class="bi x0 y0 w1 h1"
Clinicopathologic principles for
veterinary medicine
class="bi x0 y4 w3 h5"
Clinicopathologic
principles for
veterinary
medicine
Edited by
WAYNE
F.
ROBINSON and
CLIVE
R. R.
HUXTABLE
School
of
Veterinary
Studies,
Murdoch
University
Murdoch,
Western Australia
The right
of
the
University
of
Cambridge
to print and sell
all manner

© Cambridge University Press 1988
This book is in copyright. Subject to statutory exception
and to the provisions of relevant collective licensing agreements,
no reproduction of any part may take place without
the written permission of Cambridge University Press.
First published 1988
First paperback edition 2003
A catalogue record for this book is available from the British Library
Library of Congress cataloguing in publication data
Clinicopathologic principles for veterinary medicine / edited by Wayne
F.
Robinson and Clive R. R. Huxtable.
p.
cm.
Includes index.
ISBN 0 521 30883 6 hardback
I. Veterinary clinical pathology. I. Robinson, Wayne F.
II.
Huxtable, Clive R.R.
[DNLM:
1.
Pathology, Veterinary. SF 769 C641]
SF772.6.C57 1988
636.089'607-dcl9
DNLM/DLC
for Library of Congress 87-32006 CIP
ISBN 0 521 30883 6 hardback
ISBN 0 521 54813 6 paperback
Contents
Contributors

6 The cardiovascular system
Wayne F. Robinson
122
7 The alimentary tract 163
John R. Bolton and David A. Pass
8 The liver and exocrine pancreas 194
Clive R. R. Huxtable
216
249
275
12 The skeletal system 298
Wayne F. Robinson,
Robert S. Wyburn and John Grandage
13 The nervous system 330
Clive E. Eger, John McC. Howell
and Clive R. R. Huxtable
14 Muscle 378
Wayne F. Robinson
15 Metabolic disease 389
David W. Pethick
16 The reproductive system 399
Peter E. Williamson
Index 419
Contributors
John R. Bolton, B.V.Sc., Ph.D.,
M.A.C.V.Sc. Senior Lecturer in Large
Animal
Medicine
Leonard K. Cullen, B.V.Sc, M.A., M.V.Sc,
Ph.D.,

biology and Immunology
David W. Pethick, B.Ag.Sc, Ph.D. Lecturer
in Biochemistry
Wayne F. Robinson, B.V.Sc, M.V.Sc,
Ph.D.,
Dip. Am. Coll. Vet. Path,
M.A.C.V.Sc. Associate Professor of Path-
ology
Susan E. Shaw, B.V.Sc., M.Sc.,F.A.C.V.Sc.,
Dip.
Am. Coll. Int. Med. Senior Lecturer in
Small Animal
Medicine
V. E. O. Valli,* D.V.M., M.Sc, Ph.D., Dip.
Am. Coll. Vet. Path. Professor of
Veterinary
Pathology
Sheila S. White, B.V.M.S., Ph.D.,
M.R.C.V.S. Senior
Lecturer in
Anatomy
Peter E. Williamson, B.V.Sc, Ph.D. Senior
Lecturer in
Reproduction
Robert S. Wyburn, B.V.M.S., Ph.D.,
D.V.R.,
F.A.C.V.Sc, M.R.C.V.S. Associate
Professor of
Veterinary
Medicine and

this school, and it is a source of satisfaction
that all but one of the contributors teach in the
course. The approach taken is similar in many
respects to the pattern followed in other
schools throughout the world. Our experience
and no doubt that of many others is that the
two disciplines of pathology and medicine are
enriched by such integration, a merger rather
than a polarization. We have endeavoured to
encapsulate these views in the first chapter of
the book entitled The relationship between
pathology and medicine'.
To our co-authors we extend our heartfelt
thanks. Their contributions of time and
expertise are greatly appreciated.
January 1987
W. F. Robinson
C. R. R. Huxtable
Perth, Australia
VII
Acknowledgements
We are indebted to a number of dedicated
helpers who do not appear in name elsewhere.
Sue Lyons with her trusty word processor has
typed and corrected numerous chapter drafts
with dedication, speed and accuracy. Hers was
a most onerous task carried out with cooper-
ation and willingness. Pam Draper and Diane
Surtees were also of immense help with some
of the chapter typing. The creativity and

The typical veterinary medical student first
encounters disease at the level of cells and
tissues, amongst microscopes and cadavers
and then proceeds rather abruptly to a very
different world of lame horses, vomiting dogs,
panting cats, scouring calves, stethoscopes,
blood counts, electrocardiographs and
anxious owners. In this switch from the funda-
mental to the business end of disease, the link
between the two
is
often obscured. It
is
easy to
forget that all clinical disease is the result of
malfunction (hypofunction or hyperfunction)
within one or several organ systems, and that
such malfunction springs from some patho-
logic process within living tissues.
Although some disease processes are purely
functional, in most instances the pathologic
events involve structural alteration of the
affected organ, which may or may not be
reversible or repairable. At least one of the
basic reactions of general pathology, such as
necrosis, inflammation, neoplasia, atrophy or
dysplasia, will be present.
The expert clinician, having recognized
functional failure in a particular organ as the
cause of a clinical problem, is easily able to

The critical factor is the erosion of functional
reserve capacity or, conversely, the stimu-
lation of significant hyperfunction.
Modern veterinary medicine provides an
expanding battery of clinical diagnostic aids,
by which organ function may be assessed and
tissue disease processes characterized. This
happy situation catalyzes the fusion of the
clinical sciences and tissue pathology. Whilst
we cannot promise diamonds, we hope that
the veterinary student will find a crystalline
1
The relationship between pathology and medicine
and easily digestible fusion in the chapters of
this book.
These introductory remarks pave the way
for the enunciation of some general principles.
The limited nature of clinical and
pathologic responses
The clinical signs resulting from malfunction
of a particular organ may be likened to the
themes and variations of a particular musical
composition. Regardless of variations induced
by different etiology and pathogenesis, the
thread of the basic theme
is
always apparent to
the thoughtful investigator. In the case of
renal failure, for example, two basic themes -
failure of urinary concentration and elevation

is
further refined to a localization of the
problem to a particular organ or tissue, and
often the 'single' problem may prove to be a
plethora of
problems.
The next step is usually
confirmation of suspicions by the use of
appropriate clinical aids such as radiography
and the taking of blood and tissue samples.
Then follows characterization, directly or by
inference, of the underlying pathologic pro-
cess.
This is ideally accompanied by identifi-
cation of the specific cause, by further testing
or by inference from previous experience. The
culmination of all these steps and procedures
is
the prediction of the outcome of the process.
This method of investigation has widespread
acceptance and again demonstrates the
inextricable link between the clinical appear-
ance of the disease and the underlying
pathology. Recognition, localization and con-
firmation are the essence of clinical skill,
whereas characterization and identification
involve knowledge of tissue reactions. The last
and most important step of prediction is a
combination of the two disciplines.
Disease versus failure

will be able to assess the type and character of
any lesion and decide if it has nil, moderate or
marked effect on organ function.
Reversible versus irreversible disease
One of the central features of the clinician's
skill is the ability to estimate the outcome of a
disease process. While a number of factors
need to be considered, the two most important
are the conclusions reached about the nature
of the disease process and the inherent ability
of a particular tissue to replace its specialized
cells.
The nature of the disease process may, for
example, be a selective degeneration and
necrosis of specialized cells. This may be
caused by a number of agents and may be
accompanied by an inflammatory process. If
the offending cause is removed or disappears
and the architectural framework remains, a
number of organs have the capacity to replace
the lost cells. Prominent in this regard are the
skin, liver, kidney, bone, muscle and most
mucosal lining cells. However, tissues such as
the brain, spinal cord and heart muscle have
little or no capacity for regeneration.
Sometimes, when a disease process
is
highly
destructive, it matters little if the organ has the
capacity to regenerate and the only savior in

at their core immunologic mechanisms, basic
information is also required on the cells of the
immune system and their interactions and
effector mechanisms.
The immune system is extremely complex,
performing a variety of activities directed
towards maintaining homeostasis. It consists
of an intricate communications network of
interacting
cells,
receptors and soluble factors.
As a consequence of this complex organiz-
ation, it is immensely flexible and is able
greatly to amplify or markedly to diminish a
given response, depending upon the circum-
stances and momentary needs of the animal. A
normally functioning immune system is an
effective defense against the intrusion of
noxious foreign materials such as pathogenic
microbial agents, toxic macromolecules and to
some extent against endogenous cells which
have undergone neoplastic transformation.
However, by virtue of its inherent complexity,
the system has the potential to malfunction
and, since it also has the ability to trigger effec-
tor pathways leading to inflammation and cell
destruction, may then cause pathologic effects
ranging from localized and mild to generalized
and life threatening.
The intensity of a particular immune

ubiquitously distributed throughout body
tissues and has as basic operational features:
molecular recognition, amplification and
memory, together with a range of effector
pathways by which foreign material may be
eliminated. The last of these can be divided
Organization and regulation
broadly into the humoral and cell-mediated
immune responses.
In addition, such a system requires precise
regulation in order to avoid excessive and
hence wasteful responses, and also potentially
dangerous reactivity to self components.
These diverse activities are performed by a
limited number of morphologically distinct
cell types which are capable of migrating
through the organs and tissues, performing
their functions remote from their
sites
of origin
and maturation. In this section, the chief
features and interactions of these cells where
considered germane to the main theme of this
chapter will be reviewed briefly.
Cells of the immune system
The ability of the individual to recognize and
respond to the intrusion of foreign macro-
molecules resides in cells of the lymphoid
series.
Lymphoid cells are distributed

Lymphocytes are activated by contact with
appropriate antigenic determinants and then
undergo transformation, proliferation and
further differentiation (Fig. 2.1). Ultimately,
one or more effector pathways are initiated
and the antigen concerned may then be elimin-
ated. Activated cells secrete a variety of bio-
logically active effector molecules which are
responsible both for cellular regulation and
effector functions. In addition,
a
proportion
of
the expanded cell population remains dor-
mant as memory cells and accounts for the
augmented secondary response on re-
exposure to the same antigen.
Lymphocytes are divided into B and T
cell classes on the basis of ontogeny and
function. Functionally, B lymphocytes are
responsible for humoral, and T lymphocytes
for cell-mediated immune responses. These
cells also differ in their distribution within
lymphoid tissues and in their expression of cell
surface molecules (markers). Thus the
immune system can be regarded as a system
composed of dual but interacting compart-
ments.
The B lymphocyte
Cells of this lineage are the progenitors of

occurs.
The functional activities of B cells depend
on an array of
cell
surface receptor molecules,
including Ig receptors for antigen, histocom-
patibility markers, receptors for the Fc region
of IgG and for complement (C3b component).
The T lymphocyte
T lymphocytes which undergo maturation in
the thymus are key cells in the expression of
many facets of immunity, where they perform
a variety of functions essentially concerned
with immune regulation and the elimination
of
abnormal cells.
T cells orchestrate the immune response by
modulating the activities of both
B
and other T
cells.
Regulation may be either positive or
negative. So, T cells are involved in initiating
immune responses (T helper cells) and also
terminating them (T suppressor cells). T cells
are also the principal cells involved in initiat-
ing cellular immune events which include such
phenomena as delayed hypersensitivity
reactions and allograft rejection.
Another facet of cell-mediated immunity is

In major contrast to B cells, T cells recognize
antigen only when it is presented on a cell sur-
face.
Furthermore, the antigen-presenting cell
must be of histocompatibility type identical
with that of the T cell concerned. Thus, in this
instance, antigen recognition is restricted and
can only be accomplished in the context of an
appropriate histocompatibility molecule. The
latter occurs in several different classes and it
is now clear that the major subsets of T cells
described above, recognize antigen in associ-
ation with different histocompatibility classes.
Thus helper/inducer cells are restricted to the
recognition of antigen on cells bearing the
class II molecules (immune-associated anti-
( T helper
V<
cell-'.
^ (CD4
+
8") '
mr<
*W4
cell membrane
T cytotoxic
>/-/ cell /\ /
y (CD4"8
+
)

number of other important cell surface
molecules such as class I and II histocompati-
bility antigens and is evidently a member of
the immunoglobulin supergene family (Fig.
2.3).
Soluble factors
secreted
by T
cells
Following activation, T lymphocytes manu-
facture and secrete an as yet undetermined
number of biologically important soluble sub-
stances commonly called lymphokines. These
substances affect the behavior of other cells
and play a prominent role in immunologically
induced inflammatory change as well as in
• intrachain disulphide bond
areas of sequence homology
histocompatibility
T cell marker
T cell B cell
antigen immunoglobulin
receptor antigen
receptor
Fig.
2.3. The cell membrane and glycoprotein
molecules of the immunoglobulin supergene family.
_
2
,

Interferon
Osteoclast-activating factor
Colony-stimulating activity
various stages of the immune response
itself.
At present, at least 60 of these factors have
been described and it has proved to be difficult
to isolate and to characterize them biochemi-
cally. Consequently, at present, it is not
known how many distinct lymphokines are
produced but they are generally small poly-
peptides (15000-60000 M
r
) which have very
short half lives in vivo. Those characterized
can be divided into four groups according to
the target cell they affect (Table 2.1).
'Null'
lymphocytes
Although the majority of lymphocytes bear
surface markers of either T or B cells, a small
number do not and are termed 'null'
cells.
Null
lymphocytes probably encompass a number
of
cell lineages in various stages of differen-
tiation. Among them are included killer (K
cells) and natural killer (NK) cells. K cells are
characterized by membrane receptor

istic is their ability to pinocytose soluble
molecules and phagocytose particles. Certain
types have the ability also to process and pre-
sent this internalized foreign material to
immunocompetent lymphocytes. In addition,
they provide factors necessary for lymphocyte
activation and proliferation. They play a cru-
cial role in the early inductive events of the
immune response. Macrophages also respond
to external stimuli emanating from activated
lymphocytes and are important effector cells
in cell-mediated immune reactions.
Particulate antigens are taken up via phago-
cytosis, soluble antigens by pinocytosis.
Aggregated material is ingested much more
rapidly than is non-aggregated, with the bulk
of ingested foreign material rapidly degraded
by lysosomal enzymes. The remainder
(approximately 10%) is only partially
degraded and persists in macromolecular form
associated with the
cell
membrane or
in
special
vacuoles inaccessible to lysosomal enzymes.
In this latter situation it can survive within cells
in which intense phagocytosis and catabolic
activities are in progress. Some undegraded
antigen may eventually be released but most is

in this category are those factors which
influence immune function and only these
will be discussed in depth in this section.
Interleukin I (IL-1), also known as lympho-
cyte-activating factor (LAF) is a protein of
about 15000 M
r
secreted particularly after
interaction with T
cells,
immune complexes or
bacterial products. It stimulates both lympho-
cytes to proliferate and mature T cells to
release their own growth-promoting
molecules. Following infection, IL-1 can also
stimulate hepatocytes to secrete a number of
proteins known as acute phase proteins and
can also induce fever. Its main role appears to
be in the expansion of T lymphocyte clones.
IL-1 has no effect on B cells.
B lymphocyte activating factor (BAF)
affects only B cells and enhances the pro-
duction of antibodies. Its production is influ-
Organization and regulation
enced by some macrophage-activating stimuli
such as endotoxin.
In addition to the above, factors affecting
other cells are also generated during the
course of macrophage activation. One such
factor stimulates bone marrow stem cells to

cells are activated by presenting antigen to T
helper cells in association with class II MHC
molecules in a manner analogous to that of
macrophages and other antigen-presenting
cells.
Effector cells of immune reactions
A number of leukocytes and connective tissue
cells participate as effector cells in immuno-
logic reactions. These reactions will be
detailed later, but a brief reference is appro-
priate here. They include polymorphonuclear
leukocytes (granulocytes) and mast cells.
Neutrophils are involved in reactions
mediated by antigen-antibody-complement
complexes, and basophils in inflammatory
reactions mediated by IgE antibodies. Eosino-
phils are frequent participants in allergic
reactions involving IgE antibodies. Mast cells
are similarly involved in IgE-mediated reac-
tivity and like basophils carry surface recep-
tors for these immunoglobulins. However, in
contrast to basophils, these are connective-
tissue cells which are not found in the blood.
Regulation of the immune response
The precise regulation of the immune system
is crucial to the health of the individual for
reasons given on p. 22. The regulation of this
complex system is dependent on a number of
interacting mechanisms which are as yet not
fully understood. Ultimately, the extent of

which promotes T
cell
proliferation (Fig.
2.4).
Under macrophage influence, the T cell
expresses interleukin-2 (IL-2) receptors on its
10 The immune system
surface and also secretes this factor. IL-2 pro-
duction is necessary for the proliferation of all
T cells. In this way macrophages exert a very
important positive regulatory influence on the
early stages of the immune response and to a
large extent may determine its character, as,
for example, whether the response
will
be pre-
dominantly of the T cell or B cell type or to
what extent antibodies or memory cells are
generated. Once lymphocytes are activated,
they in turn influence macrophage behavior
by
secreting a variety of soluble mediators, as
previously described. Although much is still
uncertain concerning macrophage/lympho-
cyte interaction, it is clear that the macro-
phage is highly influential in both normal and
abnormal immunologic reactivity.
B-T
cell collaboration
Helper T cells interact with B cells promoting

B, B
cell;
PC, plasma
cell;
IL-1,
interleukin
1;
IL-2,
interleukin
2;
BCGF-1,
B cell
growth
factor
1
(or IL-4);
Ig,
immunoglobulin.
many unresolved issues in this collaboration
the following three main stages are recognized
(Fig. 2.4).
1 Recognition of antigen by the B cell via sur-
face immunoglobulin receptors.
2 B cells present antigen fragments to T cells,
the cells interacting in a process modulated
by class IIMHC glycoproteins.
3 T cells undergo expansion under IL-2 influ-
ence and secrete lymphokines that promote
B cell growth and differentiation and lead
ultimately to antibody production by

depending on circumstances (Fig. 2.5). T
helper and T suppressor cells can be regarded
as opposing cell types and the response to an
antigen may be the result of a critical balance
between these cells. Suppressor cells have
also been shown to be capable of specifically
suppressing other immune phenomena, such
as delayed-type hypersensitivity, contact
sensitivity and target cell killing by cytotoxic
cells.
T suppressor cells are generated concur-
Inflammation and tissue injury
11
rently with
the
appearance
of T
helper cells
and
the
development
of the
response
to
anti-
gen.
The
physiologic development
of T sup-
pressors

1 Very high
or
very
low
concentrations
of
antigen.
2
The
nature
of
antigen
- in
particular highly
soluble antigen, which
can
escape phago-
cytosis.
3 Repeated exposure
to
antigen.
4 Route
of
antigen entry
- in
particular
the
intravenous route.
5
Age -

H
,
T
helper
cell;
T
s
,
T
suppressor
cell;
IL-1, interleukin
1;
IL-2,
interleukin
2.
The termination of the immune response
Several distinct mechanisms are thought to act
in concert
to
halt
an
immune response,
thereby conserving resources.
1 The
elimination
of
antigen.
The
persistence

known
to
inactivate
B
cells
by
binding
to
their
Fc
receptors. Thus, antibody gener-
ation acts
as an
important feedback regu-
latory mechanism.
3
The emergence
of
suppressor T cells.
As
dis-
cussed, these cells
are a
significant regu-
latory component normally activated during
the immune response.
4
Anti-idiotype antibody generation.
The
unique molecular configuration

microorganisms that threaten
the
welfare
of
the host
it can
also prove
to be
deleterious.
The immune response
to an
infecting micro-
organism may lead
to its
elimination,
but the
same response may produce significant patho-
logic
or
even lethal effects
in the
host. Even
more inappropriate immune reactions, giving
rise
to
pathologic changes, may be induced by
inert non-toxic environmental antigens
or,
indeed, self-components.
12 The immune system

system is able to orchestrate a spectrum of
pathologic changes resulting from mild local
inflammation to severe and widespread tissue
necrosis or even circulatory collapse. These
immune effector mechanisms, together with
the humoral amplification systems will be dis-
cussed below.
Immune effector mechanisms involved in
disease production
The various immune mechanisms involved in
the production of damaging reactions have
been classified into four basic types and this
classification will be used in the present dis-
cussion.
Type I (anaphylactic) reaction
Essentially, this involves the rapid degranu-
lation of mast cells or basophils previously
sensitized by antibodies of the IgE class fol-
lowing contact with the corresponding antigen
(Fig. 2.8
(II) and (6)).
Only antigens which are polyvalent are able
to cause mast cell degranulation. Triggering
of
degranulation requires that adjacent IgE
molecules on the cell surface are cross-linked
by antigen. With degranulation, various
chemical mediators such as histamine and
serotonin (5-HT) are released, leading to
antigen entry

Fig.
2.6. Immunologic mechanisms in the generation
of inflammation. C, complement.
Fig.
2.7. Sequence of events leading to immune-
mediated tissue injury.
Inflammation and tissue injury 13
(a)
Type I
I Anaphylactic |
1st stage: sensitization
Cctfl antigen
penetration
lymphocyte
secretion
sensitization
(b)
plasma cells
IgE antibodies
mast cells
basophils
bronchioles
histamine
bradykinin
5HT
SRS-A
ECF-A capillaries
heparin (dog)
degranulation
vasodilation

ized by enzymatic action from cell membrane
phospholipids (Fig. 2.9) and include the
leukotrienes, prostaglandins and platelet-
activating factor. The various mediators
generated and their properties are sum-
marized in Table 2.2.
In essence, it is apparent that the binding of
antigen to IgE surface receptors results in the
release and production of potent molecules by
mast cells, basophils and perhaps other cells.
These molecules are especially important
pathologically when their large scale pro-
duction gives rise to systemic circulatory and
respiratory effects. The precise manner of
their interaction in the production of all type I
manifestations is not clear. Fortunately, the
platelet
activating
factor (PAF)
Fig.
2.9. Major secondary mediators in the anaphyl-
actic reaction, a, activated; SRS-A, slow-releasing
substance of anaphylaxis.
14 The immune system
Table 2.2.
Biologic mediators
of type I
reactions
Preformed
mediators

cells
Macrophages
via lipoxygenase action
on arachidonic acid
LTC4
LTD4
LTE4
Cell membrane of:
basophils
mast cells
macrophages
via cyclo-oxygenase
action on arachidonic acid
Stimulated
by
LT5
Cell membranes
of
Basophils
Mast
cells
Macrophages
Action
Smooth muscle contraction
Gastric secretion (increase)
Heart rate (increase)
B ronchoconstriction
Vascular permeability
(increase)
Vasoconstriction

Reactions of this type are generally cytotoxic
in character and involve the combination of
IgG or IgM antibodies with antigenic deter-
minants on a cell membrane. Alternatively, a
free antigen or hapten may
be
adsorbed on to a
tissue component or cell membrane and anti-
body subseqneutly binds with this adsorbed
antigen. The attachment of circulating anti-
body usually results in cell lysis or phago-
cytosis, depending upon the final effector
pathway (Fig. 2.10). There are situations,
however, where the combination of antibody
with cell-bound determinants does not result
in cytotoxicity but causes a pathologic effect
by blocking and inactivating physiologically
important cell surface molecules such as
hormone receptors.
The target for cytotoxic reactions may be
either a specific cell type within a tissue or the
Inflammation and tissue injury 15
circulating blood, or a variety of cell types
carrying similar surface determinants
(exogenously or endogenously derived).
The attachment of antibody to cells targets
them for attack by either the complement
sequence or by various effector cell types.
Complement-fixing antibody is not required
for the latter activity, but the cells involved

plex deposition is shown in Fig. 2.11.
A variety of factors are involved in the
deposition of complexes in vulnerable tissue
sites,
particularly the subendothelial regions
of small blood vessels.
1 Size of complex
The outcome of the formation of immune
complexes in vivo depends not only on the
absolute concentration of antigen and anti-
Type ii
C1-9
direct lysis
phagocytosis enhanced
by opsonization (IgG)
phagocytosis enhanced
by immune adherence
(IgG IgM
+
C3b)
antibody-dependent cell
mediated cytotoxity
Fig.
2.10. Type II hypersensitivity (cytotoxic). Effector
mechanisms are depicted, but the common factor is
the binding of specific antibody to the target
cell.
M(J),
macrophage; C1-9, complement factors.
Fig.

active amines. These may be supplied by
activation of mast cells, basophils and
platelets (see Fig. 2.11).
3 Hemodynamic factors
Complexes tend to become localized in
vessels where there is an increase in blood
pressure and/or turbulence which tends to
promote adherence of platelets to the endo-
thelium.
4 Efficiency of clearance
In circumstances where the activity of
phagocytes of liver and spleen decreases (as
a result, for example, of the previous uptake
of particulate matter), immune complexes
may circulate longer and may therefore
have greater opportunity to become local-
ized in vulnerable tissue sites.
5 Anatomical features of the tissue
Sites of high levels of blood filtration such as
the renal glomeruli and choroid plexus are
prime sites of deposition because of endo-
thelial fenestration, high blood flow and
hydrostatic pressure.
6 Role of complement
Complement has an important role in
modulating the size and facilitating the
removal of immune complexes, and in the
case of
C2
and C4 deficiencies the incidence

^__ Type IV
I Cell-Mediated (delayed hypersensitivity) I
other cells
lymphokines
MAF and others
Fig.
2.12. Type IV hypersensitivity (cell mediated). T
DH
,
T lymphocyte (delayed hypersensitivity); M<j>,
macrophage; MAF, macrophage-activating factor;
SMAF,
specific macrophage-arming factor.