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
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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
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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
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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
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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
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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
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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
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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
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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