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MI 211/IMM 201: Advanced Immunology I
1st Day Quiz: Answer Key
1. Simple diagram of T cell development:
2. A hapten is a small, low MW molecule that is antigenic (capable of binding to
receptors like immunoglobulins) but not immunogenic (capable of generating an
immune response). To generate hapten-specific antibodies, the hapten must be
covalently conjugated to a suitable, immunogenic carrier protein to form a
“hapten-carrier conjugate”. Upon immunizing with this conjugate,
macrophages will phagocytose and process the hapten-carrier antigen to present
carrier-derived peptides in the context of class II MHC molecules to be
recognized by the TCR of a T helper cell. In this fashion, the macrophage can
activate T helper cells that recognize carrier peptides. Meanwhile, a B cell
encoding a BCR specific for the hapten will bind and endocytose the haptencarrier antigen, and subsequently present carrier derived peptides in class II MHC
molecules for recognition by activated, carrier-specific T helper cells. These
primed T helper cells will recognize carrier:MHCII proteins on the B cell,
become reactivated, and provide appropriate signals (CD40L, cytokines) to
stimulate the B cell to differentiate and produce anti-hapten antibodies. Hence
through T cell help, a B cell capable of binding the hapten molecule can
eventually become a plasma cell secreting antibodies specific for the hapten
alone. (It is important to note that immunization with this hapten-carrier
conjugate will also generate antibodies specific for epitopes on the carrier alone
and novel epitopes formed by parts of both the hapten and carrier).
3. Receptor editing, a.k.a. light-chain editing, is the process by which an immature
B cell expressing a self-reactive BCR can escape negative selection by further
rearranging their Ig light-chain genes to create a new, nonself-reactive receptor.
This is accomplished by upregulating RAG-1/2 expression following binding to
self-antigen in the bone marrow (or in some cases, in the periphery). Light chain
genes are rearranged (often the self-reactive  light chain is replaced by a new 
light chain), and the new light chain is combined with the same  heavy chain to
form an edited mIgM which, if sucessful, no longer recognizes self antigen and
allows the cell to proceed to the mature B cell stage. As stated above, this process
occurs at the immature B cell stage (IgM+, IgD-) as B cells undergo negative
selection.
4. Class I MHC proteins are loaded with “endogenous” peptides in the rough
endoplasmic reticulum (RER), whereas class II MHC molecules bind
“exogenous” peptides in late endosomes (specifically, the MIIC compartment).
Class II molecules cannot bind endogenous peptides in the RER because the class
II-associated invariant chain peptide (CLIP) occludes the class II peptide-binding
groove. CLIP is only exchanged for exogenous peptides in the late endosomes
through the action of HLA-DM. On the other hand, nascent class I molecules are
not targeted to endosomes, and are therefore never exposed to peptides derived
from endosomal degradation.
5. The vast majority of pathogens we encounter are eliminated by components of
the innate immune system, which can be thought of as the first line of defense
against any invading pathogen. In fact, most pathogens are kept out of the body
by anatomic barriers, including the skin, mucosal membranes, saliva, and tears.
Those pathogens that do gain access to the body also encounter several
physiologic, phagocytic, and inflammatory barriers that function to eliminate
most pathogens through nonspecific immunity. In this fashion, most pathogens
are dealt with rapidly and efficiently without waiting for an adaptive immune
response to develop. Even when a pathogen elicits an adaptive immune response
involving activated effector T cells, those effector cells are short-lived and
eliminated rapidly following clearance of the infection by various mechanisms
(AICD, Fas/FasL, etc.).