Introduction 
cialized to recognize antigens only in the form of 
such a peptide:MHC complex. There are acces- 
sory molecules on the surfaces of T cells, called 
CD4 and CDS, that are selectively expressed on 
cells that recognize antigens presented by MHC II 
and MHC I molecules, respectively. Functionally 
these accessory molecules form part of the T cell 
receptor for peptide:MHC complexes by binding 
to both the MHC molecule and the T ceil recep- 
tor. For this reason CD4 and CDS are sometimes 
called co-receptors. 
Like the antigen receptors on B and T cells, 
MHC molecules show considerable diversity. 
However, this diversity is not due to the recombi- 
nation of different gene segments but rather to 
genetic polymorphism. There may be as many as 
100 different genetic sequences (alleles) at a 
single MHC locus, and T cells are selected during 
development only if they can recognize peptides 
presented by self MHC molecules. How this oc- 
curs is unknown, but its role in T cell selection is 
obviously fundamental. 
The CD4-bearing T cells (also called T4 cells, 
helper lymphocytes, or CD4"^ cells) have become 
widely known because of their role in the devel- 
opment of AIDS (acquired immune deficiency 
syndrome) . The virus that causes AIDS — the hu- 
man immunodeficiency virus (or HIV) — selec- 
tively invades these cells, because the CD4^ mole- 
cule fortuitously serves also as a specific receptor 
for the virus (Figure 1 9) • On entering the CD4^ T 
cells, the genetic material of the virus (which is 
formed of RNA) becomes transcribed into DNA, 
and this, in turn, becomes integrated into the T 
cell's own genome. In this way the virus subverts 
the cell's genetic machinery and, when activated, 
the cell produces more and more virus, which 
ultimately kills the cell. When the cell dies it re- 
leases virus into the bodily fluids, where it is free 
to invade other CD4^ T cells, and the whole pro- 
cess may be repeated until finally the entire T cell 
population is depleted. Since, as we have seen, 
these cells are essential for mounting both cell- 
mediated and humoral immune responses, pa- 
tients with AIDS become progressively more vul- 
nerable to all forms of infection and commonly 
succumb to opportunistic infections that would 
normally be easily overcome. 
A second important component of the immune 
system is the complement system, which con- 
sists of a complex series of serum and cell mem- 
brane proteins (Figure 20). These proteins per- 
form essential roles in the immune response to 
foreign organisms such as bacteria and viruses. 
and in the response to tumors. Deficiencies of any 
of the complement proteins may lead to diseases, 
including those that involve infection, hemolysis 
of red blood cells, or autoimmune diseases such 
as systemic lupus erythematosus. 
The complement system is activated by two 
general mechanisms. First, antibodies (Ab) can 
activate complement when they bind their anti- 
gen (Ag). In addition to this so-called classical 
pathway there is an alternative pathway that is 
continuously active at a low level marking for- 
eign organisms for which there are no preformed 
antibodies available. 
In addition to these roles, complement pro- 
teins help to regulate the immune system by an- 
other mechanism. This involves the interaction of 
specific activated complement protein fragments 
with receptors, or binding proteins, that are on 
the surface of immune system cells. These recep- 
tors allow for communication with the interior of 
the cell, and their activation leads to a change in 
the function or fate of the cell. 
Overall, the complement system plays a funda- 
mental role in normal or abnormal immune re- 
sponses. Current study in this area is directed to- 
ward understanding not only the molecular 
mechanisms of complement activation and regu- 
lation but also the general effects on the immune 
response of experimentally altering complement 
function. 
The devastating consequences of AIDS, congen- 
ital immunodeficiency disorders, and the fre- 
quent rejection of transplanted organs have made 
the public more aware of the importance of the 
immune system in medical practice. The develop- 
ment of immunosuppressive drugs has gone a 
long way toward overcoming the problem of tis- 
sue rejection, and there is now considerable inter- 
est in the possible development of vaccines to 
limit the spread of HIV. Many of us remember 
how some 30 years ago poliomyelitis was to all 
intents and purposes eliminated in this country 
by the development of the Salk and Sabin vac- 
cines, and we are all conscious of the fact that 
many illnesses such as measles, rubella, whoop- 
ing cough, and even smallpox have been brought 
under control. But it is still not widely appre- 
ciated that the immune system is itself subject to 
a number of serious disorders such as lymphoma 
and leukemia. Our ability to deal with these ma- 
lignant conditions is still very limited, but we are 
beginning to understand what may cause them. 
While these disorders present the most urgent 
challenges to clinical immunology, even rela- 
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