Chapter 33: The Immune System

The cells and proteins of this system work together to detect and kill foreign organisms.

The humoral immune response is caused by the production of antibodies in the circulatory system.
The immune system is an example of a system governed by the basic principles of evolution.

The structure of immunoglobulin G is discussed after the authors define essential immunological terms.

The variable and constant regions of immunoglobulins are related to the organization of genes.

They explain how a large variety of V-, D-, and J-segment genes with a few C genes, plus imprecise joining, can generate enormous diversity of antibody molecules.
There are five classes of immunoglobulins with their functions and compositions.
The five classes are generated by the same genes.
The formation of immunoglobulins is a result of alternative mRNA splicing.
The authors turn to the cellular immune response.

They describe the functions of T cells and discuss their structure and composition.

Preceding chapters in the text that deal with the structure of genes, evolution, and the flow of genetic information are important background for this chapter.

Chapter 33 contains some basic information about the immune system and a discussion of the production of monoclonal antibodies.

You should be able to complete the objectives once you have mastered this chapter.

Give the different classes of immunoglobulins their functions.

The structural bases for the function of each class are provided by H chains and the common occurrence of (k) and (l) L chains.

Discuss the distribution of the immunoglobulin-fold structural motifs in the biological distribution of the proteins.

Discuss the types of bonds that make up complexes.

The sizes and structures of the epitopes are noted.

Match the structure or feature listed in the right column with the appropriate IgG frag ment on the left.

The immunoglobulin class is listed in the left column and the right column.

There is a molecule of IgG that has a immunoglobulin domain.

Each heavy chain has a sandwich, and each light chain has one.

There are seven alpha-helical segments in the immunoglobulin fold.

The X-ray analysis shows that small antigens fit into a cleft.

There are many different copies of the V and C genes in the pools.

The following genes have an approximate number in the germ line.

Match the immunological term in the left column with its description or definition in the right column.

The right column has structural features that correspond to the left column.

The feature listed in the right column is the type of T cell you match.

T cells are subject to both positive and negative selection during fetal development.

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The Fc fragment lacks an antigen-binding site and the Fab fragment only has one.

The insoluble lattice of antigen-antibody molecules can be formed because intact IgG molecule each have two different binding sites.

The variable sequence of the L and H chains is different from one another.

The answer is incorrect because the two sites on the mol ecule are directed towards the same epitope.

The answer is incorrect because the H and L chains are hypervariable.

A, b, c, e, d, and so on.

Several B lymphocytes that are stimulated by the antigen are able to differentiate into different types of cells.
Each plasma cell has a different type of antibodies that bind the antigen through different types of interactions between the hypervariable regions of the antibody and the epitope bound.

The probe would hybridize to one region on the DNA from the plasma cell, but not the germ-line DNA.

The intact gene sequence for the V, J, and L regions of the L chain can be found on the plasma cell DNA.
The V, J, and L regions of the L chain are in distant locations because the DNA has not yet been rearranged to bring them into proximity.

There isn't enough unique V and C genes to give a sufficient number of different sequences when they are combined.

The number of combinations can be increased by joining and diversity genes.

If the small molecule becomes attached to a macromolecule, it can act as an immunogen and serve as an epitope to which an antibody can be selected to bind.

Section 33.4.3 can be found on page 933.

The Peptides are bound in a "extended" conformation.

The answer is incorrect because T-cell receptors only recognize fragments of foreign macromolecules when they are bound on the surface of a cell.

Answer (d) is incorrect because the T-cellreceptor is composed of one a and one b chain, each having a sequence that is similar to the V regions of the chains of immunoglobulins.

The answer is correct because the complement cascade is contributed to by class III MHC proteins.

The answer is incorrect because the HIV RNA and other core components enter the helpers T cells when the viral membrane is fused with the cell.

The T-lymphocytes that do not bind to any of the MHC-peptide complexes are winnowed out by the positive selection.

During the "positive selection" phase, most developing T-cells are discarded, including cells that would respond to other individuals, but not those present in "self" cells.
T-cells that bind too tightly to "self" are removed by the negative selection process.

According to the text, cancer cells can sometimes produce CEA that is inappropriat ate for the development of the individual.

Sometimes abnormal genes can be produced.
The fact that human cancer cells are basically human cells poses a serious challenge for cancer treatment, and explains the fact that chemotherapy is generally rather difficult and uncomfortable.
Antibiotics can be quite safe.
The therapeutic ratio is less favorable because the drugs have to prevent processes that occur in both cancer cells and normal cells.

There are only 40,000 genes in the human genome, but millions of them are involved in the production of antibodies.

All higher animals have some kind of self versus nonself recognition system, but this diversity generating system is limited to jawed vertebrates.

A single sharp band appears when polyacrylamide gel electrophoresis is performed.

Two bands appear when the preparation is treated with b-mercaptoethanol.

The carboxyl-terminal side of the interchain disulfide bonds between heavy chains is cleaved by Pepsin.

Suppose that the antibody is prepared against the part of the hormone that is known to carry out autophosphorylation.

Adding this antibody to target cells will cause similar responses to those obtained by adding hormones.
Adding hormones may mimic the effects of adding antibody.
Before tackling this question, 411-413 was written in the text.

In many experiments on the immune system, DNP is used as a hapten.

Light and heavy chains are produced by the addition of a bifunctional DNP affinity-labeling reagent.

Most of the antigens have more than one binding site.

It is easy to understand how a molecule might have multiple binding sites if it contains regular, repeating sequences.
It is difficult to imagine how polyvalence might be accounted for in the case of nonrepeating sequences.
There are single polypeptide chains that are polyvalent.

Quantitative measures of the interactions between antigens and antibodies are often given as association constants.

The second-order rate constant for the binding of a given hapten is108 M-1 and the association constant is109 M-1.

Suppose that dinitrophenol is attached to aProtein with many potential DNP binding sites and that the resulting antigen is used to increase the production of rabbits' antibody production.

"cut and display" is the system that supplies MHC.

College students were put to sleep in plain white T-shirts.

They had female volunteers rate the attractiveness of the shirts on a scale of 1 to 10.
The researchers were able to determine that the women preferred the scent of men with different MHC proteins because they had tissue-typed all participants.
Other researchers found that women preferred men who smelled like their fathers.

The text states that the rate of change of HIV is 65 times higher than that of the flu.

Myasthenia gravis is a disorder in which the body's immune system attacks acetylcholinereceptors, causing a decrease in their numbers.

Those with myasthenia gravis show weakness and fatigability of their muscles.

Loss of function of breathing muscles leads to death.

There are two types of drugs that can be used in medical therapy for myasthenia gravis.
Give a reason for the use of each.

There will be a large number of variable sequences in the germ-line DNA even without a diversity-generating system.

Without the power and flexibility of the vertebrate system, these will allow for an immune response.
The importance of the immune system may be lessened by the fact that most invertebrates have a short life-span.

The Ab/Ag ratio is 8/7.

The ratio is 17/6.

On the basis of size, polyacrylamide gel electrophoresis separates different types of cells.

Light and heavy chains are separated on the gel.

One piece has Fab units.

The other two pieces are from the Fc region.

The hormone-receptor com plex can be caused by the addition of hormone.

The two approximated receptor monomers will become capable of cross-phosphorylation, with an increase in their activity.
Adding bivalent antibodies would make it possible for the units to crossphosphorylate and thus cause effects in the body.

The light chain and heavy chain are involved in binding the DNP hapten, according to the observation.

The production of a mixed population of anti bodies will be stimulated by a given antigenic protein, with each type of antibody being specific for a different region in the tertiary structure.

The lymphocyte preparation could be done over a column containing the beads.

Lymphocytes that are capable of producing antibody toward the particular antigen would bound to the beads because they have a receptor on their cell surface.
The column would not be binding.
The addition of free antigen would compete with bound antigen for combination with the cell- surface receptors, which could then be released from the column.
The fact that many types of lymphocytes are produced by the immune system, each having a specificreceptor on the cell surface capable of reacting with some (previously unencountered) antigen is the reason that the purification method works.
A combination of the two causes the lymphocyte to divide.

If the haptens were clustered so densely on the antigen that bi valent antibodies combined preferentially with two neighboring haptens, the results would occur.

Most of the cells have MHC class I proteins.

Both self and nonself proteins will be degraded, and the peptides will be translocated across the ER.
The combination of peptides and MHC will eventually be displayed on the cell's exterior.

B-cells from the immune system are the only place where MHC class II proteins are found.

The peptides do not originate in the cell but in the endosomes, where acidic hydrolysis occurs.

The B-cell is stimulated to reproduce by the nonself peptides.

It is not surprising that females prefer males with different MHCs, as the scent of an individual shows.

This would ensure that the offspring would have different MHCs and that they would have better survival chances in an epidemic of a disease.
There was some variation in the results of the study when it came to whether the women were taking birth control pills.
The study on women taking birth control pills differed from Wedekind's conclusions.
It is possible that "dating" women would be interested in adventure, while "settled" or pregnant women would prefer the familiar scent of home.

The previous year's flu shot wouldn't work anymore because the virus has changed.

There are many strains of the HIV virus within the body after an individual has been HIV positive for several years.
It is difficult to design a vaccine when the target is constantly moving.
AIDS is an example of evolution because it seems to adapt to the life style of the population.
It is in line with the model of reproduction with variation and subsequent selection.
It would be possible for it to change in ways to keep spreading the disease.
It's hard to eradicate or even cure it because it's a retroviruses that becomes part of the genes of the cells.

The synthesis of many other useful and protective antibodies will be retarded by the use of immunosuppressive agents.

There will be an increase in acetylcholine concentrations at motor end plates.
The increase in mass action will lead to an increase in the number of acetylcholine-acetylcholine receptor complexes.

The value is close to the limit for combination of a small molecule with a protein.

The extent of structural change is likely to be small.

The size of the dextran-binding site is typical for an antigen-recognizing surface.

There are six sugar residues in the active site of lysozyme.
The range of sizes of the combining sites of the antibodies is similar to the active sites of the enzymes.

When the hapten is bound, the fluorescence enhancement and shift to the blue show that water is largely out of the site.

Most antigen-antibody complexes are formed by hydrophobic interactions.

It is essential to have the VH and VL domains.

A small portion of Fab fragments can be further digested to produce FV, a fragment that contains just these two domains.
The stability of Fab is dependent on CH1 and CL.

The mode of activation is similar to that of the tyrannosaurus rex.

This experiment can be carried out using a goat antibody to a mouse B cell.

T-cell receptors are not expressed by B cells.

B-cell mRNAs are used to hybridize T-cell cDNAs.

Chapters 33 and 34 are enriched with those T-cell receptors.

A closely related cell that does not express the gene of interest should be used for hybridization.

This method was used to obtain genes for T-cell receptors.

An unfolding/refolding experiment could be used to test the model.

A high temperature or a chemical denaturant would be used to reversibly unfold an antibody.
A slow refolding would be attempted by gradually lowering the temperature or removing the denaturant in the presence of different small-molecule haptens.
The model suggests that different folding should be done by refolding the presence of different antigens.

Premature terminated codons may be introduced by the gene rearrangements that generate antibody diversity.

The immune response could be adversely affected by the truncated proteins.

The regions of variable sequence are missing from the Fc fragments.

The properties of their surfaces are similar and they are able to interact with each other to form a lattice.
The group of Fab fragments have a variety of binding surfaces.

leucine is at position 2 and valine is at the C terminal.

The C-terminal of the presented peptide should be the V of the given sequence.
It is most likely that the peptide is LLQATYSAV.

The geometry of the transition state that is formed during the hydrolysis of amides or esters by serine proteases is similar to the transition-state analog.

One would expect an appropriate serine (or cysteine) in its binding site for catalytic activity.

A domain that is related to SH2 may bind to the critical phosphotyrosine residue and maintain the enzyme in an inactive state.

The second domain may not bind to the tyrosine if CD45 removes thephosphate from the phosphotyrosine.

A single codon change is likely to be a mechanism for this process.