26.

Disorders in immune system:

Hypersensitivity
Dr. Damodar Sedhai
Date:
 Hypersensitivity
• Hypersensitivity refers to altered responses of
the cells involved in the antigenic stimuli that
are often disadvantageous to the host.
• “anaphylaxis”. (Ana =against, phylaxis =
protection)
Mediators involved in hypersensitivity
reaction
• Primary mediators (which cause ) release of
histamine from the mast cells.
• Secondary mediators. They are leucotrienes
C4 and D4; prostaglandin D2, platelets
activating factors and cytokines.
 Classification of hypersensitivity

A. Broad division:
1. Immediate type (Ab-mediated): by liberation of
histamine, 5- HT, bradykinin, SRS, etc.
2. Delay type

B. On the basis of immunological mechanism

1. Hypersensitivity reaction mediated by antibody
(Ab).
2. Hypersensitivity reaction mediated by sensitized
lymphocytes (delayed type)
C. On the basis of tissue damages (according to Coombs
and Gall). This classification is accepted one. First three
reactions are immediate type reaction.
1. Hypersensitivity type I: Anaphylactic type or
immediate type reaction.
2. Hypersensitivity type II: Cytotoxic type or
cytolytic reaction.
3. Hypersensitivity type III: Immune complex
disease or toxic complex syndrome.
4. Hypersensitivity type IV: Cell-mediated
(delayed) hypersensitivity reactions.
 D. On the basis of time scale for
manifestation of immunological reactions.
1. Immediate type: -Where immune response is
deserved within 1 to 15 minutes.
a) Spontaneous b) Induced
2. Intermediate type: -Where immune response
occurs/observed within 2-6 hours.
3. Delayed type: -Where immune responses
observed after one to two days. These
responses are further classified into two such as:
a) Induced by infective agents (e.g. Tuberculosis)
b) Induced by non-infective agents
1.The immediate type of hypersensitivity reaction
depends on the liberation of the
pharamacologically active substances like
a) Histamine
b) Serotonis (5HT= 5-hydroxy tryptamine)
c) SRS –A slow reacting substances-released by
anaphylaxin acidic lipid)
d.)Bradykinin.
2. There are two types of mediators involved in
the hypersensitivity reactions. One which leads
to mast cell degranulation with discharge of
preformed activities is called primary mediator
(Histamin).
Secondary mediators are Leukotrienes C4 and
D4, prostaglandin D2, Platelet-activating factors
(PAF) and cytokines.
 The mechanism of hypersensitivity
reaction
Hypersensitivity type
I- Anaphylactic type
II- Cytotoxic type
III – Immuno-complex type
IV – Cell mediated delay type Tuberculin reaction, contact Sensitized T- lymphocytes ---
Typical disorder Immune mechanism
Anaphylaxis, some form of Formation of IgE Ab –release
bronchial asthma of vaso-active amines and
other mediators from mast
cells and basophils
Autoimmune, haemorrhage, Formation of IgG – binds to
amaemia,transfusion Ag on target cell surface –
reactions,haemolytic Phagocytosis of target cells or
disorders of new born lysis of cells by components of
activated complements
Arthus reaction,serum Ag – Ab complex – Activate
sickness,certain form of acute complement—Attaract
glomerulonephritis neutrophils--- Release
lysosomal enzymes and other
toxic substances
dermatitis, transplant Release of lymphokines and
rejection T- cell mediated cytotoxicity.
 Effects of major mediators
Species Main shock Symptoms Pathology- gross Major mediators
occurring organ
Cattle and sheep Respiratory tract Cough, dyspoenia, Lung edema, Leukotrienes,
collapse emphysema, kinins, histamine
haemorrhage
Pig Respiratory tract Cyanosis, itch, Systemic Histamine
and intestine staggering, collapse hypotension
Horse Respiratory tract Cough, dyspoenia Emphysema, Histamine, 5-HT
and intestine and diarrhoea intestinal and kinins
haemorrhage
Dog Hepatic vein Vomiting, Hepatic congestion Leukotrienes and
dyspoenia, and visceral histamine
diarrhoea and haemorrhage
death
Cat Respiratory tract Itch, vomiting, Lungs and Leukotrienes and
and intestine diarrhoea and intestinal edema histamine
dyspoenia
Chicken Respiratory tract Dyspoenia, Lung edema Histamine, 5-HT
convulsion and and Leukotrienes
collapse
Human Respiratory tract Urticaria and Lung edema and Histamine and
dyspoenia emphysema Leukotrienes
Type I Hypersensitivity (Anaphylactic
type)
• This is a rapidly occurring reaction.
• It follows the combination of antigen (Ag) with
Ab previously bound to the surface of mast cells,
which are widely distributed in the tissues
• found particularly near blood vessels and sub-
epithelial locations and basophils.
• These mast cells and basophils are most
important in the development of type I
Hypersensitivity reactions.
 Sequences of events leading to
hypersensitivity
• First exposure
• Sensitization of B-cells

• Ig E production by B-cells

• Surface arming of mast cells with Ig E antibody

Second exposure
• Release of primary and secondary mediators from mast
cells, following cross-linking of Ig E receptors by the
same antigen………. Clinical effects.
 Allergens causing Type –I
hypersensitivity reaction
• Plant pollens
• Fungal spores
• Bee venom
• Animal dander (Scales) from hair, feather
• Mites in house dust etc.
• Anaphylaxis also occurs due to drugs and vaccine.
• Different animals have different sensitive organs for
anaphylactic reactions.
– e.g. respiratory organs and heart in horse;
– intestine and liver in ruminants, swine and dogs.
 Type –I : Anaphylaxis in different
species of animals
Species Main shock Symptoms Pathology Major
occurring mediators
organ
Cattle and Respiratory Cough, Lung edema, Leukotrienes,
sheep tract dyspoenia, emphysema, kinins,
collapse haemorrhage histamine
Pig intestine, liver Cyanosis, itch, Systemic Histamine
and staggering, hypotension
Respiratory collapse
tract
Horse Respiratory Cough, Emphysema, Histamine, 5-
tract, heart dyspoenia and intestinal HT and kinins
and intestine diarrhea haemorrhage
Dog Hepatic vein Vomiting, Hepatic Leukotrienes
dyspoenia, congestion and and histamine
diarrhoea and visceral
death haemorrhage
 Type II hypersensitivity/cytotoxic
type.
• In this type of hypersensitivity, Ab is formed
against Ag that is either normal or altered cell
membrane components.
• The antigens are intrinsic to the cell, or tissues
that are damaged
 Ab – dependent mechanisms are
involved in this reaction
• A. Complement-mediated cytotoxicity. This type
of reaction occurs in
– Transfusion reaction
– Haemolytic disease of newborn.e.g. common in foal ,
rare in calves ; not in sheep; piglets
– Hypersensitivity Reaction to drugs (e.g. penicillin,
phenacetin, cephalosporins, etc./haemolytic anaemia)
– Reactions to infectious diseases.
• e.g. Salmonella lipopolysaccharides,
• Enquine infectious anemia virus,
• Anaplasma, Babesia, Trypanosomes, etc.
B. Antibody- dependent cell-mediated cytotoxicity
(ADDC). Here macrophages cause the lysis of target
cells coated with Ig G antibody.
• Besides macrophages, these include neutrophils,
eosinophils, natural killer cells, etc.
C. Antibody-mediated cellular dysfunction. In
some cases, Ab directed against cell surface
receptors impairs function without causing cell
injury as inflammation. Such cases are very rare.
Type III: Immune complex type / Toxic
complex syndrome
• In this type of hypersensitivity reactions, the
antigens are mostly exogenous.
• This reaction occurs when large dose of soluble
Ags like Diphtheria, Tetanus antitoxin sera are
injected into animals or man, since serum contain
proteins. Time of latency is about hours.
• Type III reaction may be manifested in two ways.
Such as -
1. Local immune complex disease (Arthus reaction)
2. Systematic form (Acute serum sickness, chronic
serum sickness)
 Type IV hypersensitivity reaction
(delayed type)
A. Delayed type hypersensitivity
• This type of hypersensitivity is mediated by T-
cells rather than by antibodies.
• This form of hypersensitivity can be defined as a
specifically provoked, slowly evolving (24-28 hrs
or days), mixed cellular reactions involving
lymphocytes and macrophages.
• The classical example is the tuberculin reaction of
this type of reaction in animals already sensitized
to the tubercle bacilli.
 The most important cytokines
released from Th cells
1. Gamma-interferon – most important
mediator of Type –IV reaction
2. Interleukin-2 (IL-2)- causes autocrine
and paracrine proliferation of helper T -cells
3. Tumour necrosis factor-alpha (TNF-
alpha)- acts on epithelial cells and
causes increased secretion of prostacycline and
vasodilatation, release of chemotactic factors
• B. T-cell mediated cytotoxicity
• In this case sensitized CD 8 + cytotoxic T-
lymphocytes kill Ag bearing target cells by
lysis, destroying the infected cells before virus
replication is completed.
• These celle are also involved in the tumour
immunity.
Vaccine allergy
Contact allergy in dog
Grass allergy in dog
Type II hypersensitivity reaction
Hives – allergic reaction
Thank you
 27. Autoimmunity
(Autoimmune response/ diseases)

• Dr. Damodar Sedhai

• Date:
 Autoimmunity
(Autoimmune response/ diseases)
• Autoimmunity is the condition in which an
individual provokes Ab production or the
lymphocytes get sensitized to a self -Ag.
Autoimmune Disease?
• as pathological condition produced as a
result of autoimmune response. The Ab
produced in response to the self- Ag is called
autoantibody.
 Causes and mechanism of
autoimmunity
1. Immune reactions against Ags, which are
normally inaccessible to Ab forming cells.
2. Appearance of new tissue Ags after the
development of immunologically competent
cells.
3. Emergence of forbidden clones.
4. Alteration of self -components of a tissue
forming a Ag by physical, chemical and
biological agents.
5. Combination of exogenous haptons with host
protein or cells there by forming a cross linking Ag.
6. Alteration in the immune mechanism of an
individual.
7. Breakdown of homeostatic mechanism due to
some unknown causes.
8. Breakdown of tolerance due to Freund’s
Adjuvants (which contains dead tubercle bacilli in
water-in-oil suspension of Ags.)
 Examples of autoimmune diseases

• Grave’s disease or hyperthyroidism

• Hashimoto’s disease or hypothyroidism
• Myxoedema with almost no thyroid function
• Pernicious anaemia
• Insulin-dependent diabetes (Juvenile diabetes)
• Good pasture’s syndrome in man
 Examples of autoimmune diseases….
• Primary biliary cirrhosis
• Ulcerative colitis
• Rheumatoid arthritis, etc.
• Autoimmune thyroiditis / encephalitis/ ocular
disease /reproductive disease/ skin disease,
etc. in animals.
• Myasthenia gravis of skeletal muscles:
Progressive paralysis of muscles without
sensory disturbance and atrophy.
 Categories of autoimmune diseases

• Single organ (or single cell) type disorder

• Multi system diseases (e.g. systemic lupus
erythematosus in man, dogs, cats;
Rheumatoid arthritis in man and dogs; Feline
chronic progressive polyarthritis in male cat;
Dermatomyositis in man and dogs and
Sjogren’s syndrome in humans and dogs; etc.)
 Autoimmune Diseases in Animals

Single organ or cell type Multisystem or systemic

Autoimmune thyroiditis Systemic lupus erythematosus(
Man ,dog and cat)
Autoimmune encephalitis and Rheumatoid arthritis(man and
neuritis dog)
Autoimmune ocular Feline chronic progressive poly
disease(Horse) arthritis in male cat
Autoimmune reproductive Myasthenia gravis of skeletal
diseases in male (some cases) muscles
Autoimmune skin diseases Sjogren’s syndrome( Diseases of
lachrymal and salivery glands of
man and dogs)
Autoimmune nephritis Dermatomyositis(Man and dogs)
 Autoimmune Diseases in Animals
Tumour Cell type Evidence for immunosuppression

Avian lymphoid leucosis B cells Increased susceptibility to infection

Bovine leucosis B cells Depressed serum IgM

Myeloma B cells Increased susceptibility to infection

Canine malignant B cells Pre disposition to infection

lymphoma associated with auto immune disease

Marek’s disease T cells Depressed cell mediated

cytotoxicity , depressed Ig G
production
Equine lymphosarcoma T cells Increased susceptibility to infection
Systemic lupus erythomatosus in dog
Systemic lupus erythomatosus in man
SLE in man
 Drugs used to treat autoimmune
disorders
• Anti- inflammatory drugs like:
– prednisone,
– methylprednisolone,
– dexamethasone.
• Other potent drugs that suppress the immune
system but are not corticosteroids include :
– sirolimus,
– methotrexate,
– cyclophosphamide
 Effective drugs in the treatment of
autoimmune inflammatory diseases
• gold compounds,
• sulfasalazine,
• azathioprine,
• cyclophosphamide,
• antimalarials,
• D-penicillamine,
• Cyclosporine (Gabriel et al., 2001)
 Thank you
• Any question ?