The body has three levels of defense against infection. The anatomical and physiological barriers include: · intact skin provides a physical barrier, · mucosal surfaces of the gut, respiratory urogenital and conjunctivae surfaces, · stomach acid, lysozyme and other antimicrobial body secretions. The innate immune responses are the initial internal defenses. These responses are: · quick and non-specific, · involves phagocytosis and activation of the complement proteins, · limits the spread of infection, · often resolves the infection. The adaptive immune responses are the last line of defense. These responses are: · slower to respond but specific to the particular pathogen, · involve antibody-mediated responses and cell-mediated responses. Types of white blood cells (leukocytes) . Monocytes. They have a longer lifespan than many white blood cells and help to break down bacteria. · Lymphocytes. They create antibodies to fight against bacteria, viruses, and other potentially harmful invaders. . Neutrophils. They kill and digest bacteria and fungi. They are the most numerous type of white blood cell and your first line of defense when infection strikes. . Basophils. These small cells seem to sound an alarm when infectious agents invade your blood. They secrete chemicals such as histamine, a marker of allergic disease, that help control the body's immune response. · Eosinophils. They attack and kill parasites and cancer cells, and help with allergic responses.
HSC Myeloid progenitor cell Lymphoid progenitor cell Monocyte Basophil Neutrophil Eosinophil T cell B cell NK cell Dendritic cell Macrophage ? CD8* cytotoxic T cell CD4+ helper T cell Memory B cell Plasma cell CD4 is found on T helper cells whereas CD8 is found on cytotoxic T cells. CD4 and CD8 bind to the MHC proteins on the antigen-presenting cell, but not at the site involved in peptide binding. APC MHC class I/II Antigenic peptide Co-receptor TCR B 2- 8 5 T cell P (P) P P LCK ITAM- P P CD3 T cell positive selection: During positive selection, only thymocytes that have a TCR capable of weakly binding to MHC proteins of thymic cortical epithelial cells (displaying self-peptides) are permitted to mature. Positive selection ensures that the T cells can interact with the MHC proteins. Thymocytes that have a TCR that cannot bind to MHC proteins (displaying self-peptides) are not provided with survival
signals and die of neglect. T cell negative selection: . The first round of negative selection is done by the thymic cortical epithelial cells - this occurs simultaneously during positive selection. . The next round of negative selection is mediated by bone marrow derived macrophages and dendritic cells. In both the first two rounds of negative selection, the peptides would be derived from "house-keeping" genes; that is, genes that are expressed in many cell types. . This final round of negative selection is by thymic medullary epithelial cells. (AIRE) Only thymocytes that have TCRs that bind to MHC (displaying self-peptides) with weak affinity are permitted to mature into functional T cells and leave the thymus and migrate to the peripheral lymphoid