Cells and Tissues 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 hematopoietic stem cell in the bone marrow.
• Hematopoietic stem cells give rise to a common lymphoid progenitor and a common myeloid progenitor.
• The common lymphoid progenitor gives rise to T lymphocytes, B lymphocytes, and natural killer (NK) cells.
• The common myeloid progenitor gives rise to leukocytes, erythrocytes, and platelets.
• Leukocytes include neutrophils, eosinophils, basophils, monocytes, mast cells, and dendritic cells.

Lymphoid Tissues and Organs

• Lymphoid tissues and organs are where lymphocytes develop and function.
• Primary lymphoid organs are the site of maturation of lymphocytes and include the bone marrow and thymus.
• Lymphocytes are released as naïve (virgin) and mature into the blood.
• Secondary lymphoid organs include the lymph nodes, spleen, tonsils, and Peyer's patches.
• Lymphocytes that have not previously encountered antigen (naive) reach the secondary lymphoid organs via blood and lymphatic vessels, where they recognize antigen and initiate the immune response.

Bone Marrow (BM)

• Bone marrow (BM) is the site of B cell maturation and generation of all blood cells from a common stem cell (hematopoiesis).

Thymus

• The thymus is the site of T cell maturation.
• T cells learn how to discriminate between self and non-self antigens undergo selection processes in the thymus.
• Positive selection ensures T cells can recognize and bind to self MHC or peptide + MHC molecules.
• Negative selection eliminates autoreactive T cells, which recognize self-peptides efficiently and could harm the host.
• T cells that pass both positive and negative selection tests "graduate" from the thymus and enter circulation as mature, naïve T cells.

Lymphocytes

• Lymphocytes arise from stem cells in the bone marrow and develop into B cells or T cells, depending on where they continue their maturation..
• Lymphocytes are the only cells with specific receptors for antigens and are the mediators of adaptive immunity.
• Lymphocytes can be distinguished by surface proteins called "CD" (cluster of differentiation) and a number (e.g., CD1, CD2, CD3, CD4, CD8, CD16).
• Lymphocytes include B lymphocytes (mediators of humoral immunity), T lymphocytes (mediators of cell-mediated immunity), and natural killer cells (cells of innate immunity).

B Lymphocytes

• B lymphocytes are bone marrow-derived lymphocytes that develop and mature in the bone marrow.
• B lymphocytes develop from stem cells to pre-B cells to immature B cells to mature and naive B cells, which leave the bone marrow to meet 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.
• B lymphocytes are for antibody (Ab) production (humoral immunity).
• B lymphocytes can recognize a wide variety of antigens (Ag), including proteins, polysaccharides, and lipids via Ag specific receptor called B cell receptor (BCR).
• B lymphocytes are stimulated by antigen to proliferate and differentiate into plasma cells, which secrete antibodies to eliminate Ag, and memory B cells.

T Lymphocytes

• T lymphocytes are thymus-derived lymphocytes that develop and mature in the thymus and represent the majority of blood lymphocytes.
• Phenotype markers include TCR, CD3, CD4, and CD8.
• T lymphocytes mediate cell-mediated immunity.
• Two subsets are present according to the presence of either CD4 or CD8 marker or another regulatory cell.
• Helper T cells (CD4+) are called helper cells because they help other cells through the secretion of helper factors, i.e., cytokines.
  • They help B lymphocytes to produce antibodies.
  • They help macrophage activation to destroy ingested microbes.
  • Subsets: Th1 & Th2 according to cytokine profile.
• Cytotoxic or cytolytic T cells (CD8+) are called cytolytic because they lyse target cells via killing virus-infected cells, killing tumor cells, and rejection of allografts.
• T regulatory cells (T reg) suppress the immune response.
• T lymphocytes recognize protein antigens only via antigen specific receptors, called TCR.
• TCR consists of 2 polypeptide chains are called α and β.
• T lymphocytes do not recognize antigens directly (unlike B lymphocytes).
• T lymphocytes only recognize antigens in the form of peptide fragments of protein antigens (peptide = processed antigen) plus MHC molecules on the surface of antigen presenting cells (APCs), which is called MHC restriction.
  • CD4+ cells recognize peptide + class II MHC molecules.
  • CD8+ cells recognize peptide + class I MHC molecules.

Natural Killer (NK) cells:

• Natural killer (NK) cells are a third population of lymphocytes.
• NK cells are large lymphocytes with numerous cytoplasmic granules and comprise about 10% of blood lymphocytes.
• NK cells do not express either BCR nor TCR
• Phenotype markers: CD16, Fc receptor for IgG.
• NK cells detect abnormal host cells and target them for destruction.
• NK cell receptors include:
  • Killer activation receptors (KARs) recognize stress molecules on the surface of the target cell (infected and transformed cells). Binding of KAR to stress molecules generates a kill signal (+).
  • Killer inhibitory receptors (KIRs) assess MHC I molecules on the target cell surface before killing. Sufficient binding of KIRs to MHC І generates an inhibitory signal (-) that overrides the KAR kill signal, inhibiting killing and allowing the cell to survive.
• NK cells are activated by IL-12 to perform these functions:
  • Killing tumor cells.
  • Killing virus-infected cells.
  • Produce IFN-γ, activating macrophages.
  • Antibody-dependent cellular cytotoxicity (ADCC).