>1. In the textbook it states that patients with SCID (severe combined
>immunodeficiency) "previously could be kept alive only in s sterile
>environment, but now can be cured by bone marrow transplantation.
>Patients lacking a suitable marrow donor re being treated
>experimentally by gene therapy." My response to this is: What
>constitutes a suitable vs unsuitable bone marrow donor for a person
>who completely lacks an immune response?
My guess is that a suitable donor is one who is matched at the major
histocompatibility complex locus, HLA. HLA-mismatched bone marrow
transplants are complicated by severe, lethal graft-versus-host disease.
This can be circumvented to some degree by depletion of mature T cells
from the donor marrow, but there are also problems with generating a
functional T cell compartment if the HLA type of the host thymus and the
donor antigen-presenting cells are not matched.
>
>2. In the textbook it states that tolerance can be induced in mature
>animals by inoculation with large amounts of the antigen. What is the
>mechanism behind this observation? DOes it involve B-cell anergy?
This phenomenon is called high-zone tolerance. Injection of large
amounts of antigen induces tolerance in both T and B cells. The
mechanism of high zone tolerance has not been clearly established;
however, I and Polly Matzinger have proposed that with high antigen
concentrations, B cells are the predominant antigen presenting cells for
the T cells specific for the antigen. We propose that B cells presenting
antigen induce tolerance in naive T cells. The B cells are tolerized
because they require T cell help for activation and don't get it.
> >3. Why
do we have an MHC? Why aren't these genes (encoding for
>structurally unrelated proteins such as the class I and class II
>proteins, peptidases, glycosyltransferases, cytokines, peptide
>transporters, and even some mystery genes) scattered about the genome?
>We have an MHC to ensure that T cell responses occur only at cell
surfaces. For instance, if a virus is lurking inside a cell, you need to
have a system that reacts on that cell surface and not to viral antigens
in solution. I don't wish to answer the second question.
>4. Induction of a classical immune response is dependent upon T cell
>help, in response to antigen degradation and presentation in the
>context of MHC molecules. How do large carbohydrates induce an immune
>response, if only proteins (peptides) can be found in the binding
>cleft of the MHC class II molecules?
>>Large carbohydrates evoke T cell-independent B cell responses (e.g. antibody)
Ephraim Fuchs
ejf at welchlink.welch.jhu.edu
Do I pass?
