Question

7. DC maturation.

a. How does the role of an immature to mature DC change?

b. What stimulates the change from an immature to a mature DC?

c. What key molecules are up regulated during its maturation?

d. What are the functions of these key molecules?

Answer 1

Ans. a)

• DC cells are generally found in skin , mucosal surface of digestive , respiratory and reproductive system.
• These cells are derived from blood forming stem cells of bone marrow .
• Their basic function is interaction with antigen and their presentation to immune cells after converting them to immunogen.
• These cells also express various types of chemokines, cytokine receptors on their cellular surface .
• After phagocytosis /Endocytosis / pinocytosis of antigenic molecules Dendritic cells undergo cellular modification converting them from immature antigen presenting cells to antigen presenting cells (APC) .
• After this activation they will move to lymphoid organs like lymph node , spleen and further activate lymphocytes (B cell and T cell ).

Answer (b)

• Dendritic cells are activated by different types of antigens like while bacterial cell or their specific parts like lipopolysaccharides (LPS), viral surface proteins , viral RNA , inflammatory molecules (cytokines ).
• Maturation of DC involves redistribution of MHC (Major Histocompatibility Complex ) molecules to cellular surface , increase in co stimulatory molecules transport to surface of DC , morphological changes like formation of dendrites , Secretion of chemicals like cytokines , changes in cytoskeletal elements like actin ,expression of proteases and adhesion molecules .

Answer (c)

Key molecules which are upregulated during maturation process of DC.

• Maturation of Dendritic cell involves redistribution of MHC molecules which act during antigen presentation .It also involves change in receptor molecules for interacting with other immune cells like chemokine receptors .
• These cells are attracted to inflammatory areas in our body by cytokines molecules which are received by specific cytokine receptors .
• Cell signalling leads to various types of cellular changes inside Dendritic cells .
• Most important of them are change in both intracellular receptors and cell surface receptors
• Lectin family antigen receptors, Fc receptors for immunoglobulin , macrophage mannose receptors involved in antigen handling , TLR 2 (Toll like receptors ) TLR 4, heat shock proteins for binding to antigens (hsp ) all are modulated during DC maturation .
• Protease enzymes carry out processing of antigen endocytosed by cells and modified antigenic peptides are presented on cell surface with the help of modulated MHC molecules . This helps in interaction with CD4+ and CD8+ T cells and their activation .
• P55 proteins which carry out cytoskeleton modification in these cells are also modulated.
• Ubiquitin molecules which carry out antigen processing are also modulated inside DC .
• Different types of cytokines like IL 12 , IL 6 , TNF , Interferons are secreted by mature DC.
• Change in CCR 7 a chemokine receptor also regulate DC migration to lymphoid tissue during inflammation .

Answer (d)

Function of key molecules involved with DC .

• First of all cell surface receptors which bind to antigen are required for activation of DC like TLR 2, TLR 4, hsp and lectin family receptors .This binding stimulates the maturation process via cell signalling .
• Once antigen is bound it is either phagocytosed /, endocytosed or pinocytosed with the help of receptors
• Response of DC to different inflammatory cytokines is executed by receptors like CCR6,CCR7, CCR1, CXCR1. They help in movement of DC to inflammatory areas.
• Protease enzymes present in cytoplasm will help in antigen processing by cleaving some portion of it and then it will be bound with MHC molecules. Proteases enzymes can also change the activity of various cytokine molecules . There are some inhibitory proteases too which interfere with maturation process.
• MHC type 1 molecles carry out antigen presentation to T Cells .
• Interaction with T cells is carried out by T cell receptors .
• Fascin protein which is associated with cytoskeleton remodelling is also helpful in dendrites formation . It modulated various cytoskeleton elements like actin .
• Adhesion receptors of DC like ICAM 1 also help in binding to T cell after antigen presentation is over .