Cell Death

Immunoglobulin (IgG, IgA, IgM, IgE, IgD)

Antibodies, the molecules that bind antigens, are immunoglobulins (Ig). Antibodies serve as the effectors of humoral immunity by searching out antigens and neutralizing them or marking them for elimination. In their membrane-bound form on the surface of B cells, Ig molecules confer antigen specificity on the B cell. The antigen-specific proliferation of a B cell is triggered by recognition of the target antigen by the B-cell membrane Ig. The basic unit of antibody structure contains four polypeptide chains, two identical light (L) chains and two identical heavy (H) chains. Each light chain is bound to a heavy chain via disulfide bridges to form a heterodimer (HL). Two identical heterodimers are linked to each other by disulfide bridges to form the basic antibody molecule (H₂L₂). Antibody class is determined by the nature of the heavy chain. Five major classes and several subclasses of antibodies are found in humans. The chains of immunoglobulins contain several homologous units of about 110 amino acids called domains. Variable region domains of antibodies are involved in antigen binding, and the constant region domains of the heavy chain are responsible for such biological functions as complement fixation and antibody binding to the Fc receptors of phagocytes and other cells. This interactive gallery allows exploration of the structure and properties of each class of immunoglobulins.

• Immunoglobulins Animation by W.H. Freeman

ELISA

The ELISA (enzyme-linked immunosorbent assay) employs the reaction of an enzyme with a colorless substrate to generate a colored reaction product. The ELISA assay can be used as a quantitative assay to determine the amount of a target antibody or antigen in a sample by preparing a standard curve based on known concentrations of antibody or antigen. Alternatively, the ELISA reaction can be used qualitatively to determine the presence or absence of a substance in a sample. In the pregnancy test illustrated in this animation, the principle of the sandwich ELISA shown in Figure 6-11b is used to quickly determine whether a sample of urine contains the pregnancy-associated hormone human chorionic gonadotropin (hCG). Note that the sandwich of antigen and two antibodies is assembled in a different order in the pregnancy test compared to the assay shown in Figure 6-11b. The reaction between the antibody-enzyme conjugate and the antigen (third panel of Figure 6-11b) is the first reaction in the animation of the positive pregnancy test (R zone), and the reaction between immobilized antibody and antigen (second panel in Figure 6-11b) is the second reaction in the animation (T zone). Contrast the ELISA-based method shown in the animation with an earlier version of a home pregnancy test kit that was based on agglutination inhibition

• ELISA Animation by W.H. Freeman

Signal Transduction (The Role of TGF-beta in B Cell Differentiation)

The detection and interpretation of signals from the environment is an indispensable feature of all cells, including those of the immune system. All signal transduction pathways begin with receptors that detect the arrival of the signal. The interaction of the receptor and the signal produces changes that set in motion an ordered chain of events that ultimately modifies the targeted cell. The TGF-ß signaling pathway depicted in this animation plays an important role in such immunological processes as B-cell differentiation and T-cell regulation. Some themes common to many signal transduction pathways are evident in this animation: the involvement of receptor-ligand interactions (type II TGF-ß receptor + TGF-ß dimer), the induced assembly of critical components (TGF-ß- dimer-mediated interaction of TGF-ß type I and II receptors), the action of protein kinases (phosphorylations of the type I TGF-ß receptor and of the transcription factor R-Smad), and the translocation to the nucleus of transcription factors that activate target genes (the heterodimer of phosphorylated R-Smad and its partner co-Smad).

• Signal Transduction Animation by W.H. Freeman

Leukocyte Extravasation

As an inflammatory response develops, various cytokines and other mediators are generated. These act upon the endothelial cells of the local blood vessels to produce a state of activation or inflammation. Leukocytes, such as neutrophils, recognize the inflamed endothelium and extravasate and migrate to the site of infection in a sequential (but overlapping) four-step process: (1) rolling, (2) activation, (3) arrest of rolling and adhesion to the endothelial cell layer, and (4) transendothelial migration. Activation is mediated by chemoattractants, including chemokines and other molecules such as platelet-activating factor (PAF). Binding of these chemoattractants to receptors on the leukocyte membrane triggers a G-protein-mediated activation signal that results in a large increase in the affinity of the integrin molecules on the membrane of the leukocyte. ICAM molecules are ligands for integrins. The increased affinity of the integrin molecules causes the leukocyte to bind tightly to the ICAM molecules on the surface of the endothelial cells. Using these ICAM molecules for traction, the leukocyte pushes its way between the cells of the endothelium and enters the surrounding tissue. Once in the tissue, the leukocyte moves up the concentration gradient of chemoattractant molecules generated at the site of inflammation and arrives at the site.

• Leukocyte Extravasation Animation by W.H. Freeman

Strategies For Vaccine Development

Vaccines are designed to produce a state of immunity similar to that resulting from natural exposure to the disease-causing organism. A vaccine must produce this immunity without itself causing disease. A number of different strategies have been used to develop successful vaccines. Possible candidates for vaccines include live attenuated organisms, inactivated (killed) organisms, a molecular component of an organism (such as a viral surface protein), and an inactivated bacterial toxin (toxoid). The type of vaccine that will work best to produce strong, long-lasting immunity with an absence of harmful side effects must be determined for each disease-causing organism; there is no general formula. Examination of the structure of the organism and the mechanism by which it causes disease can give critical clues concerning which components of the organism and which steps in its pathogenesis might be the best targets for a potential vaccine. Once the candidate vaccine is developed, it must pass a rigorous set of tests for safety and efficacy before it can be licensed for use in humans.

• Vaccine Strategies Animation by W.H. Freeman

Retrovirus: Infection and Replication

A retrovirus such as HIV-1 contains its genetic information in the form of RNA. The replication cycle involves attachment of the virus to a cell and entry of the RNA genome along with enzymes needed to copy (reverse transcribe) this information to DNA. This viral (or proviral) DNA is then integrated into the cell's genome and transcribed and translated using cellular mechanisms. The newly transcribed viral RNA copy is used in its full length as the genome of new viruses, and in spliced form as mRNA to direct synthesis of the proteins for new viral particles or virions. These assemble in the cell and bud from the cell surface. HIV replicates in T cells or macrophages. Attachment of HIV occurs through binding of the viral envelope protein gp120 to CD4 on the cell, and then fusion of the viral and the cell membrane is mediated by the interaction of a cellular co-receptor, CXCR4 or CCR5, with gp41. Anti-retroviral drugs act by inhibition of various steps within the replication cycle. For example, the step of reverse transcription is blocked by the insertion of nucleoside analogs into the growing viral DNA that do not allow further addition of nucleotides onto them to complete the viral DNA chain. Other successful drugs block the viral protease that cleaves viral precursor proteins into the building blocks of a mature virion.

• Retrovirus Animation by W.H. Freeman

Cloning an Army of T Cells for Immune Defense

View the animation to see how one type of immune cell—the helper T cell—interprets a message presented at the surface of the cell membrane. The message is an antigen, a protein fragment taken from an invading microbe. A series of events unfolds that results in the production of many clones of the helper T cell. These identical T cells can serve as a brigade forming an essential communication network to activate B cells, which make antibodies that will specifically attack the activating antigen.

• Click to Animations

Specific Immunity Animation

• Introducing the bloody characters of specific immunity animated by RM Chute

Summer 2004 Immunology Teacher Animations (HHMI)

The Flash animations below are based upon storyboards created by participants in our 2004 Summer Workshop for High School Teachers.

• Pathways of Defense

• Fighting The Common Cold

• Cell-Mediated Response

• Antibody Diversity

The Body's Guard

Learn how dendritic cells serve the body's immune system as "sentinels".

• The Body's Guard Animation by The Rockefeller University

MHC Class Animations

• MHC class I

• MHC class II