Immunology

E. A. JALAL

Immunologi
Immunology is the study of the
bodys 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
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
/)

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
Antibacterial peptides
Phagocytes
NK cells
Wound healing

Complement activation
Pahagocytes
Cytokines
Chemokines
Macrophage activation

Dendritic cells migrate

to lymph node
T-Cells activation
Initiating adaptive
immunity

Specific antibody
T-cell dependent
Macrophages
activation
Cytotoxic T cells

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+ Thelper 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 Bcells
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 Tlymphocytes (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 overreaction 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
IL-4
CD80/86
CD28

IL-12
IFN-g

Th2

HLA
TCR

CD4

IT

T cell

Eosinophils

IT

IL-5

+
Allergic
+ response

TGF-

Treg

IL-10

Th1

IFN-

+
B-cell

IgG

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: FcRI

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 crosslinked by
multivalen
t 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

Graves Disease

Myasthenia Gravis

Tumor Immunology

Cancer Immunoediting

Tumor Immunoediting