Cells of inflammation and Immunity

1. Cells of inflammation and Immunity G. Wharfe 2005

2. Immune system • Detect and respond to antigens • Protects against pathogenic microorganisms • Also elicits response against noninfectious foreign organisms • Used in inflammatory response and tissue repair

3. Immune response • Response needs to be quick and efficient • Two systems • Innate • Adaptive

4. Cells of IR • All derived from BM stem cells • Influenced by growth factors • Begin as multipotent stem cell • Develop into committed stem cells

5. Innate immune system • First to respond • Limits infection before adaptive response • Usually involve nonlymphoid cells • Cells are macrophages and polymorphonuclear neutrophils(PMN) • Also involves complement and acute phase proteins • If innate immunity cures infection-no adaptive immunity develops

6. Normal haematopoiesis

7. Adaptive immunity • Inducible antigen specific response • Primary lymphoid organs produce lymphocytes capable of responding to various antigens • Lymphocytes form naïve pool in blood • Lymphocytes circulate in peripheral lymphoid organs • Location for Ag-dependent IR

8. Immunoglobulin

9. Cells of innate immune system • All are bone marrow derived • Lineage commitment depends on stromal contact and cytokines • Dendritic cells-Antigen presenting cells • Develop from peripheral blood monocyte precursors • Found in the interstitium and T cell areas • Stimulate Ag specific T cells

10. Phagocytic cells • PMN’s • Macrophages

11. Granulocytes • Inflammatory cells • Contain cytoplasmic granules • Neutrophils • Eosinophils • Basophils

12. Neutrophil

13. Stages of granulocyte maturation

14. Neutrophils • Major phagocytic granulocyte • Contain multilobed nucleus • Neutrophilic granules • Respond to chemotactic stimuli • Activated by macrophage and endothelial derived cytokines • Major cell of acute inflammation • Primary effector cells in IR to pyogens

15. Neutrophils • Have Fc receptors for IgG and c’ • Bind and phagocytose opsonised antigens • Link between 2 arms of immune system • Regulates activation and recruitment of macrophages by cytokines

16. Phagocytosis • Principal mechanism of pathogens • Enter site of infection • Opsonins produced to allow phagocytosis • Taken into vacuole • Killing by aerobic or anaerobic mechanisms • Cytokine induction

17. Phagocytosis

18. Eosinophil

19. Eosinophils • Contain eosinophilic granules • Express Fc receptors for IgE • IgE prevalent in parasitic infections • IgE mediates activation of eosinophil killing mechanisms • Role in immediate hypersensitivity to allergens • Cause tissue injury and inflammation

20. Basophil

21. Basophils • In circulation –basophils • In tissue- Mast cells • Express Fc receptors for IgE • Release chemical mediators of immediate hypersensitivity

22. Monocyte

23. Macrophages • Main cells of chronic IR • Regulators of specific acquired response • Fewer numbers than neutrophils • Peaks in hours to days • Participate in both acute and chronic inflammation • Phagocytose apoptotic PMN’s

24. Tissue macrophages • Second major class of phagocytic cells • Provide innate immunity and initiate host defenses • Release inflammatory cytokines • Act as APC • Link between innate immunity and acquired humoral and cellular immunity

25. Cells of monocyte macrophage system

26. Lymphocytes • B lymphocyte • T lymphocyte • NK lymphocyte

27. Lymphocyte

28. Lymphocytes • Mediate adaptive immune response • Recognize antigen specifically • Each clone has antigen specificity • Arrange V, J and D elements if Ig and T cell receptor genes to form different clones • B lymphocytes recognize native Ag • T lymphocytes recognize processed Ag

29. Lymphocytes • Ag binds to receptor • Lymphoid activation and Clonal expansion • Effector cells or products all have same • specificity as parent cell • Inactivation of self reactive clones

30. Lymphocytes • Ag independent maturation occurs in primary lymphoid organs • Ag dependent occurs in secondary lymphoid organs • Cells are indistinguishable morphologically • Phenotypically and functionally different

31. B lymphocyte development

32. B lymphocytes • Generate Ab response • Formed with other white cells in BM • Ab neutralize pathogens, opsonize pathogens, activate complement • Act as APC for T cells • Generate memory B cells

33. Plasma cell

34. Plasma cells • Not usually found in PB • Responsible for Ig production

35. T lymphocyte development

36. T cells • Generate CMI • Directly by differentiating into cytotoxic T cells • Indirectly by activating macrophages • Help B lymphocytes • Develop from BM progenitors which migrate to thymus • CD4 and CD8

37. T cell functions • Delayed hypersensitivity • Cell mediated immunity • Graft rejection • Contact allergic reactions • Cytotoxic responses to other cells • Facilitate Ab production by B cells • Memory T cells

38. Lymphoid organs

39. Interaction of lymphocyte with virus

40. NK cells • Also known as LGL • Target virus infected cells • Target tumor cells • Have receptors for IgG • Mediate ADCC

41. Immune response

42. Differences between cells of innate immunity and lymphocytes • Different ways of recognizing microorganisms • Direct • Indirect • Specific Ag recognition

43. Cytokines • Molecules secreted by cells(lymphocytes) and which affect the function of other cells • Secreted in response to specific stimulus • Interleukin is a type of cytokine

44. Role of interleukins