Immunology in a Nutshell

M. Tevfik DORAK
http://www.dorak.info

Immune System
INNATE IMMUNITY ADAPTIVE IMMUNITY

PHYSICAL BARRIERS CHEMICAL PROTECTION

Pathogen associated molecular patterns

HUMORAL IMMUNITY
Extracellular microbes

CELLULAR IMMUNITY

PHAGOCYTES Monocyte/macrophage, neutrophils NK CELLS INTERFERON, INTERLEUKIN, CHEMOKINE, TNF COMPLEMENT SYSTEM

B LYMPHOCYTE

T LYMPHOCYTE
Phagocytosed microbes Intracellular microbes

Th

Tc

INITIAL CONTROL OF INFECTION

NEUTRALISATION

MACROPHAGE ACTIVATION

CYTOTOXICITY

Innate & Adaptive Immunity Timeline

Cambridge University Immunology Lectures (www)

Bone Marrow Derived Cells

Hoffbrand (www)

Normal White Blood Cells

Hoffbrand (www)

Normal White Blood Cells

Hoffbrand (www)

Hoffbrand (www)

Components of the Immune System

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

Components of the Immune System

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

Manson's Tropical Disease: Genetics (www)

Innate Immunity: Toll-Like Receptors Toll-

Wagner, 2004 (www)

Innate Immunity: Toll-Like Receptors Toll-

New Science Primers: Immunity (www)

Reticuloendothelial System

Hoffbrand (www)

Acute Phase Reaction

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

Complement Activation

Cambridge University Immunology Lectures (www)

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

Complement Pathway

Souhami & Mouxham (www)

Induction 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).
Kuby's Immunology Online (www)

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

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}

Antibody Responses

Souhami & Mouxham (www)

Antibody 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)

Antibodies

Souhami & Mouxham (www)

Antibodies

Hoffbrand (www)

T-cell Dependence of Antibody Response

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 Helper Cells

Hoffbrand (www)

B and T-cell Interactions T-

Dube, 2002 (www) eBiosciences Poster (www)

(www)

Endogenous and Exogenous Antigen Presenting Pathways

Roy, 2003 (www)

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 crosspresentation 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)

Endogenous and Exogenous Antigen Presenting Pathways

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

Thomas & Arend: Antigen Presenting Cells (www)

Thomas & Arend: Antigen Presenting Cells (www)

MHC II - Mediated Immune Response

Hoffbrand (www)

Nakachi, 2004 (www)

Nakachi, 2004 (www)

MHC I - Mediated Immune Response Evasion by CMV

New Science Primers: Immunity (www)

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 Epstein-Barr virus Pox virus : Inhibits proteasome activity and removal of MHC I from ER : Inhibits proteasome activity; produces IL-10 to inhibit macrophage activation : Produces soluble cytokine receptors to inhibit activation of effector cells

Cytokines

Souhami & Mouxham (www)

Pleiotropic Effects of Interleukin-1 Interleukin-

Hoffbrand (www)

Pleiotropic Effects of Interleukin-6 Interleukin-

Hoffbrand (www)

(www)