Immunity against infection and

allergy
Evy Sulistyoningrum

Immunology concept
Immunity against infection
Allergy & hypersensitivity
Outline
Immunology concepts
Variety of cells, molecules that performed immune response
Cellular components
Immune cells
Lymphoid tissue or organs
Humoral components
Soluble protein: complements, antibody
Physical, mechanical, chemical barriers
Immune system
All the cellular
elements of the
blood including the
cells of the immune
system arise from
pluripotent
hematopoietic cells
in the bone marrow
Cell of the immune system
Myeloid cells

Tissue and organs of the immune system
Response against pathogen infection
4 main tasks:
Immunological recognition
Immune effector function
Immune regulation
Immunological memory
Resulted in immunity
Distinguish self vs nonself
Classification
Innate immune response
Adaptive immune response


Immune response
Innate & adaptive immune response
Infectious pathogen
Mechanical barriers
Tissue resident cells pathogen
Elimination of pathogen
Inflammatory reaction
Chemokine & cytokine
Complement system
Inflammatory cells
Induction adaptive immune response
Interaction between innate & adaptive
immune response
Pathogen-resident cell interaction
PAMPS (Pathogen-
associated molecular
patterns)
PRR (Pattern
recognition receptors)
Activated
macrophage
Phagocytosis
Release of cytokine &
chemokine
Inflammatory process


Inflammatory process


Leucocyte migration to infection site
APC: Process & presents antigen to lymphocytes in
secondary lymphoid organs
T cell activation
B cell activation
Proliferation Differentiation into effector cell
Cellular mechanism
Humoral mechanism
Immunological memory

Adaptive immune response
Induction of adaptive response
Activation of specialized
antigen-presenting cells
(APC) is a necessary first
step for induction of
adaptive immunity
Induction of adaptive response
Antigen: substances that spesifically bound to lymphocytes
Recognized by:
Antibody/B cell receptor
T cell receptor
Major histocompatibility Complex (MHC)
Antigen recognition
T cell & B cell activation
Humoral
Extracellular form of pathogen & its products
B cell antibody producing plasma cell
Neutralization
Opsonization
Complement activation
Effector mechanism
Cellular
Intracellular pathogens
T cell
T cytotoxic/cytolitic : Destroy target cells
T helper: Activate macrophages
Induce formation of cytotoxic T cells
Stimulate B cells to produce antibodies.

Effector mechanism

Immunity against infection

Immunity against infection
Mediated by effector mechanism of innate &
adaptive immunity
Immune system responds in distinct and
specialized ways to different type of microbes
Survival and pahogenicity of a microbe influenced
by the ability to evade effector mechanism
immune evasion
Sometime, tissue injury is caused by host response
to microbe itself

General features
Single cell prokaryot
Structure: capsule, bacterial cell wall, flagella, pili
Extracellular
Replicate outside host cell
Induce inflammation tissue destruction
Produce toxin
Ex: staphylococci, streptococci, E coli, V. Cholerae, C. Tetani,
etc
Intracellular
Replicate within cell, even pahagocytes
Ex: M. tuberculosis, M. leprae


Bacteria
Bacteria
Innate immunity
Complement activation
Phagocytosis, main effector: neutrophil
Inflammatory response
Adaptive immunity
Humoral immunity
Neutralization
Opsonization

Immunity against extracellular
bacteria
Complement activation & effector
phase

Phagocytes


Inflammatory response


Innate immunity
Phagocytes & NK cell
Adaptive immunity
T cell mediated immunity most effective
Macrophage activation : Th
Cell lysis : Tc
Immunity against intracellular
bacteria


NK cell
Mechanism of immune evasion Examples
Extracellular bacteria
Antigenic variation Neisseria gonorrhoeae, E coli
Inhibition of complement activation Many bacteria
Resistance to phagocytosis Pneumonia
Intracellular bacteria
Inhibition of phagolysosome formation Mycobacterium tbc
Inactivation of reactive oxygen &
nitrogen species
M. leprae
Disruption of phagosome membrane Listeria monocytogenes
Bacterial immune evasion
Obligatory intracellular, DNA or RNA genome
Replicate within cell disrupt cell synthesis cell
death
Ex: measles, mumps, rubella, chickenpox, hepatitis
Innate immunity
Inhibition of infection by type I IFNs
NK cell killing mechanism
Adaptive immunity
Antibody mediated immunity
CTL killing mechanism
Immunity to viruses
Virus
Mechanism of immune evasion Examples
Antigenic variation Influenza, rhinovirus, HIV
Inhibition of antigen processing Herpes simplex, CMV
Production of cytokine receptor
homologs
Vaccinia, poxvirus (IL-1,
IFN-)
CMV (chemokine)
Production of immunosuppresive
cytokine
Epstein-Barr virus (IL-10)
Infection of immunocompetent
cells
HIV
Viral immune evasion
Protozoa:
Eukaryot
Ex: malaria, amoeba, trypanosoma, leishmania,
toxoplasma
Helminths :
Multicellular organism
Extracellular
Ectoparacyte:
Ex: dustmite, ticks

Immunity to paracytes

Parasites
Innate immunity
Phagocytosis
Eosinophil killing
Complement activation (alternative pathway)
Adaptive immunity
Intracellular parasites : Cell mediated immunity
Th1 activate macrophage
Humoral : IgE production & activation of
eosinophils (ADCC)
Immunity to paracytes
Eosinophilic killing
Mechanism of immune
evasion
Examples
Antigenic variation Trypanosomes
Plasmodium
Resistance to
complements
Schistosomes
Inhibition of host immune
response
Filaria, trypanosomes
Antigen shedding Entamoeba
Paracytic immune evasion
Fungal infection: mycoses
Endemic
Opportunistic
Eukaryot
Ex: Candida, histoplasma
Innate immunity
Phagocytes
Adaptive immunity
Cell mediated immunity


Immunity to fungi
Allergy & hypersensitivity
Hypersensitivity: An immunologic reaction which
produces tissue damage on reexposure to antigen
Gel & Coombs classification
Type I (IgE-mediated)
Type II (Fc and complement-mediated)
Type III (Immune complex-mediated)
Type IV (Delayed-type hypersensitivity)
Introduction
Type I Hypersensitivity Diseases
= allergy
Atopy
Mediated by IgE attached to Mast cells.
The symptoms resulting from allergic responses are
known as anaphylaxis
Allergic rhinoconjunctivitis (hay fever)
Asthma
Eczema (atopic dermatitis)
Acute urticaria
Anaphylaxis shock
Allergens
Nonparasite antigens that can stimulate a type I hypersensitivity
response.
Bind to IgE and trigger degranulation of chemical mediators.

Small 15-40,000 MW proteins.
Specific protein components
Often enzymes.
Most allergens promote a Th2 immune.




Mechanisms of allergic response
Sensitization
First exposure to allergens initiates immune response
that generates IgE isotype
IgE can attach to Mast cells by FcR receptor,
High affinity IgE receptor found on
mast cells/basophils/activated eosinophils.


Mechanisms of allergic response
Sensitization
Th2/B cell interaction
IL-4
IL-4R
CD40
B cell activation
IgE isotype switch
Busse and Lemanske NEJM Feb 2001. 344:350
Mechanisms of allergic response
Effector Stage of Hypersensitivity
Secondary exposure to allergen

Mast cells are primed with IgE on surface

Allergen binds IgE and cross-links to activate signal
with tyrosine phosphorylation, Ca++ influx,
degranulation and release of mediators.
FceRI Triggers Release of Mediators
Early mediators
cause immediate symptoms
e.g. histamine (preformed in granules)
leukotriene C4 and prostaglandin D2
are quickly made 2' mediators
Mediators of Type I Hypersensitivity
Immediate effects
Primary Mediators
Pre-formed mediators in granules
Histamine
Constriction of smooth muscles.
Bronchiole constriction = wheezing.
Constriction of intestine = cramps-diarrhea.
Vasodilation with increased fluid into tissues causing
increased swelling or fluid in mucosa.
Activates enzymes for tissue breakdown.
Cytokines TNF-a, IL-1, IL-6.
Chemoattractants for Neutrophils and Eosinophils.
Enzymes
tryptase, chymase, cathepsin.
Changes in connective tissue matrix, tissue
breakdown.


Mediators of Type I Hypersensitivity
Immediate effects
Secondary mediators
Mediators formed after activation
Leukotrienes
Prostaglandins
Th2 cytokines- IL-4, IL-5, IL-13, GM-CSF
Treatment for Type I
Drugs.
Non-steroidal anti-inflammatories
Antihistamines block histamine receptors.
Steroids
Theophylline OR epinephrine -prolongs or increases
cAMP levels in mast cells which inhibits
degranulation.
Treatment for Type I
Immunotherapy
Desensitization (hyposensitization)
Repeated injections of allergen to reduce the IgE on
Mast cells and produce IgG.
Complement-mediated cytolysis
Antibody-dependent cell-mediated cytotoxicity (ADCC)
Main Ab: IgG
Examples:
Transfusion reactions
Hemolytic disease of the newborn (Rh incompatibility)
Hyperacute graft rejection
Drug-induced hemolytic anemia
Drug induced trombocytopenia
TYPE II
Antibody mediated cytotoxicity
Mechanisms
Of Drug
Hypersensitivity

TYPE II
Rh factor incompatibility
TYPE III
Antigen antibody or immune complexes (IgG
mediated )
Large amount of soluble antigen and antibodies form
immune complexes in blood.
Phagocytes failed to eliminate immune complex
deposit in tissues and trigger inflammation mediated
by complement system (C3a, C5a)
Deposited in joints causing local inflammation =
arthritis
Deposited in kidneys = glomerulonephritis
Serum sickness
Farmers lung

Type IV Hypersensitivity
Delayed type hypersensitivity
(Th1 cells and macrophages)
DTH response:
Allergen contact recognized by Th1
Th1 cells release cytokines to activate macrophages causing
inflammation and tissue damage.
Several hours, fuly developed at 24-48 hours
Continued macrophage activation can cause chronic
inflammation resulting in tissue lesions, scarring, and
granuloma formation.
Stages of Type IV DTH:
Sensitization stage
Th1 cells recognized DTH antigens are generated by
dendritic cells during the sensitization stage.
These Th1 cells can activate macrophages and trigger
inflammatory response.
Stages of Type IV DTH
Effector stage
Secondary contact with DTH.
Th1 memory cells are activated and produce cytokines.
IFN-g, TNF-a, and TNF-b which cause tissue destruction,
inflammation.
IL-2 that activates T cells and CTLs.
Chemokines- for macrophage recruitment.
IL-3, GM-CSF for increased monocyte/macrophage
Type IV DTH

Tuberculin test
Contact dermatitis

poison ivy
Small molecules act as haptens and complex with skin proteins
taken up by APCs presented to Th1 cells to get sensitization.
During secondary exposure Th1 memory cells become activated to
cause DTH.

Contact dermatitis
Granuloma Formation from DTH
Mediated by Chronic Inflammation
Thank you very much.
Murphy K, Travers P, Walport M, Janeways Immunobiology, 7
th

ed
Abbas AK dan Lichtman AH, Pillai S, Cellular & Molecular
Immnunology, 6
th
ed
Roitt, IM., Delves, PJ, Roitts Essential Immunology
Burmester, Colour Atlas of Immunology

References