Immunology in Immunology in a Nutshella Nutshell

M. Tevfik DORAKhttp://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

PHAGOCYTESMonocyte/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 Response MHC 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)