Jawaharlal Nehru Technological University Hyderabad Pharm. D II Year PATHOPHYSIOLOGY Previous Question Paper (July/August - 2021 - R08)

Wound healing is a complex biological process involving the restoration of tissue integrity following injury. It occurs through three overlapping phases: inflammation, proliferation, and remodeling.

1. Inflammatory Phase: Immediately after injury, hemostasis occurs via platelet aggregation and fibrin clot formation. This clot acts as a scaffold for migrating cells. Neutrophils and macrophages infiltrate the area to remove debris, bacteria, and damaged tissue through phagocytosis. Macrophages also release growth factors that initiate the next phase.

2. Proliferative Phase: This phase involves the formation of granulation tissue. Fibroblasts migrate to the site and synthesize collagen and extracellular matrix components. Angiogenesis occurs, where new blood vessels sprout from existing ones to supply oxygen and nutrients. Epithelial cells migrate across the wound surface to restore the barrier, a process known as re-epithelialization.

3. Remodeling Phase: This phase can last for months or years. The initial type III collagen is replaced by stronger type I collagen. The wound undergoes contraction, mediated by myofibroblasts, which reduces the size of the wound. The tensile strength of the tissue increases as collagen fibers are reorganized and cross-linked.

Factors influencing wound healing:

• Systemic factors: Age (slower healing in elderly), nutrition (deficiency in protein, Vitamin C, or zinc impairs collagen synthesis), systemic diseases (e.g., diabetes mellitus, which impairs circulation and immune function), and medications (e.g., corticosteroids which inhibit inflammation and collagen production).
• Local factors: Infection (the most common cause of delayed healing), mechanical stress (movement or tension), foreign bodies, poor blood supply (ischemia), and the size or location of the wound.

T cells and B cells are the primary lymphocytes of the adaptive immune system, responsible for cell-mediated and humoral immunity, respectively.

T cells (Cell-Mediated Immunity): T cells mature in the thymus and recognize antigens presented by Major Histocompatibility Complex (MHC) molecules. Helper T cells (CD4+) coordinate the immune response by secreting cytokines that activate B cells, macrophages, and cytotoxic T cells. Cytotoxic T cells (CD8+) directly identify and induce apoptosis in infected or malignant host cells. Regulatory T cells maintain immune tolerance and prevent autoimmunity.

B cells (Humoral Immunity): B cells mature in the bone marrow and are responsible for antibody production. Upon activation by antigen binding and T-cell help, B cells differentiate into plasma cells, which secrete specific antibodies (immunoglobulins) to neutralize pathogens or mark them for destruction by phagocytes. A subset of B cells becomes memory B cells, providing long-term immunity.

Transplantation and Allograft Rejection: Transplantation involves transferring cells, tissues, or organs from a donor to a recipient. An allograft is a transplant between genetically non-identical individuals of the same species. Rejection occurs because the recipient's immune system recognizes the donor's MHC molecules (Human Leukocyte Antigens, HLA) as foreign.

Rejection mechanisms include:

• Hyperacute rejection: Occurs within minutes to hours due to pre-existing antibodies in the recipient binding to donor antigens, causing rapid thrombosis and ischemia.
• Acute rejection: Occurs within days to months, primarily driven by T-cell mediated infiltration and inflammation against donor HLA antigens.
• Chronic rejection: Occurs over months or years, characterized by fibrosis and gradual loss of graft function, often due to chronic inflammatory responses and vascular remodeling.

Clinical management involves immunosuppressive therapy to inhibit T-cell activation and proliferation, thereby preventing the immune system from attacking the transplanted tissue.