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Overview of the Immune System


Peter J. Delves

, PhD, University College London, London, UK

Reviewed/Revised Feb 2024

The immune system distinguishes self from nonself and eliminates potentially harmful nonself molecules and cells from the body. The immune system also has the capacity to recognize and destroy abnormal cells that derive from host tissues. Any molecule capable of being recognized by the immune system is considered an antigen (Ag).

The skin, corneas, and mucosa of the respiratory, gastrointestinal, and genitourinary tracts form a physical barrier that is the body's first line of defense. Some of these barriers also have active immune functions:

  • Outer, keratinized epidermis: Keratinocytes in the skin secrete antimicrobial peptides (defensins), and sebaceous and sweat glands secrete microbe-inhibiting substances (eg, lactic acid, fatty acids). Also, many immune cells (eg, mast cells, intraepithelial lymphocytes, antigen-sampling Langerhans cells) reside in the skin.

  • Corneas: Tears contain defensins. Macrophages and dendritic cells reside in the corneas and other immune cells, including T cells and phagocytic neutrophils, are recruited through the limbal vasculature during infection.

  • Mucosa of the respiratory, gastrointestinal, and genitourinary tracts: The mucus contains antimicrobial substances, such as lysozyme, lactoferrin, and secretory immunoglobulin (Ig) A antibody (SIgA).

Breaching of anatomic barriers can trigger 2 types of immune response:

  • Innate

  • Acquired

Innate immunity

Innate (natural) immunity does not require prior exposure to an antigen (ie, immunologic memory) to be fully effective. Thus, it can respond immediately to an invader. Innate immunity uses pattern recognition receptors (PRRs) to detect foreign pathogen-associated molecular patterns (PAMPs) and host damage-associated molecular patterns (DAMPs).

Components include

  • Phagocytic cells (eg, neutrophils, monocytes, macrophages)

  • Polymorphonuclear leukocytes (in addition to phagocytic neutrophils, including eosinophils and basophils)

  • Innate lymphoid cells (eg, natural killer [NK] cells)

Phagocytic cells (neutrophils Neutrophils The immune system consists of cellular components and molecular components that work together to destroy antigens. (See also Overview of the Immune System.) Although some antigens (Ags) can... read more in blood and tissues, monocytes Antigen-Presenting Cells in blood, macrophages Antigen-Presenting Cells in tissues) ingest and destroy invading antigens. Attack by phagocytic cells can be facilitated when antigens are coated with antibody (Ab), which is produced as part of acquired immunity, or when complement proteins opsonize antigens.

Acquired immunity

Acquired (adaptive) immunity requires prior exposure to an antigen to be fully effective and takes time to develop after the initial encounter with a new invader. Thereafter, response is quick. The system remembers past exposures and is antigen-specific.

Components include

  • B cells

  • T cells

Acquired immunity includes

B cells and T cells reach maturity within the primary lymphoid tissues. B cells mature in the bone marrow, and T cells mature in the thymus. Mature B cells and T cells subsequently work together to destroy invaders. Tissue-based antigen-presenting cells Antigen-Presenting Cells The immune system consists of cellular components and molecular components that work together to destroy antigens. (See also Overview of the Immune System.) Although some antigens (Ags) can... read more are needed to present antigens to most types of T cell.

Immune Response

Successful immune defense requires activation, regulation, and resolution of the immune response.


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 specific for

  • Structures (PAMPs) that are associated with a number of different pathogens (eg, recognition by PRRs such as Toll-like, mannose, and scavenger receptors on dendritic and other cells)

  • Structures that are specifically associated with particular pathogens (recognition by transmembrane antibodies expressed on B cells or by T-cell receptors expressed on T cells)

PRRs recognize common microbial PAMPs 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 (DAMPs) that are produced by stressed or infected human cells.

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 phagocytosed. 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 cells and T cells. This response begins in the secondary lymphoid tissues:

  • The spleen for circulating antigen

  • Regional lymph nodes for tissue antigen

  • Mucosa-associated lymphoid tissues (eg, tonsils, adenoids, Peyer patches) for mucosal antigen

For example, Langerhans dendritic cells in the skin phagocytose antigen and migrate to local lymph nodes. In the lymph nodes, 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 medications), 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.

Some of the Th cells become specialized as T follicular helper (Tfh) cells, which migrate into B cell areas of the secondary lymphoid tissues. During an active immune response, structures called germinal centers develop within secondary lymphoid tissues where the Tfh cells assist in B-cell activation, proliferation, antibody class switching, affinity maturation of the antibody response, and B-cell differentiation in memory B cells B cells The immune system consists of cellular components and molecular components that work together to destroy antigens. (See also Overview of the Immune System.) Although some antigens (Ags) can... read more and into the precursors of the antibody-secreting plasma cells. Also within the germinal centers are follicular dendritic cells (an entirely different cell type to conventional dendritic cells), which present intact antigen (in antigen-antibody complexes) to the B cell.

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.


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 cells and B cells that have differentiated into memory cells are spared this fate.

Geriatrics Essentials: Immune System

With aging, the immune system becomes less effective in the following ways:

NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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