Page 82 - Textbook of Pathology, 6th Edition

66 clinical features of GVH reaction include: fever, weight loss, graft rejection may be mediated by cellular or humoral
anaemia, dermatitis, diarrhoea, intestinal malabsorption, mechanisms. Acute cellular rejection is more common than
pneumonia and hepatosplenomegaly. The intensity of GVH acute humoral rejection.
reaction depends upon the extent of genetic disparity
between the donor and recipient. Microscopically, the features of the two forms are as
under:
Mechanisms of Graft Rejection Acute cellular rejection is characterised by extensive
infiltration in the interstitium of the transplant by lympho-
Except for autografts and isografts, an immune response cytes (mainly T cells), a few plasma cells, monocytes and
against allografts is inevitable. The development of a few polymorphs. There is damage to the blood vessels
SECTION I
immunosuppressive drugs has made the survival of and there are foci of necrosis in the transplanted tissue.
allografts in recipients possible. Rejection of allografts Acute humoral rejection appears due to poor response to
involves both cell-mediated and humoral immunity.
immunosuppressive therapy. It is characterised by acute
1. CELL-MEDIATED IMMUNE REACTIONS. These are rejection vasculitis and foci of necrosis in small vessels.
mainly responsible for graft rejection and are mediated by The mononuclear cell infiltrate is less marked as compared
T cells. The lymphocytes of the recipient on coming in to acute cellular rejection and consists mostly of
contact with HLA antigens of the donor are sensitised in B lymphocytes.
case of incompatibility. Sensitised T cells in the form of
cytotoxic T cells (CD8+) as well as by hypersensitivity 3. CHRONIC REJECTION. Chronic rejection may follow
reactions initiated by T helper cells (CD4+) attack the graft repeated attacks of acute rejection or may develop slowly
and destroy it. over a period of months to a year or so. The underlying
2. HUMORAL IMMUNE REACTIONS. Currently, in mechanisms of chronic rejection may be immunologic or
addition to the cell-mediated immune reactions, a role for ischaemic. Patients with chronic rejection of renal transplant
humoral antibodies in certain rejection reactions has been show progressive deterioration in renal function as seen by
suggested. These include: preformed circulating antibodies due rising serum creatinine levels.
to pre-sensitisation of the recipient before transplantation e.g.
by blood transfusions and previous pregnancies, or in non- Microscopically, in chronic rejection of transplanted
sensitised individuals by complement dependent cytotoxicity, kidney, the changes are intimal fibrosis, interstitial fibrosis
antibody-dependent cell-mediated cytotoxicity (ADCC) and and tubular atrophy. Renal allografts may develop
antigen-antibody complexes. glomerulonephritis by transmission from the host, or
General Pathology and Basic Techniques
rarely may be de novo glomerulonephritis.
Types of Rejection Reactions
Based on the underlying mechanism and time period, DISEASES OF IMMUNITY
rejection reactions are classified into 3 types: hyperacute,
acute and chronic. The word immunity is synonymous with resistance meaning
protection from particular diseases or injuries, whereas the
1. HYPERACUTE REJECTION. Hyperacute rejection term hypersensitivity is interchangeable with allergy meaning
appears within minutes to hours of placing the transplant a state of exaggerated or altered immune response to a given
and destroys it. It is mediated by preformed humoral agent. The diseases of the immune system are broadly
antibody against donor-antigen. Cross-matching of the classified into the following 4 groups:
donor’s lymphocytes with those of the recipient before
transplantation has diminished the frequency of hyperacute I. Immunodeficiency disorders characterised by deficient
rejection. cellular and/or humoral immune functions. This group is
comprised by a list of primary and secondary immunodeficiency
Grossly, hyperacute rejection is recognised by the surgeon diseases including the dreaded acquired immunodeficiency
soon after the vascular anastomosis of the graft is syndrome (AIDS).
performed to the recipient’s vessels. The organ becomes
swollen, oedematous, haemorrhagic, purple and cyanotic II. Hypersensitivity reactions characterised by hyper-
rather than gaining pink colour. function of the immune system and cover the various mecha-
Histologically, the characteristics of Arthus reaction are nisms of immunologic tissue injury.
present. There are numerous neutrophils around dilated III. Autoimmune diseases occur when the immune system
and obstructed capillaries which are blocked by fibrin and fails to recognise ‘self’ from ‘non-self’. A growing number of
platelet thrombi. Small segments of blood vessel wall may autoimmune and collagen diseases are included in this group.
become necrotic and there is necrosis of much of the
transplanted organ. Small haemorrhages are common. IV. Possible immune disorders in which the immunologic
mechanisms are suspected in their etiopathogenesis. Classical
2. ACUTE REJECTION. This usually becomes evident example of this group is amyloidosis discussed later in this
within a few days to a few months of transplantation. Acute chapter.