Innate and Adaptive Immunity

Innate and Adaptive Immunity

• The immune system has two lines of defense: innate (non-specific) and adaptive (specific) immunity.

Immune System Cells

• All immune system cells originate from a single cell in bone marrow (BM) which is a stem cell.
• Hematopoietic stem cells in the bone marrow are the origin of a common lymphoid progenitor.
• A common lymphoid progenitor produces: T lymphocytes, B lymphocytes, and Natural killer (NK) cells.
• A common myeloid progenitor produces: Leukocytes, Erythrocytes, and Platelets.
• Leukocytes include: neutrophils, eosinophils, basophils, monocytes, mast cells, and dendritic cells.

Lymphoid Tissues and Organs

• Lymphoid organs can be divided into primary and secondary organs.
• Primary lymphoid organs are the site of maturation of lymphocytes.
• Lymphocytes are released as naïve (virgin) and mature into the blood.
• Primary lymphoid organs include the bone marrow & thymus.

Bone Marrow (BM)

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

Thymus

• Thymus is the site of T cell maturation.
• The thymus is where T cells learn how to discriminate between self and non-self-antigens.
• Selection processes occur in the thymus.
• Positive Selection in the thymus: cells that recognize and bind to self MHC, or to peptide + MHC molecules, are selected to grow. Negative Selection: cells that recognize and efficiently bind self-peptides are autoreactive cells and undergo apoptotic cell death.
• Cells that pass both positive and negative selection tests "graduate" from the thymus.
• These cells enter circulation as mature naïve T cells.

Secondary Lymphoid Organs

• Include the lymph nodes and the spleen.
• The tonsils and Peyer's patches also act as secondary lymphoid aggregates.
• Lymphocytes that have not previously encountered antigen (naive) reach the secondary lymphoid organs via blood and lymphatic vessels.
• Lymphocytes recognize antigens and initiate an immune response in secondary lymphoid organs.

Lymphocytes

• Lymphocytes arise from stem cells in the bone marrow & they later 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, T lymphocytes, and Natural killer cells.
• B lymphocytes are mediators of humoral immunity.
• T lymphocytes are mediators of cell-mediated immunity.
• Natural killer cells are cells of innate immunity.

B Lymphocytes

• B lymphocytes refers to bone marrow-derived lymphocytes.
• B lymphocytes develop and mature in the bone marrow.
• Stem cell differentiates into pre-B cell, which differentiates into immature B cell, and then mature & naïve B cells Mature & naïve B cells leave the bone marrow to encounter antigen in the secondary lymphoid tissues.
• B lymphocytes constitute 10-15% of total blood lymphocytes.
• Phenotype markers: Surface immunoglobulins, CD19, CD21, class II MHC, and Fc receptors.
• B lymphocytes produce Ab (humoral immunity).
• B lymphocytes recognize a wide variety of Ag, including proteins, polysaccharides, and lipids.
• B lymphocytes recognize Ag by an Ag-specific receptor called a B cell receptor (BCR).
• B lymphocytes are stimulated by antigen to proliferate and differentiate into plasma cells, which secrete antibodies to eliminate Ag and form memory B cells.

T Lymphocytes

• T lymphocytes refers to Thymus-derived lymphocytes.
• T lymphocytes develop and mature in the thymus, the BM stem cells migrate to it and mature there.
• T lymphocytes represent the majority of blood lymphocytes.
• Phenotype markers on T lymphocytes: TCR, CD3, CD4, CD8
• T lymphocytes mediate cell-mediated immunity. Two subsets of T cells exist due to the presence of either CD4 or CD8 cell markers -or another regulatory cell.
• Helper T cells (CD4+): act as helpers to other cells by secreting Helper factors i.e. cytokines.
• CD4+ cells help B lymphocytes to produce antibodies.
• CD4+ cells help macrophage activation to destroy ingested microbes.
• Subsets of CD4+ include Th1 & Th2 according to cytokine profile.
• Cytotoxic or cytolytic T cells (CD8+): are called cytolytic because they lyse target cells.
• CD8+ cells kill virus-infected cells.
• CD8+ cells kill tumor cells.
• CD8+ cells cause rejection of allografts.
• T regulatory cells (T reg): suppress the immune response.
• T lymphocytes recognize protein antigens only.
• T lymphocytes recognize antigens using antigen-specific receptors called TCRs.
• TCR consists of 2 polypeptide chains called α and β.
• T lymphocytes recognize antigen only in the form of peptide fragments of protein antigens (peptide = 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

• Natural killer (NK) cells are a third population of lymphocytes.
• Natural killer (NK) cells are large lymphocytes with numerous cytoplasmic granules.
• Natural killer (NK) cells comprise about 10% of blood lymphocytes.
• Natural killer (NK) cells do not express BCR nor TCR.
• Phenotype markers for Natural killer (NK) cells: CD16, Fc receptor for IgG.
• NK cell responses: 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 cell (infected and transformed cells).
• Binding of KAR to stress molecules generates a kill signal (+).
• NK cell receptors: Killer inhibitory receptors (KIRs) assess MHC I molecules on the target cell surface before killing.
• Sufficient binding of KIRs to MHC І, generate an inhibitory signal (-) that overrides the KAR kill signal, and the killing will be inhibited to allow the cell to survive.
• Functions of Natural killer (NK) cells: Activated by IL-12
• Natural killer (NK) cells target and kill tumor cells.
• Natural killer (NK) cells target and kill virus-infected cells.
• Natural killer (NK) cells produce IFN-γ which activates macrophages.
• Natural killer (NK) cells are involved in antibody-dependent cellular cytotoxicity (ADCC)