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Immunology in a Nutshell M. Tevfik DORAK

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1 Immunology in a Nutshell M. Tevfik DORAK

2 Immune System INNATE IMMUNITYADAPTIVE IMMUNITY HUMORAL IMMUNITYCELLULAR IMMUNITY B LYMPHOCYTET LYMPHOCYTE ThTc Extracellular microbes Phagocytosed microbes Intracellular microbes NEUTRALISATIONMACROPHAGE ACTIVATION CYTOTOXICITY PHYSICAL BARRIERS CHEMICAL PROTECTION PHAGOCYTES Monocyte/macrophage, neutrophils COMPLEMENT SYSTEM INTERFERON, INTERLEUKIN, CHEMOKINE, TNF NK CELLS INITIAL CONTROL OF INFECTION Pathogen associated molecular patterns

3 Cambridge University Immunology Lectures (www)www Innate & Adaptive Immunity Timeline

4 Bone Marrow Derived Cells Hoffbrand (www)www

5 Normal White Blood Cells Hoffbrand (www)www

6 Normal White Blood Cells Hoffbrand (www)www

7 Hoffbrand (www)www

8 Immune System. In: Encyclopedia of Life Sciences (www)www Components of the Immune System

9 Immune System. In: Encyclopedia of Life Sciences (www)www Components of the Immune System

10 Manson's Tropical Disease: Genetics (www)www

11 Innate Immunity: Toll-Like Receptors Wagner, 2004 (www)www

12 Innate Immunity: Toll-Like Receptors New Science Primers: Immunity (www)www

13 Reticuloendothelial System Hoffbrand (www)www

14 Immune System. In: Encyclopedia of Life Sciences (www)www Acute Phase Reaction

15 Cambridge University Immunology Lectures (www)www Complement Activation

16 Immune System. In: Encyclopedia of Life Sciences (www)www

17 Souhami & Mouxham (www)www Complement Pathway

18 Kuby's Immunology Online (www)www Induction of Immune Responses Activation and proliferation of T H cells. (a) is required for generation of humoral response (b) and cell-mediated response to altered self-cells (c).

19 Cells of the Immune System. In: Encyclopedia of Life Sciences (www)www

20 Functions of antibodies Neutralization Agglutination (antigen cross-linking) Complement activation (classical pathway) Antibody-dependent cell-mediated cytotoxicity (ADCC) {Fc receptors - NK cells} Opsonization {Fc receptors - phagocytes} Degranulation of inflammatory cells {Fc receptors - macrophages, basophils, eosinophils}

21 Souhami & Mouxham (www)www Antibody Responses

22 Once activated by direct interaction with antigens and with some help from T H cells, some B-cell become IgM secreting plasma cells. Some migrate to the B cell rich areas of lymph nodes and form germinal centres. Here B cells proliferate and give rise to progeny with high affinity for antigen through a process called affinity maturation. The products of germinal centres become IgG, A etc, plasma cells and memory B cells. Cambridge University Immunology Lectures (www)www

23 Souhami & Mouxham (www)www Antibodies

24 Antibodies Hoffbrand (www)www

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26 Protein antigens do not induce antibody responses in the absence of T lymphocytes, they are T-dependent. The antibodies to these antigens go through affinity maturation resulting in development of strong memory responses. Non-protein antigens, polysaccharides and lipids for example, can give antibody responses without T cells (T-independent). T independent antigens are usually polymeric and it is believed that they cross link membrane Ig on B cells sufficiently well to activate them without co-operation from T cells. The antibodies to these antigen are invariably IgM and do not demonstrate affinity maturation. T-cell Dependence of Antibody Response

27 T Helper Cells Hoffbrand (www)www

28 B and T-cell Interactions Dube, 2002 (www)www eBiosciences Poster (www)www

29 (www)www

30 Roy, 2003 (www)www Endogenous and Exogenous Antigen Presenting Pathways

31 Figure 1. Professional antigen-presenting cells process intracellular and extracellular pathogens differently. In the endogenous pathway, proteins from intracellular pathogens, such as viruses, are degraded by the proteasome and the resulting peptides are shuttled into the endoplasmic reticulum (ER) by TAP proteins. These peptides are loaded onto MHC class I molecules and the complex is delivered to the cell surface, where it stimulates cytotoxic T lymphocytes (CTLs) that kill the infected cells. In contrast, extracellular pathogens are engulfed by phagosomes (exogenous pathway). Inside the phagosome, the pathogen-derived peptides are loaded directly onto MHC class II molecules, which activate helper T cells that stimulate the production of antibodies. But some peptides from extracellular antigens can also be 'presented' on MHC class I molecules. How this cross- presentation occurs has now been explained: it seems that by fusing with the ER, the phagosome gains the machinery necessary to load peptides onto MHC class I molecules. Roy, 2003 (www)www

32 Immune System. In: Encyclopedia of Life Sciences (www)www Endogenous and Exogenous Antigen Presenting Pathways

33 Thomas & Arend: Antigen Presenting Cells (www)www

34 Thomas & Arend: Antigen Presenting Cells (www)www

35 MHC II - Mediated Immune Response Hoffbrand (www)www

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38 Nakachi, 2004 (www)www

39 Nakachi, 2004 (www)www

40 MHC I - Mediated Immune Response Evasion by CMV New Science Primers: Immunity (www)www

41 Immune Evasion Examples Mycobacteria : Inhibits phagolysosome fusion so that it survives within the phagosome Herpes simplex virus : Interferes with TAP transporter (inhibits antigen presentation) Cytomegalovirus : Inhibits proteasome activity and removal of MHC I from ER Epstein-Barr virus : Inhibits proteasome activity; produces IL-10 to inhibit macrophage activation Pox virus : Produces soluble cytokine receptors to inhibit activation of effector cells

42 Souhami & Mouxham (www)www Cytokines

43 Pleiotropic Effects of Interleukin-1 Hoffbrand (www)www

44 Pleiotropic Effects of Interleukin-6 Hoffbrand (www)www

45 (www)www


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