Immunology additional notes

For chapters: 2, 3, and 4

 Antigen presenting cells: Macrophages :Has dual function . Also act as intermediate between innate and adaptive immunity. Dendritic cells :possess many appendages, for antigen presentation. B cells :have dual function. Also produce antibodies. T-lymphocytes are activated when they are triggered by an antigen presenting cell (ex. Macrophages), so in order for the T-lymphocyte to be activated it has to recognize both antigen component and MHC component .If these conditions are met, then activation of T-lymphocytes is going to take place. All of these are going to take place if the antigen presenting cell is doing its function. But if it fails, B-cells can weakly interact with few antibodies of IgM type, with no memory cells. Difference between neutrophils and macrophages: NEUTROPHILS -very large number. -very short half-life (6-12 h) then die. -form pus which can lead to tissue injury . -more efficient than macrophages in phagocytosis. MACROPHAGES -few cells . -long half-life. -Can phagocytosize many times , but because of their number they are less efficient than neutrophils.

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 N-K CELLS : - Look like lymphocytes but not specific. - When we look under the microscope ,we see large granular cells, with no receptors. - Body use as survalent cells. - Use different immune response, which is the ADCC (antibody dependence cells cytotoxicity). Where it recognizes the antibodies tails that are attached on the surface of tumor or virally infected cell. When it recognizes that, it releases its granules, leading to apoptosis.

Interferons: - Species specific - Interferon gamma :dual function first ,it enhances cell mediated immune function. Second, more expression of MHC complex. In the thymus, any cell that would react against self-antigens will be destructed or inactivated. If there is a problem in the thymus, autoimmune disease may develop.

Active and Passive immunity: If a person got infected with a contaminated needle with hepatitis ,passive vaccination must be given. The active and passive immunity can be both natural and artificial.

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Review test

1.

Pattern recognition receptors (PRR) can be found on:

a) b) c) d)

B cells T cells Dendeitic cells Defensins Ans: C) pattern recognition receptors for PAMP occur on host phagocytic cells. Kappa chains Lambda chains Heavy chains Light chains Ans: C) heavy chain

2. Antibodies are grouped into five classes based on differences in their

a) b) c) d)

3. Depressed levels of MHC class I molecules on virus infected host cells can be detected by:

a. b. c. d.

T cytotoxic cells T suppressor cells Activated macrophage NK cells Ans: D) common amino acid sequence on the heavy chain common amin acid sequence on L chain common amino acid sequence on the hinge region common disulfide bond
Done by: Razan Ghareeb

4. All five antibody classes are grouped together as immunoglobulins due to a

a. b. c. d.
Ans: B)

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Chapter 3:
Major histocompatibility antigens: 3 classes but the classes that are involved in the immune system are class 1 and class 2. Cells utilize these antigens as recognition markers. Cells recognize each other by having similar markers on the surface of the cell: Class1 and Class 2. The genes that code for the T cell receptors have many different diversities. We have around 10^18 10^19 different diversities.

In immunoglobulins, we have 10^11 different specificities. And the significance of that is having more response to foreign antigens.

To calculate how we can get these different specificities. It has to do with Gene splicing, gene manipulation and how genes can be transferred from one chromosome into another to get these different polymorphism and diversities of those antibodies that are going to be produced. The complement as innate immune system that has escaped a type of mechanism: classical pathway, alternative pathway, and the mannan-binding lectin (MBL) pathway. The complement are set of proteins, present in the serum that get activated by an antigen-antibody reaction as in the classical pathway (IgG and IgM antibodies and an antigen), for the alternative pathway lipopolysaccarides of bacteria and for the mannann-binding lectin, lectin binding to mannann for example bacteria and then the complement is going to be activated. The outcomes: cell destruction, immune complexes are cleaned off, help in phagocytosis(opsinaization), chemotactic factors , recognition of self and non-self (it has this property as the adaptive immune system).

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 Somatic hypermutation: even when that specificity develops something enhancement has to take place to make a better fit, better affinity or a better binding. MHC genes are present on the short arm of chromosome number 6. They are located in locus A, locus B, and locus C. And we have many different allelic forms; you get one from your father and one from your mother if the parents are heterozygous. But in case they are homozygous, you will get one form and you will be less diverse which means heterozygous individuals are more immune than homozygous. So minimum of 6 genes for the homozygous and 12 genes for the heterozygous.

Class 2 plays a major role in antigen presentation. T cell receptors recognize antigens only if presented with class 2 MHC. Interferon Gamma enhances the expression of MHC, so it is an immune modulator, while herpes virus destroys them.

T cells can be activated without the MHC but it won't be efficient, with no memory cells development, and the antibodies that are going to be produced are weak. The virus antigen has to be presented with MHC Class 1 in order to be recognized by the T cytotoxic cells.

Chapter 4:
Sometimes antibodies dont react with the antigens that were responsible for their production as in case of cross reactivity.

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 We can modify weak antigens to become stronger antigens by mixing them with protein carriers.

Conjugated vaccines: The capsule of Hemophilus influenza or Streptococcus pneumonia, those capsules are weak antigens, and we modify them to become more immunogenic by mixing them with a protein carrier. The most specific part of an antigen is called an antigenic determinant or an epitope, and the part that goes to an immunoglobulin or a T cell receptor is called a paratope.

An adjuvant is a substance that has the ability to enhance an immune response. We have complete adjuvant or incomplete adjuvant. Incomplete adjuvant if you get a weak antigen and mix it with an oil lipoid which slowly releases the protein into the circulation, so the chance of the lymphoid cells to be exposed to the antigen will be much higher. So the immune response is going to be enhanced. Complete adjuvant when we mix it up with antigens of Mycobacterium Tuberculosis which can call upon macrophages to come into the area, so the macrophages can enhance the antigenicity. Affinity is the strength of binding at that site, and if you have more than one binding two three pentamer we call that avidity. Avidity is the collection of affinities that are involved.

Multiple myeloma or multiple cytoma (monoclonal gammapathies): malignancy related to one of the plasma cells of one clone( one specificity) so the immunoglobulins that are going to be formed are of massive number of specificity. Immune electrophoresis: antibodies against antibodies (eg. anti-IgG antibody)

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 In IgE and IgM we have constant heavy 4. But the rest we only have constant heavy 3. We have Gamma 1 , 2 , 3 ,4 and Alpha 1, 2.

The most specific area of the antibody is part of the variable light chain and the variable heavy chain. And we call it the hypervariable region or the complementary determining region or the idiotype. And here we have the specificity. We have on the cells something called Fc receptors which binds to the Fc portion of the antibody. We have a carbohydrates part which is less than 5% and provides more stability for the immunoglobulin as they protect from proteolytic enzymes.

Hinge region is the area between the Fab and the Fc which is flexible. IgM can't cross the placenta as it's very huge. And in intrauterine infections the first immunoglobulin that we are looking for is IgM as it has never come from the mother to her baby instead it was developed from the baby. The IgG could develop later but it could come from the mother because it can cross the placenta.

The immunoglobulins can switch due to isotypes switching. These classes and the subclasses: Gamma 1,2,3 Alpha 1,2 epsilon and delta we call them isotypes. And those are species specific, so if I inject those in any of
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us nothing is going to happen because we share the same isotypes. But if we inject those into animals then they are going to develop antibodies against these isotypes. And this is the principle of making secondary antibodies by injecting into animals.

When we are infected for the first time IgM antibodies will be produced and maybe few IgG. But in the secondary immune response, you will see a mechanism that is going to be evolved which is called isotypes switching, that the same cell that produces the IgM is going to select the IgG keeping the specific part intact changing only the biological function of the immunoglobulin to IgG. Producing higher number of IgG, thats why it has the highest concentration. The colostrums are very rich in IgA antibodies.

The clumping activity is lost with the papain enzyme. But in pepsin enzyme it still has it, but the biological activity is lost. And they use these for lots of research purposes, also they noticed when we give the RhoGam or the anti-D antibodies for Rh incompatibility when a baby is an Rh+ and the mother is an Rh- , the Anti-D antibodies of the mother are going to cross the placenta to the second baby and sensitize his Red blood cells . So the treatment of that is to give the RhoGam or anti-D antibodies to the mother, and they are going to neutralize the antigens that have crossed the placenta into the mother. If the job is simply neutralization, so we give the Fab portion without the Fc portion but they saw that it didnt work, so the important part here is the Fc portion which plays a role in the immune suppression phenomena in hemolytic disease of the new born. Done by: Rand Rawashdeh

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