Immune System in Health and Disease PDF

immune system in health and disease immunity - types and features innate (natural) macrophages, NK cells early, rapid but limited in strength non-specific adaptive (acquired) B and T lymphocytes takes time but pwoerful specific and has m...

immune system in health and disease immunity - types and features innate (natural) macrophages, NK cells early, rapid but limited in strength non-specific adaptive (acquired) B and T lymphocytes takes time but pwoerful specific and has memory memory in adaptive immunity first infection (slow response) -> pathogens proliferate, disease, symptoms memory -> 2nd infection (fast response) -> pathogen killed no disease no symptoms general principle but w exceptions (e.g HIV hiding inside T cells) principle of vaccination characteristics of secondary immune response subsequent contact w antigen short lag (1-4 days) and early peak (3-5 days) of antibody production lasts longer stronger (100-1000x more antibody produced) memory B cells similar for T cell response (from 1st infection) other characteristics only thymus (T) dependent antibodies (require T cell help) antibody production occurs mainly in bone marrow high antibody affinity - affinity maturation due to somatic hyper mutation of Ig variable region genes mainly IgG - antibody class switch v region actvated by enzume to change affinity selection for high affinity so antibodies produced have higher affinity  change in recombination in the formation of immunoglobulin middle part spliced to form IgM molecule VDJ genes joined w gamma genes -> IgG infectious organisms - pathogens bacteria prokaryotic  extracellular or intracellular fungi eukaryotic single-celled and multicellular yeasts, mold parasites host dependent worms and protozoa viruses replicate only in living cells, hence intracellular RNA and DNA viruses immune response to infections types of pathogens extracellular intracellular types of immune responses humoral responses (mediated by molecules) non specific complements histamine acute phase proteins specific (antibodies, B cell derived effector molecules) neutralization (viruses, toxins) opsonization, binds pathogens for recognition by other immune cells (phagocytes) promote complement mediated lysis nonspecific/specific perforins/granzyme cytokines/chemokines cell-mediated responses - T-independent, non specific (Early phase) - phagocytes - macrophages (MQ) - natural killer cells (NK)  - T dependent, specific - cytotoxic T cells, kill infected cells - helper T cells, help other cells T cells and main effector functions Tc -> kill infected cells (perforin, granzymes) Th (T-helper, CD4+) -> secrete cytokines central role in immune responses  CD4+ T cells (Th) in HIV infection interferons (broad class of cytokines, cytokines play role in interaction of inflammatory cells) T-dependent macrophage activation IFN gamma secreted by Th1 activates macrophage functions in intracellular way secretes IL-12 which reactivates Th1 => positive feedback loop result - macrophage activated and MHC expression of macrophage is increased, phagocytic function increased by increasing fusion between phagosome and lysosome NO synthetase, lysosomal oxidants???/ macrophages can become dormant? cytokine-mediated direct target cell killing TNF alpha/beta sig direct killing effect cytokines can kill cells directly phagocytes (macrophaes, granulocytes) non specific, innate part neutrophils circulate in blood, when person gets infected infection is not inside blood vessels neutrophils inside blood vessels has to move to site of infection chemotaxis - induce cells to move is specific direction complements attract phagocyte to approach bacteria effector mechanisms for phagocute mediated killing of microorganisms reactive oxygen intermediates (ROIs) - superoxide anion reactive nitrogen intermediates (RNIs) - nitric oxide other mediators (lysozyme, prostaglandins) cytokines: IL-1, IL-6, TNF, IFN-gamma chronic granulomatous disease inborn error of immune system  affect neutrophils and monocytes enzyme NADPH oxidase produces defective ROIs many peptides, all of which is responsible for CDG? X-linked is most severe (70% of cases) immunodeficiencies primary intrinsic most genetic linked e.g SCID - lack T, B cells types traditional T, B or both phagocyte, complement current immune dysregulation, hemophagocytic lymphohhistiocytosis (HLH) and EBV susceptibility symdromes w autoimmunity (IPEX) innate immunity defects (MSMD) autoinflammatory disorders (familial Mediterranean fever) associated w somatic mutations or auto antibodies (anti IFN gamma antibody) secondary extrinsic - acquired infections, e.g AIDS - HIV infects Th cells drugs irradiation malnutrition infections recurrent (pyogenic) infections  defects in immunoglobulins defects in complements defects in phagocytosis pathogens - encapsulated bacteria opportunistic infections defective CMI (defects in T cells) pathogens - common viruses, yeast (microorganisms that causes infectious disease only in indidviduals w compromised host defense mech) Pyrogenic toxins are related with fever and rash, while pyogenic toxins are related with pus filled lesions. scope of immunity immunity against infectious agents immunity against "non self" (allergy, transplantation immunity) immunity against "self" (autoimmunity, anti tumor immunity) tumor pathogenesis genetic mutations - inherited or acquired virus induced (HPVm cervical cancer, HBVm HCC) others - chemical carcinogens, radiation immunodeficiency (Kaposi's sarcoma, Burkitt's lymphoma) vaccines against viruses can prevent cancers tumor and antitumor immunity neonatal or old age > adults immune cells infiltrate in tumors spontaneous regression of tumors post-mortem: tumors > clinically diagnosed graft vs leukemia (GVL) responses -> tumor regression (immune cells of graft can attack lymphocytes) immune escape mechanisms of tumors tumour surveillance theory tumor cells sneak thru lack of moelcules important in immunity tumor derived factors suppress immunity immune checkpoint inhibitors T-cell) normally when tumor cells recognized by cytotoxic cells, PD1 can bind tyo ligand PDL1 on cancer cells, resulying inactivation of T cells blocking PDL1/PD1 allows for killing  APC prevention of binding, allows for killing immune system can cause diseases hypersensitivity. - state of heightened reactivity to innocuous antigens (allergens) anaphylactic response to bee venom autoimmunity - adaptive immune response directed against self antigens concepts of "self" and "non-self" health immune system is effective in generatiing immune respnses to pathogens ("nonself") does not attack, under normal conditions, bodys own cells and tissues "self" mechanisms of self tolerance central tolerance ("Thymic education") peripheral tolerance (failed-safe mechanisms)