available. The unknown is usually in the patients specimen, and can be either antigen or antibody.
Acute phase serum refers to specimen taken during the disease state, used to diagnose the disease.
Convalescent phase serum is taken after the disease has been treated, and can be used to determine if titre has decreased due to effective treatment.
Serum has no clotting factors present; usually specimen taken in brown top blood collection tube (with no anticoagulants)
Plasma has all clotting factors present; usually collected in purple top tube (containing anticoagulants)
Sterility is not an issue in serology as we are looking for presence of Ag or Ab. Any organisms present will not affect the results
Sensitivity refers to the ability of a serologicl test to identify the Ag or Ab in minute amounts. There will not be any false negative results due to the Ag or Ab being present in very small amounts.
Specificity refers to the ability of a serological test to identify the exact Ag or Ab being tested for. There are no cross reactions giving false positive results.
All serological tests have to be controlled. These controls are put up at the same time as the tests, and must give the correct expected readings/results before the test results can be taken as being accurate.Both positive and negative controls are used.
There is increasing automation in serology. Even in tests that are not automated, the equipment used are designed to save time and space. Microtitre plates replace test tubes. Slides with either Ag or Ab absorbed onto their wells save time in processing.Most procedures use very small amounts of substances/reagents. This saves money as reagents are usually very expensive.
Due to the precise and small amounts of reagents used in serological tests, serology requires the lab worker to be accurate and precise in their work. Amounts are not negotiable. any deviation from this will lead to inaccurate results.
A serial dilution is any dilution where the concentration decreases by the same quantity in each successive step.
double dilutions are a series of ½ dilutions. Each successive tube will ½ the amount of the original concentrated solution.
In any serological test done in the lab, we are looking for an unknown using a known. The known are the reagents that we use, usually commercialy available. The unknown is usually in the patients specimen, and can be either antigen or antibody.
Acute phase serum refers to specimen taken during the disease state, used to diagnose the disease.
Convalescent phase serum is taken after the disease has been treated, and can be used to determine if titre has decreased due to effective treatment.
Serum has no clotting factors present; usually specimen taken in brown top blood collection tube (with no anticoagulants)
Plasma has all clotting factors present; usually collected in purple top tube (containing anticoagulants)
Sterility is not an issue in serology as we are looking for presence of Ag or Ab. Any organisms present will not affect the results
Sensitivity refers to the ability of a serologicl test to identify the Ag or Ab in minute amounts. There will not be any false negative results due to the Ag or Ab being present in very small amounts.
Specificity refers to the ability of a serological test to identify the exact Ag or Ab being tested for. There are no cross reactions giving false positive results.
All serological tests have to be controlled. These controls are put up at the same time as the tests, and must give the correct expected readings/results before the test results can be taken as being accurate.Both positive and negative controls are used.
There is increasing automation in serology. Even in tests that are not automated, the equipment used are designed to save time and space. Microtitre plates replace test tubes. Slides with either Ag or Ab absorbed onto their wells save time in processing.Most procedures use very small amounts of substances/reagents. This saves money as reagents are usually very expensive.
Due to the precise and small amounts of reagents used in serological tests, serology requires the lab worker to be accurate and precise in their work. Amounts are not negotiable. any deviation from this will lead to inaccurate results.
co receptors in cell to cell interactions
We have learnt that TH cells express CD4 which interacts with MHC class II expressed by APC's.
There are other co receptors involved in the above interaction.
TH cell -------------- APC
LFA-2 LFA-3
LFA-1 ICAM-1
CD28 B7
TCR+CD4 MHC class II + peptide
The most important interaction is between CD28 and B7
There are other co receptors involved in the above interaction.
TH cell -------------- APC
LFA-2 LFA-3
LFA-1 ICAM-1
CD28 B7
TCR+CD4 MHC class II + peptide
The most important interaction is between CD28 and B7
HIV infection
2 types: HIV-1 and HIV-2.
HIV-1 is more prevalent and largely responsible for the AIDS pandemic
HIV infection takes place or refers to when a person acquires the HIV virus. The initial illnes (which does not appear in all people) is a ild glandular fever like infection. There is a huge rise in virus levels.
The host's immune response controls the infection and there follows an asymptomatic period. This can last for 8-10 years depending on the host's immune status.The virus continues to multiply during this period.The antigenic makeup of the virus changes as the infection proceeds, which hampers the host's immune response to eradicate the infection.
The HIV virus requires both CD4 and either CXCR5 or CCR5 as co receptors for entry into the host's cells. During the asymptomatic period, the co receptor preference changes from CCR5 to CXCR4.
The level of CD4 cells decreases until AIDS develops. AIDS is characterized by infections with opportunistic organisms.
HIV-1 infections have a shorter asymptomatic period, a quicker progression of disease and higher rates of transmission when compared to HIV-2
Most HIV-1 strains use CCR5 as a co receptor and are known as R5 strains. HIV-1 strains that use CXCR4 as a co receptor are known as X4 strains.
There are some individuals who have had repeated exposure to HIV and not become infected. Their CCR5 genes have mutated. People with homozygous mutations express no CCR5 on their cells and are highly resistant to infection. People with heterozygous mutations have increased resistance to HIV.
HIV-1 is more prevalent and largely responsible for the AIDS pandemic
HIV infection takes place or refers to when a person acquires the HIV virus. The initial illnes (which does not appear in all people) is a ild glandular fever like infection. There is a huge rise in virus levels.
The host's immune response controls the infection and there follows an asymptomatic period. This can last for 8-10 years depending on the host's immune status.The virus continues to multiply during this period.The antigenic makeup of the virus changes as the infection proceeds, which hampers the host's immune response to eradicate the infection.
The HIV virus requires both CD4 and either CXCR5 or CCR5 as co receptors for entry into the host's cells. During the asymptomatic period, the co receptor preference changes from CCR5 to CXCR4.
The level of CD4 cells decreases until AIDS develops. AIDS is characterized by infections with opportunistic organisms.
HIV-1 infections have a shorter asymptomatic period, a quicker progression of disease and higher rates of transmission when compared to HIV-2
Most HIV-1 strains use CCR5 as a co receptor and are known as R5 strains. HIV-1 strains that use CXCR4 as a co receptor are known as X4 strains.
There are some individuals who have had repeated exposure to HIV and not become infected. Their CCR5 genes have mutated. People with homozygous mutations express no CCR5 on their cells and are highly resistant to infection. People with heterozygous mutations have increased resistance to HIV.
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