Question

1. Antigen presentation is an important link between innate and acquired (adaptive) immunity. Explain in detail how the process occurs. Please include: what cells might be involved, the differences between MHC 1 and MHC 2 and how antigen presentation leads to differential activation of acquired immunity.

Answer 1

• Immune response is initiated when the body encounters any foreign molecules acting as exogenous or endogenous antigens).
• The innate immunity or non-specific immunity acts as the first line of defense, provides barrier against the foreign substances.
• Various cytokines released from specific cells, like interleukins (IL), tumor necrosis factor alpha (TNFα), activates the production of mature phagocytic cells, like neutrophils, macrophages and dendritic cells and induce their migration to the site of infection or invasion.
• Phagocytic cells, engulf the foreign substances by phagocytosis or endocytosis.
• The phagocytosed molecules processed and, then the peptide fragments of antigens are expressed through membrane bound glycoproteins called major histocompatibility complex (MHC).

• Major histocompatibility complex (MHC) are multi-loci bearing polygenic complex (located in chromosome 6, in human), that encodes three classes of proteins molecules, called Major histocompatibility complex class I (MHC I) and Major histocompatibility complex class II (MHC II).Major histocompatibility complex class III (MHCIII).
• Major histocompatibility complex (MHC) are highly polymorphic membrane bound glycoproteins, that can bind to a wide spectrum of antigenic peptides. The distal part of the MHC molecules exhibit variable in amino acid sequences, which aid in binding to the antigenic peptide sites.

Specific characteristics of different classes of MHC molecules include:

1)Major histocompatibility complex class I (MHC I)- they are present on the surface of all nucleated cells (absent on red blood cells or RBCs) and, also platelets. Class I MHC proteins are mainly associated with endogenous antigens or cytosolic proteins, representing endogenous or cytosolic antigen presentation. These proteins include proteins produced by viral infected cells and cancerous cells.

Antigen presented by class I MHC molecules are recognized by cluster of differentiation (CD) 8 receptors of Tcytotoxic (TC) cells and killer T cells.

2) Major histocompatibility complex class II (MHCII)- they are normally expressed by antigen presenting cells (APC), like B-cells, macrophages, and dendritic cells. When exogenous foreign substances enter the body, they are phagocytosed and are processed by the antigen presenting cells. Class II MHC molecules then express the peptide fragments of exogenous antigens (exposing the antigenic epitope). CD 4 receptors of T helper cells (TH) interacts with class II MHC- exogenous peptide complexes.

3) Major histocompatibility complex class III (MHCIII)-they contribute to physiological role in immune system, such as secretion of cytokines like tumor necrosis factor- alpha (TNF α), components of complement system (C2, C4), heat shock proteins.

• The antigenic polypeptide bound to MHC molecules further induces B-lymphocytes (designated from Bursa of Fabricus in birds) and T-lymphocytes (lymphocytes maturing in thymus), generating humoral or cell mediated immune responses, as well as immunogenic memory. Such specific activations lead to clonal selection, clonal expansion and clonal deletion.
• Clonal deletion is the process by which immune cells (B-cells or T-cells) that have receotors against self-antigens are eliminated.