IMM: BLOCK 2: LECTURE 3: ANTIGEN-PRESENTATION (PART 1 OF 2)

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Questions and Answers

What is the primary role of Major Histocompatibility Complex (MHC) proteins?

To produce antibodies against infections

To enhance phagocytosis by macrophages

To display antigen peptides to T-cells (correct)

To destroy pathogens directly

Which class of MHC is mainly expressed by professional antigen-presenting cells (APCs)?

MHC Class I

MHC Class IV

MHC Class III

MHC Class II (correct)

What contributes to the unique MHC pattern in individuals?

Polymorphism of MHC genes (correct)

Single allele mutations

Natural immunity

Environmental factors

Where is the human MHC molecule located?

Chromosome 6 Signup and view all the answers

What is the significance of MHC heterozygosity in relation to HIV-1 infection?

It delays the progression to AIDS Signup and view all the answers

Which of the following is true regarding tissue distribution of MHC molecules?

Microglial cells express MHC Class II Signup and view all the answers

What is the result of a lack of diversity in HLA class I and class II allotypes for humans?

Increased susceptibility to viral infections Signup and view all the answers

Which of the following best describes the source of MHC proteins in an individual?

Combined genetic contributions from both parents Signup and view all the answers

What is the primary role of antigen presenting cells (APCs) in the immune system?

To present foreign antigens to T cells Signup and view all the answers

Which type of molecule is primarily involved in the binding of peptide antigens for T cell recognition?

MHC molecules Signup and view all the answers

What important function do MHC molecules serve in the immune response?

Process and present peptides to T cells Signup and view all the answers

In the context of antigen presenting cells, what differentiates professional APCs from atypical or amateur APCs?

Professional APCs provide additional signals required for T cell activation Signup and view all the answers

What is the significance of MHC restriction in T cell activation?

It determines which T cells can respond to specific peptide-MHC combinations Signup and view all the answers

How does the immune system prevent T cells from mistakenly attacking the body’s own cells?

Through the action of professional APCs and regulatory signals Signup and view all the answers

What mechanism do human cells utilize to process proteins for MHC presentation?

Degradation into small peptides Signup and view all the answers

Which statement accurately describes the structure of MHC I and MHC II molecules?

MHC I molecules are composed of two chains, while MHC II has three chains Signup and view all the answers

What is a key structural component of MHC class I molecules?

A membrane-bound heavy chain and β2-microglobulin Signup and view all the answers

Which genetic loci are involved in the expression of MHC class I molecules?

HLA-A, -B, -C Signup and view all the answers

What type of cells typically express MHC class II molecules?

Antigen-presenting cells and specialized epithelial cells Signup and view all the answers

How many amino acids can MHC class I molecules typically bind in their peptide cleft?

8-9 amino acids Signup and view all the answers

What feature distinguishes 'nonclassical' class I molecules from classical class I molecules?

They show limited variability and tissue distribution. Signup and view all the answers

What is the main function of MHC class II molecules?

To present peptide antigens to CD4+ T cells Signup and view all the answers

What structural components do MHC class II molecules consist of?

A co-dominantly expressed α and β chain Signup and view all the answers

Which aspect of MHC class I binding grooves contributes to polymorphism?

Slight structural variations in the binding cleft Signup and view all the answers

Which does NOT correctly describe MHC class II molecules?

They can only accommodate peptides larger than 20 amino acids. Signup and view all the answers

Which factor influences the binding preferences of different MHC class I molecules?

The allelic variation in the binding groove Signup and view all the answers

Why is it necessary for other cells to process and present foreign antigens to T cells?

To prevent T-cells from rapidly attacking the body’s own tissues Signup and view all the answers

What is the primary role of peptide-MHC (pMHC) complexes in the immune response?

To present peptide antigens for recognition by T-cell receptors Signup and view all the answers

What mechanisms do human cells use to produce pathogen-derived peptides for MHC presentation?

Degradation of proteins into small peptides Signup and view all the answers

Which of the following describes a characteristic of professional antigen-presenting cells (APCs)?

They efficiently process and present foreign antigens to T-cells Signup and view all the answers

What does MHC restriction refer to in the context of T-cell activation?

The requirement for T-cells to recognize antigens only when presented by MHC molecules Signup and view all the answers

What role do housekeeping mechanisms play in human cells regarding antigen presentation?

They help to degrade and recycle damaged proteins Signup and view all the answers

How does the immune system control the activity of T-cells during antigen processing and presentation?

By having a system of checks and balances Signup and view all the answers

What type of study was referred to as the “Sweaty T-Shirt” Study in the context of immunology?

A research study on scent and immune response Signup and view all the answers

What is the main consequence of MHC heterozygosity in relation to immune response?

Increased flexibility in responding to various infections Signup and view all the answers

Which gene regions are included in the human MHC class I gene complex?

A, B & C Signup and view all the answers

What is the relationship between MHC genes and tissue typing for transplants?

MHC proteins help match donor and recipient immune profiles. Signup and view all the answers

What role do microglial cells have concerning MHC class II molecules?

They express MHC class II and contribute to brain immunity. Signup and view all the answers

Why do humans maintain diversity in HLA class I and class II alleles?

To ensure survival against a variety of infections. Signup and view all the answers

Which cells primarily express MHC class II molecules?

Professional antigen-presenting cells (APCs) Signup and view all the answers

How do MHC class I and class II molecules differ in terms of cellular expression?

Class I is expressed by all nucleated cells, class II mainly by APCs. Signup and view all the answers

What is a characteristic feature of MHC molecules that contributes to their function?

They exhibit high genetic polymorphism. Signup and view all the answers

What is the primary structural component that distinguishes MHC class I molecules from MHC class II molecules?

MHC class I has a single membrane-bound heavy chain and a light chain. Signup and view all the answers

Which amino acid length can MHC class II molecules typically accommodate in their binding groove?

18-20 amino acids Signup and view all the answers

What role do the α3 domain and β2-microglobulin serve in MHC class I molecules?

They stabilize the structure of the heavy chain. Signup and view all the answers

Which genetic loci are responsible for encoding MHC class II molecules?

HLA-DP, HLA-DQ, HLA-DR Signup and view all the answers

Which of the following best describes the binding cleft of classical MHC class I molecules?

It is formed by α1 and α2 domains. Signup and view all the answers

What defines the polymorphism observed in MHC class I molecules?

Variations in the binding groove across different allelic forms. Signup and view all the answers

Which class of MHC molecules is typically expressed on all nucleated cells?

MHC class I Signup and view all the answers

What type of cells predominantly express MHC class II molecules?

Professional antigen-presenting cells (APCs) Signup and view all the answers

What is the function of nonclassical MHC class I molecules such as CD1d?

They present carbohydrate and peptide fragments. Signup and view all the answers

What is a distinctive feature of the α and β chains of MHC class II molecules?

They combine only with others encoded within the same region. Signup and view all the answers

What must occur for the activation of T cells during an immune response?

Antigens must be processed and presented to T cells with additional signals. Signup and view all the answers

What is the relationship between a pathogen and MHC molecules during antigen presentation?

MHC molecules bind peptides derived from both synthesized and extracellular antigens. Signup and view all the answers

How does the immune system prevent T cells from causing autoimmunity?

Other cells present foreign antigens with signals to modulate T cell activity. Signup and view all the answers

What is the primary importance of MHC restriction in T cell activation?

It ensures T cells only respond to specific antigen-MHC combinations. Signup and view all the answers

How are the peptides that bind to MHC molecules produced?

They are degraded from damaged or unwanted proteins within human cells. Signup and view all the answers

Which statement accurately reflects the role of professional antigen-presenting cells (APCs)?

They can present both endogenous and exogenous antigens to T cells. Signup and view all the answers

In what manner do atypical or amateur APCs differ from professional APCs?

Only professional APCs present antigens effectively to T cells. Signup and view all the answers

What aspect of T cell activation makes it challenging to control once initiated?

Once activated, T cells become difficult to regulate and can rapidly proliferate. Signup and view all the answers

What is the primary structural feature of MHC class I molecules that allows for peptide binding?

A closed peptide cleft formed between α1 and α2 domains Signup and view all the answers

Which genetic loci are responsible for encoding classical MHC class II molecules?

HLA-DP, HLA-DQ, HLA-DR Signup and view all the answers

What is a characteristic feature of MHC class II molecules compared to MHC class I?

They can accommodate longer peptides of 18-20 amino acids. Signup and view all the answers

What distinguishes 'nonclassical' class I molecules from classical class I molecules?

Limited variability and specific tissue distribution. Signup and view all the answers

Which of the following statements correctly describes the expression of MHC class I molecules?

They are co-dominantly expressed on all nucleated cells. Signup and view all the answers

What is the role of the α3 domain and β2-microglobulin in MHC class I molecules?

They stabilize the structure of the peptide-binding cleft. Signup and view all the answers

What type of cells primarily express MHC class II molecules?

Professional antigen-presenting cells and activated T cells. Signup and view all the answers

Which aspect of MHC class I binding contributes to its polymorphism?

Structural variation in the peptide-binding groove. Signup and view all the answers

Which of the following best describes the peptide-binding groove of MHC class II molecules?

It can accommodate peptides longer than those for MHC class I. Signup and view all the answers

How do MHC class I and class II molecules differ in terms of their association with chains?

MHC class I consists of a heavy and a light chain, while class II consists of two similar chains. Signup and view all the answers

What is a consequence of having a diverse range of HLA class I and class II alleles in humans?

It enables the immune system to better recognize a variety of pathogens. Signup and view all the answers

Which statement correctly describes the role of MHC molecules?

They bind to foreign antigens and help T cells recognize infected cells. Signup and view all the answers

Which cells do NOT typically express MHC class II molecules?

Nucleated somatic cells Signup and view all the answers

What is the likely effect of MHC heterozygosity on the progression of diseases such as AIDS?

It delays disease progression. Signup and view all the answers

Which major loci are associated with MHC class I molecules?

A, B, C Signup and view all the answers

What does the presence of multiple alleles per MHC gene family provide in terms of immune system function?

It enhances the capacity to present diverse antigens. Signup and view all the answers

Which is true regarding the expression of MHC class I molecules?

All nucleated cells express MHC class I molecules. Signup and view all the answers

Which feature is essential for the recognition of self from non-self in the immune system?

The diversity of MHC molecules. Signup and view all the answers

Study Notes

Antigen Processing and Presentation

T-cells require strict regulation to avoid autoimmunity.
Other cells process foreign antigens and present to T-cells with additional signals required for full activation.
Antigens are displayed on the cell surface bound to MHC (Major Histocompatibility Complex) molecules.

MHC: Major Histocompatibility Complex

MHC molecules are membrane-bound proteins that display antigen peptides to T-cells.
Each person has a unique MHC pattern due to parental genetic contributions.
MHC variability impacts the ability to fight infection as each individual's response to microbes is unique.
The human MHC molecule is located on chromosome 6.

MHC Class I

Found on the surface of ALL NUCLEATED CELLS.
Composed of 45-kDa MHC class I molecules with Beta2 microglobulin (β₂m).
MHC Class I three genetic loci (HLA-A, HLA-B, HLA-C) are highly polymorphic with >100 alleles at each locus.
MHC class I molecules combine with β₂m creating a closed peptide cleft that binds 8-9 amino acid peptides.
The peptide-binding groove of different allelic forms may preferentially bind different peptides.

MHC Class II

Typically expressed only on the surface of APCs (Antigen Presenting Cells), some activated T-cells, and some specialized epithelial cells.
Composed of a 32-38 kDa α chain and a 29-32 kDa β chain, forming a groove that accommodates 18-20 amino acid peptides.
Encoded within the HLA-DP, HLA-DQ, and HLA-DR regions.
DPα associates only with DPβ, DQα only with DQβ, and DRα only with DRβ.

Antigen Processing and Presentation

T cell activation requires tight regulation to prevent uncontrolled cell-mediated immune responses and autoimmunity.
Cells process and present foreign antigens to T cells, ensuring a controlled immune response.

Professional vs. Amateur Antigen Presentation

Professional APCs (e.g., Dendritic cells (DCs), Macrophages, B cells) are specialized cells that efficiently present antigens to T cells.
Amateur APCs (e.g., epithelial cells, fibroblasts, endothelial cells) can also present antigens, but are not as specialized as professional APCs.
Professional & amateur APCs differ in the types of antigens they present and how they present them.

Major Histocompatibility Complex (MHC)

MHC is a membrane-bound protein that displays peptides to T cells.
MHC genes are inherited from both parents, leading to diverse MHC molecules.
Each MHC gene has multiple alleles, resulting in a unique MHC pattern for each individual (except identical twins).
MHC diversity plays a crucial role in immune system response to infections.
The MHC molecule is located on chromosome 6.
Class I gene complex (HLA-A, -B, -C), Class II gene complex (HLA-DP, -DQ, -DR).

MHC Structure and Function: MHC Class I

Found on all nucleated cells.
Forms a closed peptide cleft between α1 and α2 domains that binds 8-9 amino-acid peptides.
Slight structural variations in the binding cleft allow for different peptide preferences.
"Nonclassical" class I molecules (HLA-E, -F, -G, -H) show limited variability and may present carbohydrates and peptide fragments.

MHC Structure and Function: MHC Class II

Primarily expressed on the surface of APCs.
Forms a binding groove between α1 and β1 domains that can accommodate larger peptides (18-20 amino acids).
MHC class II α & β chains combine only with those encoded within the same region (e.g., DPα only with DPβ).

MHC Restriction

T cells are restricted to recognizing peptides presented by specific MHC molecules:
- CD8+ T cells recognize peptides presented by MHC Class I.
- CD4+ T cells recognize peptides presented by MHC Class II.

Sweaty T-Shirt Study

Demonstrated that humans can unconsciously detect and respond to other individuals' MHC genes through smell.
Participants preferred the scent of individuals with different MHC genes, indicating a potential evolutionary advantage in promoting genetic diversity.

Antigen Processing and Presentation

T cell activation is tightly regulated to prevent unchecked immune responses
Cells present processed foreign antigens to T cells, requiring additional signals for recognition and full activation

Antigen Presenting Cells (APCs)

Professional APCs: process and present antigens to T cells
Amateur APCs: express MHC molecules, but are not specialized antigen presenting cells

MHC Molecules

Major Histocompatibility Complex (MHC): membrane-bound protein that presents antigen peptides to T cells
Encoded by genes from both parents
Genetically diverse (polymorphic), each person has a unique MHC profile (except identical twins)
Located on chromosome 6
Class I gene complex: HLA-A, HLA-B, HLA-C
Class II gene complex: HLA-DP, HLA-DQ, HLA-DR

MHC Class I

Found on all nucleated cells
Composed of heavy chain (α) and β2-microglobulin (β2m)
Binds 8-9 amino acid peptide
Exhibits genetic polymorphism, leading to variations in peptide binding

MHC Class II

Found on APCs, activated T cells, and specialized epithelial cells in the thymus and intestine.
Composed of α and β chains
Binds 18-20 amino acid peptide
Each gene region (DP, DQ, DR) has α and β loci: DPα binds only with DPβ, not DQβ or DRβ

The Sweaty T-Shirt Study

Investigated human mate choice
Demonstrated potential for T cell-mediated immune responses to influence attractiveness

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Description

Explore the fascinating world of antigen processing and presentation in T-cells. Learn about the Major Histocompatibility Complex (MHC), its types, and its significance in immunity. This quiz covers MHC variability and its implications for individual immune responses.