98 Questions
What increases the expression of MHC class II on macrophages and dendritic cells?
IFNγ
Which of the following is true about MHC I and II?
MHC I and II are polymorphic, each allele can bind a different set of antigenic peptides.
What happens if a foreign antigenic peptide does not fit the MHC molecule?
It does not stimulate an immune response.
Why are heterozygous animals more likely to respond to a variety of antigens?
They express more alleles and bind more antigenic peptides.
Which animal species is at risk for decimation by infectious pathogens due to genetic homogeneity?
African cheetahs
What is the function of MHC class I molecules in presenting antigens?
Present antigens to T cells.
What is the main discovery recognized by the Snell Prize?
The discovery of genetically determined structures on the cell surface that regulate immunological reactions
What is the term used to describe the region that controls graft rejection or survival?
Major histocompatibility complex (MHC)
What is a typical feature of Class I MHC molecules?
They are expressed on all nucleated cells
Which of the following species has the most functional Class I loci?
Rats
Which of the following statements is true about histocompatibility molecules?
All animals have histocompatibility molecules
Which class of MHC gene loci is less polymorphic and located outside the MHC on a different chromosome?
Class Id
What is the main function of T cells?
To protect the body against intracellular pathogens and to activate other cells such as macrophages and B lymphocytes
Which type of cells are involved in the activation of T cells?
Dendritic cells, macrophages, or B cells
What is the role of MHC molecules in T cell activation?
They present antigens to T cells
How were MHC genes initially discovered?
As a locus containing genes responsible for graft rejection
Which of the following is a possible outcome of a skin graft between two animals?
The graft will either survive and function or be rejected
Which of the following is a common characteristic of MHC molecules?
They are involved in the presentation of antigens
Which method is used to determine polymorphism in both class I and class II regions in cattle?
Microlymphocytotoxicity test
What is a possible explanation for why a particular MHC allele makes an animal more susceptible to a certain disease?
The MHC allele does not bind and present a critical antigen
Which of the following is a consequence of an overreaction or cross-reaction of the immune system?
The immune system attacks synovial cells and causes progressive arthritis
What is the significance of MHC typing in cattle?
To determine the resistance/susceptibility to disease
Which of the following diseases is associated with MHC alleles in goats?
Caprine Arthritis-Encephalitis Virus (CAEV) infection
What is the role of MHC proteins in the immune response?
To present antigens to T cells
Which of the following is a characteristic of MHC class I molecules?
They are not usually found on red blood cells, gametes, neurons or trophoblast.
Which of the following is a function of the class III genes in the MHC?
They encode proteins that have many different functions in the innate immunity, such as complement proteins.
Which of the following is the correct gene structure for MHC molecules?
Each individual animal has 2 complete sets of MHC molecules, one on each of the paternally and maternally derived chromosomes, and each gene is expressed co-dominantly.
Which of the following is the most variable part of the MHC class I molecule?
The binding groove.
Which of the following is a characteristic of T cell receptors (TCR)?
Each T cell receptor (TCR) has a single peptide-binding cleft that binds one peptide a time, and each TCR can bind one peptide and ONLY that peptide.
Which of the following is a common misconception about self peptides presented by MHC molecules?
If self peptides are continuously being presented, individuals will develop autoimmunity.
Which of the following is a characteristic of MHC class II molecules?
They are expressed on professional antigen presenting cells such as dendritic cells, macrophages and B cells.
Which of the following is a characteristic of the class III genes in the MHC?
They encode proteins that have many different functions in the innate immunity, such as complement proteins.
Which of the following is a characteristic of MHC molecules in individuals?
MHC genes are co-dominantly expressed.
What increases the expression of MHC class I molecules?
IFNγ secreted by NK cells
Which type of cells increase the expression of MHC class II on macrophages and dendritic cells?
NK cells
What is the effect of a foreign antigenic peptide that does not fit the MHC molecule?
It leads to tolerance towards that peptide
How does the MHC help in regulating the immune response?
By presenting antigens to T cells
What can be said about heterozygous animals in relation to MHC and immune response?
They are more likely to generate an immune response to a variety of antigens
What is the term used to describe the genes responsible for the survival or rejection of a graft?
Tissue genes
Which animals are at risk of decimation by infectious pathogens due to genetic homogeneity?
Florida panthers
How many functional Class I loci do humans typically have?
20
Which animals may not respond to stimulation with specific antigens based on their MHC haplotypes?
Animals with certain MHC haplotypes
Where are Class Id MHC loci located, which are less polymorphic than Class I loci?
On a different chromosome outside the MHC
What is the function of Class I MHC molecules in terms of expression?
Expressed on all nucleated cells
How many MHC class Ia loci do mice typically have?
30
Why might an animal with MHC alleles unable to bind to a critical antigen succumb to an infection?
The animal cannot mount a protective immune response
Which scenario explains how a particular MHC allele can lead to an autoimmune response?
The MHC allele cross-reacts with self antigens
In which case does an animal with specific MHC alleles face a risk of developing progressive arthritis?
When the alleles bind to self antigens
How does the binding of an MHC allele to an epitope Z during an infection contribute to disease susceptibility?
It triggers an autoimmune reaction
What role do MHC proteins play in disease susceptibility?
Determining resistance or susceptibility to diseases
How does MHC typing in cattle contribute to understanding disease resistance/susceptibility?
By identifying genetic factors that influence immunity
What is the main function of T cells in the immune response?
To protect the body against intracellular pathogens and activate other cells
Which of the following is not a characteristic of MHC class I molecules?
Heterodimeric structure composed of two different protein chains
Which of the following is not a possible outcome of a skin graft between two animals?
The graft will induce tolerance to the recipient's MHC molecules
What was the main discovery recognized by the Snell Prize in 1980?
The discovery of the role of MHC molecules in graft rejection
Which of the following is not a characteristic of MHC class II molecules?
Heterodimeric structure composed of two identical protein chains
What happens if a foreign antigenic peptide does not fit the MHC molecule?
The T cell will not be activated and will not mount an immune response
Which type of cells do not usually express MHC class I molecules?
Neurons
What is the common term used to describe the set of MHC alleles present on a chromosome?
Haplotype
Which MHC class does not participate in antigen presentation?
Class III
What is the most variable part of the MHC class I molecule?
Binding groove
Which type of T lymphocytes recognize peptides presented by MHC class II molecules?
CD4+ T lymphocytes
Which of the following species has the most functional Class I loci?
Humans
Which proteins do Class III loci code for?
Complement proteins
Which type of cells express MHC class II molecules?
Professional antigen-presenting cells
Why are heterozygous animals more likely to respond to a variety of antigens?
They have a greater diversity of MHC alleles
Which of the following is a common misconception about self peptides presented by MHC molecules?
Self peptides are recognized as foreign antigens
Why does the MHC class II gene give greater diversity compared to MHC class I?
MHC class II genes contain more polymorphic loci than MHC class I
What is the role of MHC class I molecules in antigen presentation?
Present peptide antigens to CD8+ T lymphocytes
Why is it significant that each individual has 2 complete sets of MHC molecules?
To allow for diverse antigen presentation by different MHC alleles
Why do all individuals not develop autoimmunity even when self peptides are continuously presented?
An excess of different peptides can competitively inhibit presentation
Which statement accurately describes the structure of MHC class II molecules?
Has a binding groove made up of alpha1 and beta2 parts
What is the main reason why each MHC molecule can bind different peptides?
MHC molecules have broad specificity for peptide binding
In the context of antigen presentation, what is the significance of T cell receptor (TCR) fine specificity for peptide binding?
Ensures that TCRs can only bind one specific peptide
What is the main function of MHC class II molecules in the immune response?
To present exogenous antigens to CD4+ T cells
Which type of cells express both MHC class I and class II molecules?
Antigen-presenting cells
What is the primary role of T cells in the immune response?
To activate other immune cells and eliminate intracellular pathogens
Which type of cells do not usually express MHC class II molecules?
Red blood cells
What is the primary outcome of an incompatible graft between two animals?
The graft will be rejected
What is the primary protein responsible for presenting antigens to T cells?
MHC molecules
What is the main discovery recognized by the Snell Prize?
The discovery of tissue or histo-compatibility genes
Which of the following species has the most functional Class I loci?
Rats
Which of the following is a common misconception about self peptides presented by MHC molecules?
They are not self-peptides if they are foreign
Which type of cells increase the expression of MHC class II on macrophages and dendritic cells?
B cells
What is the role of MHC proteins in disease susceptibility?
They determine the immune response to pathogens
Why are heterozygous animals more likely to respond to a variety of antigens?
They have more MHC alleles
Which cytokine increases the expression of MHC class II on macrophages and dendritic cells?
IFNγ
What is the relationship between the variety of an animal's MHC and its ability to respond to antigens?
The more variety in an animal's MHC, the more antigens it can respond to.
Which animal species is at risk for decimation by infectious pathogens due to genetic homogeneity?
African cheetahs
Which disease association is true for cattle with the BoLA-DRB3.2*23 allele?
Increased incidence of severe coliform mastitis
Which of the following statements is true about MHC molecules and autoimmune disease?
The optimal number of MHC genes is to balance the need to respond to microbial antigens without triggering autoimmune disease.
Which of the following is a common characteristic of MHC molecules?
MHC molecules are polymorphic and bind to a set of different antigenic peptides.
Which of the following best describes why a particular MHC allele might make an animal more susceptible to a certain disease?
The MHC molecule fails to bind and present the critical antigen, preventing the animal from mounting a protective immune response.
Which of the following best describes how a certain MHC allele might indirectly contribute to disease progression?
The MHC molecule binds to a synovial cell protein, causing the immune system to attack the animal's own cells.
Which of the following methods is used to determine polymorphism in both class I and class II regions in cattle?
Microlymphocytotoxicity test
Which of the following best describes the role of MHC molecules in the immune response?
MHC molecules present critical antigens to T cells, triggering an immune response.
Which of the following best describes the relationship between heterozygous animals and their ability to respond to a variety of antigens?
Heterozygous animals have a better ability to respond to a variety of antigens due to a greater number of MHC alleles.
Which of the following best describes the process that occurs when a foreign antigenic peptide does not fit the MHC molecule?
The MHC molecule will not bind to the foreign antigenic peptide, and the animal will succumb to the infection.
Study Notes
Regulation of MHC Expression
- Expression of MHC molecules increases in the presence of cytokines during innate and adaptive immune responses.
- IFNα, IFNβ, or IFNγ increase expression of MHC class I.
- IFNγ increases expression of MHC class II on macrophages and dendritic cells.
- Recognition of pathogens by dendritic cells (PAMPs) through Toll-like receptors increases expression of MHC class II.
- Cytokines secreted by CD4+ helper T cells increase expression of MHC class II.
- Macrophages increase expression of MHC class II in the presence of IFNγ secreted by NK cells.
MHC Molecules and Disease
- The MHC regulates the immune response.
- A foreign antigenic peptide that does not fit the MHC molecule will not stimulate an immune response.
- MHC I and II are polymorphic, each allele can bind a set of different antigenic peptides.
- The more variety in an animal's MHC, the more antigens it can respond to.
- Heterozygous animals will express more alleles and bind more antigenic peptides.
- Homozygous animals will have less variety and are more likely not to generate an immune response to certain antigenic peptides.
Examples of MHC and Disease
- African cheetahs are genetically very homogeneous and at risk for decimation by infectious pathogens.
- Infectious peritonitis causes 60% mortality in Cheetahs compared to 1-2% in domestic cats.
- All of the Florida panthers alive in the twentieth century appear to have come from a single female.
- Five Texas pumas were introduced into panther habitat (1995), and the resulting hybrids appear to be doing well.
- The optimal number of MHC genes is a balance between the need to respond to microbial antigens and the need to avoid autoimmune disease.
Disease Associations
- BoLA-Aw7: Resistance to bovine leukemia virus.
- BoLA-Aw12: Susceptibility to bovine leukemia virus.
- BoLA-A*16: Resistance to mastitis.
- BoLA-DRB3.2*23: Increased incidence of severe coliform mastitis.
- BoLA-DRB3*3: Lower risk of retained placenta.
- BoLA-DRB3*22: Lower risk of cystic ovarian disease.
- BoLA-DR locus: Resistance to Dermatophilus.
- ELA-Aw7: Allergic reactions to Culicoides midges.
- ELA-A3, A15, Dw13: Development of sarcoid tumors.
- ELA-A9: Equine recurrent uveitis.
- SLA: Serum antibodies, ovulation rate, and number of larvae of the parasite Trichinella spiralis.
MHC Summary
- CLASS I:
- Loci: A, B, and C.
- Distribution: Most nucleated cells.
- Function: Present antigen to cytotoxic T cells.
- Result: T cell mediated toxicity.
- CLASS II:
- Loci: DP, DQ, and DR.
- Distribution: B cells, macrophages, and DC.
- Function: Present antigen to T helper cells.
- Result: T-cell mediated help.
MHC History
- The MHC was discovered as a locus containing genes responsible for graft rejection.
- There are two possible outcomes to a skin graft from one animal to another:
- The graft will survive and function.
- The graft will be rejected.
- The Nobel Prize in Physiology or Medicine 1980 was awarded to Baruj Benacerraf, Jean Dausset, and George D. Snell for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions.
The Major Histocompatibility Complex
- The MHC is a region that controlled graft rejection or survival.
- Each MHC cluster of genes has at least 3 classes of the gene loci.
- A typical mammalian MHC has the following arrangement of genes:
- Class I MHC molecules: expressed on all nucleated cells.
- Class II MHC molecules: expressed on antigen presenting cells.
- Class III MHC molecules: do not participate in antigen presentation.
Activation of T Cells
- The main function of T cells is to protect the body against intracellular pathogens and to activate other cells.
- T cells require activation before functioning as effector cells.
- Activation is achieved through interaction of T cells with antigen presenting cells.
- The role of presenting antigen to T cells is performed by specialized proteins called MHC molecules expressed on antigen presenting cells.Here are the study notes in markdown format:
Class I and Class II MHC Molecules
- Found on antigen presenting cells
- Class I: expressed on all nucleated cells, present peptide antigens to CD8+ T lymphocytes
- Class II: expressed on professional antigen presenting cells, present antigens to CD4+ T lymphocytes (helper T lymphocytes)
MHC Genetics
- Each individual has 2 complete sets of MHC molecules, one on each of the paternally and maternally derived chromosomes
- MHC genes are co-dominantly expressed
- Each individual has six MHC I genes (A, B, and C)
- Class II genes give greater diversity due to pairing of different α and β chains
Class I MHC Molecule Structure
- Heterodimer consisting of an α (α1, α2, α3) chain, β2-microglobulin chain, and a bound peptide
- Stable expression requires all three components
- Antigen binding groove is the most variable part of the MHC class I molecule
- CD8 binding region is non-variable
Class II MHC Molecule Structure
- Similarly structured to Class I
- Consists of α (α1, α2) and β (β1, β2) chains
- Peptide binding groove is made up by the α1 and β1 parts of the appropriate chains
- Stable expression requires assembly of the 3 components: the 2 chains and a bound peptide
Peptide-MHC Interactions
- Each class I or class II MHC molecule has a single peptide-binding cleft that binds one peptide at a time
- Each MHC molecule can bind different peptides, so MHC molecules have broad specificity for peptide binding
- T cell receptors (TCRs) have fine specificity for peptide binding
Outcomes of Antigen Presentation
- MHC class I molecules present peptide antigens to CD8+ T lymphocytes
- MHC class II molecules present antigens to CD4+ T lymphocytes (helper T lymphocytes)
MHC and Disease
- The MHC regulates the immune response
- The more variety in an animal's MHC, the more antigens it can respond to
- Heterozygous animals will express more alleles and bind more antigenic peptides
- Homozygous animals will have less variety and may not generate an immune response to certain antigenic peptides
Learn about the general characteristics of the mammalian MHC, distinguish between class I and class II MHC molecules, understand the role of MHC molecules in immunity, explore the expression profile of MHC molecules on cells, and understand the structure of MHC class I and II. Delve into how certain MHC genes may predispose animals to diseases.
Make Your Own Quizzes and Flashcards
Convert your notes into interactive study material.
Get started for free
