Page 93 - Textbook of Pathology, 6th Edition

PATHOGENESIS. It may be mentioned here that both type i) The antigen is recognised by CD8+ T cells (cytotoxic T cells) 77
II and type III reactions have antigen-antibody complex and is processed by antigen presenting cells.
formation but the two can be distinguished— antigen in type ii) Antigen-presenting cells migrate to lymph node where
II is tissue specific while in type III is not so; moreover the antigen is presented to helper T cells (CD4+ T cells).
mechanism of cell injury in type II is direct but in type III it iii) Helper T cells release cytokines that stimulate T cell
is by deposition of antigen-antibody complex on tissues and proliferation and activate macrophages.
subsequent sequence of cell injury takes place. iv) Activated T cells and macrophages release proinflam- CHAPTER 4
Type III reaction has participation by IgG and IgM matory mediators and cause cell destruction.
antibodies, neutrophils, mast cells and complement. The EXAMPLES OF TYPE IV REACTION. Type IV reaction can
sequence of underlying mechanism is as under (Fig. 4.7, C): explain tissue injury in following common examples:
i) Immune complexes are formed by interaction of soluble 1. Reaction against mycobacterial infection e.g. tuberculin
antibody and soluble or insoluble antigen. reaction, granulomatous reaction in tuberculosis, leprosy.
ii) Immune complexes which fail to get removed from body 2. Reaction against virally infected cells.
fluid get deposited into tissues. Generally, small and 3. Reaction against malignant cells in the body.
intermediate sized antibodies and antigens precipitate out 4. Reaction against organ transplantation e.g. transplant
of the body fluid and get deposited in tissues. rejection, graft versus host reaction.
iii) Fc component of antibody links with complement and
activates classical pathway of complement resulting in AUTOIMMUNE DISEASES
formation of C3a, C5a and membrane attack complex.
iv) C3a stimulates release of histamine from mast cells and Autoimmunity is a state in which the body’s immune system
its resultant effects of increased vascular permeability and fails to distinguish between ‘self’ and ‘non-self’ and reacts Immunopathology Including Amyloidosis
oedema. by formation of autoantibodies against one’s own tissue
v) C5a releases proinflammatory mediators and chemotactic antigens. In other words, there is loss of tolerance to one’s
agents for neutrophils. own tissues; autoimmunity is the opposite of immune tolerance.
vi) Accumulated neutrophils and macrophages in the tissue Immune tolerance is a normal phenomenon present since
release cytokines and result in tissue destruction.
foetal life and is defined as the ability of an individual to
EXAMPLES OF TYPE III REACTION. Common examples recognise self tissue and antigens. Normally, the immune
of cell injury by type III injury are as under: system of the body is able to distinguish self from non-self
i) Immune complex glomerulonephritis in which the antigen antigens by the following mechanisms:
may be GBM or exogenous agents (e.g. Streptococcal 1. Clonal elimination. According to this theory, during
antigen). embryonic development, T cells maturing in the thymus
ii) Goodpasture syndrome having GBM as antigen. acquire the ability to distinguish self from non-self. These T
iii) SLE in which there is nuclear antigen (DNA, RNA) and cells are then eliminated by apoptosis for the tolerant
there is formation of anti-nuclear and anti-DNA individual.
autoantibodies. 2. Concept of clonal anergy. According to this mechanism, T
iv) Rheumatoid arthritis in which there is nuclear antigen. lymphocytes which have acquired the ability to distinguish
v) Farmer’s lung in which actinomycetes-contaminated hay self from non-self are not eliminated but instead become non-
acts as antigen. responsive and inactive.
vi) Polyarteritis nodosa and Wegener’s granulomatosis with 3. Suppressor T cells. According to this mechanism, the
antineutrophil cytoplasmic antigen. tolerance is achieved by a population of specific suppressor
vii) Henoch-Schönlein purpura in which respiratory viruses T cells which do not allow the antigen-responsive cells to
act as antigen. proliferate and differentiate.
viii) Drug-induced vasculitis in which the drug acts as
antigen. PATHOGENESIS (THEORIES) OF AUTOIMMUNITY
The mechanisms by which the immune tolerance of the body
Type IV: Delayed Hypersensitivity (Cell-Mediated) is broken causes autoimmunity. These mechanisms or
Reaction
theories of autoimmunity may be immunological, genetic,
Type IV or delayed hypersensitivity reaction is tissue injury and microbial, all of which may be interacting.
by cell mediated immune response without formation of 1. Immunological factors. Failure of immunological
antibodies (contrary to type I, II and III) but is instead a slow mechanisms of tolerance initiates autoimmunity. These
and prolonged response of specifically-sensitised T mechanisms are as follows:
lymphocytes. The reaction occurs about 24 hours after i) Polyclonal activation of B cells. B cells may be directly
exposure to antigen and the effect is prolonged which may activated by stimuli such as infection with microorganisms
last up to 14 days.
and their products leading to bypassing of T cell tolerance.
ETIOLOGY AND PATHOGENESIS. Type IV reaction ii) Generation of self-reacting B cell clones may also lead to
involves role of mast cells and basophils, macrophages and bypassing of T cell tolerance.
CD8+ T cells. Briefly, the mechanism of type IV reaction is iii) Decreased T suppressor and increased T helper cell activity.
as under (Fig. 4.7, D): Loss of T suppressor cell and increase in T helper cell