BASIC IMMUNOLOGY

Basic Immunology

 Fundamental to understanding pathophysiology,

diagnosis and treatment

Allergic Rhinitis

Immunologically mediated disease

- High and increasing prevalence
- Affects children and adults (peak incidence: 17 – 22 y.o)
- Increasing economic impact
 The Unified Airway

 Terminology:
“The United Airway”, “Chronic Allergic Respiratory
Syndrome”, “Allergic Inflammatory Airway Syndrome”

Upper Airway Lower Airway

AR Asthma

 Treatment of one airway system may enhance other

airway system control.
 The Immune Response

 Identifies and destroys elements foreign to the body while

recognizing and protecting self-components.
 Autoimmunity disorders: inability to properly recognize
“self”.

• Innate Immune System

Immune System
• Adaptive Immune System
The Immune System
The Immune System
 Innate Immune System

 First line of defense against foreign substances.

 Comprises physical barriers and receptors &
antimicrobial compounds.
 Cells:
 Neutrophils
 Monocytes
 Mast cells Microbes
 Eosinophils
 Basophils
 Dendritic cells (DCs)

Activate Work to rid the body of infection

 Innate Immune System

Pattern Recognition Receptors (PRRs) - Opsonize bacteria

- Activate coagulation &
On the surface of innate immunity system cells, complement cascades
intracelluler compartments & bloodstream. - Induce phagocytosis &
-TLRs apoptosis
- RIG-I-like receptors PAMPs - implement proinflammatory
- Nod-like receptors signaling pathways
- C-type lectin receptors

(PAMPs : pathogen associated molecular patterns)

 Innate Immune System

NK cells  maturation  - killing cells

(bone marrow) (blood, spleen, lymphoid, - production of cytokines (IL-4)
lungs, liver)

Complement system Routes in complement activated:

1. Classical pathways
- Only in innate immune system 2. Lectin pathway
- Mediator of Ag-Ab reactions 3. Alternative pathway

Antimicrobial peptides

- Expressed in sinonasal & - Lysozyme

lower airway epithelium) - Lactoferrin
- In innate & adaptive immune - Secretory leukocyte protinase inhibitor
system
10
 Adaptive Immune System

 Activated when innate immune system is unable to

mount an inflammatory response to remove pathogens.
 Utilizes many of the same cells as the innate immune
system.
 Recognizes specific Ag that are processed and presented
by APC with MHC receptors.
 Priming occurs during the 1st exposure to Ag by MHC II
on APC.
 Major difference: the capability of memory in adaptive
immune system.
 Adaptive Immune System
12

 Creates millions of different B and T cells for

specific antibody-mediated and cell-mediated
immunity
 Antibody-Mediated Immunity (AMI)
 Involves B lymphocytes, plasma cells and antibodies
 Humoral immunity
 Name derives from antibodies found in body fluids (humors -
old medical term)
 Cell-Mediated Immunity (CMI)
 Involves T lymphocytes, antigen-presenting cells and MHC
(major histocompatibility complex) molecules
 Cellular immunity

Mohamad R. Chaaban, Robert M. Naclerio, Immunology and Allergy, in Bailey”s , Byron J.; Head & Neck Surgery
Otolaryngollogy, . 5th ed. 2014 p.379-411
 Immune responses
13 Skin & Mucous membranes
Barriers
rapidly regenerating surfaces, peristaltic
Invasion movement, mucociliary escalator,
& infection vomiting, flow of urine/tears, coughing

Innate immunity Cellular and humoral defences

+ lysosyme, sebaceous/mucous secretions,
stomach acid, commensal
organisms,complement proteins,
phagocytosis, NK cells

Inflammation
+
Cellular and humoral defences
Adaptive immunity Antibodies, cytokines, T helper cells,
cytotoxic T cells
 The Link Between the Innate and
Adaptive Immune System

 Activation of TLRs on APCs 

 upregulation of costimulatory molecules that induce type-I
INF
 Facilitate APC-T-cell interactions

 TLR activation through several pathways contributes

to polarization to Th1 immune responses-leading to
the hypothesis that this polarization may prevent
Th2 immune responses and allergy.
 Cells of The Immune System

 Derived from pluripotent hematopoietic cells.

Neutrophil Eosinophil Basophils

- Principal phagocytic cell -Circulate in the blood -Functions similar to
of innate immunity. and localize to inflamed eosinophils and mast
- Circulating and tissues. cells.
marginal pool. -Principal defender -Granulocytes that posses
- In allergy, neutrophils against parasites. high-affinity IgE
are recruited during the receptors.
late response to Ag -Contain histamine and
challenge. other mediators,
including cytokines.
 Cells of The Immune System

Monocyte Macrophage Dendritic Cell

-Leukocytes with bean -Mononuclear phagocytic -Cells with dendriform
shaped or brain-like cells in tissue (star shaped)morphology
convoluted nuclei -Derive from blood -Interdigitating reticular
-Circulate in blood with monocytes cells (synonym)
half life of 8 hours -Participate in innate and -Capture and present
- Precursors of tissue adaptive immunity antigens to T
macrophages lymphocytes
 Cells of The Immune System

Mast Cell Small Lymphocytes * Lymphocytes *

refers to small
lymphocytes
-Located in mucous - B cells (CD19)
membrane and - T cells (CD3, CD4 or
connective tissue CD8)
throughout body - Adaptive immunity
-Major effector cell in
allergy
-Modulation of initial
immune response

* : Just in adaptive immune system

Role of T reg and B reg Cells
18
 Antibody-Mediated (Humoral) Immunity
19

 Directed against extracellular microorganisms and toxins

 B-lymphocytes (B cells)
 Differentiate into plasma cells which produce antibodies
 Function as antigen-presenting cells (APC’s)

 Classification of Antibodies (Immunoglobulins)

 IgM
 IgG
 IgA
 IgD
 IgE
 Cell-Mediated Immunity (CMI)
20

 Directed against intracellular microorganisms

 Non-phagocytic cells and phagocytic cells

 T-lymphocytes (T cells)
 Differentiate into effector cells following antigen presentation
by antigen presenting cells (APC’s)

 Functional types of T cells

 Helper (CD4 T cells)
 TH1 and TH2 cells
 Cytotoxic (CD8 T cells)
 Regulatory
 CD4 and CD8 Tregs
 21

 Physical barriers:
 Skin and airway mucosa (epithelial) cells  release and express
mediators and receptors to initiate elimination mechanisms.
 Mucus secretion by goblet cells prevents adherence of micro-
organisms to the epithelial cells, preventing their entrance into the
body. trapped in the mucus and removed from the airway by ciliary
movements.
 Cytokines, Interferon and Chemokins
22

 Cytokines are soluble mediators that have growth,

differentiation, and activation functions for immune
responses.

 Cytokines predominantly APCs or T lymphocyte derived,

mediate cytotoxic (antiviral and anticancer), humoral, cell-
mediated (Th1 and Th17), or allergic immunity (Th2), or
that are immuno suppressive (Treg cells) by lymphocytes
 Cytokines, Interferon and Chemokins
23

 Chemokines are a group of small (8 to 12 kD) proteins

with the ability to affect cell migration or chemotaxis

 These cells include the neutrophils, monocytes,

lymphocytes, eosinophils, fibroblasts, and keratinocytes.
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 Development of Allergy
25

Allergic conditions
 Genetic predisposition
 The timing of environmental exposures
Triggers : dust mite, molds, animal dander, and the pollens
of trees, grasses, and weeds
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The Hygiene Hypothesis
27
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 The Allergic Rhinitis Response
29

 The development of AR pivots on the interplay

between genetic predisposition and environmental
exposure.
 Environmental triggers include allergens such as dust mite,
molds, animal dander, and the pollens of trees, grasses, and
weeds.
 The Early/Immediate Response
30

 The allergen occurs within minutes and is characterized by

mast cell degranulation
 The release of preformed mediators, including histamine
and proteases vasodilatation, vasculature leakage of
fluids, and glandular and neural stimulation
 It is symptomatically characterized initially itching,
sneezing, rhinorrhea, watering of the eyes, nasal congestion
 The Late Response
31

 The late response to nasal challenge with antigen occurs

hours after antigen exposure with a recrudescence of
allergic symptoms mediated by influx of cellular elements
such as eosinophils (responding to the early phase release
of IL-5) and activated T cells.
 Immediate & Late Phase Reaction
32

Abbas, AK, Lichtman AH, Pillai S. Immediate Hypersensitivity.

In: Cellular And Molecular Immunology, International Edition, Sixth edition, Saunder Elsivier, 2007
PATHOGENESIS OF ALLERGIC RHINITIS
PETER S. CRETICOS, MD
Late-Phase Allergic Reactions

33
 Pathophysiology Of Rhinitis
34

Pathophysiology of Allergic and Nonallergic Rhinitis, Betul Sin and Alkis Togias
 Pathophysiology Of Rhinitis
35

Pathophysiology of Allergic and Nonallergic Rhinitis, Betul Sin and Alkis Togias
Mechanism Immunotherapy
36
 THE NEURAL COMPONENT OF ALLERGY
37

 The nose is innervated by afferent,efferent,and

postganglionic autonomic nerves.
 The nasal cycle is the periodic congestion and decongestion
of the nasal venous sinusoids that lead to partial
obstruction and patency of each nostril, in reciprocating
manner over approximately 4 to 6 hour intervals.
Neuropeptides and Neurogenic lnflammation
38

 The secretion of neuropeptides  Tachykinins and

Neurokinin A  role in the pathogenesis of AR.
 Mechanism called neurogenic inflammation.
 NGF (Neurogenic Growth Factor)  the early response to
allergens by inducing maturation, stimulation, and
consequent activation of mast cells and release of
mediators.
Neuropeptides and Neurogenic lnflammation
39

 NGF promoted allergic responses.

 NGF augments the production of substance P (SP) by
neurons and SP is increased in mucosal nerve fibers.
 SP does increase TNF-a and IL-12 production by monocytes
and macrophages, it can degranulate mast cells.
 Schematic presentation of the processes involved in
“neurogenic inflammation” leading to itching and sneezing
40

Oliver Pfaar. Pathophysiology of Itching and Sneezing in Allergic Rhinitis. Swiss Med 2009;139 35-40