THE IMMUNE RESPONSE &

ACUTE BACTERIAL
RHINOSINUSITIS
ACE WILLIAM G. PASION, MD-3
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THE IMMUNE RESPONSE

How does the body mount an immune response?
“
Important to remember:
Self-tolerance is the ability of the
immune system to recognize
self-produced antigens as a
non-threat while appropriately
mounting a response to foreign
substances
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BASICS OF THE IMMUNE SYSTEM
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BASICS OF THE IMMUNE SYSTEM

INNATE ACQUIRED
Self/ non-self
Present Present
discrimination
Lag phase Present Absent
Specificity Limited High
Diversity Limited Extensive
Memory Absent Present
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INNATE IMMUNE SYSTEM

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INNATE IMMUNE SYSTEM

External Defenses Internal Defenses
▸ Skin and mucosa ▸ Cellular
▸ Secretions (acids ▹ Phagocytes
and enzymes) ▸ Humoral
▸ Mucous secretions ▹ APR’s
▸ Cilia ▹ Complement
▸ Flushing action ▹ Pattern receptors
▸ Competetive ▹ Enzymes
exclusion
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EXTERNAL DEFENSES

▸ 1st Line of defense

▸ Essentially present in:
▹ Integumentary system
▹ Respiratory system
▹ Gastrointestinal system
▹ Genitourinary system
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INTERNAL DEFENSES
A. Cellular
1. Phagocytosis
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INTERNAL DEFENSES
A. Cellular
1. Phagocytosis
2. Mast Cells
▸ Resemble basophils
▸ Release powerful chemical
mediators
▸ E.g. Histamine, cytokines,
GM-CSF
▸ Plays a role in hypersensitivity
reactions
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INTERNAL DEFENSES
A. Cellular
1. Phagocytosis
2. Mast Cells
3. NK cells
▸ Mediate cytolytic reactions and
kill target cells without prior
exposure to them
▸ Transitional cell bridging innate
and acquired immune response
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INTERNAL DEFENSES
B. Humoral
1. Complement
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INTERNAL DEFENSES
B. Humoral
1. Complement
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INTERNAL DEFENSES
B. Humoral
1. Complement
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INTERNAL DEFENSES
B. Humoral ▸Major APR is CRP
1. Complement
2. APR’s
▸CRP functions in:
▹Opsonization
▹Activation of
complement
▹Agglutination
▹Precipitation
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INTERNAL DEFENSES
B. Humoral ▸TLR-2 =recognizes
1. Complement
2. APR’s
teichoic acid and
3. Toll-like receptors peptidoglycan
▸TLR-4=recognizes
lipopolysaccharides
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INTERNAL DEFENSES
B. Humoral
1. Complement
2. APR’s
3. Toll-like receptors
4. Cytokines
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HOW DOES INNATE

IMMUNE SYSTEM WORK?
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HOW DOES INNATE IMMUNE SYSTEM WORK?

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HOW DOES INNATE IMMUNE SYSTEM WORK?

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ACQUIRED IMMUNE SYSTEM

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ACQUIRED IMMUNE SYSTEM

Cellular Humoral
▸ T-cell ▸ Antibodies
▸ B-cell ▸ Cytokines
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ACQUIRED CELLULAR IMMUNITY

B-cell Plasma cell Memory B-cell
▸ Produced by ▸ Responsible for ▸Responsible for
bone marrow the production heightened and
▸ Differentiate into of antibodies of faster response of
plasma cell and humoral acquire immunity in
memory B-cell
immunity the status of
when activated
▸ Naïve B-cells re-exposure or
reacts to infection
antigens and can
generate
immunologic
memory
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ACQUIRED CELLULAR IMMUNITY

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ACQUIRED CELLULAR IMMUNITY

T-cell T-helper cell (CD4+) T-killer cell CD8+
▸ Produced in the ▸ Recognizes antigen (Cytotoxic T-cell)
along MHC II
thymus ▸ Has 2 subsets:
▸ Recognizes
▸ Can be CD4+ (Th) ▸ Th1-produces IFN-y antigen along
or CD8+(Tc) with and TNF-B, for MHC I
various functions intracellular ▸ Produces
pathogens
▸ One subset of cytokines
▸ Th2- produces
CD8+ is Treg IL-4,5,10,13, for ▸ Kills
which is extracellular infected/foreign
responsible for pathogens via cells
suppresion antibody production
response
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ACQUIRED CELLULAR IMMUNITY

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ACQUIRED HUMORAL IMMUNITY

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HOW DOES THE ACQUIRED

IMMUNE SYSTEM WORK?
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Want big impact? USE BIG IMAGE
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Want big impact? USE BIG IMAGE
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CLINICAL
CORRELATE:ACUTE
BACTERIAL RHINOSINUSITIS
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IMMUNE RESPONSE IN ABRS

“In the event of pathogenic
exposure of the nasal cavity
and the sinuses. What does
the immune system do to
ward off the infection?”
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IMMUNE RESPONSE IN ABRS

1. Innate immune response
External defenses:
2. Mucosal lining of the nasal
cavity
3. Mucosal secretions
4. Ciliated epithelium
5. Patent sinus drainage
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IMMUNE RESPONSE IN ABRS

1. Innate immune response
Internal defenses:
2. Role of pattern recognition
receptors and acute phase
reactants
3. Role of phagocytes to process
and digest foreign substances
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IMMUNE RESPONSE IN ABRS

2. Specific immune response
▸ The specific immune response
will have a lag phase unless
memory has been established
already
Cellular components
▸ With help of APC’s, CD8+ T-cell
will be activated and kill
pathogens
▸ CD4+ T-cell can also be
activated to assist CD8+ T-cell
or B-cell (antibody production)
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IMMUNE RESPONSE IN ABRS

1. Specific immune response
Cellular components
2. B-cell are stimulated, and transforms
to plasma cell to produce antibodies
Humoral components
3. Antibodies helps in binding to
foreign antigens, for subsequent
elimination
4. Antibodies in the mucosal secretion
(esp IgA) provides essential
immunity in the mucosa
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IMMUNE RESPONSE IN ABRS

Generally immune response to infection
can be viewed in the following steps:
1. Activation of Innate immunte system
2. Uptake for antigen presentation by
APC’s
3. T-cell priming and activation
4. Th1 cells promote inflammation at
infection site
5. Acute phase response
6. Th2 cells promote B-cell activation and
differentiation (antibody production)
7. B and T- cell memory
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IMMUNE RESPONSE IN ABRS

The most common pathogens seen in cases
of ABRS are Streptococci pneumoniae and
Haemophilus influenzae
▸ These bacteria are encapsulated which
helps evade the immune response
▸ The polysaccaride capsule helps in poor
mounting of immune response
▸ This became the rationale of vaccination
against these two pathogens
▸ Specific immune response (acquired)
with antibodies accelerate elimation of
these bacteria
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CLINICAL CORELATE: ABRS

In 0.5-2% of cases, ARBS is a resultant of Viral Upper
Respiratory Infection. The response of the immune
system mediates the progression to ARBS.
1. A viral infection precedes bacterial infection.
2. Innate immune system gets activated with resultant
inflammation
3. Inflammation results to edema of mucosal surfaces
of nasal cavity which is contiguous to sinus mucosa
(which may become edematous)
4. Edema makes mucosa prone to infection and
disrupts ciliary function and mucus secretion
5. Bacterial growth (e.g S. pneumoniae) and infection
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CLINICAL CORELATE: ABRS

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CLINICAL CORELATE: ABRS

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DIAGNOSIS AND
MANAGEMENT OF ACUTE
BACTERIAL RHINOSINUSITIS
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0.5-2% of adult cases

ARBS following antecedent viral upper respiratory infection

2-10%
Estimated prevalence of ARBS

90-98%
Large proportion which is viral caused
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What is Acute Rhinosinusitis

▸ Inflammatory condition
involving the paranasal
sinuses
Symptoms:

▸nasal drainage ▸hyposmia/anosmia

▸nasal congestion ▸fever, cough, fatigue
▸facial pressure/pain ▸maxillary dental pain
▸postnasal drainage ▸and ear
pressure/fullness
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Predisposing factors for RS

▸ Allergic rhinitis
▸ Nasal polyps
▸ Rhinitis medicamentosa
▸ Trauma
▸ Dental infections
▸ Immunodeficiency (HIV, CF, Immotile cilia
syndrome)
 Diagnosis of ABRS
PSOHNS-CPG for ABRS
Diagnosis is based on the following criteria:
▸Acute onset of some or all of the following symptoms:
nasal congestion, purulent nasal discharge
(anterior/posterior nasal drip) with or without facial
pain/pressure, dental pain and ear pressure/fullness,
fever, cough, fatigue, hyposmia/anosmia that fail to
improve after 10 days
▸• Symptoms worsening within 5-10 days after an
initial improvement (i.e. double worsening)
▸• Symptoms not lasting beyond 4 weeks
GoR D, LoE 5
 Diagnosis of ABRS
PSOHNS-CPG for ABRS
Other recommendations:
1. A thorough physical examination should include
inspection, palpation of the maxillary and frontal sinus, as
well as anterior and posterior rhinoscopy. (GoR D, LoE 5)
2. Nasal endoscopy is a safe, radiation-free, and relatively
inexpensive office procedure. It may be used to examine
the nasal cavity and nasopharynx for anatomical
abnormalities and the origin of purulent discharge. (GoR C,
LoE 4)
3. Imaging Studies are NOT recommended for the routine
diagnosis of ABRS. (GoR A, LoE 1A)
 Treatment of ABRS
PSOHNS-CPG for ABRS

▸The primary treatment for Acute Bacterial Rhinosinusitis

(ABRS) is empiric antibiotic therapy. (GoR A, LoE 1A,1B)
First line antimicrobial regimen with low risk for resistance:

▸Amoxicillin-Clavulanic Acid 625mg q8h or 1g q12h OR

▸Amoxicillin alone at 500mg q8h or 1g q12h
Recommended duration of treatment is 7 to 10 days

For Penicillin allergy:

▸Doxycycline 100mg q12h OR
▸Levofloxacin 500mg OD OR
▸Moxifloxacin 400mg OD
 Treatment of ABRS
PSOHNS-CPG for ABRS
In case of failure of first-line treatment:
▸ Failure of first-line treatment should be considered in all
patients with worsening or no improvement of symptoms
after 5-7 days and second-line antimicrobial regimen
should be started. (GoR C, LoE 2B)
Second-line treatment options are the following:
▸Amoxicillin-Clavulanic Acid 2g q 12h
▸Doxycycline 100mg q 12h
▸Levofloxacin 500mg OD
▸Moxifloxacin 400mg OD
 Treatment of ABRS
PSOHNS-CPG for ABRS
In case of failure of second-line treatment
▸ Patients with ABRS with inadequate response to
treatment should be worked up for other conditions and
possible disease modifiers. (GoR B, LoE 2B)

Further work-up may include, but not limited to, the following:
▸3.1 CT of the Paranasal Sinuses
▸3.2 Sinus or meatal culture
▸3.3 Immune system studies
 Treatment of ABRS
PSOHNS-CPG for ABRS
Other recommendations:
▸1. Watchful waiting is an option in uncomplicated ABRS
(Temperature 4. <38.3oC, no extra-sinus complications),
provided that there is good follow-up. (GoR A, LoE 1A)
▸2. Nasal saline irrigation (NSI) is safe to use and is
recommended as an adjunctive treatment. (GoR A, LoE 1A)
▸3. Intranasal Corticosteroid Sprays (INCS) may be used as
monotherapy or adjunct therapy to antibiotics in the empiric
treatment of ABRS. (GoR A, LoE 1A)
4. There is a lack of available RCTs supporting the efficacy
and use of 7. topical and oral decongestants, and
antihistamines in the treatment of ABRS (GoR D, LoE 5)
 Treatment of ABRS
PSOHNS-CPG for ABRS
Other recommendations:
▸5. In the management of patients with ABRS, patient
education is 8. important and should emphasize avoidance
of inciting factors like allergens, environmental irritants or
microbes (bacteria, fungi, virus), as well as discussing
treatment options with emphasis on antibiotic resistance
patterns. (GoR D, LoE 5)
53 On a Global Scale

Antimicrobial resistance is a global health problem. It causes prolonged

illness, which may lead to mortality and risk of spreading the disease. It also
creates a financial burden to the patient due to increased cost and prolonged
duration of treatment.
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THANKS!
Any questions?
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References:

▸ Stevens (2009). Clinical Immunology and Serology:

A Laboratory Perspective. Third Edition. Pages 2-38
▸ Longo et al (2015). Harrison’s Principle of Internal
Medicine 19th Edition. Pages 227-228.
▸ 2016. Philippine Society of
Otorhinolaryngology-Head and Neck Surgery.
Clinical Practice Guidelines (for Acute Bacterial
Rhinosinusitis). Pages 32-35.