Overview of the Immune System

The cells of the immune system are activated when a foreign antigen (Ag) is recognized by cell surface receptors. These cell surface receptors may be

Broadly specific receptors recognize common microbial pathogen-associated molecular patterns such as gram-negative lipopolysaccharide, gram-positive peptidoglycans, bacterial flagellin, unmethylated cytosine-guanosine dinucleotides (CpG motifs), and viral double-stranded RNA. These receptors can also recognize molecules that are produced by stressed or infected human cells (called damage-associated molecular patterns).

Activation may also occur when antibody-antigen and complement-microorganism complexes bind to surface receptors for the crystallizable fragment (Fc) region of IgG (Fc-gamma R) and for C3b and iC3b.

Once recognized, an antigen, antigen-antibody complex, or complement-microorganism complex is internalized. Most microorganisms are killed after they are phagocytosed, but others inhibit the phagocyte’s intracellular killing ability (eg, mycobacteria that have been engulfed by a macrophage inhibit that cell's killing ability). In such cases, T cell–derived cytokines, particularly interferon-gamma (IFN-gamma), stimulate the phagocyte to produce more lytic enzymes and other microbicidal products and thus enhance its ability to kill or sequester the microorganism.

Unless antigen is rapidly phagocytosed and entirely degraded (an uncommon event), the acquired immune response is recruited via recognition of antigen by the highly specific receptors on the surface of B and T cells. This response begins in

For example, Langerhans dendritic cells in the skin phagocytose antigen and migrate to local lymph nodes; there, peptides derived from the antigen are expressed on the surface of dendritic cells within class II major histocompatibility complex (MHC) molecules Human Leukocyte Antigen (HLA) System The human leukocyte antigen (HLA) system (the major histocompatibility complex [MHC] in humans) is an important part of the immune system and is controlled by genes located on chromosome 6.... read more , which present the peptide to CD4 helper T (Th) cells. When the Th cell engages the MHC-peptide complex and receives various costimulatory signals (which can be inhibited by some immunosuppressive drugs), it is activated to express receptors for the cytokine interleukin (IL)-2 and secretes several cytokines. Each subset of Th cells secretes different combinations of substances and thus effects different immune responses.

Class II MHC molecules typically present peptides derived from extracellular (exogenous) antigen (eg, from many bacteria) to CD4 Th cells; in contrast, class I MHC molecules typically present peptides derived from intracellular (endogenous) antigens (eg, from viruses) to CD8 cytotoxic T cells. The activated cytotoxic T cell then kills the infected cell.

The immune response must be regulated to prevent overwhelming damage to the host (eg, anaphylaxis Anaphylaxis Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms... read more , cytokine storm Pathophysiology Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more , cytokine release syndrome, and widespread tissue destruction). Regulatory T cells (most of which express Foxp3 transcription factor) help control the immune response via secretion of immunosuppressive cytokines, such as IL-10 and transforming growth factor-beta (TGF-beta), or via cell contact dependent mechanisms.

These regulatory cells help prevent autoimmune responses and probably help resolve ongoing responses to nonself antigen.

The immune response resolves when antigen is sequestered or eliminated from the body. Without stimulation by antigen, cytokine secretion ceases, and activated cytotoxic T cells undergo apoptosis. Apoptosis tags a cell for immediate phagocytosis, which prevents spillage of the cellular contents and development of subsequent inflammation. T and B cells that have differentiated into memory cells are spared this fate.