Major Histocompatibility Complex (MHC)

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Questions and Answers

Which of the following characteristics distinguishes MHC class II molecules from MHC class I molecules?

  • MHC class II molecules present antigens derived from intracellular pathogens, while MHC class I molecules present antigens from extracellular sources.
  • MHC class II molecules are composed of two polypeptide chains (alpha and beta), while MHC class I molecules consist of a single alpha chain and beta2-microglobulin. (correct)
  • MHC class II molecules are expressed on all nucleated cells, while MHC class I molecules are expressed only on antigen-presenting cells.
  • MHC class II molecules primarily activate CD8+ T cells, while MHC class I molecules activate CD4+ T cells.

How does the expression of both MHC class I and MHC class II molecules on B cells contribute to a comprehensive immune response?

  • It enhances the ability of B cells to present antigens to natural killer (NK) cells, leading to ADCC (antibody-dependent cell-mediated cytotoxicity).
  • It allows B cells to directly kill infected cells and produce antibodies simultaneously.
  • It increases the efficiency of B cells in phagocytosing pathogens and presenting antigens in the context of both MHC classes, without affecting T cell interactions.
  • It enables B cells to interact with both CD4+ T cells for antibody production and CD8+ T cells for eliminating infected B cells. (correct)

Consider a scenario where a viral infection downregulates the expression of MHC class I molecules on infected cells. What is the most likely immunological consequence of this downregulation?

  • Compensatory upregulation of NK cell activity, leading to increased elimination of infected cells.
  • Increased susceptibility to antibody-mediated neutralization of the virus.
  • Reduced recognition of infected cells by CD8+ T cells, leading to impaired cytotoxic T lymphocyte (CTL) response. (correct)
  • Enhanced activation of CD4+ T cells due to increased MHC class II expression.

What is the functional significance of the 'open' ends in the peptide-binding cleft of MHC class II molecules, compared to the 'closed' ends in MHC class I molecules?

<p>The open ends allow MHC class II molecules to bind longer peptides, accommodating a wider variety of antigens. (A)</p> Signup and view all the answers

How does the genetic diversity within the MHC region contribute to the adaptability of the immune system in a population?

<p>Greater MHC diversity allows the population to recognize and respond to a wider array of antigens, increasing resistance to diverse pathogens. (B)</p> Signup and view all the answers

In the context of organ transplantation, what is the primary immunological rationale for matching MHC alleles between a donor and a recipient?

<p>Matching MHC alleles ensures that the recipient's immune system will not recognize the transplanted organ as foreign, preventing rejection. (B)</p> Signup and view all the answers

Which statement best describes the role of professional antigen-presenting cells (APCs) in initiating adaptive immune responses?

<p>Professional APCs process and present antigens on both MHC class I and MHC class II molecules, activating both CD4+ and CD8+ T cells to coordinate an immune response. (D)</p> Signup and view all the answers

How might the ectopic (abnormal) expression of MHC class II molecules on non-APCs contribute to the pathogenesis of autoimmune diseases?

<p>It leads to enhanced presentation of self-antigens, triggering autoreactive T cells and causing tissue damage. (C)</p> Signup and view all the answers

Upon activation, T cells can upregulate the expression of MHC class II molecules. What is the primary function of this upregulation?

<p>To enhance interactions with other immune cells, amplifying the immune response through presentation of antigens to other T cells. (A)</p> Signup and view all the answers

What accounts for the codominant expression of MHC class II molecules?

<p>Both maternal and paternal MHC alleles are expressed equally, increasing the diversity of antigen presentation. (A)</p> Signup and view all the answers

Flashcards

Major Histocompatibility Complex (MHC)

A complex of genes encoding antigen recognition, determining the adaptive immune response. Also known as HLA complex in humans.

MHC Class I

Found on all nucleated cells, presents endogenous antigens to CD8+ T cells.

MHC Class II

Expressed on antigen-presenting cells (APCs), presents exogenous antigens to CD4+ T cells.

Antigen-Presenting Cells (APCs)

Cells that display antigens with Class II MHC molecules to CD4+ T cells.

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β2-microglobulin

A small polypeptide necessary for the stability and expression of MHC class I molecules on the cell membrane.

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Antigen Presentation by B cells

Process where B cells take up exogenous antigens, process them, and display the resulting peptides on MHC class II molecules for CD4+ helper T cells.

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Cellular Expression of MHC class II

MHC class II molecules are primarily expressed by professional antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells.

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Study Notes

  • The major histocompatibility complex (MHC) contains genes that encode for antigen recognition, determining the adaptive immune response.
  • MHC is also known as the human lymphocyte antigen (HLA) complex in humans.
  • In humans, the MHC is found on chromosome 6; in mice, it's on chromosome 17.
  • MHC genes encode enzymes and molecules that are critical for B and T cell activation.
  • This activation leads to foreign antigen recognition and an appropriate immune response.

MHC Class I Structure

  • MHC class I molecules form a cleft between the alpha 1 and alpha 2 domains.
  • This cleft is shaped like a pita sandwich.
  • It accommodates peptides (epitopes) of 8 to 9 amino acids.

MHC Class II Structure

  • MHC class II complexes codominantly express heterodimers (alpha and beta domains).
  • These can accommodate larger peptides of 18 to 20 amino acids.
  • The shape of the peptide-binding cleft is akin to a hot dog.

Antigen Presentation

  • T cell receptors (TCRs) interact with antigen presented by a peptide or antigen MHC complex for T and B cell activation.
  • Antigen-presenting cells (APCs) present antigens via MHC complexes.
  • CD8+ T cells recognize antigen presented by MHC class I, which is closed on both ends.
  • CD4+ T cells recognize antigen presented by MHC class II, which is open on both ends.

Cellular Distribution

  • Cells that display antigens with class I MHC molecules to CD8+ T cells are target cells.
  • Cells that display antigens with class II MHC molecules to CD4+ T cells are antigen-presenting cells (APCs).
  • A variety of cells can function as APCs (typically present with class I MHC) and are referred to as nonprofessional APCs.

MHC Class I and II Cellular Distribution

  • MHC class I molecules are expressed on all nucleated cells; red blood cells do not express MHC molecules.
  • Cells expressing MHC class I can be probed by cytotoxic T cells and targeted for elimination.
  • MHC class II molecules are typically expressed by professional antigen-presenting cells.
  • In humans, activated T cells can express MHC class II molecules.

Activated T Cells and MHC Class II

  • MHC class II molecules are primarily expressed by professional APCs such as dendritic cells, macrophages, and B cells.
  • CD4+ T cells can upregulate the expression of MHC class II molecules on their surface when activated.
  • The expression of MHC class II molecules on activated T cells allows them to interact with other immune cells and enhance the immune response.
  • This ability helps amplify immune responses and can have implications in immune regulation and certain disease states.

B Cells and MHC Classes

  • B cells express both MHC class I and MHC class II molecules for different functions.
  • MHC class I on B cells presents endogenous antigens to CD8+ cytotoxic T cells, enabling immune surveillance.
  • MHC class II on B cells presents exogenous antigens to CD4+ helper T cells, aiding in T cell-dependent B cell activation and antibody production.
  • By expressing both, B cells participate in both cell-mediated and humoral immunity.

MHC Complex Role

  • The human MHC is called the HLA complex (human leukocyte antigen complex).
  • The MHC in mice is called the H2 complex.
  • MHC genes encode cell surface proteins essential for the immune system to recognize foreign molecules, determining histocompatibility.
  • These proteins help cells distinguish between self and non-self.
  • MHC determines compatibility for organ transplants and susceptibility to autoimmune diseases.
  • MHC molecules bind to protein-derived fragments from pathogens and display them on the cell surface for recognition by immune cells.
  • Each MHC molecule on the cell surface presents an epitope (molecular fraction of a protein), which can be self or non-self, preventing the immune system from targeting self.

Question 1

  • β2-microglobulin is important for the expression of MHC class I on the cell membrane.
  • MHC class I molecules are made up of an alpha chain and β2-microglobulin.
  • B2-microglobulin is a necessary polypeptide for the stability and expression of MHC class I molecules on the cell membrane.

Question 2

  • MHC class II is recognized by CD4+ T helper (TH) cells.

Question 3

  • MHC class I recognizes CD8+ cytotoxic T cells (TC).

Question 4

  • In humans, MHC class II molecules are expressed by B cells, dendritic cells, and macrophages.

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