DMF Week 4 SAQ

1

Which one of the following statements regarding the complement cascade is incorrect?


  The components of the complement system are normally found in an inactive state in the serum.

  The interaction of mannose binding lectin (MBL) and mannose residues on the surface of bacteria and viruses is an innate mechanism which enables activation of the complement cascade.

  IgA antibodies are the most efficient antibody class in activating the complement cascade

  The activation of the classical, lectin and alternative pathways of the complement cascade all result in the degradation of C3

  C3b binds efficiently to pathogen surfaces, but less efficiently to host cell surfaces.


The degradation of C3 to C3a, C3b and the generation of C5 convertases is the central step in the activation of the complement cascade

2

Which of the following is NOT common to the lectin and alternative pathway of complement activation


  C3

  C4

  C5

  C6

  C7


C4 is activated by the lectin pathway, but not the alternative pathway

3

Pattern recognition receptors (PRR) are important recognition molecules of the innate immune system. Which one of the following statements best describes their function?


  Interaction with their ligands predominantly results in activation of the complement cascade

  Interaction with their ligands typically leads to phagocytosis of the organism expressing the PRR ligand.

  Ligation of PRR by pathogen associated molecular patterns (PAMPs) can aid in the control of extracellular but not intracellular pathogens

  PRR recognise pathogen but not host cell molecules

  The interaction of PRR on dendritic cells by pathogen associated molecular patterns (PAMPs) can initiate the activation of adaptive immunity.


1 is incorrect: Whilst the interaction of fluid phase PRR with their pathogen associated molecular patterns (PAMPs) commonly triggers the complement cascade, the interaction of cell associated PRR with their ligands may result in a range of outcomes, depending on the location of the PRR.

2 is incorrect: The outcome of PRR - PAMP ligation depends on the cell type expressing the PAMP. Although phagocytes such as macrophages and neutrophils may be induced to phagocytosis, another outcome may result from the same PAMP interaction with PRR on other cell types.

3 is incorrect: PRR are found not only on a range of cell types but also in different locations in those cell types. External and internal membranes may express TLR where extracellular or endocytosed organisms may interact with them, and NODs and RIGs are expressed in the cytosol, thus enabling interaction and activation by intracellular cytoplasmic micro-organisms.

4 is incorrect: Heat shock proteins expressed by damaged tissue interact with PRR, e.g. TLR-4, and initiate the inflammatory response.

5 is correct: In fact these interactions are now being utilised to boost responses to infections, cancers and vaccines.

4

Which one of the following statements is correct?


  T and B lymphocytes differentiate in the thymus and bone marrow respectively, after interaction with antigens

  The interaction of naive T and B cells with antigen (priming) takes place at the site of infection.

  An individual B cell displays hundreds of thousands of membrane bound immunoglobulin molecules which all bind a single antigenic epitope.

  Antibody diversity is due mainly to the rearrangement of immunoglobulin gene segments.

  Antibodies produced by a single B cell are identical in their variable region and constant region genes.


1 is incorrect: B and T cell differentiation in the primary lymphoid tissues is independent of antigen stimulation

2 is incorrect: Naive T and B cells interact with antigen which has drained to secondary lymphoid tissue from the infected site via the efferent lymphatics (lymph nodes) or blood (spleen)

3 is correct.

4 is incorrect: Antibody diversity is generated by multiple gene rearrangements and imprecise" joining of the V-D and D-J gene segments because of deletion and insertions (n-region diversity). Somatic hypermutation which occurs in the lymphoid follicles after antigen stimulation also contributes to antibody diversity.

5 is incorrect: Following antigen stimulation, and under the influence of T cell help, B cells may switch their isotype by acquiring a new constant region gene.

5

Which one of the statements about B cell interaction with their antigen is incorrect?


  The interaction of na├»ve B cells with their antigen takes place at the T cell - B cell border of the secondary lymphoid tissue.

  Antigenic stimulation of B cells results in the generation of antibody producing cells, and long-lived memory cells.

  The B cell response to protein antigens is characterised by the initial secretion of antigen specific IgM, followed by switching to other immunoglobulin classes (isotypes), e.g. IgG.

  After repeated exposures to a protein antigen, specific B cells undergo multiple rounds of cell division, during which time somatic mutations occur in the VH and VL chains resulting in the production of antibodies which have higher affinity for their antigen.

  Affinity maturation results from the outcome of somatic mutation, together with the persistence of high amounts of antigen.


T cell help is important.

6

Which one of the following is correct regarding the structure of MHC molecules?


  They have a peptide-binding cleft that can bind peptides of any lengths

  They are comprised of highly polymorphic light and heavy chains

  They all directly interact with CD4 molecules on T cells

  They consist of rearranging heavy and light chains

  They are both found on mature B cells


1 is incorrect: Whilst MHC class II may bind peptides of varying lengths, due to the closed nature of their peptide binding cleft MHC class I molecules can only bind short peptides 8 - 10 aa long.

2 is incorrect: Whereas MHC class II molecules consist of a polymorphic heavy and light chain, MHC class I molecules consist of a polymorphic heavy chain associated with an invariant molecule, beta-2 microglobulin

3 is incorrect: Only MHC class II molecules associate with CD4. MHC class I molecules associate with CD8

4 is incorrect: Gene rearrangement is not a feature of MHC molecules

5 is correct: Thus B cells as well as macrophages and dendritic cells may act as antigen presenting cells for T cells.

7

Which one or more of the following statements about T cell function is correct?

A: T cells which express CD4 can interact with HLA A, B and C antigens.

B: Helper T cells interact with MHC Class II - peptide complexes displayed by antigen activated B cells in secondary lymphoid tissues, resulting in isotype switching

C: T cells which express CD4 can bind free antigens in infected tissues, and help phagocytes to remove them.

D: Cytotoxic T cells recognise viral peptides held in Class I MHC molecules on infected tissue cells.


  If A, B, and C, are correct

  If A and C are correct

  If B and D are correct

  If D is correct

  If all are correct


Helper (CD4)T cells recognise peptides displayed on MHC Class II molecules (HLA-DR, HLA-DP and HLA-DQ) on the surface of antigen presenting cells. This activates the CD4+ T cells to provide help for macrophages, B cells and cytotoxic T cells. In contrast, cytotoxic (CD8+) T cells recognise antigens as peptides presented in the surface of MHC Class I molecules (HLA-A, HLA-B, and HLA-C). T cells are not phagocytic cells.

8

Which one or more of the following statements is correct regarding T cell receptors?

A: T cell activation can only proceed in vivo when the V and J domains of the alpha chain and V, D and J domains of the beta chain of a T cell receptor interacts with peptides held in the cleft of an MHC molecule.

B: Most thymic T cells die, either because they fail to bind self MHC-peptide complexes displayed on cells in the thymus, or because they bind the complexes with too high an affinity.

C: Somatic mutation and somatic gene rearrangements resulting in combinatorial and junctional diversity contribute to the generation of diversity of both B and T cell receptors.

D: T cells which exit the thymus express either CD4 or CD8 co-receptors, and bind self MHC-peptide complexes with low affinity.


  If A, B, and C, are correct

  If A and C are correct

  If B and D are correct

  If D is correct

  If all are correct


T cell activation may proceed when processed peptide-MHC complexes displayed on APC's interact with V alpha, J alpha and V beta, D beta and J beta regions of a T cell receptor. However, T cell activation may also occur when superantigens bind directly to MHC of an APC and the V beta of a TCR. Other mechanisms of activation of T cells (eg by mitogens) are also possible. Diversity of T cell receptors is generated in the thymus, where most T cells are deleted because their TCR's bind either too strongly or not at all to peptide MHC complexes displayed by thymic cells. T cell receptors do not undergo somatic mutation.

9

Which one of the following statements about T cell activation is correct?


  Both the induction and suppression of T cell proliferation is controlled by the interaction of CD80 and CD86 on antigen presenting cells with ligands on T cells.

  T cell receptor interaction with an MHC-peptide complex alone is sufficient to activate T cells to provide "help" for B cells.

  The response of memory CD8 T cells to a second exposure to antigen is the same in magnitude as the response of naive CD8 T cells.

  Naive CD4 T cells express CD 40L and can provide co-stimulation to dendritic cells, to enable them to activate CD8T cells.

  Naive CD8 T cells can be activated by binding virus infected epithelial cells.


1 is correct: When T cells react with MHC-peptide complexes present on an antigen presenting cell, the interaction of CD 28 on the T cell with CD80 and CD86 on the APC provides costimulation which allows productive activation of the T cell. Late in the process, activated T cells express CTLA-4, which also interacts with CD80 and CD86 (with higher affinity than CD28), which suppresses the activation process, and ensures it does not get out of control.

2 is incorrect: B cells also need co-stimulation.

3 is incorrect: Memory responses are faster and of higher magnitude than primary responses.

4 is incorrect: CD40L is induced on T cells after they have been activated by an antigen presenting cells provided the correct MHC-peptide complex combination, together with costimulatory signals.

5 is incorrect: Naive T cells (CD4 or CD8) can only be activated by antigen presenting cells.

10

Which one of the following statements regarding immunodeficiencies is incorrect?


  The principle consequence of immunodeficiency is an increased susceptibility to infection

  Patients with a B cell deficiency may have small or absent follicles and germinal centres in the B cell zones of secondary lymphoid tissue

  Patients with a B cell deficiency are likely to have significantly reduced T cell responses

  Patients with complement deficiencies may be defective in their removal of extracellular pathogens

  Defects in the expression of LFA-1 can result in impaired T cell activation


1 is correct.

2 is correct: The failure of B cells to be produced or activated can be recognised by failure to populate or proliferate in germinal centres and follicles.

3 is incorrect: T cell activation is not mediated by antibodies, and although T cells may be activated when B cells act as antigen presenting cells, absence of B cells does not have a significant effect in this regard.

4 is correct: Impaired production of C3b will result in impaired removal of pathogens by phagocytes. In contrast, impaired production of the terminal components of the complement cascade, resulting in impaired production of the membrane attack complex seems only to compromise the removal of Neisseria sp which appear to be able to survive phagocyte killing processes.

5 is correct: Adhesion to APC's is an important step in the formation of the immunological synapse, which results in effective T cell signalling and activation.