Imunolog BMD 2010i

8/14/2019 Imunolog BMD 2010i

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Immunology

E. A. JALAL


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Immunology

adalah ilmu yang mempelajaritentang pertahanan tubuhterhadap infeksi


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Immune System

vital for survival

protects us from infectious pathogens

immune deficiencies render individuals easy prey toinfections

= A variety of effector cells and molecules that protect the body


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The mechanisms of protectionagainst infections

Innate immunity: natural, or native, immunity defense mechanisms that are present even before infection

is the first line of defense

Adaptive immunity acquired, or specific, immunity mechanisms that are stimulated by (adapt to) microbes

and are capable of recognizing microbial andnonmicrobial substances develops later, after exposure to microbes is even more powerful than innate immunity in combating

infections


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INNATE IMMUNITY


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The major components ofinnate immunity

epithelial barriers that block entry ofmicrobes,

phagocytic cells (mainly neutrophils andmacrophages),

dendritic cells,

natural killer (NK) cells, and several plasma proteins, including the

proteins of the complement system.


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EPITHELIAL BARRIERS

Epitheliaof the skin and gastrointestinal andrespiratory tracts provide mechanicalbarriers to the entry of microbes from theexternal environment.

Epithelial cells also produce anti-microbialmolecules such as defensins

lymphocytes located in the epithelia combatmicrobes at these sites.

If microbes do breach epithelial boundaries,other defense mechanisms are called in.


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Epithelial Barriers


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Responsimmune:

Respons yang dibuat tubuh melawan

infeksi


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Respons to an initial infection occurs in three phases


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The early innate immune response not only provides the initialdefense against infections but is also involved in triggering thesubsequent, more powerful adaptive immune response


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Monocytesand neutrophils are phagocytes in the blood that can rapidly be recruited

to any site of infection;

monocytes that enter the tissues and mature are called

macrophages

Dendritic cells produce type I interferons, anti-viral cytokines that inhibit

viral infection and replication Antigen presenting cells (APC)


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Natural killer cells

provide earlyprotection againstmany viruses andintracellular bacteria


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Plasma Proteins

The complement system, are some of the most importantplasma proteins of the innate immune system.

In innate immunity, the complement system is activated bymicrobes using the alternative and lectin pathways

In adaptive immunity it is activated by antibodies using theclassical pathway.

Other circulating proteins of innate immunity are mannose-binding lectin and C-reactive protein which coat microbes for

phagocytosis.

Lung surfactant is also a component of innate immunity,providing protection against inhaled microbes


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The two most important cellularreactions of innate immunity are:

inflammation,

the process in which phagocytic leukocytes arerecruited and activated to kill microbes, and

anti-viral defense,

mediated by dendritic cells and NK cells.


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Pathogen-associated molecularpatterns

Leukocytes and epithelial are capable of recognizingcomponents of microbes that are:

shared among related microbes

often essential for the infectivity of these pathogens (and thuscannot be mutated to allow the microbes to evade the defensemechanisms)

These microbial structures are calledpathogen-associated

molecular patterns

The cellular receptors that recognize these molecules areoften calledpattern recognition receptors (PRRs).


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PATTERN RECOGNITION RECEPTOR

The best-defined PRR family ofproteins called Toll-like receptors

(TLRs)

Other cellular receptors bindmicrobes for phagocytosis:

mannose receptorsforresidues, which are typicalof microbial but not host

glycoproteins, receptors for opsonins

such as antibodies andcomplement proteins


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Adaptive Immune System

The adaptive immune system consists oflymphocytes and their products, including

antibodies.

.


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Lymphocytes

Capable of migrating among lymphoid and other tissues and thevascular and lymphatic circulations. This feature permitslymphocytes to home to any site of infection.

Different classes of lymphocytes are anatomically segregatedinsuch a way that they interact with one another only whenstimulated to do so (by encounter with antigens and otherstimuli)

Mature lymphocytes that have not encountered the antigen are

said to be naive(immunologically inexperienced).

After they are activated by recognition of antigens and othersignals, lymphocytes differentiate into effector cells, andmemory cells,


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The Adaptive Immunity

There are two types of adaptive immunity:

Humoral immunity

protects against extracellular microbes and their toxins

mediated by B (bone marrowderived) lymphocytes and theirsecreted products, antibodies (also called immunoglobulins,Ig)

cell-mediated (or cellular) immunity

responsible for defense against intracellular microbes.Cellular immunity is mediated by T (thymus-derived)lymphocytes


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The humoral response 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)

Two Types of Adaptive Immunity

Antibody-mediated immunity Cell-mediated immunity


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Antigen:

Semua yang dapat memicu pembentukanantibodi (ANtibodyGENerator)

Immunogen: antigen yang dapat menimbulkankekebalan

Pathogen: antigen yang dapat meimbulkan

infeksi dan kerusakan jaringan Allergen: antigen yang dapat menimbulkan

reaksi alergi


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Antibodi

Immunoglobulin M Macroglobulin, reseptor permukaan limfosit B. dibentuk paling awal pada respons imun primer Ig utama yang diproduksi oleh janin

Immunoglobulin G: Terbanyak dalam darah, dapat menembus plasenta

Immunoglobulin A Secretory Ig, terdapat pada ASI, air mata, ludah, mukosa

Immunoglobulin E Mudah diikat oleh reseptor pada permukaan sel mast, basofil dan eosinofil.

Kadar tinggi pada alergi dan infeksi cacing Immunoglobulin D

Kadar dalam serum paling rendah, komponen utama permukaan limfosit B


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T Lymphocytes

T lymphocytes develop from precursors in thethymus.

Mature T cells are found in the blood, and in T-cell

zones of peripheral lymphoid organs. Each T cell recognizes a specific cell-bound antigen

by means of an antigen-specific T-cell receptor(TCR).

The TCR recognizes peptide antigens that aredisplayed by major histocompatibility complex(MHC) molecules on the surfaces of antigen-presenting cells (APCs).


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Cellular Immune Respons


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T-Cells Mediated Immunity


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Humoral immune response

The humoral response refers tothe production of antibodies

by B-cells

activation of T-helper2 cells

cytokine productionmemory cell generation

complement system

activation


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Humoral Immune Response


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Germinal center

Medullary cords and sinuses

Humoral immune response is mediated by

Antibody molecules secreted by plasma cells


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.....if immunity gone wrong

a hyperactive immune system may cause diseases thatcan sometimes be fatal:

disorders caused by immune responses includeallergic reactions

reactions against an individual's own tissues andcells (autoimmunity).


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Allergy and Hypersensitivity

Autoimmunity

Failure of Host Defense Mechanism

Immunodeficiency Diseases Acquired Immune Deficiency Syndrome


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What is allergy ?

Allergy is an abnormalover-reaction of the

immune system toward anantigens that are normallynotharmful.


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For someone to have an allergic reaction, they have tobe sensitized to the allergen.

All i i


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Allergies can present in manyforms, a multi-organ disease.

Conjunctivitis allergica Allergic rhinitis

Asthma

Urticaria


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Components of allergy

Allergen

Immunoglobulin E productions

Mast cells sensitization

Mast cells degranulation

Clinical effects


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Allergens

Are antigens thatselectively evoke CD4+ TH2cells that drive IgE

response

Practically could be any

substance


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Immunoglobulin E

The antibodies involvedin allergies

Produced by plasmacells located in lymph

nodes Isotype switching from

IgM requires TH2secreted IL-4

IgE-mediated responsesare important inresistance to parasiticinfection


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IgE distribution

Predominantly localized intissuesUnder the epithelial of theskin intestinal mucosarespiratory tract and bodycavitiesTightly bound to mast cellssurface through high-affinityIgE receptor: FcRI


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APC

IgE

IL-4

IL-5 Allergic

response

EosinophilsTh2

B-cell

+

+

Treg

IL-10

TGF-

--

+

IT

Th1

IgG

IFN-gB-cell

IT-

CD4

CD80/86

T cell

Allergen

TCRHLA

CD28

Mechanisms

IL-4

IL-12

IFN-g

ll


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Mast Cells Degranulation

Primary mediators,Immediate response /Preformed Histamines

Proteases

Chemotactic factors

Secondary Mediators /synthesized mediators /

Late phase reaction Leukotrienes

Prostaglandin

PAF


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Mast cells

Derived from progenitors in thebone marrow

Not found in the bloodcirculation 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 Fcreceptor (FcRI)


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Mast cellsactivation

Mast cellsactivation

occurs whenthe boundIgE is cross-linked bymultivalentantigen


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How is allergy diagnosed?

A good medicalhistory

Skin Prick Tests

RAST

(radioallergosorbent test)

Double-Blind, FoodChallenge


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Autoimunity

Penyakit yang terjadi karena respons imunterhadap antigen dari tubuh sendiri (autoantigen).

Failure of the mechanism of self-tolerance

Specific cause? Mostly unknown

Genetic factors, environmental factors, both

Common autoimmune diseases


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Common autoimmune diseases


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SLE

Discoid lupus Vitiligo

Rheumatoid joints


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Immunodeficiency

Primary: genetics

Secondary: Hamil Malnutrisi

Setelah sakit

Acquired Immuno Deficiency Syndrome(AIDS) Karena infeksi HIV


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Table. Prevalence of Primary Immunodeficiencies

Disease Prevalence

IgA deficiency 1/600

X-linked agammaglobulinemia (XLA)X-linked lymphoproliferative syndromeX-linked immunodeficiency with hyper-IgM

X-linked severe combined immunodeficiency

JAK3-deficient severe combined immunodeficiency (autosomal recessive T-BSCID)

Adenosine deaminase deficiencyB-cell negative SCID, Omenn syndrome

Ataxia-telangiectasia

Leukocyte adhesion deficiency type I

X-linked chronic granulomatous disease (X-CGD)Autosomal CGD p22phox deficiency 1

Autosomal CGD p47phox deficiency

Autosomal CGD p67phox deficiency

1/600

1/200,000

1/1,000,000

live births in males

1/50,000 to 1/100,000

1/500,000 live births12-1/100 live births1/100,0001/100,000

1/100,000

1/250,000

1/2,000,000

1/500,0001/2,000,000


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Infeksi

HIV


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Acquired Immuno Deficiency Syndrome

(AIDS)


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Documents

Imunolog BMD 2010i