1. 1. Overview of the immune response
David D. Chaplin, MD, PhD 
Journal of Allergy and Clinical Immunology 
Volume 111, Issue 2, Pages S442-S459 (February 2003)
DOI: /mai
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2. Fig. 1
Hematopoietic stem cell-derived cell lineages. Pluripotent hematopoietic stem cells differentiate in bone marrow into lymphoid or myeloid stem cells. Lymphoid stem cells give rise to B cell, T cell, and NK cell lineages. Myeloid stem cells give rise to a second level of lineage-specific colony forming unit (CFU) cells that go on to produce neutrophils, monocytes, eosinophils, basophils, mast cells, megakaryocytes, and erythrocytes. Monocytes differentiate further into macrophages in peripheral tissue compartments.
Journal of Allergy and Clinical Immunology  , S442-S459DOI: ( /mai )
Copyright © 2003 Mosby, Inc. Terms and Conditions

3. Fig. 2
Molecular map of the human major histocompatibility complex. The human MHC, designated HLA, is encoded on the short arm of chromosome 6. The genes encoding the class I HLA heavy chains are clustered at the telomeric (TEL) end of the complex. The genes encoding the class II HLA α and β chains are clustered at the centromeric end of the complex. In between the class I and the class II genes are additional genes designated class III. These include genes encoding the cytochrome P hydroxylase (P450 C21A and B), complement components C4, C2, and factor B (Bf), TNF, and the two lymphotoxin chains (LTA, LTB). There are two isoforms of complement C4 designated C4A and C4B. C4A interacts more efficiently with macromolecules containing free amino groups (protein antigens), whereas C4B interacts more efficiently with macromolecules containing free hydroxyl groups (glycoproteins and carbohydrates).
Journal of Allergy and Clinical Immunology  , S442-S459DOI: ( /mai )
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4. Fig. 3
Structure of HLA molecules. Molecular models derived from crystal structures of class I (A-C ) and class II (D-F ) HLA molecules. A, The class I α1, α2, and α3 domains are shown (light blue) in noncovalent association with the β2m molecule. Coils represent α-helices, and broad arrows represent β-strands. Antiparallel β-strands interact to form β-sheets. The α-helices in the α1 and α2 domains form the sides and floor of a groove that binds processed antigenic peptides (yellow). The transmembrane and intracytoplasmic portions of the heavy chain are not shown. B, Top view of the α1 and α2 domains displaying the antigenic peptide in a molecular complex for recognition by the TCR of a CD8+ T cell (recognition site outlined by pink rectangle). C, Side view of the α1 and α2 domains highlighting the TCR contact points on both the α-helices and antigenic peptide. D, Side view of the HLA class II molecule showing the α chain (light blue) and the β chain (dark blue). In the class II protein, the peptide-binding groove is made of helices in both the α1 and β1 domains and a β-sheet formed again by both the α1 and β1 domains. E, Top view of the both the α1 and β1 domains and the processed antigenic peptide fragment as they would be seen by the TCR of a CD4+ T cell. F, Side view highlighting the α1 and β1 domains and the antigenic peptide.
Journal of Allergy and Clinical Immunology  , S442-S459DOI: ( /mai )
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5. Fig. 4
Cellular pathway of antigen processing and presentation. Endogenous proteins are digested by the proteasome to small peptide fragments that then enter the ER by the TAP transporter. There the peptides are loaded into a class I heavy chain that associates with a β2m subunit before transport to the cell surface where it can be recognized by CD8+ T cells. Exogenous antigens are taken up by phagocytosis or endocytosis, digested by the action of lysosomal enzymes, and transported to a class II+ endosome for loading into a class II protein. The newly synthesized class II proteins associate with an invariant chain protein that protects the antigen-binding groove until it is transported to the class II+ endosome. There the invariant chain is proteolytically degraded and replaced by antigenic peptide with the help of the HLA-DM protein. The assembled class II protein-peptide complex is then delivered to the plasma membrane where it can be recognized by CD4+ T cells. Modified with permission from Huston.75
Journal of Allergy and Clinical Immunology  , S442-S459DOI: ( /mai )
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6. Fig. 5
Differentiation and maturation of T cells in the thymus. Hematopoietic stem cells committed to T cell differentiation move from the bone marrow to the thymic subcapsular zone. There they begin rearrangement of the TCR genes. Once a productive TCR β chain has been produced, they move the thymic cortex, where TCR α chain rearrangement occurs and the cells express both the CD4 and CD8 surface proteins. These DP cells are positively selected on cortical epithelial cells for their ability to recognize self HLA proteins. Selected cells then move to the thymic medulla, where they are negatively selected on medullary epithelial cells to remove cells with excessive affinity for self antigens presented in HLA molecules. Cells emerge from positive selection SP for CD4 or CD8 expression and then are exported to the periphery. Cells that fail positive or negative selection are removed by apoptosis. A small fraction of cells differentiate to rearrange their TCR γ and β chains, rather than their α and β chains. Modified with permission from Huston (see reference 75).
Journal of Allergy and Clinical Immunology  , S442-S459DOI: ( /mai )
Copyright © 2003 Mosby, Inc. Terms and Conditions

7. Fig. 6
T-cell receptor complex and T-cell activation. A, The complete TCR complex includes both rearranged TCR α and β chains and the CD3γ, CD3δ, CD3ϵ, and CD3ζ chains. The CD3 chains contain ITAMs in their cytoplasmic domains that can be phosphorylated to activate the intracellular signaling cascade for T-cell activation. TCR engagement by MHC plus peptide without the presence of costimulatory proteins results in anergy. B, TCR engagement by MHC plus peptide with costimulatory interactions between CD28 on the T cell and CD80 or CD86. (B7.1 or B7.2) on the APC results in T-cell activation. C, Polyclonal activation of T cells can be elicited by superantigens which interact outside the peptide-binding groove with the β1 chain of the class II molecule and with all Vβ chains of a particular subclass.
Journal of Allergy and Clinical Immunology  , S442-S459DOI: ( /mai )
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8. Fig. 7
B-cell differentiation and development. B cells differentiate in the bone marrow from stem cells to become mature surface IgM- and IgD-expressing cells. This occurs in the absence of antigens. In peripheral lymphoid tissues, the B cell can then mature further under the influence of antigen and T cell help to undergo isotype switching and affinity maturation by somatic mutation. The factors controlling the final differentiation from antibody-secreting B cell to plasma cell are not well characterized. Correlations are shown between the stage of cell differentiation and the expression of key molecules in the cell (TdT, RAG1/RAG2, cytoplasmic μ) and on the cell surface (class II, CD19, CD21, CD25, CD45, and surface Ig). Modified with permission from Huston (see reference 75).
Journal of Allergy and Clinical Immunology  , S442-S459DOI: ( /mai )
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9. Fig. 8
The activation pathways of complement. Three pathways lead to activation of complement. The classical pathway is initiated by complexes of IgM, IgG1, or IgG3 with antigens. This activates proteolysis of C1, which cleaves C4 and C2 to form the classical pathway C3 convertase. The Mannose Lectin pathway is activated by interaction of mannan-containing microbes with MBL, which activates MASP-1 and MASP-2 to cleave C4 and C2, again forming a C3 convertase. The alternative pathway is initiated by interactions between microbial antigens and inhibitory complement regulatory proteins. This permits autoactivation of the pathway in which C3 interacts with factor B and factor D to generate the alternative pathway C3 convertase. These convertases all cleave C3 to generate the anaphylatoxic C3a fragment and depositing C3b on the activating microbial particle or immune complex. This opsonizes the particle for phagocytosis and initiates the activation of the membrane attack complex. C5 is also cleaved proteolytically into C5a and C5b fragments. The C5b fragment nucleates the membrane attack complex, leading to cell lysis. The C5a fragment, like C3a, is highly anaphylatoxic and induces intense local inflammation..
Journal of Allergy and Clinical Immunology  , S442-S459DOI: ( /mai )
Copyright © 2003 Mosby, Inc. Terms and Conditions