IMMUNOLOGY
IN ENT
Moderator: Dr. Bharathi MB Presenter: Dr.Sreenivas Kamath
Immunity ?
• The ability of an organism to resist a
particular infection or toxin by the action
of specific antibodies or sensitized white
blood cells.
Why is immunology
important?
Types of immunity
• Innate
 Genetic driven
 Present at birth
 NON SPECIFIC
 Doesn’t require sensitisation
• Acquired
 Requires sensitisation
 SPECIFIC
 ADAPTIVE
INNATE IMMUNITY
ACQUIRED IMMUNITY
Antibody mediated Cell mediated
ANTIBODY
• Also called as immunoglobulin
• Special protein
• Produced by plasma cells
• Antibodies bind to antigen to initiate immune response
CLASSIFICATION OF
ANTIBODIES
• IgG
• IgA
• IgM
• IgE
• IgD
LYMPHOCYTES
• Lymphocytes are the specialized cells that react in a
specific manner to antigens and elicit and propagate
immune responses.
• B cells, T cells, Natural killer cells.
• B cells- Antibody synthesis.
• T cells- 1. Cytotoxic T cells- Kill infected cells
2. Helper T cells- modulate immune response to
antigen
Lymphoid organs ?
• Primary lymphoid organs
• Secondary lymphoid organs.
Immune Response
• Primary Response
• The primary immune response is the resultant response when
the immune system is exposed to an antigen for the first time
• Lag period present
• IgM mediated
• Secondary response
• The secondary immune response results if the immune
system is challenged with antigen after sensitization
• No lag period
• IgG mediated
Hypersensitivity Reaction
• When the immune mechanism results in injury to the
own body- its called hypersensitivity reaction.
• 4 types of hypersensitivity reaction
Type 1
• Immediate Hypersensitivity reaction
• IgE mediated
• Mast cells, Basophils, eosinophils
• Eg- Allergic rhinitis
Type 2
• Cytotoxic Hypersensitivity
• IgG mediated
• Complement, phagocytes
• Eg-Hemolytic anemia
Type 3
• Immune complex reaction
• IgG
• Complement and phagocytes
• Eg- Serum sickness, SLE
Type 4
• Cell Mediated Hypersensitivity
• T cells
• Macrophages
• Contact dermatitis.
Clinical implications
1. Immunology of tonsils
2. Immunology of allergic rhinitis
3. Immunology of allergic fungal sinusitis
4. Immunology of autoimmune ear disease
5. Immunology of autoimmune thyroid diseases
6. Rheumatological disease.
7. Immunotherapy
Are tonsils important ?
• Heinrich Wilhelm Gottfried von Waldeyer-
Hartz
Described in 1884 about Waldeyers ring.
The tonsils are lymphoepithelial structures
that provide a protective immunological ring
at the openings of both digestive and
respiratory tracts
Immunology of Tonsils
• Tonsils are secondary lymphoid organs
• It generates antigen sensitized B cells
• Histologically tonsils are just like any other lymphoid
organ – with all active and differentiation stages of B
cells
What is the function of crypts ?
• Tonsils differ from other lymphoid organs in that it lacks
the afferent lymphatics
• Epithelial surface area of tonsils- 45cm2
• Crypts increase the surface area
 295cm2.
How does antigen
sensitization occur ?
• Tonsils receive the antigen through their crypts
• At the base of these crypts are specialized transport
channels called M pores.
• Near these crypts are the langerhan like giant
cells(APC)
• These APC will match with MHC II T cells- which will
further activate the B cells and produce antibodies.
• Tonsils also produce IgA
• IgA acts as a mucosal antiseptic paint.
• This IgA combines with antigens , toxins either reduce
their absorption or render them harmless
• Tonsils also contain- Natural killer cells and provide
innate immunity
• Recurrent throat infection with Clinical no tonsils
enlargement in a paediatric age group ???
• BRUTONS disease, or any other dysglobulinaemia
Why does tonsils get inflamed ??
• During the activation of these immune cells there is
local release of inflammatory cytokines.
• PHYSIOLOGICAL INFLAMMATION
• This inflammations need not be always infective in
nature.
• LATE IMMUNE RESPONSE.
Does Tonsillectomy cause any
change in Immunity ??
• DONOVAN Et.Al study showed that activated B cells
population declined and the level of IgA secreted were
lower than normal levels of other immunoglobulins in
the same patient pre and post tonsillectomy
Allergic fungal sinusitis
• Caused by aspergillus and other fungi.
• The patients suffering from this has been found to have
immediate type of hypersensitivity to skin prick. And
raised IgE specific to Aspergillus.
• Hypothesised to be Type 1 or 3 hypersensitivity reaction
• Invasive forms of fungal sinusitis is noted in patient
with conditions that lead to reduced number of
immunoglobulins.
Allergic Rhinitis
• Incidence : 10-15%
• Type one hypersensitivity reaction.
• Degranulation of IgE-sensitized basophils and
mast cells, leading to mediator release.
• Histamine results in immediate reactions-
nasal obstruction, itching, sneezing-
Controlled with Antihistamines
• Delayed reactions due to T cells mediated
response is controlled with steroid
administrations.
• Chronic allergen exposure tends to cause obstruction,
possibly via a continuing inflammatory response, with
less itch and sneeze and with posterior catarrh rather
than anterior rhinorrhoea
Autoimmune inner ear
disorders
• Old concept- inner ear is protected from systemic
immunoglobulin cause it is protected by the blood-
labrynthine barrier.
• Endolymphatic sac is the centre of immunological
activity of inner ear.
Autoimmune thyroid disease.
• Grave’s disease
• Hashimoto Thyroiditis.
Graves disease.
• Autoimmune
• HLA DR3
• Possible trigger factor is antigenic mimicry
• Yersinia Enterocolitica
• Thyroid stimulating Immunoglobulins- Binds to TSH
receptors and increase T3 and T4
Autoantibodies to TSH
Receptors
• Thyroid stimulating immunoglobulin
• Thyroid growth immunoglobulin
• Thyrotrophin binding inhibiting immunoglobulis.n
Hashimotos Thyroiditis.
• Autoimmune
• CTLA 4 (cytotoxic T lymphocyte Antigen 4)
• HLA DR5
• Assoc. with other autoimmune diseases like type 1 DM,
vitiligo, Pernicious anemia.
• Autoantibodies are present against- Thyroid peroxidase,
thyroglobulin and TSH receptors.
• Hypothesised to be Type IV reaction
Rheumatological diseases in
ENT
Disease Autoimmune Disease
RA Rheumatoid factor, ACPA
SLE dsDNA, Sm, Ro (SS-A), La
(SS B), PCNA,
Vasculitis PR3, MPO
Relapsing polychondritis.
• HLA DR4 associated
• Predominantly affects the cartilage- Probably immune
response to collagen type 2.
•
• Laryngo-tracheal involvement: initial stages may
present with hoarseness of voice, tenderness of the
trachea. Later on may present with breathing difficulty
due to laryngotracheomalacia.
• Associated with Cardiac valvular pathology, Necrotizing
glomerulonephritis, joint deformity.
Behcets Disease
• Behçet's syndrome is a multisystem disorder presenting
with recurrent oral and genital ulcerations as well as
ocular involvement
• The etiology and pathogenesis of this syndrome remain
obscure
• Circulating autoantibodies against enolase of
endothelial cells, selenium binding protein and anti-
Saccharomyces cerevisiae antibodies
• The ulcers are usually painful, are shallow or deep with
a central yellowish necrotic base, appear singly or in
crops, and are located anywhere in the oral cavity.
• The ulcers persist for 1–2 weeks and subside without
leaving scars
Sjogren’s syndrome
• Sjögren's syndrome is a chronic, slowly progressive autoimmune
disease characterized by lymphocytic infiltration of the exocrine
glands resulting in xerostomia and dry eyes.
• Enlargement of major salivary glands
• Xerostomia
• Dysphagia
• Lymphadenopathy
• Primary or secondary
• Non-organ-specific antigens (rheumatoid factors) and extractable
nuclear and cytoplasmic antigens (Ro/SS-A, La/SS-B).
Granulomatosis with Polyangiitis
(Wegener's)
• Granulomatous vasculitis of the upper and lower
respiratory tracts together with
glomerulonephritis.
• Paranasal sinus pain, purulent or bloody nasal
discharge, with or without nasal mucosal
ulceration.
• Nasal septal perforation, saddle nose deformity.
• Serous otitis media.
• Subglottic tracheal stenosis resulting from active
disease
• demonstration of necrotizing granulomatous vasculitis
on tissue biopsy
• antiproteinase-3 ANCA
Immunotherapy
• It is the only treatment that can lead to a life-long
tolerance.
• Increases serum IgG1, IgG4 and Local IgA
• Specifically acts on T cells – Th1 activation is favoured
over Th2 cells.- DEVELOPS TOLERANCE
• IL10
Indications of immunotherapy
• The primary indication is that of symptoms not
adequately controlled by avoidance measures and
pharmacotherapy.
• CI: Beta blockers, pregnancy, acute asthma.
• Started with low dose once a week
• Then dosage increased to reach the maintenance level- frequency
lowered once maintenance is attained
• 2 to 5 years
• At a time 6-10 allergens can be used.
• Lessening of symptoms may begin as soon as 12 weeks
• Patients who do not achieve symptomatic improvement after 1
year of immunotherapy should have it discontinued
Immunotherapy in head and
neck malignancy
• Used alone or in adjuvant with other modalities of
treatment.
• How they act ?
• Mark the cancer cells so that the immune system can
identify them as harmful
• Boost the immune mechanism to make it more effective
in the killing of cancer cells
Type of immunotherapy for
HNC
• Check point inhibitors: which disrupt the signals that
allow the cancer cells hiding from the immune system
• Cytokines: that promote and direct the immune
mechanism in a particular manner to kill the cancer
cells
• Vaccine which are used to activate the immune
mechanism as well to prevent certain cancers.
Immunotherapy in other areas
of ENT
• RIBOMUYL immunotherapy- a combination of antigen
derived from 3 most common bacteria affecting
paediatric age group. (Klebsiella pneumoniae,
Streptococcus pyogenes, haemophilus Influenzae)
• Dosage: 1 tablet/ sachet morning empty stomach for 4
consecutive days per week for 3 consecutive weeks.
• 1 tablet/ sachet morning empty stomach for 4
consecutive days in a month for 5 months.
Reference
• Scott brown 7th edition
• Ballengers 17th ed
• Harrison- textbook of internal medicine 17th ed
• Immunology in ENT- springers publication

Immunology in ent

  • 1.
    IMMUNOLOGY IN ENT Moderator: Dr.Bharathi MB Presenter: Dr.Sreenivas Kamath
  • 3.
    Immunity ? • Theability of an organism to resist a particular infection or toxin by the action of specific antibodies or sensitized white blood cells.
  • 4.
  • 5.
    Types of immunity •Innate  Genetic driven  Present at birth  NON SPECIFIC  Doesn’t require sensitisation • Acquired  Requires sensitisation  SPECIFIC  ADAPTIVE
  • 6.
  • 7.
  • 8.
    ANTIBODY • Also calledas immunoglobulin • Special protein • Produced by plasma cells • Antibodies bind to antigen to initiate immune response
  • 9.
    CLASSIFICATION OF ANTIBODIES • IgG •IgA • IgM • IgE • IgD
  • 10.
    LYMPHOCYTES • Lymphocytes arethe specialized cells that react in a specific manner to antigens and elicit and propagate immune responses. • B cells, T cells, Natural killer cells. • B cells- Antibody synthesis. • T cells- 1. Cytotoxic T cells- Kill infected cells 2. Helper T cells- modulate immune response to antigen
  • 12.
    Lymphoid organs ? •Primary lymphoid organs • Secondary lymphoid organs.
  • 13.
    Immune Response • PrimaryResponse • The primary immune response is the resultant response when the immune system is exposed to an antigen for the first time • Lag period present • IgM mediated • Secondary response • The secondary immune response results if the immune system is challenged with antigen after sensitization • No lag period • IgG mediated
  • 14.
    Hypersensitivity Reaction • Whenthe immune mechanism results in injury to the own body- its called hypersensitivity reaction. • 4 types of hypersensitivity reaction
  • 15.
    Type 1 • ImmediateHypersensitivity reaction • IgE mediated • Mast cells, Basophils, eosinophils • Eg- Allergic rhinitis
  • 16.
    Type 2 • CytotoxicHypersensitivity • IgG mediated • Complement, phagocytes • Eg-Hemolytic anemia
  • 17.
    Type 3 • Immunecomplex reaction • IgG • Complement and phagocytes • Eg- Serum sickness, SLE
  • 18.
    Type 4 • CellMediated Hypersensitivity • T cells • Macrophages • Contact dermatitis.
  • 19.
    Clinical implications 1. Immunologyof tonsils 2. Immunology of allergic rhinitis 3. Immunology of allergic fungal sinusitis 4. Immunology of autoimmune ear disease 5. Immunology of autoimmune thyroid diseases 6. Rheumatological disease. 7. Immunotherapy
  • 20.
    Are tonsils important? • Heinrich Wilhelm Gottfried von Waldeyer- Hartz Described in 1884 about Waldeyers ring. The tonsils are lymphoepithelial structures that provide a protective immunological ring at the openings of both digestive and respiratory tracts
  • 21.
    Immunology of Tonsils •Tonsils are secondary lymphoid organs • It generates antigen sensitized B cells • Histologically tonsils are just like any other lymphoid organ – with all active and differentiation stages of B cells
  • 22.
    What is thefunction of crypts ? • Tonsils differ from other lymphoid organs in that it lacks the afferent lymphatics • Epithelial surface area of tonsils- 45cm2 • Crypts increase the surface area  295cm2.
  • 23.
    How does antigen sensitizationoccur ? • Tonsils receive the antigen through their crypts • At the base of these crypts are specialized transport channels called M pores. • Near these crypts are the langerhan like giant cells(APC) • These APC will match with MHC II T cells- which will further activate the B cells and produce antibodies.
  • 24.
    • Tonsils alsoproduce IgA • IgA acts as a mucosal antiseptic paint. • This IgA combines with antigens , toxins either reduce their absorption or render them harmless • Tonsils also contain- Natural killer cells and provide innate immunity
  • 25.
    • Recurrent throatinfection with Clinical no tonsils enlargement in a paediatric age group ??? • BRUTONS disease, or any other dysglobulinaemia
  • 26.
    Why does tonsilsget inflamed ?? • During the activation of these immune cells there is local release of inflammatory cytokines. • PHYSIOLOGICAL INFLAMMATION • This inflammations need not be always infective in nature. • LATE IMMUNE RESPONSE.
  • 27.
    Does Tonsillectomy causeany change in Immunity ?? • DONOVAN Et.Al study showed that activated B cells population declined and the level of IgA secreted were lower than normal levels of other immunoglobulins in the same patient pre and post tonsillectomy
  • 28.
    Allergic fungal sinusitis •Caused by aspergillus and other fungi. • The patients suffering from this has been found to have immediate type of hypersensitivity to skin prick. And raised IgE specific to Aspergillus. • Hypothesised to be Type 1 or 3 hypersensitivity reaction • Invasive forms of fungal sinusitis is noted in patient with conditions that lead to reduced number of immunoglobulins.
  • 29.
    Allergic Rhinitis • Incidence: 10-15% • Type one hypersensitivity reaction. • Degranulation of IgE-sensitized basophils and mast cells, leading to mediator release. • Histamine results in immediate reactions- nasal obstruction, itching, sneezing- Controlled with Antihistamines • Delayed reactions due to T cells mediated response is controlled with steroid administrations.
  • 31.
    • Chronic allergenexposure tends to cause obstruction, possibly via a continuing inflammatory response, with less itch and sneeze and with posterior catarrh rather than anterior rhinorrhoea
  • 32.
    Autoimmune inner ear disorders •Old concept- inner ear is protected from systemic immunoglobulin cause it is protected by the blood- labrynthine barrier. • Endolymphatic sac is the centre of immunological activity of inner ear.
  • 36.
    Autoimmune thyroid disease. •Grave’s disease • Hashimoto Thyroiditis.
  • 37.
    Graves disease. • Autoimmune •HLA DR3 • Possible trigger factor is antigenic mimicry • Yersinia Enterocolitica • Thyroid stimulating Immunoglobulins- Binds to TSH receptors and increase T3 and T4
  • 38.
    Autoantibodies to TSH Receptors •Thyroid stimulating immunoglobulin • Thyroid growth immunoglobulin • Thyrotrophin binding inhibiting immunoglobulis.n
  • 39.
    Hashimotos Thyroiditis. • Autoimmune •CTLA 4 (cytotoxic T lymphocyte Antigen 4) • HLA DR5 • Assoc. with other autoimmune diseases like type 1 DM, vitiligo, Pernicious anemia. • Autoantibodies are present against- Thyroid peroxidase, thyroglobulin and TSH receptors. • Hypothesised to be Type IV reaction
  • 40.
  • 41.
    Disease Autoimmune Disease RARheumatoid factor, ACPA SLE dsDNA, Sm, Ro (SS-A), La (SS B), PCNA, Vasculitis PR3, MPO
  • 42.
    Relapsing polychondritis. • HLADR4 associated • Predominantly affects the cartilage- Probably immune response to collagen type 2. •
  • 43.
    • Laryngo-tracheal involvement:initial stages may present with hoarseness of voice, tenderness of the trachea. Later on may present with breathing difficulty due to laryngotracheomalacia. • Associated with Cardiac valvular pathology, Necrotizing glomerulonephritis, joint deformity.
  • 44.
    Behcets Disease • Behçet'ssyndrome is a multisystem disorder presenting with recurrent oral and genital ulcerations as well as ocular involvement • The etiology and pathogenesis of this syndrome remain obscure • Circulating autoantibodies against enolase of endothelial cells, selenium binding protein and anti- Saccharomyces cerevisiae antibodies
  • 45.
    • The ulcersare usually painful, are shallow or deep with a central yellowish necrotic base, appear singly or in crops, and are located anywhere in the oral cavity. • The ulcers persist for 1–2 weeks and subside without leaving scars
  • 47.
    Sjogren’s syndrome • Sjögren'ssyndrome is a chronic, slowly progressive autoimmune disease characterized by lymphocytic infiltration of the exocrine glands resulting in xerostomia and dry eyes. • Enlargement of major salivary glands • Xerostomia • Dysphagia • Lymphadenopathy • Primary or secondary • Non-organ-specific antigens (rheumatoid factors) and extractable nuclear and cytoplasmic antigens (Ro/SS-A, La/SS-B).
  • 48.
    Granulomatosis with Polyangiitis (Wegener's) •Granulomatous vasculitis of the upper and lower respiratory tracts together with glomerulonephritis. • Paranasal sinus pain, purulent or bloody nasal discharge, with or without nasal mucosal ulceration. • Nasal septal perforation, saddle nose deformity. • Serous otitis media. • Subglottic tracheal stenosis resulting from active disease
  • 49.
    • demonstration ofnecrotizing granulomatous vasculitis on tissue biopsy • antiproteinase-3 ANCA
  • 51.
    Immunotherapy • It isthe only treatment that can lead to a life-long tolerance. • Increases serum IgG1, IgG4 and Local IgA • Specifically acts on T cells – Th1 activation is favoured over Th2 cells.- DEVELOPS TOLERANCE • IL10
  • 53.
    Indications of immunotherapy •The primary indication is that of symptoms not adequately controlled by avoidance measures and pharmacotherapy. • CI: Beta blockers, pregnancy, acute asthma.
  • 54.
    • Started withlow dose once a week • Then dosage increased to reach the maintenance level- frequency lowered once maintenance is attained • 2 to 5 years • At a time 6-10 allergens can be used. • Lessening of symptoms may begin as soon as 12 weeks • Patients who do not achieve symptomatic improvement after 1 year of immunotherapy should have it discontinued
  • 55.
    Immunotherapy in headand neck malignancy • Used alone or in adjuvant with other modalities of treatment. • How they act ? • Mark the cancer cells so that the immune system can identify them as harmful • Boost the immune mechanism to make it more effective in the killing of cancer cells
  • 56.
    Type of immunotherapyfor HNC • Check point inhibitors: which disrupt the signals that allow the cancer cells hiding from the immune system • Cytokines: that promote and direct the immune mechanism in a particular manner to kill the cancer cells • Vaccine which are used to activate the immune mechanism as well to prevent certain cancers.
  • 57.
    Immunotherapy in otherareas of ENT • RIBOMUYL immunotherapy- a combination of antigen derived from 3 most common bacteria affecting paediatric age group. (Klebsiella pneumoniae, Streptococcus pyogenes, haemophilus Influenzae) • Dosage: 1 tablet/ sachet morning empty stomach for 4 consecutive days per week for 3 consecutive weeks. • 1 tablet/ sachet morning empty stomach for 4 consecutive days in a month for 5 months.
  • 58.
    Reference • Scott brown7th edition • Ballengers 17th ed • Harrison- textbook of internal medicine 17th ed • Immunology in ENT- springers publication