1. IMMUNOPATHOLOGY
Dr Russell Watkins

2. HYPERSENSITIVITY
 Overview:
– Types I - IV, each varying in severity
from mild to life-threatening
– Inappropriate or excessive activation
of immune system, often to usually
harmless antigens

3. TYPE I HYPERSENSITIVITY
 Appears within minutes of exposure to
antigen
 Interaction of antigen, specific IgE &
tissue mast cells
 IgE is normally found at low serum
concentrations but is raised in people
susceptible to Type I hypersensitivity
 IgE raised in parasitic infections

4. TYPE I HYPERSENSITIVITY
 Previous exposure to antigen is
necessary
 Mast cells have specific IgE receptors
 IgE bind to receptors & crosslink

5. TYPE I HYPERSENSITIVITY
 Mast cell degranulation results - release
of intracellular contents
 Histamine, heparin, proteases & other
substances

8. TYPE I HYPERSENSITIVITY
 These mediators affect local smooth
muscle, blood vessels, cause neutrophil
& eosinophil chemotaxis
 This is the immediate response

9. TYPE I HYPERSENSITIVITY
 Arachidonic acid metabolism is also
invoked resulting in formation of
leukotrienes, prostaglandins,
thromboxanes etc
 These products are released 4-6 hrs
later & exacerbate the disease &
contribute to the clinical picture

10. TYPE I HYPERSENSITIVITY
 Effects include
– Vasodilatation
– Increased vascular permeability
– Bronchoconstriction et al

11. TYPE I HYPERSENSITIVITY
 Examples include
– Allergic rhinitis
– Asthma
– Eczema
– Urticaria
– Systemic anaphylaxis
 Such people are called “atopic” & suffer
from “atopy”

12. TYPE I HYPERSENSITIVITY
 Systemic anaphylaxis
– Precipitous drop in BP due to
vasodilatation
Bronchoconstriction
Laryngeal oedema
Rash

17. TYPE II HYPERSENSITIVITY
 Also antibody mediated but IgG & IgM
 Ig is expressed against antigenic
components of cell surfaces
 Thus tend to be tissue specific
 Binding of Ig to cell antigen causes:
– Complement activation
– Antibody-dependent cell-mediated
cytotoxicity (ADCC)

18. TYPE II HYPERSENSITIVITY
 These responses are normally mounted
against infection
 ?Molecular mimicry
 Examples include:
– Graves’ disease
– Myasthenia gravis
– Hyperacute graft rejection

19. TYPE II HYPERSENSITIVITY
 Graves’ disease
– Thyroid cells are not destroyed
– IgG binds to TSH receptor
– Mimics effect of TSH & causes cell to
secrete excess thyroxine

22. TYPE III HYPERSENSITIVITY
 Also antibody mediated
 Antigenic target is soluble & not cell
surface bound
 The combination of IgG/IgM & antigen
is termed an immune complex
 These circulate & lodge in tissues at
remote sites throughout the body

23. TYPE III HYPERSENSITIVITY
 The formation of immune complexes is
a normal antibody response
 Usually cleared by macrophages
 If immune complexes persist, they may
promote an inflammatory response &
then become defined as a
hypersensitivity reaction

24. TYPE III HYPERSENSITIVITY
 Antigens may be exogenous (infection,
environmental agents)
 Endogenous antigens may cause an
autoimmune response
 Factors influencing IC persistence:
– Complex size
– Antigen exposure duration
– Host response
– Local tissue factors

25. TYPE III HYPERSENSITIVITY
 Complex size
– Large & small ICs are efficiently
cleared - intermediate sized ICs
cause hypersensitivity
 Duration of exposure
– Chronic exposure allows continuous
IC formation & accumulation

26. TYPE III HYPERSENSITIVITY
 Host response
– Deficiency of some complement
components impairs clearing of ICs
 Local tissue factors
– Blood pressure, turbulence & filtration
affect IC deposition

27. TYPE III HYPERSENSITIVITY
 Examples:
– Systemic lupus erythematosus
– Post-streptococcal glomerulonephritis

30. TYPE IV HYPERSENSITIVITY
 Cell mediated rather than antibody
mediated (especially Tdth-cell)
 Also called “delayed-type
hypersensitivity” as reactions occur
>12hrs after exposure
 Tdth-cell activation causes chemotaxis of
other lymphocytes, macrophages,
neutrophils

31. TYPE IV HYPERSENSITIVITY
 Classified as
– Contact (peaks at 48-72hrs)
– Tuberculin (peaks at 48-72hrs)
– Granulomatous (peaks at 21-28
days)

32. TYPE IV HYPERSENSITIVITY
 Contact hypersensitivity
– LMW “haptens” bind to normal body
proteins eliciting response
– Occurs in epidermis of skin
– E.g nickel hypersensitivity, drug
sensitivity

34. TYPE IV HYPERSENSITIVITY
 Tuberculin hypersensitivity
– Occurs in dermis of skin
– Basis of Mantoux test for TB

35. TYPE IV HYPERSENSITIVITY
 Granulomatous hypersensitivity
– Granulomata form when antigen
persists
– Occurs in many organs, not just skin
– E.g. leprosy, tuberculosis, sarcoidosis

36. AUTOIMMUNE DISEASE
 A failure of discrimination between self
& non-self antigens
 Self-reactivity normally prevented by a
number of processes which occur in
early lymphocyte development

37. AUTOIMMUNE DISEASE
 These mechanisms may break down &
the immune system attacks normal
body structures
 Almost every organ may be affected

38. AUTOIMMUNE DISEASE
 Autoimmune disease may be
– Organ-specific
 e.g. Grave’s disease, type I DM,
myasthenia gravis, pemphigus &
pemphigoid
– Systemic
e.g. SLE, rheumatoid arthritis,
scleroderma

40. AUTOIMMUNE DISEASE
 Explanatory theories
– Microbial antigens cross-reacting with
host tissues induce a response
against self
– Alteration of self-antigens exposing
new antigenic determinants
unavailable at the time of induction of
fetal tolerance

41. AUTOIMMUNE DISEASE
 Explanatory theories
– Attachment of hapten to self-molecule
forming a hapten-carrier complex
– Deficiency of suppressor T-cells
– Spontaneous emergence of clones of
cells capable of mounting an
autoimmune response

42. AUTOIMMUNE DISEASE
 There is often overlap of features in the
systemic group e.g. patients with SLE may
have features of RA
 Patients may be predisposed to suffer more
than one organ-specific autoimmune disease
e.g. pernicious anaemia is more common in
sufferers of type 1 DM
 Both organ-specific & systemic autoimmune
disease are associated with specific HLA
types

43. AUTOIMMUNE DISEASE
 Cytokines & Th -cells are implicated - certain
cytokines influence expression of HLA types
 Antibodies (autoantibodies) & the B-cells
producing these are a normal finding. Under
normal conditions, they are not auto-
aggressive
 Th-cells induce the B-cells to produce more
auto antibodies in response to triggering by
self-antigen

45. AUTOIMMUNE DISEASE
 Contributory factors
– Genetics
 Familial tendencies, twin concordance (less than
100% for IDDM)
 HLA associations (e.g. DR1 & DR4 in RA)
– Hormone effects
 Autoimmune diseases tend to be more common
in females
– Environment
 Infectious agents
 Drugs & chemicals

61. IMMUNODEFICIENCY
 Immunodeficiency causes increased
susceptibility to infections & other diseases
 The immune system essentially consists of:
– Humoral immunity
– Cell-mediated immunity
– Phagocytosis
– Complement

62. IMMUNODEFICIENCY
 Deficiencies in each of the functional
systems may occur. They may be
– Genetically determined
– Due to disease states
– Due to environmental factors
Drugs
Viral infections