Bismillahirrahmanirrakhim

ASSALAMUALAIKUM WR WB
 IMMUNOLOGY
INTRODUCTION AND OVERVIEW

Harijono Kariosentono
Dermato-Venerologist
Topics:
1. Introduction and overview of Immunology
2. The Element of Immune System
3. Antibody and Lymphocyte structure
4. Immunity in Defence and Disease:
5. -Immunity to Fungi and Parasites
6. -Immunity to bacteria and Viruses
7. Complement System
8. The Controle Mechanism of Immune
Response
 9. Diseases cause by Immune Responses:
- Hypersensitivity
- Autoimmunity
- Immunodeficiencies
10. Immunity to Tumors
11. Immuno-prophylaxis and immuno therapy
12. Laboratory Techniques in Immunology &
Immunohematology
 INTRODUCTION

IMMUNOLOGY :Understanding how the body

distinguish between what is self and what is
nonself

Immunology is the study of immunity

and of the cellular and molecular event
that occur after an organism
encounters microbes and other foreign
macromolecules

DEFINITION
IMMUNITY

Historically, immunity meant protection from

disease and more spcifically infectious
disease

Immune response :
All mechanisms used by the body as protection against
enviromental agent that are foreign to the body :
microorganisms or their product, macromolecules such
as protein & polysaccharides from foods, chemicals,
drugs, pollen or animal hair and dander
 IMMUNITY

IMMUNE RESPONS
Collective and coordinated response to the introduction of
foreign substances

IMMUNE SYSTEM
Cells & molecules responsible for immunity
 I IV
ANTIGEN Protective
(Immune physiology)

III
IMMUNE
RESPONSE

II Tissue injury Disease

IMMUNE (Immunopathology)
SYSTEM 1. Hypersensitivity
2. Autoimmune
3. Immunodeficiency
HISTORY
The ancient Chinese : custom of making
children resistant to smallpox by inhale
powders made from skin lesions patient
recovering of the disease
1798 : Edward Jenner IMMUNITY could be
induced against microorg or their product
vaccination against smallpox

Vaccination :- process of inducing acquired

immunity
-the most effective method for
preventing infections.
1960 transformation in our
understanding of the immune system
and its functions. ----

Advances In :
Cell culture technique ( incl. monoclonal
antibody production )
Immunochemistry
Recombinant DNA methodology
Genetics altered animal ( transgenic and
knock-out mice )
 Immunology is an experimental
science, explanations of immune
phenomena based on experimental
observations and the conclutions drawn
from them.
The evolution of immunology has
depend on our ability to manipulate the
function of immune system under controle
condition
IMMUNOLOGY
=the study of Immunity

Immunity :
- Innate immunity
- Acquired/adaptive immunity
 INNATE AND ADAPTIVE IMMUNITY
Host defence against microbes other molecules
mediated by early reaction ( < 12 hours) of innate
immunity later responses of adaptive immunity

INNATE ( = natural, native ) IMMUNITY :

Used by the host to defend itself immediately,
consist of mechanisme that exist before infection,
since an indiv was born
Rapid responses to microbes, short lived & have
no memory
INNATE IMMUNITY :
React in the same way to repeated
infection
Early/first line of defence mechanism
against microbes, or their product,
macromolecules such as protein &
polysaccharides from foods, chemicals,
drugs, pollen or animal hair and dander
The components of Innate
Immunity
1. Physical : -skin & mucosal epithel tr resp, GI tract and
genito-urin tract.
2. Phagocytes cells :- monocytes/macrophages (M), PMN
leucocytes: take up patogen recognieddestroyed
(PMN : the earliest phagocytes cells to be recruited)
- dendritric cell (DCs); NK cells: large gran.lymph
killed/lysis transformed/neoplasm or infected cells,
via : perforin/granzym, Fas-FasL, indirect (IFN-gamma).
3. Molecules: Blood proteins -
complement system: classic /alternative pathway, -
mediator of inflamation,
- AMP (antimicrobial peptides):bind membrane of
microb. produced by corneocytes(HBD1,2, LL37,
psoriasin) or sweat gld (dermicidin)
- PRR: receptor on phagocytes cells recognized &
destroyed pathogen via interaction w/ PAMP
(pathogen-associated mol pattern) specific to micr,
eg. TLR ,
4. Cytokines regulate an coordinate many of
activities of the cells of Innate Immunity
 NORMAL EPIDERMAL BARRIER

The first line of defense against invanding allergens,

irritants, microbials (bacteri,fungus, virus) or from
physical injury.

Regulation of water release= transcutaneous evaporated

water loss (TEWL), skin as permeabilty barrier,
hydrations of the skin

4 epidermal element work synergislly like a tightly

orchestrated symphony
4 epidermal elements
barrier
1 physicall barrier

2
chemically barier : AMP, fam.
S100protein, FLG breakdown

3 skin microbial flora

4 immunologic barrier
 1. Physical Barrier
A. Stratum Corneum (SC) :

.Consist:
-1. protein-enriched cells (corneosit) connected
by corneodesmosome (iron rods) and protein
(cornified enveloped protein: loricrin, involucrin &
filagrin=FLG)
-2. intercellular matrix, as a lamelar lipid: ceramid,
cholesterol and free fatty acid.

.The structur of SC like brick and mortar : corneosit

as the brick and lipid lamelar as mortar.
.The Integrity of SC corneodesmosome
B. Tight Junction (TJ)

Directly below SC as 2nd physical barrier in epidermis

Made up of a complex adhesive proteins, incl:

- claudin fam.(CLDN), -junctional adhesion molecule
(JAM)A, - zonula ocludin and -triselulin

TJ as the gate control passage of water and solutes

through paracellular pathway.
Play a role in epid regeneration basic barrier : function
in permeability
barier fisik
 2. CHEMICAL BARRIER
(ANTI MICROBIAL PEPTIDE = AMP)

Product by: Function : as

BIO-CHEMICAL
KERATINOCYTES & ENDOGEN
BARRIER ANTIBIOTIC
ECRIN GLAND

LL-37 - defensin
(Cathelicidin) (HBD)1-4
- defensin
dermicidine
IMPAIRMENT 0F SKIN BARRIER

FILAGRIN ABNORMALITY
DEFICIENT OF TIGHT
JUNCTION
IMPAIRMENT OF
SKIN BARIER
PROTEASE & ANTIMICROBIAL
PROTEASE INHIBITOR BARRIER
EKSPRESSION DYSFUNCTION
IMPAIRMENT OF SKIN BARRIER

AD : - TEWL increase
- abnormality of KC differensiation ceramid, filagrin
and AMP level
AD : - impaiment skin barrier homeostasis abnormal:
increase of endogen protease aktivity (epidermis) or
exsogen (from HDM and St.aureus) leakage of
corneodesmosome juntions penetration of antigen,
irritant, patogen.
- DC interact & present Ag to CD4+Tcell TH2.
respons imun (+)
Defective epidermal barrier in
individuals with atopic dermatitis
Filagrin Deficiency (FLG)

Filagrin is the primary protein of SC, derived from Profilagrin

phosphorilated : dissolved and deaminated peptides Filagrin
free amino acids:

- Lactic acids,
- trans-urocanic acid (t-UCA),
- carboxilic acids sod.pirolidon Natural Moisturizing Factors
- Urea
(NMF)
water retention

OPTIMAL HYDRATION
FILAGRIN

Main function of FLG: a key protein to facilitate terminal

epid deff & formation skin barrier protecting against
environment agent & prevent epid water loss.

FLG: protect alpha staphylococcal toxin as the cause of

keratinocyte death

2006: Palmer, et al filagrin gene mutation is a

significant predisposition factor for AD
Filagrin

Loss-of-function FLG mutation : observed in less than

one third AD population

FLG mutation:
- early-onset AD, - more severe & persistent AD
- increasing IgE total and allergen sensitization,
- incidence of herpes vi skin infection > high and
- higher risk to have multiple allergy ( compared with
AD with no FLG mutation).
 The pathogenicity of microbes
related to their ability to resist the
mechanism of Innate Immunity

Antigen : foreign substances induce

immune responses antigen as targets
of the such responses
ADAPTIVE IMMUNITY
( Spesific, Acquired Immunity)
An immune response to infection and adapts
to antigen, ability to remember and
respond more vigorously to repeated
exposures to the same antigen/ eg. microbe
have memory
Spesifics to microbes or macromol (non
microbial antigen), even closely related
have specificity
ADAPTIVE IMMUNITY :

Acquired: it by experience, are long lasting

Component :
- T lymphocytes and
Antibodies : produced by B cells
- APC (in epidermis =LC, and
dermal: DC)
 Cardinal Features of Adaptive Immun
Response
1. Specificity: Immune Response are specific for distict
Ag, elicit spec response
2. Diversity: capable recognizing a wide variety of Ag.
-Mammalian immun system can discrminate 109 -
1011 Ag (lymphocyte repertoire)
3. Memory: enhanced responses to re-exposures to
same microbes.
4. Specialized response : special ways to different types
of microbes
-Response optimal for defence against different
type of microbes.
Cardinal Features

5. Self-limitation : Ab levels decline with time/

after each immunization homeostasis
(returning to its resting basal state)
6. Non reaction to self : ability to discriminate
between self and non-self = foreign Ag.
Eliminate nonself Ag while not reacting
harmfully to self substance.
immunologic unresponsive = tolerance
Cellular component
of Adaptive Immun System
1. Lymphocytes :
-. B lymphocytes
-. T lymphocytes : - helper T cells (Th)
- cytolytic T cells (CTLs)
-.NK cells (Natural Killer) against virus and
intracellular micr (in IIR)

2. Accessory cells : - MNC (phagocytes), dendritic

cells, and several other cells function as accessory
cells

3.Effector cells : activated lymph, phagocytes, & other

leucocytes
The Link between Innate and Adaptive respons :

1. IIR to microbes stimulates AIR and influences the nature

of adaptive response
2. AIR use many of the effector mech of innate immunity to
eliminate microbes

Types of Adaptive Immune Responses

Humoral Immunity Cell-mediated Immunity

 Types of Adaptive Immune Responses

Humoral Immunity Cell-mediated Immunity

 1. HUMORAL IMMUNITY

Mediated by molecules in the blood, called ANTIBODY (Ab)

produced by B lymphocytes

recognize specifically microbial/ ANTIGEN (Ag)

neutralize the infectivity elimination (by effectors mech)
Defence mech against extracellular microbes
Could be transferred to naive indiv as adoptive transfer

-Substance bound Ab
Ab -Induce production of Ab

Ag
Protective immunity against microbes:

Hosts response to the microbe =

active immunity
Transfer of antibodies specific for the microbe
from a immunized individual (adoptive transfer)
= passive immunity
- 1890 : Von Behring & Kitasato :

serum from animal recovered from diphteri

transferred to naive animal

recipient animal specifically resistant to diphteri

infection

Active component of serum (as anti toxin ) can

neutralized the pathogen of diphteri toxin
- Early 1900 : Lansteiner et al :
not only toxin, non-microbial substance
could induced humoral immune response
Ab : serum proteins that mediate
Humoral Immunity

-1900 : Paul Ehrlich

The specificity of Ag Ab reaction :
physicochemical complementarity of
antigens and antibodies
2. CELL MEDIATED IMMUNITY

Mediated by T cells
Defence mech to intracell microbial ( virus & some bact )
Promotes destruction of microbial residen in cell
phagocytes or lysis of infective cells
Can be transferred to naive individu with T cells from
immunizes indiv

Active acquired by
Respond to Ag
Cellular immunity
Passive
Transfer of cells
CELLULAR THEORY OF IMMUNITY:

1893 : Eli Metchnikoff cell respond to foreign invanders

1900 : Sir Almroth Wrights observation opsonization :

Factors in immune serum

Coating of bacteri

Phagocytosis by phagocytes increase.

Antibodies prepared microbes for ingestion

by phagocytes
 1950 : Mackaness :
resistance to an intra cellular bacterium,
Leisteria monocytogenes, could be adoptively
transferred with cells but not with serum
Now : the specificity of CMI is due to
LYMPHOCYTES, often function in concert with
other cells, eg phagocytes, to eliminate
microbes.
.>
Adaptive Immune Response
Process :

Ag recocnation

Lymphocytes active proliferating &

differentiating

Memory cells Effector cells

Re-exposure response
Eliminate Ag
increase
Immune Phases of Adaptive Response

Recocnation phase

Activation phase

Effector phase

Decline (homeostasis)

Memory
Summary
Immunology is a study about immunity
Immunity means the body distinguish between
what is self and what is nonself, then protect
from nonself/antigen toward homeostatis

Immunity : may be acquired by a response to Ag

(= active imm.) or by transfer of Ab or cell from
immunized indiv (=passive imm.)

Immunity : immune response by immune

system
 The Immune system posseses several
properties: specificity, diverse repertoire of
wide var of Ag, memory, specialized
responses, self-limitation and ability to
discriminate between Ag and self Ag

Immunity innate and adaptive immunity

Innate immunity is first line defence of

mechanism against microbes or antigen;
the component are physical &, molecules,
cellular
 Adaptive Immune Response is initiated by
recognition by spec lymph response :
proliferating and defferentiating into ecffector
cells eliminate Ag and defferentiated to
memory cells enhanced responses on
subsequent expos.

Adaptive imm response : humoral and cellular

mediated immunity
 Humoral Imm is mediated by B cells and
their secreted products: Ab extracellular
microbes
CMI is mediated by T cells and their
products, eg cytokines intracellular
microbes
 The activation of lymph requires Ag and
additional signals by microbes or by innate
immune responses to microbes

The Effector phase of Adaptive Immune

Response requires participation of variant
defence mech , incl complement sytem and
phagocytes, that also operate in Innate
Immunity

* The Adaptive Imm. Response enhances the

defence mechanisms of innate immunity.
 THANK YOU

Jazakalloh Wassalamualaikum wr wb