HLA Molecules and Haemochromatosis
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What is the primary role of non-HLA class II molecules in relation to MHC class II molecules?

  • They form the groove on the cell surface for MHC class II molecules.
  • They are involved in the actual presentation of antigens on the cell surface.
  • They assist in the transportation of MHC class II molecules to the cell surface. (correct)
  • They mimic classical HLA II molecules to enhance immune response.

How do LNP2 and LNP7 contribute to the antigen processing pathway?

  • They regulate the conformation of non-HLA class II molecules.
  • They directly bind antigens to MHC class II molecules.
  • They act as carriers that transport class I molecules to the cell surface.
  • They are part of the immune proteasome that cuts proteins into small peptides. (correct)

What distinguishes class III molecules from class I and II molecules?

  • Class III molecules are exclusively membrane-bound.
  • Class III molecules are more heterogeneous and secreted. (correct)
  • Class III molecules have a similar function to HLA class I molecules.
  • Class III molecules are essential for cellular immune responses.

What does tapasine do within the endoplasmic reticulum?

<p>It completes the binding of antigens to MHC class I molecules. (D)</p> Signup and view all the answers

Which statement is true regarding the polymorphism of HLA class III molecules compared to class I and II?

<p>HLA class III molecules possess limited polymorphism compared to classes I and II. (D)</p> Signup and view all the answers

Which of the following belongs to the complement system found within the HLA complex?

<p>C4 (C)</p> Signup and view all the answers

What is the primary importance of polymorphism in HLA/MHC genes during organ transplantation?

<p>To ensure compatibility between donor and recipient (B)</p> Signup and view all the answers

Which cytokine is released by macrophages and is critical for the activation of cytotoxic T cells?

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

In the context of HLA molecule matching, which alleles are most critical to match?

<p>HLA A, HLA B, and HLA DR (D)</p> Signup and view all the answers

Which enzyme associated with steroid biosynthesis is encoded by genes in the class III complex?

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

What is the consequence of not properly matching biological identity in organ transplantation?

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

When looking for potential organ donors, which is NOT typically considered in the matching process?

<p>Complement factor levels (C)</p> Signup and view all the answers

Which of the following statements is true regarding the HLA class II antigens?

<p>They usually undergo matching for organ transplantation. (B)</p> Signup and view all the answers

What is cis-codominance in relation to HLA class II molecules?

<p>It results in the formation of a molecule identical to that of a parent. (A)</p> Signup and view all the answers

What occurs during trans-codominance?

<p>Chains from both parents combine in unique pairings. (B)</p> Signup and view all the answers

What role does the C28 transcriptional factor play in gene expression?

<p>It enhances the expression of certain immune system genes. (A)</p> Signup and view all the answers

How many potential gene combinations can arise from the six genes mentioned in the context?

<p>There can be up to twelve different combinations. (D)</p> Signup and view all the answers

What does the nude lymphocyte syndrome result from?

<p>Defects in the genes responsible for HLA molecules. (D)</p> Signup and view all the answers

What effect do interferon gamma and type I have on the expression of C28?

<p>They induce the expression of C28 in response to stimuli. (C)</p> Signup and view all the answers

What distinguishes HLA class II molecules from other classes?

<p>They are composed of two distinct chains, alpha and beta. (C)</p> Signup and view all the answers

What is the underlying purpose of the different combinations of HLA molecules?

<p>To increase the diversity of recognition capabilities in the immune system. (B)</p> Signup and view all the answers

What role does β2-microglobulin play in the synthesis of MHC class I molecules?

<p>It substitutes the chaperonins, allowing peptide allocation. (B)</p> Signup and view all the answers

Which chaperonin is involved with MHC class I molecules before the synthesis of β2-microglobulin?

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

How do peptides enter the reticulum in the context of MHC class I molecules?

<p>By the action of TAP transporters. (B)</p> Signup and view all the answers

What is the primary function of MHC class II molecules as mentioned?

<p>To present exogenous peptides derived from outside the cell. (C)</p> Signup and view all the answers

What process occurs during the formation of a phagosome in relation to exogenous peptide presentation?

<p>It leads to the invagination of the membrane. (C)</p> Signup and view all the answers

Which structure is primarily responsible for post-translational modifications of MHC class I molecules?

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

What is the fate of proteins within the vesicles formed by the phagosome?

<p>They undergo degradation without proteasome involvement. (A)</p> Signup and view all the answers

What is the role of tapasine in relation to MHC class I molecules?

<p>It supports MHC class I molecules during peptide allocation. (A)</p> Signup and view all the answers

What is the primary function of the invariant chain in the MHC class II molecule synthesis?

<p>To fill and protect the binding pocket of the MHC class II complex (A)</p> Signup and view all the answers

Which of the following molecules is responsible for maintaining the conformation of MHC class II molecules?

<p>DM or DO molecules (B)</p> Signup and view all the answers

What occurs if MHC class II molecules begin binding endogenous peptides during their transport from the ER?

<p>They will not be able to present exogenous peptides (A)</p> Signup and view all the answers

Which protein plays a crucial role in the degradation of the invariant chain to facilitate peptide binding?

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

The binding pocket of MHC class II molecules needs to bind what type of peptides?

<p>Exogenous peptides from extracellular sources (A)</p> Signup and view all the answers

What is the consequence of the trimerization of the invariant chain?

<p>Construction of HLA class II molecules (DP, DM, DO) (B)</p> Signup and view all the answers

What role do chaperonins play in the transport of MHC class II molecules?

<p>Facilitating correct folding of the MHC class II molecules (A)</p> Signup and view all the answers

What happens to the clipped portion of the invariant chain after the MHC class II complex is formed?

<p>It occupies the groove of MHC class II molecules (A)</p> Signup and view all the answers

What results from T cells recognizing the HLA molecule as foreign after organ transplantation?

<p>The patient can experience organ rejection. (B)</p> Signup and view all the answers

What phenomenon describes the ability of a single MHC molecule to bind multiple different peptides?

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

Which outcome occurred when splenocytes from a strain A mouse were tested with autologous dendritic cells infected with LCMV?

<p>Complete lysis of target cells was observed. (A)</p> Signup and view all the answers

What happens when TCRs encounter antigen-presenting cells from a different strain expressing the same viral antigen?

<p>No lysis occurs due to MHC differences. (B)</p> Signup and view all the answers

How does the TCR's specificity impact T cell maturation in the thymus?

<p>T cells that recognize HLA class I and class II are rescued. (A)</p> Signup and view all the answers

Which type of molecules can present different antigens besides proteins?

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

What was the purpose of conducting a cytotoxic assay with different target cells?

<p>To assess the ability of T cells to recognize self and foreign antigens. (C)</p> Signup and view all the answers

What is the outcome when TCRs recognize self-peptides presented by self-MHC molecules?

<p>T cells are allowed to mature and survive. (A)</p> Signup and view all the answers

Flashcards

HLA class II co-dominance

The expression of HLA class II molecules, which are composed of two chains (alpha and beta), is determined by both parental genes. This leads to either cis- or trans-codominance.

Cis-codominance

A form of HLA class II co-dominance where the alpha and beta chains of a molecule originate from the same parent.

Trans-codominance

A form of HLA class II co-dominance where the alpha and beta chains of a molecule originate from different parents.

Genetic defects (HLA class II)

Mutations in genes encoding HLA class II molecules can cause a severe immunodeficiency known as nude lymphocyte syndrome.

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Nude lymphocyte syndrome

A severe immunodeficiency caused by genetic defects in genes that code for HLA class II proteins.

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Transcriptional Factor C28

A factor that controls the expression of HLA class II genes, influenced by tissue-specific stimuli, interferons (type I and gamma).

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MHC Class II molecules

Molecules that present antigens on the cell surface, crucial for immune response.

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Non-HLA Class II molecules

Molecules, not part of the HLA complex, that assist in moving MHC Class II molecules to the cell surface; act as chaperones.

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HLA class III molecules

Diverse group of secreted molecules within the cell, with various functions, and relatively limited polymorphism.

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Antigen processing

Breaking down antigens into smaller peptides for presentation to the immune system.

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TAP1 and TAP2 (transporter associated with antigen processing)

Transporters that move peptides from the cytosol into the endoplasmic reticulum, facilitating antigen presentation.

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Tapase

A molecule in the endoplasmic reticulum that assists in binding antigens to MHC class I molecules.

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Immune Proteasome

A specialized type of proteasome involved in antigen processing by cleaving proteins into smaller peptides.

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MHC Class I Peptide Allocation

MHC class I molecules initially bind to chaperonins (calnexin and calreticulin) during synthesis. β2-microglobulin replaces these chaperonins, and tapasine helps peptides enter the endoplasmic reticulum.

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MHC Class I Presentation

MHC class I molecules, along with β2-microglobulin and peptides, are transported to the cell membrane via vesicles, including the Golgi for modifications.

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Exogenous Peptide Presentation (Class II)

MHC class II molecules present peptides derived from outside the cell. These peptides are processed by degrading proteins inside vesicles, without the proteasome.

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Phagosome Formation

The invagination of the cell membrane creates vesicles called phagosomes that fuse with lysosomes.

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MHC Restriction

T cell receptors (TCRs) bind to both the MHC molecule and the peptide antigen.

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MHC Class II Molecule Synthesis

MHC class II molecules are created inside vesicles, and peptides (from digested material) bind to their pockets.

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Organ Rejection

A patient's T cells recognize a different MHC molecule from a transplanted organ as foreign, causing rejection.

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Invariant Chain Function

Protects the MHC class II molecule's pocket until the right peptide binds; helps form HLA class II molecules (DP, DM, DO).

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T Cell Maturation

T cells that recognize self-MHC are preserved during development in the thymus.

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HLA Class II Molecule Transport

HLA class II molecules (DP, DM, DO) travel from the ER to Golgi and then to vesicles (post-Golgi) without binding to peptides.

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Zinkernagel and Doherty Experiment

Demonstrated that T cells are specific for both MHC and an antigen (such as viral peptide), not just the antigen alone.

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Peptide Binding Prevention

The invariant chain prevents MHC class II molecules from binding endogenous peptides to ensure the molecules only bind extracellular material.

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Invariant Chain Degradation

Cathepsin degrades the invariant chain, leaving "CLIP" peptides in the groove.

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Cytotoxic Assay

A lab test to determine the ability of a T cell to kill infected cells.

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Lipid Antigen Presentation

Lipids, in addition to proteins, can be presented as antigens to immune system cells.

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MHC Class II Conformation

DM or DO molecules maintain the correct shape of MHC class II molecules.

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MHC Class II Exposure

MHC class II molecules are exposed on the cell surface after fusion of vesicles with lysosome or phagosome and binding with the correct peptide.

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Class III genes

Genes in the major histocompatibility complex (MHC) that encode proteins not directly involved in antigen presentation, but have roles in the immune response.

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HLA molecules

Proteins found on the surface of cells that display fragments of proteins (antigens) on the cell surface, for immune system surveillance. Crucial for transplant matching.

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HLA Class I molecules

These molecules are important for displaying viral antigens on infected cells, essentially triggering an immune response to eliminate the infected cells.

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HLA Class II molecules

Display antigens from pathogens to helper T cells, activating adaptive immune responses.

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Organ transplant rejection

The immune system's response to recognizing the transplanted organ as foreign, leading to its destruction.

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HLA matching

The process of finding a donor with similar HLA alleles as the recipient to minimize rejection risk during a transplant.

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HLA allele

A specific variant form of a gene that codes for an HLA molecule, affecting its structure and function.

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Complement system

A group of proteins in the immune system that work together to eliminate pathogens, and are part of the HLA Class III complex.

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Cytokine

A signaling protein released by cells that affects the behavior of other cells, crucial in activating immune response.

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Lymphotoxin

A cytokine crucial for activating T cells that helps destroy infected cells, is part of the class III complex.

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TNF

Tumor Necrosis Factor, a cytokine that plays a crucial role in cell death and activating immune responses.

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Study Notes

HLA Molecules

  • HLA molecules (HLA-A, B, C, and others) are responsible for presenting antigens to T cells.
  • HLA molecules are highly polymorphic, meaning they show significant variation among individuals.
  • This polymorphism is crucial for immune responses and organ transplantation.
  • HLA-E, F, G present non-classical peptides, unlike their counterparts.
  • HLA-G is relevant during pregnancy to prevent the rejection of the fetus by the mother's immune system.
  • MIC-A and MIC-B are stress ligands.

Haemochromatosis

  • Mutations in the HFE gene cause haemochromatosis.
  • This disease leads to iron accumulation in cells.
  • The iron receptor binds transferrin and transports iron outside the cell.

HLA Class II Molecules

  • HLA Class II molecules are heterodimers composed of alpha and beta chains.
  • These molecules are highly polymorphic.
  • HLA Class II molecules are constitutively expressed by specific immune cells (dendritic, Langerhans, epithelial etc).
  • Induction of class II molecules also occurs in various cells due to factors such as cytokines.
  • HLA-DP, DQ, and DR genes coding for alpha and beta chains are highly polymorphic.

HLA Class II Co-dominance

  • HLA Class II alleles inherited from both parents are expressed.
  • The combination creates cis and trans co-dominance scenarios.
  • This increases diversity.

Nude Lymphocyte Syndrome

  • Genetic defects in CIITA cause a deficiency in the expression of MHC class II molecules.
  • This syndrome impairs T cell development and function, resulting in a serious immunodeficiency.
  • IFN-γ induces CIITA synthesis, increasing MHC class II expression.
  • Interferon gamma signaling is crucial for CIITA induction in various cells.

Antigen Presentation

  • MHC class I and II molecules present different peptides.
  • HLA Class I present endogenous peptide fragments.
  • HLA Class II presents exogenous peptide fragments processed in antigen presenting cells.
  • Non-classical HLA class II molecules (DM, DO) are involved in facilitating antigen presentation by MHC class II molecules.
  • The peptides are loaded inside a groove.

Antigen Processing

  • Proteasome processes protein antigens into peptides, then these peptides are transported to the ER.
  • In some cases, proteins are transported to the lysosomes for enzymatic degradation before being displayed on the MHC groove.
  • TAP-transporters are crucial for protein peptide transport.
  • Many proteins are targeted by ubiquitination for degradation by the proteasome.
  • Some peptides associated with MHC I or MHC II during cellular infections.

Lipids, Peptide presentation

  • CD1 molecules present lipids to T cells.
  • Lipids are presented to T cells via CD1 molecules (nonclassical HLA)

MHC Restriction

  • Demonstrated by Zinkernagel and Doherty's experiments.
  • The same viral peptide but different MHC molecules could lead to different cell responses.

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Immunology Lecture Notes PDF - 21/10/2021

Description

Explore the functions and significance of HLA molecules in the immune system, along with the genetic basis of haemochromatosis. This quiz covers HLA polymorphism, their roles during pregnancy, and the consequences of iron accumulation due to mutations. Understand the link between HLA molecules and various immune responses.

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