Immunology Chapter on HLA Class II Molecules
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Questions and Answers

What is the primary function of HLA class II molecules?

  • To process endogenous antigens
  • To initiate the cytosolic pathway
  • To enhance antibody production
  • To present exogenous antigens to CD4+ T helper cells (correct)

Which cell types are known to constitutively express HLA class II molecules?

  • Tissue-based macrophages and endothelial cells
  • Cytotoxic T cells
  • Neutrophils and erythrocytes
  • Dendritic cells, B cells, and thymic epithelial cells (correct)

What triggers the induced expression of HLA class II molecules on certain cell types?

  • Inflammatory stimuli (correct)
  • T cell activation
  • Increased phagocytic activity
  • Cellular apoptosis

What role does the invariant chain (Ii) play in MHC class II processing?

<p>It prevents premature peptide loading in the endoplasmic reticulum (B)</p> Signup and view all the answers

What is the source of endogenous antigens processed via the cytosolic pathway?

<p>Proteins synthesized within the host cell cytosol (C)</p> Signup and view all the answers

What is the purpose of the exogenous antigen processing pathway?

<p>To activate CD4+ T helper cells with small polypeptides. (B)</p> Signup and view all the answers

Which class of HLA molecules is primarily associated with presenting endogenous antigens?

<p>HLA class I (C)</p> Signup and view all the answers

Which cell type is responsible for processing and presenting antigens via the exogenous pathway?

<p>Macrophages (A)</p> Signup and view all the answers

What is the primary function of CD8+ cytotoxic T lymphocytes in the immune response?

<p>To kill cells presenting foreign antigens. (A)</p> Signup and view all the answers

What is one of the primary characteristics of the major histocompatibility complex (MHC)?

<p>They include HLA genes specific to humans. (D)</p> Signup and view all the answers

What results from the activation of CD4+ T helper cells?

<p>Enhanced activation of B cells. (A)</p> Signup and view all the answers

Which proteins are loaded onto HLA class II molecules for presentation?

<p>Polypeptides from exogenous antigens. (B)</p> Signup and view all the answers

Which statement accurately reflects the role of MHC in T cell responses?

<p>MHC molecules are crucial for the recognition of processed antigens by T cells. (A)</p> Signup and view all the answers

What is the role of ubiquitin in the degradation of viral proteins?

<p>It tags proteins for degradation by proteasomes. (A)</p> Signup and view all the answers

What is the size range of the peptide fragments generated by proteasomes for presentation on MHC class I?

<p>8-10 amino acids (C)</p> Signup and view all the answers

What triggers the release of protein chaperones from MHC class I molecules?

<p>Loading of peptide fragments into the binding groove (B)</p> Signup and view all the answers

Which components are responsible for transporting degraded peptide fragments to the endoplasmic reticulum?

<p>TAP-1 and TAP-2 transporters (A)</p> Signup and view all the answers

What happens to HLA class I-peptide complexes after they are formed?

<p>They are transported to the cell surface. (D)</p> Signup and view all the answers

What is the primary function of CD8+ cytotoxic T lymphocytes (CTL) upon activation?

<p>To kill the presenting cell displaying the antigenic peptides (B)</p> Signup and view all the answers

Which of the following statements is true regarding the expression of HLA class I molecules?

<p>They are constitutively expressed on all nucleated cells. (C)</p> Signup and view all the answers

Which Nobel Prize-winning discovery is linked to the function of ubiquitin?

<p>Protein tagging for degradation (D)</p> Signup and view all the answers

What is the primary structural feature that differentiates HLA class I molecules from class II molecules?

<p>HLA class I molecules possess a cytoplasmic tail linked to a single chain, while class II molecules have two chains. (C)</p> Signup and view all the answers

What is the length of the polypeptides typically bound by HLA class I molecules?

<p>8-9 amino acids (D)</p> Signup and view all the answers

Which component is critical for the shape of the HLA class I molecule?

<p>β2-microglobulin (B)</p> Signup and view all the answers

What type of co-receptor does the α3 subunit of HLA class I bind to?

<p>CD8 (D)</p> Signup and view all the answers

What is the primary function of the cleft formed between the α1 and β1 domains of HLA class II molecules?

<p>It serves as the binding site for polypeptides derived from endosomes. (A)</p> Signup and view all the answers

Which characteristic is true of HLA class II molecules compared to HLA class I molecules?

<p>HLA class II molecules consist of a dimer structure. (B)</p> Signup and view all the answers

What type of antigens do HLA class II molecules typically bind?

<p>Exogenous antigens from endosomes or phagosomes (A)</p> Signup and view all the answers

What role do the cytoplasmic tails of HLA molecules play?

<p>They link to intracellular signaling pathways. (D)</p> Signup and view all the answers

What type of cells can CD4+ T helper cells recognize?

<p>HLA class II molecules plus processed peptides from the endosome (C)</p> Signup and view all the answers

What is the primary function of CD8+ cytotoxic T cells?

<p>Recognize HLA class I molecules with processed antigens (A)</p> Signup and view all the answers

Which cells constitutively express HLA class II molecules?

<p>Thymic epithelial cells, dendritic cells, and B cells (A)</p> Signup and view all the answers

T cells must undergo additional maturation in which organ?

<p>Thymus (D)</p> Signup and view all the answers

What signals can upregulate the expression of HLA class I molecules?

<p>Cytokine signaling and viral infections (A)</p> Signup and view all the answers

What is the characteristic of T cell responses regarding antigen recognition?

<p>They require HLA molecules to be presented by other cells (B)</p> Signup and view all the answers

Which of the following statements is true regarding the activation of naïve T helper cells?

<p>They necessitate a two-signal process for activation (D)</p> Signup and view all the answers

What is the role of the T cell antigen receptor (TCR) in T cell activation?

<p>It helps in the recognition of antigens bound to MHC molecules (C)</p> Signup and view all the answers

What happens to most T cell precursors during their development?

<p>They die during the selection process in the thymus. (D)</p> Signup and view all the answers

What defines the HLA restriction of T cells?

<p>T cells recognize foreign antigens presented with self HLA molecules. (A)</p> Signup and view all the answers

Which co-receptor is possessed by cytotoxic T lymphocytes?

<p>CD8 (B)</p> Signup and view all the answers

What type of cells do naïve T helper cells become upon activation?

<p>Effector cells or memory cells (C)</p> Signup and view all the answers

Which Th cell type is primarily involved in promoting humoral immunity?

<p>Th2 (C)</p> Signup and view all the answers

What is the function of the thymus in T cell development?

<p>To educate T cells regarding self-tolerance (C)</p> Signup and view all the answers

What is thymic involution?

<p>The gradual decrease in thymus size after puberty (D)</p> Signup and view all the answers

Which statement about Th cytokine responses is correct?

<p>Th1 responses can inhibit Th2 and Th17 responses. (D)</p> Signup and view all the answers

Flashcards

Major Histocompatibility Complex (MHC)

A complex genetic region in vertebrates that plays a crucial role in immune responses.

Human Leukocyte Antigens (HLA)

Proteins encoded by MHC genes in humans that are responsible for presenting processed antigens to T cells.

HLA class I molecules

Proteins encoded by MHC genes that are expressed on the surface of most cells. They present processed antigens from the cell's own protein synthesis machinery to CD8+ T cells.

HLA class II molecules

Proteins encoded by MHC genes that are expressed on the surface of immune cells (e.g., macrophages, dendritic cells, B cells). They present processed antigens from outside the cell to CD4+ T cells.

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Exogenous antigen processing pathway

The process by which a cell breaks down proteins from outside the cell (e.g., from pathogens) and displays them in complex with HLA class II molecules on its surface.

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Endogenous antigen processing pathway

The process by which a cell breaks down proteins from its own protein synthesis machinery and displays them in complex with HLA class I molecules on its surface.

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MHC restriction

The ability of T cells to recognize and respond to antigen only when it is presented in complex with a specific MHC molecule.

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CD8+ cytotoxic T cell activation

The process by which a T cell recognizes and kills a cell displaying a specific antigen that is presented in complex with MHC class I molecules.

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Exogenous antigen

Antigen that originates from outside the cell, such as from a virus or bacteria.

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Antigen-presenting cells (APCs)

Special immune cells that present antigen to T cells, including dendritic cells, B cells, and macrophages.

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Antigen processing

The process by which an antigen is broken down into smaller peptides and presented on MHC class II molecules to CD4+ T cells.

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Invariant chain (Ii)

A protein that binds to MHC class II molecules and prevents them from interacting with peptides in the endoplasmic reticulum.

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CD4+ T helper cells

A type of immune cell that recognizes antigens presented on MHC class II molecules and activates other immune cells.

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Immunoglobulin Supergene Family

A family of proteins that include HLA molecules and immunoglobulin molecules. They share a common structural feature known as immunoglobulin domains.

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Peptide Binding Groove (HLA Class I)

A groove formed between the α1 and α2 domains of HLA Class I molecules where processed peptides bind.

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β2-Microglobulin

A molecule associated with HLA Class I molecules. It contributes to the overall structure and shape of the complex.

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Peptide Binding Groove (HLA Class II)

A groove formed between the α1 and β1 domains of HLA Class II molecules where processed peptides bind.

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Ubiquitin

A small protein that tags proteins for degradation by proteasomes.

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Proteasomes

Cylindrical protein complexes that break down proteins tagged with ubiquitin.

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TAP-1 and TAP-2

Transporter molecules in the ER that move degraded peptide fragments from the cytosol to the ER lumen.

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Endogenous antigen processing

A process by which a cell breaks down its own proteins and presents fragments to CD8+ T cells on MHC class I molecules.

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MHC class I

A protein complex on the surface of most cells that presents processed antigens to CD8+ T cells.

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Loading of peptides in MHC class I

A conformational change in MHC class I molecules triggered by binding to a peptide fragment, leading to the release of chaperones.

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CD8+ cytotoxic T lymphocytes (CTL)

Cytotoxic T lymphocytes that recognize and kill cells displaying foreign antigens on MHC class I molecules.

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CTL activation

The process by which CTLs are activated to kill infected or cancerous cells.

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T helper cell

A special type of immune cell that can activate other immune cells, such as B cells and macrophages.

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Cytotoxic T cell

A type of T cell that directly kills infected cells by releasing cytotoxic molecules. They are able to recognize antigens presented by HLA class I molecules.

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T cell tolerance

The process by which the immune system learns to tolerate self-antigens, preventing autoimmune reactions. This involves the elimination or inactivation of T cells that react strongly to self-antigens in the thymus.

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HLA restriction

The ability of T cells to recognize foreign antigens only in the context of being presented by a specific HLA molecule from the same individual. This ensures that T cells only attack foreign invaders and not healthy cells.

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Thymus

The primary lymphoid organ where T cells mature and differentiate. It's responsible for acquiring antigen specificity, learning tolerance of self-antigens, and achieving HLA restriction.

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Th1 cells

T helper cells that produce cytokines associated with cell-mediated immunity. They help activate macrophages and cytotoxic T cells to combat intracellular pathogens.

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Th2 cells

T helper cells that produce cytokines associated with humoral immunity (antibody production). They activate B cells to produce antibodies against extracellular pathogens.

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Th17 cells

T helper cells that produce cytokines associated with inflammation and autoimmune responses. They play a role in defending against extracellular pathogens but can also contribute to autoimmunity.

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T cell ontogeny

The process of T cell development from immature precursors into mature T cells. This occurs primarily in the thymus and involves acquiring the TCR, learning tolerance, and becoming HLA-restricted.

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Naive T cells

Immature T cells that haven't encountered their specific antigen yet. They reside in the periphery and can differentiate into various T cell subtypes upon activation.

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Study Notes

Antigen Processing and Presentation - HLA Molecules

  • T lymphocytes recognize antigens derived from inside a cell, unlike B cells that recognize antigens on the outside of a cell.
  • Antigens are processed by the cell in which they are located and presented to T cells via two pathways.
  • Exogenous pathway: Denatures and degrades proteins/glycoproteins from endosomes/phagosomes to polypeptides.
  • These polypeptides are loaded into HLA class II molecules and transported to the cell surface for presentation to CD4+ helper T cells.
  • Endogenous pathway: Uses polypeptides from the cell's protein synthesis machinery (ER and ribosomes). Loaded into HLA class I molecules and transported to the cell surface for presentation to CD8+ cytotoxic T cells.
  • MHC (Major Histocompatibility Complex)/HLA (Human Leukocyte Antigens): Nearly every vertebrate species has MHC genes; their proteins are crucial in tissue transplant rejection/acceptance.
  • MHC class I and class II genes / HLA molecules are located on chromosome 6.
  • MHC is a complex of closely linked genes inherited as a unit.
  • HLA class I molecules consist of three a domains, and a closely associated, but non-covalently bound, ẞ2-microglobulin (ẞ2m).
  • The a domains form a peptide binding groove. Typically holds 8-9 amino acid long polypeptides, and the a3 subunit binds the CD8 co-receptor on T cells.
  • HLA class II molecules consist of one α and one β chain, forming a peptide binding groove that binds polypeptides (usually 12-17 amino acids long.)
  • The β2 domain of the HLA class II molecule binds the CD4 co-receptor on T helper cells.

The Exogenous Pathway (Endosomal Pathway)

  • Phagocytosis or endocytosis of foreign substances (bacteria, viruses) leads to protein denaturation and degradation into small peptides.
  • HLA class II molecules are synthesized in the ER with an associated invariant chain (Ii).
  • Ii helps stabilize HLA class II molecules and blocks the binding of endogenous self-antigens.
  • Vesicles containing HLA-Ii migrate and fuse with the phagolysosome.
  • The Ii protein is degraded and a small peptide fragment (CLIP) remains in the binding groove.
  • The HLA-DM protein facilitates peptide exchange, allowing the foreign peptide to bind to the HLA Class II molecule.
  • The resulting complex HLA class II- foreign protein peptide moves to the cell surface.

The Endogenous Pathway (Cytosolic Pathway)

  • Endogenous antigens are derived from intracellular proteins made by the cell itself or viruses.
  • Endogenous antigens are degraded by proteasomes to peptides (8-10 amino acids).
  • These peptides are transported to the ER by TAP-1 and TAP-2 (transporters associated with antigen processing).
  • HLA class I molecules are associated with ẞ2microglobulin in the ER.
  • Peptide-loaded class I molecules and transported out of the ER.
  • Presented on the cell surface for recognition.

HLA Molecules and Cell Types

  • HLA class I molecules are expressed on all nucleated cells.
  • HLA class II molecules are constitutively expressed on thymic epithelial cells, dendritic cells, and B cells.
  • Their expression can be upregulated in response to inflammatory stimuli in other cell types.

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Immunology Exam 2 PDF, Winter 2024-2025

Description

Test your knowledge about HLA class II molecules and their role in the immune system. This quiz covers various aspects including cell types, antigen processing pathways, and the functions of T cells. Perfect for students studying immunology or related fields.

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