Overview of Immune Disorders

Hypersensitivity
• Is an exaggerated or inappropriate immune response
to a particular antigen (allergen) results in harmful
affects in a previously sensitized person.
• There are 4 types of Hypersensitivities reactions
based on the mechanisms involved and time taken
for the reaction.
1. Type I (immediate) allergic or anaphylaxis an
IgE mediated
2. Type II is Cytotoxic hypersensitivity
3. Type III is immune complex mediate
4. Type IV is delayed or cell-mediated
hypersensitivity
Various Types Of Hypersensitivity Reactions
TYPE-1 HYPERSENSITIVITY
Type I: IgE-Mediated Immediate Hypersensitivity

 Define as a state of rapidly developing

or anaphylactic type of immune
response to an antigen(allergen)
(1) First exposure an allergens such as dust,
pollen, animal dander , penicillin causes
Clonal expansion of B and T cells specific to
the allergen.
(2) Subsequent exposure results in a rapid
response (often within minutes).
(3) TH2 response results in activation of B cells
and secretion of IgE against the allergen .
(1)IgE bind on mast cell and result
degranulation, of mast cells and release
of its contents like histamine, heparin,
platelet activating factor etc. which
induce allergic response.

(2) Depending upon the route of exposure

and the severity of the reaction, e.g.
swelling, hives, hay fever, asthma or even
death by systemic anaphylaxis.
MECHANISM OF TYPE-1 HYPERSENSITIVITY
EXAMPLE
Local (Atopy):
• Bronchial Asthma
• Urticaria, Hay fever
• Allergic rhinitis
• Atopic dermatitis
• Allergic gastritis
Systemic Anaphylaxis:
• Sever immediate reaction occur after
injection of foreign proteins
(antisera ,hormones, enzymes).
• Systemic anaphylaxis
• Respiration becomes difficult, Blood pressure
drops ,Smooth muscles of bladder and GI
tract contract
Bronchoconstriction, Slurred speech, Swollen
tongue Fluctuating pulse
ANAPHYLAXIS
 Chemical Mediators of Immediate Hypersensitivity
Preformed Mediators EFFECT
bronchoconstriction, mucus secretion,
Histamine
vasodilatation, vascular permeability
Bronchial mucus secretion , degradation of
Protease
vascular basement membrane.
kinins and vasodilatation, vascular permeability,
kininogenase
edema
Eosinophil
chemotactic factor It attract eosinophil and neutrophils
of Anaphylaxis (ECF-
A)
Newly formed mediators EFFECTS
Leukotriene B4 Recruit PMN and induce inflammation
Contraction of smooth muscle lead to
Leukotriene C4 & D4 bronchoconstriction and vasoconstriction. It also
increases vascular permeability.
increase vascular permeability (edema) and act
Prostaglandins D2
as chemoattractant
Platelet
platelet aggregation and heparin release:
aggregating factor
 LAB DIAGNOSIS:
• Skin Test to
diagnose
allergies:
• RIST(/
radioimmuno-
sorbent Test) total
serum IgE count
• Radio
Allergosorbent
test (RAST). IgE
specific for a single
allergen
 TYPE-II
HYPERSENSITIVITY
 TYPE-II HYPERSENSITIVITY
In a cytotoxic reaction, the antibody reacts directly
with the antigen that is bound to the cell
membrane to induce cell lysis ( e.g. RBC, WBC,
platelet, liver, lung, Kidney etc) through
complement activation, functional loss, or
damage to tissues .
These antigens may be intrinsic or “self” as in
autoimmune reactions or extrinsic or “non-
self.” Cytotoxic reactions are mediated by IgG and
IgM
It mediated by 3 different mechanisms.
• Complement mediated:
• Antirceptor antibody
• Antibody dependent cellular toxicity
 Transfusion reactions
 Erythroblastosis fetalis
 Myasthenia gravis
 Graft rejection
 Hemolytic Disease of New born
( Erythroblastosis fetalis)

1. enlarge liver and spleen with abdominal swelling

2. Raised Bilirubin due to RBC break down
Myasthania Gravis: Antibody is directed against acetylcholine receptors at
the motor end plate of a muscle, blocking the receptors and diminishing the
muscular response. This is the mechanism for muscle weakness in
myasthenia gravis.
Type III: Immune Complex Reaction
 TYPE-III Immune Complex
Hypersensitivity
• Immune-Complexes deposits. An
abnormal immune response is mediated
by the formation of antigen-antibody
aggregates called "immune complexes."
• In type III Hs the antigen is freely
circulating multivalent and soluble
which form large web-like complexes.
• These "immune complexes." deposits in
various tissues such as skin, joints,
vessels, or glomeruli, and induces the
classical complement pathway activation
.
• Immune complexes activate
Complement which results in PMN
chemotaxis and activation. PMNs
then release lyosome enzymes
tissue damaging. causes
inflammation tissue damage.
• Type III HS may cause localized
inflammatory reaction e.g. Arthus
reaction or generalized
inflammatory response e.g. Serum
sickness
 Arthus Reaction (Localized)
is a localized inflammatory response, against
antigen antibody complexes mainly in the
vascular walls lead to blockage and necrosis
of vessels,
Example: The clinical presentation is hypersensitivity
pneumonitis.(so-called "farmer's lung" ,
“woodworker lung”, “Cheese-worker lung” &”
wheat millers lung
• Most of these occur by inhalation of some
microorganisms either bacteria or fungus growing
on starting material.
• The Arthus reaction also occur at the site of tetanus
injection if they are given on same site with short
interval
 Allergic Vasculitis, Type III Erythematous Skin Lesion
Reaction
 Serum sickness (Generalized )
• Serum sickness is systemic inflammatory response.
• Immune complexes deposited in many areas of the
body serosa (pleura , pericardium, synovium), and
glomeruli.
• After the injection of foreign serum and certain
drugs. When foreign substances have long half life
and administer repeatedly.
The clinical manifestation like fever,
urticaria ,arthralgia, lymphadenopathy, splenomegaly
and eosinophilia occur with in few days or few weeks.
Examples: Post Streptococcus glomerular nephritis.
Systemic Lupus Erythematosus (SLE),Poly arteritis
nodosa,Viral infection (HIV & Dengue fever)
* Rheumatoid arthritis .
Type IV: Cell-Mediated (Delayed Hypersensitivity)
 TYPE- IV HYPERSENSITIVITY
• This reaction is called "Delayed
hypersensitivity" because it is mediated
by sensitized T lymphocytes
• The response is delayed it start after hours
or days and last for days.
• In contact hyper sensitivity from plant material
( poison oak & ivy) and simple chemical
(Nickle , formaldehyde) produce red itchy
vesicle caused CD8 cytotoxic cell
• In tuberculin skin test the indurated skin rash is
caused by memory CD4 + T cells and
Macrophages that reside near the injection site.
Contact dermatitis due to poison Tuberculin skin test
oak exposure
 Hypersensitivity reactions with
this mode of action include:
• Granulomatous diseases (mycobacteria, fungi)
• Tuberculin skin reactions
• Transplant rejection
• Contact dermatitis
• Erythema multiform
• Steven – Johnson syndrome
• Toxic epidermal necrolysis
 Specific mechanisms of type IV HS reaction
• The classic example of DTH is the tuberculin reaction,
which is produced by the intracutaneous injection of purified
protein derivative (tuberculin), a protein-containing antigen of
the tubercle bacillus. In a previously sensitized individual,
reddening and induration of the site appear in 8 to 12 hours,
reach a peak in 24 to 72 hours, and thereafter slowly subside.
■ Delayed form of type IV hypersensitivity reaction: CD4+
helper T cells (TH1 type) sensitized from previous exposure to
an antigen secrete Interferon-γ, which activates
macrophages. Activated macrophages secrete IL-12, which
causes differentiation of TH1 cells.
• Macrophage as well as CD4 T-cell activate mononuclear cell to
release certain cytokines e.g. IL-1 TNF etc and induction of
inflammation which lead to indurations and granuloma
formation.
• Granuloma: is cellular attempt
to contain an offending agent
that is difficult to eradicate .
Microscopically contain central core
of epitheloid cells surrounded by rim
of lymphocytes there may be central
caseous necrosis and presence of
langhan’s giant cells in TB.
Tuberculin ( Mantoux) Test
 Comparison of Different Types of
hypersensitivity
characteristics type-I type-II type-III type-IV
anaphylactic cytotoxic immune delayed
complex type
Antibody IgE IgG, IgM IgG, IgM None
Antigen exogenous cell surface soluble tissues &
organs
Response time 15-30 minutes- 3-8 hours 48-72 hrs
minutes hours
Appearance weal & flare lysis and Erythema, Erythema
necrosis edema, ,indurati
necrosis on
Histology Basophil, antibody and compleme Monocyte
eosinophil complement nt & ,lymphoc
neutrophil yte
Transferred antibody antibody antibody T-cells
with
Examples allergic erythroblasto SLE, tuberculi
asthma, hay sis allergic n test,
fever fetalis, pneumonit poison
Goodpasture‘ is ivy,