Introduction to the immune system

The immune system safeguards us from harmful organisms, toxins, and tumor cells. It comprises organs, tissues, cells, and molecules that collaborate to produce an immune response. This response can identify a threat, attack it, eliminate the pathogen, and remember it for future encounters. There are two main branches: the innate immune response and the adaptive immune response. The innate response is non-specific, fast-acting (minutes to hours), and has no memory. It includes physical and chemical barriers like skin, cilia, tears, and stomach acid. The adaptive response is highly specific, diverse, and develops immunologic memory, but it takes longer to activate (weeks).

White blood cells, or leukocytes, are the immune system's soldiers. Hematopoiesis, primarily in the bone marrow, produces these cells from multipotent hematopoietic stem cells. These differentiate into myeloid progenitor cells (forming neutrophils, eosinophils, basophils, mast cells, dendritic cells, macrophages, and monocytes) and lymphoid progenitor cells (forming B cells, T cells, and natural killer cells).

Myeloid cells are part of the innate immune response. Neutrophils, eosinophils, and basophils are granulocytes. Neutrophils phagocytose pathogens, destroying them with cytoplasmic granules and oxidative bursts. Eosinophils combat large parasites and are involved in allergic reactions, degranulating to release pro-inflammatory molecules. Basophils are non-phagocytic and, like mast cells (which reside in tissues), initiate allergic responses by releasing histamine and other pro-inflammatory molecules. Monocytes, macrophages, and dendritic cells are phagocytic, gobbling up pathogens, presenting antigens, and releasing cytokines.

Monocytes circulate in the blood and differentiate into macrophages in tissues. Dendritic cells, often found in areas exposed to external antigens (like skin and gut), are key antigen-presenting cells. Immature dendritic cells are excellent at phagocytosis. Upon encountering a pathogen, they digest it, break its proteins into antigens, and then migrate to lymph nodes. Here, they present these antigens on MHC molecules to T-cells, thus bridging the innate and adaptive immune systems. Macrophages and monocytes also act as antigen-presenting cells.

Lymphocytes include B cells, T cells (adaptive immunity), and natural killer cells (innate immunity). B cells develop in the bone marrow, T cells in the thymus, and natural killer cells in the bone marrow. Natural killer cells target virus-infected and cancer cells by releasing cytotoxic granules that induce apoptosis. B cells have surface receptors for specific antigens and can internalize, degrade, and present antigens to T-cells via MHC II. Activated B cells mature into plasma cells, which secrete large quantities of antibodies that tag pathogens for destruction, a process called humoral immunity.

T-cells are responsible for cell-mediated immunity and are antigen-specific but cannot secrete their receptors. Naive T-cells are activated by antigen-presenting cells, typically dendritic cells. There are two main types: CD4+ T-cells (helper cells) and CD8+ T-cells (cytotoxic T-cells). Helper T-cells, presenting antigens on MHC II, secrete cytokines that coordinate macrophages and B cells. Cytotoxic T-cells kill target cells (like virally infected cells) that present specific antigens on MHC I molecules.

When bacteria enter the lungs, resident macrophages ingest them and release cytokines, initiating inflammation by making blood vessels leaky and attracting other innate immune cells like eosinophils, basophils, and neutrophils. If it were a virus, natural killer cells would also act. Immature dendritic cells then digest pathogens, move to lymph nodes, and present antigens on MHC II to naive T-cells. B-cells can also directly phagocytose bacteria and present antigens to CD4+ T-cells. Activated CD4+ T-cells release cytokines, inducing B-cells to become plasma cells that secrete antibodies, and activating macrophages to kill resistant bacteria. If it was a viral infection, CD8+ T-cells would kill infected cells presenting viral antigens on MHC I. After the pathogen is eliminated, most B and T cells die, but some become memory cells, ensuring a faster, stronger response to future infections.