Immunology Questions I

Ephraim Fuchs ejf at
Tue Sep 27 21:51:05 EST 1994

>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

Do I pass?

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