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Cells of the immune system
- 1. 1. Lymphoid cellsT cells 4. Mast cells B cells NK cells (Null cells) 2. Mononuclear cells Monocytes 5. Dendritic cells Langerhans cells Interstitial DC Macrophages Interdigitating DC Circulating DC 3. Granulocytic cells Neutrophils Eosinophil Basophil Cells of the immune system
- 2. III. Granulocytic cells 1.Neutrophils 2. Eosinophils 3. Basophils
- 3. Formation of Granulocytes Myeloidstem cells (myeloblast) Promyeloblast Myelocyte Metamyelocytes Granulocytes (N, E and B) Differentiation Takes app 14 days Growth factors reqd are G-CSF GM-CSF
- 4. • has amultilobed nucleus (mostly has 2-5 lobes) • it is often called as polymorphonuclear leukocyte (PMN) (for its multilobed nucleus) •are the most abundant white blood cells in humans approximately 108 - 1011 are produced daily) •they account for approximately 70% of all white blood cells (leukocytes). 1. Neutrophils
- 5. •They have granulatedcytoplasm- it stains with both acid and basic dyes Hematopoiesis in Bone marrow Neutrophils formed Released into the peripheral blood and circulate for 7–10 h After that migrate into the tissues, where they have a life span of only a few days. 1. Neutrophils
- 6. Granules present inneutrophils 1. Primary 2. Secondary 3. Tertiary In the presence of Ag- degranulation occurs (which is release of contents from granules) Release of contents from Granules Ag
- 7. Proteins present inthe granules Azurophilic granules (or "primary granules") Myeloperoxidase bactericidal/ permeability increasing protein (BPI) defensins the serine proteases neutrophil elastase cathepsin G Specific granules (or "secondary granules") Lactoferrin cathelicidin tertiary granules cathepsin gelatinase
- 8. Azurophilic granules (or "primary granules") Myeloperoxidase bactericidal/ permeability increasing protein (BPI) defensins the serine proteases neutrophil elastase cathepsin G
- 9. hCAP 18- humancathelicidin HOBr- Hypobromous acid HOI- Hypoiodous acid
- 10. BPI (bactericidal/ permeabilityincreasing protein) is a highly cationic, 55KD protein Is a cytotoxic protein Found only in the cells of myeloid series Has strong affinity for LPS, so has potent toxicity exclusively towards gram-negative bacteria Azurophilic granules (or "primary granules") Myeloperoxidase bactericidal/ permeability increasing protein (BPI) defensins the serine proteases neutrophil elastase cathepsin G
- 11. Azurophilic granules (or "primary granules") Myeloperoxidase bactericidal/ permeability increasing protein (BPI) defensins the serine proteases neutrophil elastase cathepsin G also known as ELA2 (elastase 2, neutrophil) is a serine protease Secreted by neutrophils during inflammation Hydrolyze elastin (protein present in the extracellular matrix) Degrades outer membrane protein A (OmpA) of E. coli, and virulence factors of organisms like Shigella, Salmonella and Yersinia Neutrophil elastase (or leukocyte elastase)
- 12. Cathelicidin (in secondarygranules) Is an antimicrobial peptide were originally found in neutrophils, but later found to be present in other cells including epithelial cells and macrophages increased in immune cells after activation by bacteria, viruses, fungi The human cathelicidin is called as hCAP-18 (Inactive proprotein) Specific granules (or "secondary granules") Lactoferrin cathelicidin
- 13. hCAP-18 (Inactive proprotein) Ag activepeptide (LL-37) (37 amino acids from the C-terminal) is released exerts antimicrobial activity Other biological effects of LL-37 neutralizing the biological effects of LPS promotion of angiogenesis and wound healing angiogenesis is physiological process involving the growth of new blood vessels from pre-existing vessels chemotaxis of neutrophils, monocytes and T- cells
- 14. Mechanism of killingby neutrophil -Mainly phagocytosis -Through garanule release
- 15. Neurtrophils are the firstto arrive at a site of inflammation transient increase in the number of circulating neutrophils, is called leukocytosis- is an indication of infection employ both oxygen-dependent and oxygen independent pathways to generate antimicrobial substances. exhibit a larger respiratory burst and express higher levels of defensins than macrophages
- 16. Recruitment of Neutrophilsinto inflamed tissue Neutrophil extravasation- rolling, adherance---- into tissues and elimination of pathogen in tissues Ag
- 17. Neutrophils aregenerally the first cell type to bind to inflamed endothelium and extravasate into the tissues. Neutrophils first recognize the inflamed endothelium and adhere strongly enough so that they are not swept away by the flowing blood. The bound neutrophils then penetrate the endothelial layer and migrate into the underlying tissue. Site of injury
- 18. The process ofneutrophil extravasation are divided into four sequential steps: (1) Rolling (2) activation by chemoattractant (3) arrest and adhesion and (4) Transendothelial migration Site of injury
- 19.
- 20. When thereis an inflammatory response develops, various cytokines and other inflammatory mediators act upon the local blood vessels and induces the increased expression of endothelial CAMs (cell adhesion molecules). Endothelium CAM This neutrophil is called as activated or inflamed neutrophil Neutrophil Ag
- 21. Rolling (Step 1) During an inflammatory response, cytokines and other mediators act upon the local endothelium and induces the expression of adhesion molecules of the selectin family. Neutrophils attach loosely to the endothelium by a low-affinity interaction which involves selectins and their Ligands. Selectins are a family of glycoprotein surface adhesion molecules The E-selectin (expressed exclusively on endothelial cells) and and P- selectin (expressed on platelets and endothelial cells) bind to mucin like cell-adhesion molecules on the neutrophil membrane or with a sialylated lactosaminoglycan called sialyl Lewisx endothelium
- 22. Rolling: Though Neutrophil getsattached to endothelium Due to blood flow, it sometimes gets detached from the endothelium, but gets attached to the selection present in the nearby endothelium This process is reapeated until the neurtophil gets firmly attached to an endothelium This is made possible by the rolling of neutrophils
- 24. Step 2 (Activation) Chemoattractantson the endothelium binds to its respective R on Neutrophils Eg., 1. Chemoattractive cytokines called as Chemokines like interleukin 8 (IL-8) and macrophage inflammatory protein (MIP) 2. Other Chemoattractants like platelet- activating factor (PAF), the complement split products C5a, C3a, and C5b67 and various N- formyl peptides produced by the breakdown of bacterial proteins during an infection. Chemoattractants like such as IL-8 then binds to a G-protein–linked receptor on the neutrophil, triggering an activating signal. G protein linked receptor
- 25. Step 3 This signalinduces a conformational change in the integrin molecules, enabling them to adhere firmly to Ig-superfamily molecules on the endothelium. G protein linked receptor
- 26. After attachmentto endothelium, the neutrophil migrates through the vessel wall into the tissues (it is transendothelial migration)
- 27. Eosinophils are likeneutrophils- ie., are motile phagocytic cells that can migrate from the blood into the tissue spaces play a role in the defense against parasitic organisms EOSINOPHILS
- 28. The granules containsubstances like histamine and proteins like eosinophil peroxidase, ribonuclease (RNase), deoxyribonucleases, lipase, plasminogen, and major basic protein. These mediators are released by a process called degranulation following activation of the eosinophil The secreted contents of eosinophilic granules may damage the parasite membrane and is also toxic to the host tissue.
- 29. Basophils are nonphagocyticgranulocytes They can be stained with basic dyes (eg toulidine blue) Are least common (represent about 0.01% to 0.3% of circulating white blood cells) They function by releasing pharmacologically active substances from their cytoplasmic granules. BASOPHILS
- 30. Nucleus has2 lobes they contain anticoagulant heparin they contain vasodilator histamine (which promotes blood flow to tissues) These substances play a major role in certain allergic responses. they appear in tissues where allergic reactions are occurring and probably contribute to the severity of these reactions
- 31. Basophils Ig R IgEAb Allergens B cells Release IgE Bind to R on Basophils Degranulation of basophils occurs
- 32. Degranulation- is extracellularrelease of the mediators like 1.Histamine 2.Proteoglycans (like heparin and chondroitin) 3.Proteolytic enzymes (elastase, lysophospholipase) 4.Lipid mediators (leukotrienes) 5.Many Cytokines Cause inflammation
- 33. Basopenia- is adecrease in B count Basophilia- is a increase in B count
- 34. 1. Lymphoid cellsT cells 4. Mast cells B cells NK cells (Null cells) 2. Mononuclear cells Monocytes 5. Dendritic cells Langerhans cells Interstitial DC Macrophages Interdigitating DC Circulating DC 3. Granulocytic cells Neutrophils Eosinophil Basophil Cells of the immune system
- 35. Mast cells Myeloid stemcells Basophil Progenitor produce either Mast Cells or Basophils Mast cells and basophils play a central role in inflammatory and immediate allergic reactions
- 36. Both mastcells and basophils contain special cytoplasmic granules which store mediators of inflammation. The extracellular release of the mediators is known as degranulation Mast cells Basophil usually do not circulate in the blood stream are the smallest circulating granulocytes. They arise in the bone marrow, and following maturation and differentiation, are released into the blood circulation Are present in connective tissues If they are adequately stimulated they may settle in the tissues
- 37. MAST CELLS ormastocyte Mast-cell precursors (in bone marrow) (undifferentiated cell) ---------------------------------------------------------- enter to blood Blood undifferentiated cell --------------------------------------------------------- Tissue enter to tissue Differentiated cell
- 38. first described byPaul Ehrlich in 1878 Tissues where mast cells are present -Present in tissues nearby to blood vessels 1. Skin 2. connective tissues of various organs 3. mucosal epithelial tissue of the respiratory, genitourinary, and digestive tracts. 4. Mucosa of mouth, conjunctiva and nose cytoplasmic granules contain 1. histamine and 2. other pharmacologically active substances.
- 39. Mast cell- playsimportant role in 1. Allergy and 2. Anaphylaxis (a type I hypersensitivity reaction)
- 40. 2 types ofmediators in mast cells and basophils are 1. Preformed mediators and 2. Newly generated mediators Preformed mediators, These are the mediators which are stored in secretory granules They are secreted upon cell activation by agents (eg., a biogenic amine, histamine, proteoglycans, heparin, chondroitin sulphates and a spectrum of neutral proteases). Newly generated mediators they are often absent in the resting mast cells they are produced during IgE-mediated activation eg of such mediators are arachidonic acid metabolites (leukotriene C and prostaglandin D) , TNF, IL-4, IL-5 and IL-6.