Question

Describe molecules involved in homing of effector T cells to the gut

6. Describe molecules involved in homing of effector T cells to the skin

7. Describe all types of Hypersensitivity reaction mediated by immunological mechanisms that cause tissue damage

Answer 1

ANSWER:- HOMING OF EFFECTOR T CELLS TO THE GUT

Gut-specific homing is the mechanism by which activated T cells and antibody-secreting cells are targeted to both inflamed and non-inflamed regions of the gut in order to provide an effective immune response.

Receptors involved

MadCAM-1

MadCAM-1expression is continuous in the high endothelial venules of Peyer's patches and in the micro-vessels of the intestinal tract. MadCAM-1 inhibitors prevent T cell migration to the gut.

The MadCAM-1 protein has structural homology to the vascular surface receptors VCAM1 and ICAM at 28% and 32% respectively.

Α4β7 integrin

This is expressed on activated T cell imprinted for gut-specific homing. It is the counter receptor for the MadCAM-1 protein and the interactions of which cause the initial interaction step in rolling cell model of lymphocyte migration.

CCR9

CCR9 receptors are presented on the T cells and are involved in forming a more stable interaction between the lymphocyte and the vessel wall. The ligand for CCR9 proteins is the CCL25 chemokine protein. CCL25 is a chemokine which, upon binding to its receptor CCR9 on the lymphocyte, activates a conformational change in surface integrins on that lymphocyte,enabling high-affinity binding to the vessel wall and subsequent transmigration (movement from one site to another).

ANSWER;6) HOMING OF EFFECTOR T CELLS TO THE SKIN

The cutaneous lymphocyte-associated antigen (CLA) is a carbohydrate epitope present on effector T cells that infiltrate inflamed skin. E-selectin is the ligand for CLA and is induced under inflammation on endothelial cells. Effector T cells that respond to antigens and reach the body through inflamed skin. Existence of a regionalization of the immune system and in particular of the skin immune system. It may allow an efficient distribution of the immune defense to different sites of the body.

Acts as a method of recruiting a large number of memory T cells to the skin, which poses a high risk of infection. Again this involves the expression of different integrins. In this case, in humans α4β1 and cutaneous lymphocyte antigen cutaneous lymphocyte associated antigen are expressed on the T cell surface. These integrins interact with E- selectin molecules found on inflamed skin.

ANSWER:- 7)

Types of Hypersensitivity Reactions

The response of the host to the presence of foreign substances can trigger four types of hypersensitivity reactions:

Immediate

Cytotoxic

Immune complex

Cell-mediated

Immediate Hypersensitivity (Anaphylactic Reaction)

The reaction is the result of an antigen cross-linking with membrane-bound IgE antibody of a mast cell. Histamine, serotonin, bradykinin are released during the anaphylactic reaction. These released substances have the potential to cause tissue damage.

Cytotoxic Reaction (Antibody-dependent)

The antibody reacts directly with the antigen that is bound to the cell membrane to induce cell lysis through complement activation. These antigens may be intrinsic or "self" as in autoimmune reactions or extrinsic or "non-self." Cytotoxic reactions are mediated by IgG and IgM. Examples :- blood transfusion reactions.

Immune Complex Reaction

IgG and IgM bind antigen, forming antigen-antibody complexes. These activate complement, which results in PMN chemotaxis and activation. PMNs then release tissue damaging enzymes. Tissue damage present in autoimmune diseases and chronic infectious diseases (e.g., leprosy) can be attributed, in part, to immune complex reactions.

Cell-Mediated (Delayed Hypersensitivity)

These reactions are initiated by T-lymphocytes and mediated by effector T-cells and macrophages. This involves the interaction of antigens with the surface of lymphocytes. This type of reaction takes 48-72 hours, or longer, after contact with the antigen to fully develop. Many chronic infectious diseases, including tuberculosis and fungal infections, exhibit delayed hypersensitivity.