Summmary of Effector Mechanisms for Antibodies


In the case of a toxin molecule in the blood, the simple binding of an antibody to the toxin molecule is probably all that is required to remove the problem. But with microbes, an antibody by itself can't be expect to remove the microbe. Also required are "hit-men" to deal with the microbe after the antibody provides the identification.

Phagocytosis

Earlier, in the context of innate immunity, we encountered the concept of an opsonin. But by far the most effective opsonins are antibodies of the type IgG and IgM. Once the antibody binds to its antigen on a microbe, the Fc region of the antibody can now bind to an Fc receptor on a neutrophil or macrophage. Phagocytosis then rapidly follows.




Activation of Macrophages

Phagocytosis by itself may not be enough to kill the microbes engulfed, allowing certain infections to develop into longer term, chronic infections. Macrophages are the phagocytes involved in this type of situation. As we have discussed, tuberculosis is a particularly important example. The lysosomes are prevented from fusing with the phagosome.

As we also have discussed, macrophages can become "activated". In this supercharged state, more of the killing factors are synthesized, and the lysosomes are more likely to fuse with the phagosome. In this way a more potent mix is released into the phagolysosome.

The cells that cause this activation are CD4+ Tcells of the type TH1 . These travel to macrophages, bind to the macrophage via their T cell receptor, and release IFN-gamma.

Complement System

The figure to the right is from the earlier page on the complement system. Recall that the complement system can be activated either in innate immunity or via antibodies bound to microbes. The antibodies can be either IgG or IgM, especially the pentameric form.




Which one of the following best describes how a TH1 cell identifies a macrophage to activate?

a. By binding to the macrophage using molecules of innate immunity
b. By its T cell receptor binding to peptide antigen displayed on MHC II molecules
c. By its T cell receptor binding to peptide antigen displayed on MHC I molecules
d. By binding to the macrophage with C3b attached.
e. By the macrophage using a Fc receptor to bind to IgG.



Eosinophils

Eosinophils have an Fc receptor for IgE. After IgE binds to the cuticle of a helminth worm, the Fc receptor on an eosinophil can bind to the Fc region on the IgE.


Mast Cells

Mast cells are found throughout the body and especially under epithelia. They are jam-packed with large secretion vesicles filled with inflammatory paracrines, including much histamine. On their membranes, the mast cells have Fc receptors for IgE. Observe below how IgE binds to these receptors. When the multivalent antigen appears again, it causes the the Fc receptors to cluster. As a result, the receptors phosphorylate each other through the action of a type of protein kinase called tyrosine kinase. This leads to exocytosis of the vesicles and synthesis of prostaglandins and leukotrienes.



Mucosal Immunity

Recall that IgA is joined into dimers with a J-chain. In this form, it binds to the basal surface of the intestinal or respiratory epithelium. It is then engulfed by the cell, transported to the luminal membrane, and released into the lumen. There the dimeric IgA binds to bacteria or viruses, which prevent their binding to the epithelium. It also tends to cause agglutination.

In addition, there also is a class of lymphocytes found within the epithelium itself. These are largely T cells, with the majority of the CD8+ variety. They respond to some of the more common microbes in the lumen.





Quick Quiz

Fill in Answer Correct False Correct Answer
Name an important cytokine released by Th1 cells (and natural killer cells) that activates macrophages. (Spell out Greek letter.)
What type of antibody do B cells especially tend to make if Th2 cells predominate?
What type of helper T cell predominates as a result of a strong innate immune response in which pathogens wind up in vesicles? (Give 3 character abbreviation.)
What molecule on the membrane of a mast cell binds IgE?

(Spelling must be correct)
OK, Go ahead and give me: