imunolog bmd 2010i
TRANSCRIPT
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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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