Question

Immune responses working to protect the host need to be carefully regulated, since overt immune function may be harmful to the host. There are several feed back inhibitory loops evolved to regulate immune cell activation. Briefly describe how B cells and T cells are equipped with such feed back regulatory circuits upon activation.

Answer 1

When the immune system encounters a foreign molecule, it activates innate and adaptive immune pathways to take necessary measures to eliminate the foreign element .Once this has been achieved, the immune response needs to be switched off to maintain homeostasis. Immune response is partly regulated through the natural death of immune cells, but one of the dominant regulatory mechanisms that is the presence of feedback and feedforward loops

T cell activation:

· Dendric cells present the peptide-MHCII complex on their surface to the T cells.

· The complex binds to T cell and activates the T cell receptor (TCR).

· This leads to the production of IL-2 and other cytokines.

· T cell activation promotes enhanced expression of CD40L which binds to CD40 on activated dendritic cells

· T cells enhance activation of dendritic cells and thus increase their own proliferation

· After T cells have effectively controlled or eliminated foreign antigen, the immune response is terminated via cell apoptopsis.

· TCR activation and CD80/86-CD28 interaction is important in the development and survival of

· another class of T cells, called regulatory T cells (Tregs) .

· The primary function of Tregs is to inhibit activated T cells and dendritic cells, and giving rise to two cellular-level negative feedback loops.

· There are Several mechanisms for Tregs-mediated inhibition

· These can be divided into three main classes:

· cell-cell contact, b) inhibitory cytokine secretion and c) competition.

· Tregs can inhibit dendritic cells through mechanisms a and b, and effector T cells through mechanisms a, b and c.

· Tregs also inhibit B cell antibody production by secreting inhibitory factors IL-10, TGFβ,

· Tregs may also inhibit B cell activity by disrupting the mechanical interaction between T cells and B cells .

Bcell activation:

· B cells can get activated through T-cell dependent or independent manner.

· In T-cell independent B cell activation mechanism, the antigens with their repetitive structure make cross-linking of the B-cell receptors (BCR) and elicit B cell activation.

· In T-cell dependent activation mechanism, activated T cells may directly bind to B cells forming immunological synapses or secrete stimulatory cytokines (IL-4, IL-5 etc.) to activate B cells.

· In many immune settings B cells function as APCs for T cells, thus creating a positive feedback loop. A an APC, B cell binds antigen to its surface expressed immunoglobulin (BCR), internalizes antigen, processes antigen by internal machinery, binds antigenic peptides to MHCII molecules and present them on the cell surface like dendritic cells .

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