Immune cells play critical roles in the defense of the body against infectious agents and the development and spread of cancer. The immune system involves two primary lines of defense against non-self pathogens. The innate immune system is the first line of defense that quickly responds in a broad way. This involves natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, and eosinophils. The adaptive immune system takes over if needed and specifically targets and remembers the pathogen to provide long-lasting immunity. The adaptive immune system includes T lymphocytes (T cells), B lymphocytes (B cells), and antibodies.

Tissues and Organs Involved

Many cells work together as part of the innate and adaptive immune system.

One of the primary components of the immune system is the bone marrow, which produces both T and B lymphocytes. While B cells will remain in the bone marrow to mature, T cells continue to another organ, the thymus.

The thymus is a specialized primary lymphoid organ where T cells develop and mature, including the acquisition of antigen receptors such as CD4 and CD8, and differentiate into helper T cells and cytotoxic T cells.

Mature T and B lymphocytes move to other tissues and organs of the immune system, the lymph nodes and spleen, in preparation for activation. The spleen filters the blood, where macrophages engulf and digest cellular debris, pathogens, and other foreign substances, and aids the immune system by identifying pathogenic microorganisms.

Immune Cell Types

Immune cells are derived from blood stem cells through two lineages: myeloid stem cells and lymphoid stem cells.

Myeloid Lineage Cells

  • Granulocytes are leukocytes of the innate immune system that have enzyme containing granules in their cytoplasm.
    • Neutrophils are the most abundant innate immune cells. As first responders, they ingest harmful foreign particles, bacteria, and dead or dying cells in the blood, and also modulate inflammation by various mechanisms.
    • Eosinophils help in killing parasites, tumor cells, and immune system regulation.
    • Basophils travel to the site of infection and release histamines when damaged, which contributes to the inflammatory response, and prostaglandins that help increase blood flow to the infection site.
Immunophenotyping- Myeloid cell maturation

Lymphoid Lineage Cells

  • T cells have several roles and are divided into CD8+ T cells or CD4+ T cells depending on which cluster of differentiation (CD) protein is present on the cell surface.
    • CD8+ T cells (cytotoxic T cells, cytotoxic lymphocytes, or CTLs) recognize and eliminate virus-infected cells and cancer cells.
    • CD4+ T cells are divided into subsets:
      • T-helper (TH)1 cells coordinate immune responses against intracellular microbes.
      • TH2 cells coordinate immune responses against extracellular pathogens such as parasites by alerting B cells, granulocytes, and mast cells.
      • TH17 cells produce interleukin 17 (IL-17) that activates immune and nonimmune cells, and they recruit neutrophils.
      • Tregs (regulatory T cells) monitor and inhibit the activity of other T cells.
    • Killer T cells (cytotoxic T cells) are the primary effector cells of adaptive immunity. They can attach to and kill cancer cells.
  • B cells make antibodies and can also internalize antigens and present them to T cells. Memory B cells are long lived and remember previous exposure to antigens. Plasma B cells are activated B cells, each making one specific antibody in significant quantity.
  • Natural killer (NK) cells are cytotoxic lymphocytes that are critical to the innate immune system. They respond rapidly to infection by viruses and other intracellular pathogens, and tumor formation without the need for antibodies and major histocompatibility complex (MHC).
  • Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer cells.
Immunophenotyping- Lymphoid cell maturation

Monocytes

Monocytes are produced in the bone marrow and move into tissues throughout the body to differentiate into macrophages and dendritic cells.

Macrophages

Macrophages engulf and digest pathogens by phagocytosis. The macrophages identify the pathogens, which can include cancer cells, microbes, cellular debris, and foreign substances by the presence of nonself surface proteins that distinguish the pathogen from healthy body cells. Macrophages play a critical role in innate immunity and also help initiate specific defense mechanisms (adaptive immunity) by
recruiting other immune cells such as lymphocytes. They can increase inflammation but also have an anti-inflammatory role through the release of cytokines.

Dendritic Cells

Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that form an interface between innate and adaptive immunity. Once activated, DCs migrate to the lymph nodes and interact with T cells and B cells to initiate and shape the adaptive immune response.

DCs present endogenous and exogenous antigens to T cells in the context of MHC molecules, resulting in antigen tolerance or priming and triggering of an effector T cell response. DCs also help maintain the immune memory of B cells, including the production of cytokines and oth