The Immune System: Lymphoid and Myeloid Progenitors

• The immune system uses two lines of defense: innate (non-specific) and adaptive (specific) immunity
• Hematopoietic stem cells in bone marrow differentiate into different cell types

Lymphoid Progenitor

• This progenitor gives rise to T lymphocytes, B lymphocytes, and Natural Killer (NK) cells
• T lymphocytes include T helper cells (Th), T cytotoxic cells (Tc), and T regulatory cells (T reg)
• B lymphocytes differentiate into plasma cells that secrete antibodies
• Natural killer (NK) cells are also derived from this progenitor

Myeloid Progenitor

• This progenitor gives rise to Leukocytes, Erythrocytes and Platelets
• Leukocytes include Neutrophils, Eosinophils, Basophils, Monocytes, Mast cells and Dendritic cells

Lymphocyte Maturation and Release

• Lymphocytes mature in lymphoid organs and are released into the blood as naïve or mature cells

Primary Lymphoid Organs

• These organs include Bone Marrow (BM) and the Thymus
• The Bone Marrow is the site of B cell maturation and the generation of all blood cells from a common stem cell (hematopoiesis)
• The Thymus is the site of T cell maturation and T cell education, where T cells learn to discriminate between self and non-self antigens
• Selection Processes occur in the Thymus

T Cell Selection in the Thymus

• Positive Selection selects cells that can recognize and bind to self MHC or peptide + MHC molecules
• Negative Selection induces apoptosis in autoreactive cells that recognize and efficiently bind self peptides
• Cells that pass both positive and negative selection tests "graduate" and enter circulation as mature naïve T cells

Secondary Lymphoid Organs

• Include lymph nodes, spleen, tonsils, and Peyer's patches
• Lymphocytes reach secondary lymphoid organs via blood and lymphatic vessels, recognize antigens, and initiate immune responses

Lymphocyte Origin and Characteristics

• Lymphocytes originate from stem cells in bone marrow and differentiate into B or T cells
• Lymphocytes have specific receptors for antigens and mediate adaptive immunity
• Lymphocytes are distinguished by surface proteins called "CD" (cluster of differentiation), such as CD1, CD2, CD3, CD4, CD8, CD16

Role of Lymphocytes

• B lymphocytes mediate humoral immunity
• T lymphocytes mediate cell-mediated immunity
• Natural killer cells function in innate immunity

B Lymphocytes

• B lymphocytes originate from bone marrow
• They develop and mature in the bone marrow
• They leave the bone marrow to encounter antigens in secondary lymphoid tissues
• They constitute 10-15% of total blood lymphocytes
• Phenotype markers include surface immunoglobulins, CD19, CD21, Class II MHC, Fc receptors
• B cells are responsible for antibody (Ab) production (humoral immunity)
• Recognize antigens via B cell receptor (BCR)
• Antigen stimulation leads to proliferation and differentiation into plasma cells, which secrete antibodies to eliminate antigens and memory B cells

T Lymphocytes

• T lymphocytes originate from the thymus
• The cells develop and mature in the thymus
• They represent the majority of blood lymphocytes
• Phenotype markers include TCR, CD3, CD4, CD8
• Function in cell-mediated immunity
• Two subsets exist according to the presence of CD4 or CD8 markers or T regulatory cell phenotypes

Helper T Cells (CD4+)

• Release helper factors, or cytokines
• Help B lymphocytes produce antibodies
• Help macrophage activation to destroy ingested microbes
• Subsets Th1 & Th2 exist according to cytokine profile

Cytotoxic or Cytolytic T Cells (CD8+)

• Lyse target cells
• Kill virus-infected cells and tumor cells
• Responsible for rejection of allografts

T Regulatory cells (Treg)

• Suppress the immune response

T Lymphocyte Antigen Recognition

• T lymphocytes recognize protein antigens only via a receptor called TCR
• TCR consists of 2 polypeptide chains, α and β
• T lymphocytes recognize antigen only as peptide fragments presented by MHC molecules on antigen-presenting cells (APCs)
• CD4+ cells recognize peptide + class II MHC molecules
• CD8+ cells recognize peptide + class I MHC molecules

Natural Killer (NK) Cells

• Represent a third lymphocyte population
• Large lymphocytes with cytoplasmic granules
• Comprise about 10% of blood lymphocytes
• Do not express BCR nor TCR
• Phenotype markers include CD16, Fc receptor for IgG
• NK cells detect abnormal host cells
• Targeting these cells for destruction

NK Cell Receptors

• Killer Activation Receptors (KARs), recognize stress molecules on target cells, generating a kill signal (+)
• Killer Inhibitory Receptors (KIRs), assess MHC I molecules on the target cell surface before killing, generating an inhibitory signal (-)

NK Cell Function

• Activated by IL-12
• Killing tumor cells and virus-infected cells
• Produce IFN-γ to activate macrophages
• Mediate antibody-dependent cellular cytotoxicity (ADCC)