22-1 Hemocytoblast Myeloid stem cell Lymphoid stem cell Myeloblast Myeloblast Monoblast Myeloblast Lymphoblast Stem cells Committed cells Promyelocyte Promyelocyte Promyelocyte Promonocyte Prolymphocyte Eosinophilic myelocyte Neutrophilic myelocyte Basophilic myelocyte Eosinophilic band cells Neutrophilic band cells Basophilic band cells Developmental pathway Eosinophils Neutrophils Basophils Granular leukocytes (a) (b) (c) (d) (e) Monocytes Lymphocytes Agranular leukocytes Some become Some become Immunity dendritic cells mast cells:Innate Immunity (non-specific) --Decrease speed of or inhibits invasion • 1st line of defense; – Physical barriers: prevent entry or remove particles. Skin, tears, saliva, mucous membranes, mucus. • 2nd line of defense; – Chemical mediators: promote phagocytosis and inflammation **Responses you are born with Adaptive immunity (specific) • last line of defense; – Specificity of a particle – Slower to react than innate system **Responses you develop throughout lifeInnate Immunity: protective barriers • Protective chemicals inhibit or destroy microorganisms – Skin acidity – Lipids in sebum and dermcidin in sweat – HCl and protein-digesting enzymes of stomach mucosae – Lysozyme of saliva, tears, mucus, breast milk • Respiratory system modifications – Mucus-coated hairs in the nose – Cilia of respiratory tract sweep dust- and bacteria-laden mucus from respiratory passages• Phagocytes • Inflammatory responses • Antimicrobial proteins (complement proteins) • Pyrogens (Fever) Innate Immunity: chemical mediatorsPhagocytes: •Macrophages • develop from monocytes to become the chief phagocytic cells • Free macrophages wander through tissue spaces E.g., alveolar macrophages aka dust cells • Fixed macrophages are permanent residents of some organs E.g., Kupffer cells (liver) and microglia (brain) •Neutrophils – Fist on site, short lived (~hrs) •Dendritic cells – not WBC Innate Immunity: chemical mediatorsInflammatory Response • Basophils and mast cells – Promote inflammation when activated by innate or adaptive system. – Basophils are motile, leave blood and enter infected tissues – Mast cells are non-motile; in C.T. **Eosinophils: – leave blood and enter tissues – Reduce inflammation by breaking down chemicals produced by basophils and mast cells. – Secrete enzymes that kill some parasites. Innate Immunity: chemical mediatorsInflammatory Response contd • Triggered with tissue injury or infection • Prevents the spread of damaging agents • Disposes of cell debris and pathogens • Sets the stage for repair • Cardinal signs of local inflammation – Redness, Heat, Swelling, Pain, and sometimes loss of function Innate Immunity: chemical mediatorsInflammatory Response contd • Systemic inflammatory Response *same as acute/local + – Increase in neutrophil numbers – Fever dt pyrogens – Widespread increased vascular permeability dt histamines. Large volume of plasma enters interstitial spaces leading to hypovolemic shock Innate Immunity: chemical mediatorsInflammatory chemicals cause – Dilation of arterioles, resulting in hyperemia – Increased permeability of local capillaries and edema (leakage of exudate) Exudate • Brings in large quantities of oxygen and nutrients needed for repair • Allows entry of clotting proteins (to minimize spread of infection) • Moves foreign material into lymphatic vessels Innate Immunity: chemical mediatorsInnate defenses Internal defenses Leukocytosis. Neutrophils enter blood from bone marrow. Margination. Neutrophils cling to capillary wall. Diapedesis. Neutrophils squeeze out of capillaries Chemotaxis. Neutrophils follow chemical trail. Capillary wall Basement membrane Endothelium Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents. 1 2 3 4Complement proteins • ~20 blood proteins in circulation in inactive form • Major mechanism for destroying foreign substances • Kills bacteria by cell lysis • Utilizes both innate and adaptive immunity Innate Immunity Antimicrobial ProteinsComplement proteins • Alternative pathway: part of innate immunity. Attract macrophages. • Classical pathway: part of adaptive immunity. Requires antibodies bound to antigens. • Activated complement proteins – Form membrane attack complexes (MAC) = holes in plasma membrane – Attach to surface of bacterial cells, stimulate phagocytosis – Attract immune system cells to site of infection and promote inflammation Innate Immunity Antimicrobial Proteins22-13 Pyrogens • Systemic response to invading microorganisms • Secreted by WBCs and macrophages exposed to foreign substances • Benefits of moderate fever – Causes the liver and spleen to sequester iron and zinc (needed by microorganisms) – Increases metabolic rate, which speeds up repair – Increases efficiency of immune systems • High fevers are dangerous because heat denatures enzymes • E.g., cytokines (IL 1)Adaptive Immunity • Specific, systemic, and has memory • Activates inflammatory response • Two separate overlapping types – Humoral (Antibody-mediated): B cells – Cellular (Cell-mediated): T cells • Stimulated by – Antigens: usu large/complex foreign molecules that stimulates adaptive defenses • Foreign: Microbes, Pollen, animal dander, feces of mites, foods, drugs, etc. • Self-antigens: produced by body as markers to identify self. Reaction to self-antigens can cause auto immune diseases – Haptens: non-immunogenic, but when combined to something, exacerbates an antigenic responseSelf-antigens (cell surface proteins) e.g., MHC Antigenic to others in transfusions or grafts • Classes of MHC proteins – Class I MHC proteins, found on virtually all body cells – Class II MHC proteins, found on certain cells in the immune response (ie, antigen presenting cells: APC; B-cells, macrophages, dendritic cells) • MHC proteins display peptides (including self antigens) • In infected cells, MHC proteins display fragments of foreign antigens Adaptive Immunity: AntigensAdaptive Immunity: cells • Two types of lymphocytes – T lymphocytes (T cells) mature in the Thymus and are responsible for cell-mediated immunity – B lymphocytes (B cells) mature in the Bone marrow -humoral immunity o When mature-- immunocompetent; able to bind to a specific antigen o Immunocompetent