Cells of the Immune System

Cells of the Immune System

• The immune system has two lines of defense: innate (non-specific) immunity, and adaptive (specific) immunity.
• All immune system cells originate from a single cell in the bone marrow.
• Hematopoietic stem cells in the bone marrow give rise to common lymphoid progenitors and common myeloid progenitors.

Common Lymphoid Progenitors

• These give rise to T lymphocytes which include T helper cells (Th), T cytotoxic cells (Tc), and T regulatory cells (T reg).
• B lymphocytes, develop from common lymphoid progenitors and produce plasma cells that create antibodies.
• Natural killer (NK) cells are also derived from common lymphoid progenitors.

Common Myeloid Progenitors

• These give rise to leukocytes: neutrophils, eosinophils, basophils, monocytes, mast cells, and dendritic cells.
• Erythrocytes and platelets are also derived from common myeloid progenitors.

Lymphoid Tissues and Organs

• Lymphoid tissues and organs are categorized as primary and secondary.
• Primary lymphoid organs are sites of lymphocyte maturation.
• Lymphocytes are released as naive (virgin) and mature cells into the blood.
• Primary lymphoid organs: bone marrow and thymus.
• Secondary lymphoid organs: lymph nodes, spleen, tonsils, and Peyer's patches.

Bone Marrow

• The bone marrow (BM) is the site of B cell maturation and the generation of all blood cells through hematopoiesis.

Thymus

• The thymus is the site of T cell maturation, serving as an education center where T cells learn to discriminate between self and non-self antigens.
• Selection processes occur in the thymus to select cells able to recognize self MHC or peptide + MHC molecules.
• Negative selection eliminates cells that recognize self peptides, preventing autoimmunity.
• Cells that pass both positive and negative selection graduate from the thymus and enter circulation as mature, naive T cells.

Secondary Lymphoid Organs

• Lymph nodes and the spleen are secondary lymphoid organs; tonsils and Peyer's patches act as secondary lymphoid aggregates.
• Lymphocytes that have not encountered an antigen reach the secondary lymphoid organs via blood and lymphatic vessels where they recognize antigens and initiate an immune response.

Lymphocytes

• Lymphocytes originate from stem cells in the bone marrow and develop into B cells or T cells.
• Lymphocytes are the only cells with specific receptors for antigens, making them mediators of adaptive immunity.
• Lymphocytes are distinguished by surface proteins called "CD" (cluster of differentiation) markers.

Types of lymphocytes:

• B lymphocytes: mediators of humoral immunity.
• T lymphocytes: mediators of cell-mediated immunity.
• Natural killer cells: cells of innate immunity.

B Lymphocytes

• B lymphocytes are bone marrow-derived lymphocytes.
• They develop and mature in the bone marrow.
• Stem cells mature into pre-B cells, then immature B cells, and finally mature/naive B cells, which leave the bone marrow to encounter antigens in secondary lymphoid tissues.
• B lymphocytes represent 10-15% of total blood lymphocytes.
• Phenotype markers include: surface immunoglobulins, CD19, CD21, class II MHC, and Fc receptors.
• Function: antibody (Ab) production (humoral immunity).
• B cells recognize a wide variety of antigens, including proteins, polysaccharides, and lipids, by antigen-specific B cell receptors (BCR).
• Stimulation by an antigen leads to proliferation and differentiation into plasma cells which secrete antibodies to eliminate the antigen, and memory B cells.

T Lymphocytes

• T lymphocytes are thymus-derived lymphocytes.
• They develop and mature in the thymus after the BM stem cells migrate there.
• T lymphocytes represent the majority of blood lymphocytes.
• Phenotype markers include TCR, CD3, CD4, and CD8.
• Function: cell-mediated immunity.
• Two subsets exist based on the presence of either CD4 or CD8 marker or another regulatory cell.

Helper T Cells (CD4+)

• Helper T cells assist other immune cells through the secretion of cytokines, which are helper factors.
• They aid B lymphocytes in producing antibodies.
• Help macrophage activation to destroy ingested microbes.
• Subsets: Th1 & Th2 according to cytokine profile.

Cytotoxic T Cells (CD8+)

• Cytotoxic T cells lyse target cells, including virus-infected cells and tumor cells.
• They are involved in the rejection of allografts.

T Regulatory Cells (T reg)

• T regulatory cells suppress the immune response.
• T lymphocytes recognize protein antigens only.
• T cells recognize antigens via antigen-specific receptors called TCRs.
• TCR: consisting of 2 polypeptide chains, called α and β.
• T lymphocytes recognize antigens in the form of peptide fragments of protein antigens (processed antigen) plus MHC molecules on the surface of antigen-presenting cells (APCs); this recognition is called MHC restriction.
• CD4+ cells recognize peptide + class II MHC molecules.
• CD8+ cells recognize peptide + class I MHC molecules.

Natural Killer (NK) Cells

• NK cells constitute a third population of lymphocytes.
• They are large lymphocytes containing numerous cytoplasmic granules.
• NK cells comprise about 10% of blood lymphocytes.
• NK cells do not express BCR or TCR.
• Phenotype markers: CD16, Fc receptor for IgG.
• NK cells detect abnormal host cells and target them for destruction.

NK Cell Receptors

• Killer activation receptors (KARs) recognize stress molecules on the surface of target cells. Binding of KAR to stress molecules generate a kill signal (+).
• Killer inhibitory receptors (KIRs) assess MHC I molecules on the target cell surface before killing; sufficient binding of KIRs to MHC I generates an inhibitory signal (-) that overrides the KAR kill signal, inhibiting cell killing.
• NK cells are activated by IL-12.

Functions of NK Cells

• Killing tumor cells.
• Killing virus-infected cells.
• Production of IFN-γ which activates macrophages.
• Antibody-dependent cellular cytotoxicity (ADCC).