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Immunology inImmunology in
a Nutshella Nutshell
M. Tevfik DORAK
http://www.dorak.info
Immune SystemImmune System
INNATE IMMUNITY ADAPTIVE IMMUNITY
HUMORAL IMMUNITY CELLULAR IMMUNITY
B LYMPHOCYTE T LYMPHOCYTE
Th Tc
Extracellular
microbes
Phagocytosed
microbes
Intracellular
microbes
NEUTRALISATION MACROPHAGE
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
Cambridge University Immunology Lectures (www)
Innate & Adaptive Immunity TimelineInnate & Adaptive Immunity Timeline
Bone Marrow Derived CellsBone Marrow Derived Cells
Hoffbrand (www)
Normal White Blood CellsNormal White Blood Cells
Hoffbrand (www)
Normal White Blood CellsNormal White Blood Cells
Hoffbrand (www)
Hoffbrand (www)
Immune System. In: Encyclopedia of Life Sciences (www)
Components of the Immune SystemComponents of the Immune System
Immune System. In: Encyclopedia of Life Sciences (www)
Components of the Immune SystemComponents of the Immune System
Manson's Tropical Disease: Genetics (www)
Innate Immunity: Toll-Like ReceptorsInnate Immunity: Toll-Like Receptors
Wagner, 2004 (www)
Innate Immunity: Toll-Like ReceptorsInnate Immunity: Toll-Like Receptors
New Science Primers: Immunity (www)
Reticuloendothelial SystemReticuloendothelial System
Hoffbrand (www)
Immune System. In: Encyclopedia of Life Sciences (www)
Acute Phase ReactionAcute Phase Reaction
Cambridge University Immunology Lectures (www)
Complement ActivationComplement Activation
Immune System. In: Encyclopedia of Life Sciences (www)
Souhami & Mouxham (www)
Complement PathwayComplement Pathway
Kuby's Immunology Online (www)
Induction of Immune ResponsesInduction of Immune Responses
Activation and proliferation of TH cells. (a) is required for generation of humoral response (b)
and cell-mediated response to altered self-cells (c).
Cells of the Immune System. In: Encyclopedia of Life Sciences (www)
Functions of antibodiesFunctions 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}
Souhami & Mouxham (www)
Antibody ResponsesAntibody Responses
Antibody ResponsesAntibody Responses
Once activated by direct interaction
with antigens and with some help
from TH 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)
Souhami & Mouxham (www)
AntibodiesAntibodies
AntibodiesAntibodies
Hoffbrand (www)
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 ResponseT-cell Dependence of Antibody Response
T Helper CellsT Helper Cells
Hoffbrand (www)
B and T-cell InteractionsB and T-cell Interactions
Dube, 2002 (www)
eBiosciences Poster (www)
(www)
Roy, 2003 (www)
Endogenous and Exogenous Antigen Presenting PathwaysEndogenous and Exogenous Antigen Presenting Pathways
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)
Immune System. In: Encyclopedia of Life Sciences (www)
Endogenous and Exogenous Antigen Presenting PathwaysEndogenous and Exogenous Antigen Presenting Pathways
Thomas & Arend: Antigen Presenting Cells (www)
Thomas & Arend: Antigen Presenting Cells (www)
MHC II - Mediated Immune ResponseMHC II - Mediated Immune Response
Hoffbrand (www)
Nakachi, 2004 (www)
Nakachi, 2004 (www)
MHC I - Mediated Immune ResponseMHC I - Mediated Immune Response
Evasion by CMVEvasion by CMV
New Science Primers: Immunity (www)
Immune Evasion ExamplesImmune 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
Souhami & Mouxham (www)
CytokinesCytokines
Pleiotropic Effects of Interleukin-1Pleiotropic Effects of Interleukin-1
Hoffbrand (www)
Pleiotropic Effects of Interleukin-6Pleiotropic Effects of Interleukin-6
Hoffbrand (www)
(www)

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Immunology in a Nutshell

  • 1. Immunology inImmunology in a Nutshella Nutshell M. Tevfik DORAK http://www.dorak.info
  • 2. Immune SystemImmune System INNATE IMMUNITY ADAPTIVE IMMUNITY HUMORAL IMMUNITY CELLULAR IMMUNITY B LYMPHOCYTE T LYMPHOCYTE Th Tc Extracellular microbes Phagocytosed microbes Intracellular microbes NEUTRALISATION MACROPHAGE 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) Innate & Adaptive Immunity TimelineInnate & Adaptive Immunity Timeline
  • 4. Bone Marrow Derived CellsBone Marrow Derived Cells Hoffbrand (www)
  • 5. Normal White Blood CellsNormal White Blood Cells Hoffbrand (www)
  • 6. Normal White Blood CellsNormal White Blood Cells Hoffbrand (www)
  • 8. Immune System. In: Encyclopedia of Life Sciences (www) Components of the Immune SystemComponents of the Immune System
  • 9. Immune System. In: Encyclopedia of Life Sciences (www) Components of the Immune SystemComponents of the Immune System
  • 10. Manson's Tropical Disease: Genetics (www)
  • 11. Innate Immunity: Toll-Like ReceptorsInnate Immunity: Toll-Like Receptors Wagner, 2004 (www)
  • 12. Innate Immunity: Toll-Like ReceptorsInnate Immunity: Toll-Like Receptors New Science Primers: Immunity (www)
  • 14. Immune System. In: Encyclopedia of Life Sciences (www) Acute Phase ReactionAcute Phase Reaction
  • 15. Cambridge University Immunology Lectures (www) Complement ActivationComplement Activation
  • 16. Immune System. In: Encyclopedia of Life Sciences (www)
  • 17. Souhami & Mouxham (www) Complement PathwayComplement Pathway
  • 18. Kuby's Immunology Online (www) Induction of Immune ResponsesInduction of Immune Responses Activation and proliferation of TH 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)
  • 20. Functions of antibodiesFunctions 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) Antibody ResponsesAntibody Responses
  • 22. Antibody ResponsesAntibody Responses Once activated by direct interaction with antigens and with some help from TH 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)
  • 23. Souhami & Mouxham (www) AntibodiesAntibodies
  • 25.
  • 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 ResponseT-cell Dependence of Antibody Response
  • 27. T Helper CellsT Helper Cells Hoffbrand (www)
  • 28. B and T-cell InteractionsB and T-cell Interactions Dube, 2002 (www) eBiosciences Poster (www)
  • 29. (www)
  • 30. Roy, 2003 (www) Endogenous and Exogenous Antigen Presenting PathwaysEndogenous 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)
  • 32. Immune System. In: Encyclopedia of Life Sciences (www) Endogenous and Exogenous Antigen Presenting PathwaysEndogenous and Exogenous Antigen Presenting Pathways
  • 33. Thomas & Arend: Antigen Presenting Cells (www)
  • 34. Thomas & Arend: Antigen Presenting Cells (www)
  • 35. MHC II - Mediated Immune ResponseMHC II - Mediated Immune Response Hoffbrand (www)
  • 36.
  • 37.
  • 40. MHC I - Mediated Immune ResponseMHC I - Mediated Immune Response Evasion by CMVEvasion by CMV New Science Primers: Immunity (www)
  • 41. Immune Evasion ExamplesImmune 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) CytokinesCytokines
  • 43. Pleiotropic Effects of Interleukin-1Pleiotropic Effects of Interleukin-1 Hoffbrand (www)
  • 44. Pleiotropic Effects of Interleukin-6Pleiotropic Effects of Interleukin-6 Hoffbrand (www)
  • 45. (www)