Immunology

E. A. JALAL
 Immunologi
Immunology is the study of the
body’s defense against infection
Nature of the Immune system
 Innate Immune System

• Induction of primary immunological

response

• First line of defence

• Constitutively present and reacts

immediately to infection

• The innate immune system is not specific

in its response and reacts equally well to a
variety of organisms

• The innate immune system does not

possess a memory
Innate immunity cells
NK cells
NKT cells
γ δ T lymphocytes
Macrophage
Dendritic cells
Phagocytic Cells
• Pathogen Recognition:
– Macrophages and dendritic cells
expressed Pattern-recognition
receptors (PRRs) ex. TLRs
– Stimulation of TLRs induces
proinflammatory cytokine genes
and also type I interferon genes
• Expression of
– Inflammatory cytokines : TNF,
IL-1, IL-12
– Chemokines: IL-8, MCP-1,
RANTES
– Endothelial adhesion molecules
E-selectin
– Costimulatory molecules (CD 80,
CD 86)
– Antiviral cytokines (Interferon
α/β)
 Sistem Imun terdiri dari:
• Sel Penyaji Antigen (APC): Dendritic Cells.
– Sel yang menangkap dan menyajikan antigen kepada limfosit T
• Sel limfosit T helper (CD4+)
– Mengenali antigen dan diaktifkan oleh APC
– Bereaksi mengaktifkan sel lainnya untuk memberikan respons yang sesuai
terhadap antigen
• Sel limfosit T Cytotoxic (CD8+)
– Mencari dan membunuh sel target (respons selular)
• Sel limfosit B
– Memproduksi antibodi (respons humoral)
• Sel T regulator (CD25+Foxp3 T reg)
– Regulator/supressor respons imun
• Cytokine
– Diproduksi oleh sel untuk berkomunikasi dan mempengaruhi sel lain
Epithelial barrier Complement activation Dendritic cells migrate Specific antibody
Antibacterial peptides Pahagocytes to lymph node T-cell dependent
Phagocytes Cytokines T-Cells activation Macrophages activation
NK cells Chemokines Initiating adaptive Cytotoxic T cells
Wound healing Macrophage activation immunity
Respons to an initial infection occurs in three phases
• Induction of a primary
immunological response begins
when an antigen penetrates
epithelial surfaces
• It will come into contact with
macrophages or other Antigen
Presenting cells (APCs), which
include B cells, dendritic cells and
endothelial cells
• Complement and NK cells are
activated, cytokines produced

• Antigens, are internalized and

"processed“ by APC, Dendritic
cells migrate to lymphonodus,
mature and initialized adaptive
immune response
• Antigen "presented" to a CD4+ T-
helper cells
• Activation of CD4+ T cells
required co stimulatory molecules,
CD80 (B7.1) & CD86 (B7.2)
Antigen presentation to T lymphocyte
T lymphocyte activation
TH Differentiation
Bacterial LPS induces Langerhans cells to migrate
to lymphonodus, mature and initiating adaptive
immunity

Activation of CD4 T cells required co stimulatory

molecules, CD80 (B7.1)& CD86 (B7.2)
Activation of B cells required the help of activated CD4
T cells

Lymphocyte activation occur in T-cell dependent zone

of lymphonodus
 Adaptive Immune Response
Two Types of Adaptive Immunity
• The humoral response (antibody
mediated immunity) refers to
– the production of antibodies by B-
cells
– activation of T-helper2 cells
– cytokine production
– memory cell generation
– complement system activation

• Cell-mediated immunity involves

– the activation of macrophages and
natural killer cells
– antigen-specific CD8+ cytotoxic T-
lymphocytes (lyse infected cells)
– the release of cytokines (influence
functions of other cells)

Antibody-mediated immunity Cell-mediated immunity

 Germinal center

Humoral immune response is mediated by

Antibody molecules secreted by plasma cells

Medullary cords and sinuses

Humoral Immune Response
.....if immunity gone wrong…
 Immune Disorders
• Hypersensitivity

• Immunodeficiency
Diseases

• Autoimmunity

• Tumor Immunology
 Hypersensitivity
– TYPE I HYPERSENSITIVITY
• Immediate hypersensitivity

– TYPE II HYPERSENSITIVITY
• Transfusion Reactions
• Hemolytic Disease of the Newborn (erythroblastosis fetalis)
• Autoimmune Hemolytic Anemia

– TYPE III HYPERSENSITIVITY

• Arthus Reaction
• Serum Sickness
• Autoimmune Diseases

– TYPE IV HYPERSENSITIVITY
• Contact Dermatitis
• Tuberculin-Type Hypersensitivity
Type I Hypersensitivity
What is allergy ?

• Allergy is an abnormal over-

reaction of the immune system
toward an antigens that are
normally not harmful.
 Components of allergy
• Allergen
• Immunoglobulin E productions
• Mast cells sensitization
• Mast cells degranulation
• Clinical effects
 Allergens

• Are antigens that selectively

evoke CD4+ TH2 cells that drive
IgE response
• Practically could be any
substance
Mechanisms IgE
IL-4
B-cell
Allergen
APC
Th2 Eosinophils +
IL-4
CD80/86
CD28
HLA
TCR IL-5 Allergic
IL-12 T cell
IT - + response
IFN-g
CD4 IT
- TGF-b
-
Treg
IL-10
+
IgG
IFN-g B-cell
Th1
Allergies can present in many forms,
a multi-organ disease.

• Conjunctivitis allergica
• Allergic rhinitis
• Asthma
• Urticaria
For someone to have an allergic reaction,
they have to be sensitized to the allergen.
Type I Hypersensitivity
(Allergic Reaction)

Occur when an
individual who has
produced IgE antibody
as a result of previous
contact to an allergen,
subsequently
encounters the same
allergen.
Immunoglobulin E

• The antibodies involved in

allergies
• Produced by plasma cells
located in lymph nodes
• Isotype switching from
IgM requires TH2 secreted
IL-4
• IgE-mediated responses
are important in resistance
to parasitic infection
Immune response to
Helminth parasite
 IgE distribution

•Predominantly localized in
tissues
•Under the epithelial of the
skin, intestinal mucosa,
respiratory tract and body
cavities
•Tightly bound to mast cells
surface through high-affinity
IgE receptor: FcεRI
 Mast Cells Degranulation
• Primary mediators,
Immediate response /
Preformed
– Histamines
– Proteases
– Chemotactic factors

• Secondary Mediators /
synthesized mediators /
Late phase reaction
– Leukotrienes
– Prostaglandin
– PAF
Mast cells

• Derived from progenitors in the

bone marrow
• Not found in the blood circulation
• Matured in peripheral tissue
• Two types of mast cells:
– Connective tissue mast cells
• In the skin
– Mucosal mast cells
• Alveoli, intestinal mucosa
• Expressed high-affinity IgE Fc
receptor (FcRI)
 Mast cells
activation
• Mast cells
activation
occurs when
the bound
IgE is cross-
linked by
multivalent
antigen
How is allergy diagnosed?
• A good medical
history
• Skin Prick Tests
• RAST
(radioallergosorbent
test)
• Double-Blind, Food
Challenge
 Type II
Hypersensitivity

Hemolytic Disease of the Newborn (erythroblastosis fetalis)

Type III
Type IV
 Immunodeficiency
• Immunodeficiency
– Primary
– Secondary
• Hamil
• Malnutrisi
• Setelah sakit
• Acquired Immuno Deficiency Syndrome
(AIDS)
– Karena infeksi HIV
AUTOIMMUNITY
 Autoimmune Diseases
• Penyakit yang terjadi karena respons imun
terhadap antigen dari tubuh sendiri (auto
antigen).
– Failure of the mechanism of self-tolerance
– Specific cause? Mostly unknown
– Genetic factors, environmental factors, both
Common autoimmune diseases
Two Types of Autoimmune Disease
Organ Specific Non Organ Specific
Molecular Mimicry
Grave’s Disease
Myasthenia Gravis
Tumor Immunology
Cancer Immunoediting
Tumor Immunoediting