Mock exams

Question 1

What is the role of chemokines and chemokine receptors in the migration process of leukocytes over activated endothelium. Please shortly describe associated signalling events

Answer 1

Chemokines are presented on the endothelial cell surface upon activation and attract the leukocytes to this site. Leukocytes will role over the endothelium (via selectins), bind to the chemokines via chemokine receptors. Chemokine receptors then signal into the leukocyte (via G-protein coupled receptors) to modify the conformation of the integrins that then firmly bind to their receptors on the endothelium (IgSF) and change the cytoskeleton. Leukocytes become firmly attached and can start to migrate. Points: 5 (1 for chemokines on endothelium, 1 for signalling into the leukocyte, 1 for integrin changes, 1 for cytoskeleton changes and 1 for firmly attached and migration)

Question 2

Name 3 structures that are recognized by Toll-like receptors.

Answer 2

proteins, DNA, RNA, lipids and carbohydrates (0.5 p.)

Question 3

Describe the processes that occur when a pathogen interacts with Toll-like receptor 4 on the cell-surface of an immature dendritic cell that resides in the skin

Answer 3

DC becomes activated/matures, migrates to lymphoid tissues and secretes cytokines and upregulates co-stimulatory molecules (CD80, CD83, CD86) as well as HLA-DR (0.5 p.)

Question 4

Give three differences between immature and mature dendritic cells (6 p.)

Answer 4

IMM: 1) receptors for inflammatory chemokines; 2) expression of inflammatory chemokines; 3) high endocytosis/phagocytosis; 4) low levels of MHC-peptide; 5) low levels of costimulatory molecules

MAT: 1) receptors for lymphoid chemokines; 2) expression of lymphoid chemokines; 3) secretion of T cell attracting chemokines; 4) low endocytosis/phagocytosis; 5) high levels of MHC-peptide; 6) high levels of costimulatory molecules

Question 5

Induction of an effective anti-tumour CD8+ T cell response is a multi step process. Name 5 of the 6 steps that are required for this process. (5x2p.)

Answer 5

Tumour antigens must be present *These antigens must reach/ load professional APC in the draining lymph node * Specific T cells must respond by proliferation *Circulating CTL must enter the tumour *Once in the tumour the T cells must be able to overcome local immune-suppressive molecules to recognize and kill targets *Memory cells should be generated

Question 6

What are the three antigen presentation pathways? Define for each antigen presentation pathway in which cells this pathway is working, the origin of the antigen, where the antigen is degraded, to which MHC molecule it binds, which T cell subset it can activate, and what the general function of this pathway is.

Answer 6

Endogenous antigen presentation pathway: all cells, endogenous, cytosol/proteasome, MHC class I, CD8 T cell, detection of intracellular pathogens/viruses by cytotoxic T cells for elimination Exogenous antigen presentation pathway: antigen presenting cells, exogenous, endosome, MHC class II, CD4 T cell, to elicit help to eradicate extracellular pathogens by inducing antibody production en activation of macrophages Cross-presentation pathway: (CD8+) dendritic cells, exogenous, endosome/cyotosol/proteasome, MHC class I, CD8 T cell, to elicit cytotoxic T cells/ CD8 T cells for antigens that are not endogenously expressed in DCs themselves