Introduction 
ity complex (MHC). The membrane proteins 
encoded by these genes (of which there are two 
types called class I and class II) are able to selec- 
tively bind short segments of partially digested 
protein antigens, termed peptides. These pep- 
tides, arising from protein breakdown inside the 
cell, reach the surface of the cell together with 
the relevant MHC molecule. Recent x-ray crystal- 
lographic studies indicate that the peptide anti- 
gen is lodged within a distinctive groove on the 
outer surface of the MHC molecule, where it can 
be detected by a lymphocyte bearing the appro- 
priate receptor. The receptors on T cells are spe- 
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 cell 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 defi- 
ciency syndrome) . The virus that causes AIDS 
— the human immunodeficiency virus (or 
HIV) — selectively invades these cells, because 
the CD4^ molecule fortuitously serves also as a 
specific receptor for the virus (Figure 19). On 
entering the CD4^ T cells, the genetic material of 
the virus (which is formed of RNA) is reverse 
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 machin- 
ery and, when activated, the cell produces more 
and more virus, until ultimately the cell is killed. 
When the cell dies it releases virus into the bodily 
fluids, where it is free to invade other CD4^ T 
cells, and the whole process may be repeated un- 
til the entire T cell population is effectively de- 
pleted. Since, as we have seen, T helper cells are 
essential for mounting both cell-mediated and 
humoral immune responses, patients with AIDS 
become progressively more vulnerable to all 
forms of infection and commonly succumb to op- 
portunistic infections that would normally be eas- 
ily overcome. 
A second important component of the immune 
system is the complement system, which con- 
sists of a complex series of proteins in the serum 
and in cell membranes (Figure 20). These pro- 
teins perform essential roles in the immune re- 
sponse to foreign organisms such as bacteria and 
viruses, and in the response to tumors. Deficien- 
cies 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 
toward 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, con- 
genital immunodeficiency disorders, and the 
frequent rejection of transplanted organs have 
made the public increasingly aware of the im- 
portance of the immune system in medical prac- 
tice. The development of immunosuppressive 
drugs has gone a long way toward overcoming 
the problem of tissue rejection, and there is now 
considerable interest in the possible develop- 
lii 
I 
