Innate Immunity Lecture Notes PDF

Innate Immunity: The Early Defense Against Infections How does the innate immune system recognize microbes and damaged cells? How do the different components of innate immunity function to combat different types of microbes? How do innate immune reactions stimulate adaptive immune respons...

Innate Immunity: The Early Defense Against Infections How does the innate immune system recognize microbes and damaged cells? How do the different components of innate immunity function to combat different types of microbes? How do innate immune reactions stimulate adaptive immune responses? Blood  Blood Blood is the fluid contained within the heart, arteries, capillaries and veins of the circulatory system. It delivers oxygen and nutrients to organs and tissues and carries carbon dioxide and metabolic ‘waste’ products to excretory organs such as the kidneys, liver and lungs. Blood consists of several components: Plasma Cells (red cells, white cells, platelets) Electrolytes (e.g., Na + , K + , Ca ++ ) Proteins (including hormones and immunoglobulins) Lipids Glucose The cellular components of blood are synthesized in the bone marrow in a process called ‘haematopoiesis’.  Haematopoiesis Haematopoiesis is the formation and development of blood cells. The haematopoietic system is composed of the bone marrow, spleen, liver, lymph nodes and thymus. Haematopoiesis is the formation and development of blood cells. The haematopoietic system is composed of the bone marrow, spleen, liver, lymph nodes and thymus. Pluripotent haemopoietic stem cells All blood cells originally derive from a population of pluripotent, CD34 + haemopoietic stem cells, residing in haematopoietic tissues. Remain as pluripotent stem cells, dividing to form identical daughter cells, maintaining the haemopoietic population Differentiate into specific progenitor cells, which ultimately develop into specific cellular components of blood. Myeloid lineage multipotent progenitor cell Red cell progenitor (BFU-E) Platelet progenitor (CFU-Meg) Eosinophil progenitor (CFU-Eos) Basophil progenitor (CFU-Baso) Neutrophil/monocyte progenitor (CFU-GM)  Myeloid lineage multipotent progenitor cell Red blood cells Red blood cells (‘erythrocytes’) are derived from the erythroid blast-forming unit (BFU-E) progenitor cell. Red cells lack a nucleus and have a biconcave discoid shape. They contain haemoglobin and their primary role is the transportation of oxygen (from lung to tissue) and carbon dioxide (from tissue to lung).  Myeloid lineage multipotent progenitor cell Platelets Platelets (thrombocytes) are derived from megakaryocytes, which derive from the colony- forming unit megakaryocyte (CFU-Meg) progenitor cell. Like red cells, platelets lack nuclei. They play an important role in haemostasis.  Myeloid lineage multipotent progenitor cell Basophils Basophils have bilobed nuclei and granular cytoplasm. Basophils represent ≤ 1% of the bloodstream’s white cell population. They contribute strongly to innate and adaptive immunity.  Myeloid lineage multipotent progenitor cell Eosinophils Eosinophils have bilobed nuclei and granular cytoplasm. Eosinophils represent 1 – 6% of the bloodstream’s white cell population. Eosinophils migrate into areas of inflammation or infection and release specific cytotoxic and messenger molecules. They are also important in both innate and adaptive immunity and allergic responses  Myeloid lineage multipotent progenitor cell Neutrophils Neutrophils have multilobed nuclei comprise ≈ 60% of the bloodstream white cell population. Neutrophils are an essential component of the innate immune system, due to their ability to phagocytose (engulf) microorganisms and kill them by releasing cytotoxic molecules from their granules. Neutrophils therefore represent a key component of the first-line defence against bacterial infections.  Myeloid lineage multipotent progenitor cell Monocytes/macrophages Monocytes and macrophages account for ~ 2%– 10% of the white cell population. They circulate for 1–3 days, then leave the circulation and enter the tissues, where they differentiate further, developing into macrophages. They phagocytose cellular debris and pathogens and produce various cytokines  Lymphoid lineage multipotent progenitor cell Pre-B cell (B cell precursor) Pre-T cell (T cell precursor) NK cell precursor These cells are all derived from the lymphoid lineage.  Lymphoid lineage multipotent progenitor cell Pre-B cell (B cell precursor) Pre-T cell (T cell precursor) NK cell precursor These cells are all derived from the lymphoid lineage. Lymphocytes These white blood cells are small and have a relatively large, round nucleus relative to their nongranular, basophilic cytoplasm volume. They all originate from the lymphoid lineage.  Lymphoid lineage multipotent progenitor cell B lymphocytes These cells are small lymphocytes (diameter 6–9 μm) expressing the B cell receptor. They secrete immunoglobulins (antibodies). A large proportion of B lymphocytes reside in lymph node germinal centres, where they are known as memory B cells. Some B lymphocytes also mature further into plasma cells.  Lymphoid lineage multipotent progenitor cell T lymphocytes These cells are small lymphocytes (diameter 6–9 μm) expressing the T cell receptor. T cells are subclassified by type of surface glycoproteins they express, indicated by the CD prefix. Cytotoxic T cells (CD8 + ve) mediate destruction of cells infected by intracellular organisms, while T helper cells (CD4 + ve) release cytokines to regulate and assist in the adaptive immune response.  Lymphoid lineage multipotent progenitor cell Natural killer cells These large granular lymphocytes are also cytotoxic lymphocytes, like T cells, but natural killer (NK) cells are larger. Their behaviour differs from that of T cells in that they do not require major histocompatibility complex (MHC) or antibody- bound antigen complexes to recognize and destroy foreign or infected cells. They are prominent in the innate immune response. Haematopoiesis