k3 - konsep dasar imunologi
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K3 - Konsep Dasar ImunologiTRANSCRIPT
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Basic concepts in immunology
Evy Sulistyoningrum
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Introduction
Immune system & components
Immune response
Immunological regulation
Immunity
Immunological memory
Defects in immunity
Outlines
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Immunology: the study of the body’s defense against infection
To protect individual from infectious agents and damage they cause
Introduction
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Edward Jenner discovered in 1796 that cowpox, or vaccinia, induced protection against human smallpox vaccination
The eradication of smallpox by vaccination.After a period of 3 years in which no cases of smallpox were recorded, the World Health Organization was able to announce in 1979 that smallpox had been eradicated.
History of Immunology
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Robert Koch (1843–1910) proved that infectious diseases are caused by microorganisms
History of Immunology
Louis Pasteur (1822–1895) devised a vaccine against cholera in chickens, and developed a rabies vaccine that proved a success upon its first trial in a boy bitten by a rabid dog
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Shibasaburo Kitasato (1892–1931) in collaboration with Emil von Behring (1854–1917) discovered specific antitoxin activity against tetanus and diphtheria in serum
Elie Metchnikoff (1845–1916) :central role of phagocytes in host defense.
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Variety of organs, tissues, cells, molecules that performed immune response and produce immunity
Cellular components
Immune cells
Lymphoid tissue or organs
Humoral components
Soluble protein: complements, antibody
Physical, mechanical, chemical barriers
Non-immune system “inherent component”
Performed by other structure not specific to immune system but acts as first line defense againts pathogen
Immune system
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Immune system: barrier
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Cells of the immune system
Origin: Pluripotential hematopoietic stem cells
Located within the bone marrow, fetal liver and yolk sac of the fetus
Stem cells differentiate into 2 types of “committed” stem cells
produce platelets, erythrocytes (red blood cells), monocytes or granulocytes (myeloid progenitor)
produces cells of the lymphoid line (lymphoid progenitor)
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Myeloid cells
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3 subsets :
B lymphocytes
T lymphocytes
NK cell
Functions:
B & T cell : adaptive immune response
NK cell : innate immune response
Distributions:
Circulation
Lymphoid organs
Lymphocytes
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T Lymphocytes (T cells)
Derived from stem cells in the bone marrow.
Leave bone marrow and travel to the Thymus to mature
Have T Cell Receptor (CD3)
Can be found in circulation and lymphoid tissues
Approximately 75 to 80% of lymphocytes are T cells
Subsets: Th : helper
Tc : killer
Tsup : suppressor
Treg: regulator
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B lymphocytes (B cells)
Derived from stem cells and become mature in the Bone marrow in human / Bursa of fabricius in birds
Have BCR (B cell receptor) (CD19/CD20)
Can be found in circulation and lymphoid tissues
Transform into plasma cells and produce antibodies (immunoglobulins)
Undergo a process called clonal expansion
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Derived from stem cells in the bone marrow
Circulate in the blood
No TCR and BCR null cell
Large cells, contain cytolytic granules kill cell targets
Important in the defense from certain tumor cell andfrom virally infected cells.
Innate immune response
Act without prior activation
NK cells
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Reticuloendothelial System
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Lymphocytes are produced in bone marrow
Mature in the bone marrow and thymus (primary /central
lymphoid organs) => mature naive lymphocyte
Congregate in lymphoid tissues throughout the
body to be exposured by antigen
(secondary/ peripheral lymphoid organs)
Tissue and organs of the immune system
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Tissue and organs of the immune system
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Circulation
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Primary lymphoid organs: development & maturation
Bone marrow: B cell maturation
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Primary lymphoid organs: development & maturation
Thymus: T cell maturation
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Circulating lymphocytes encounter antigen in peripheral lymphoid organs(lymph node, spleen, Mucosal-Associated Lymphoid Tissue)
Lymph node
Secondary lymphoid organs: antigen processing
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Circulating lymphocytes encounter antigen in peripheral lymphoid organs(lymph node, spleen, Mucosal-Associated Lymphoid Tissue)
Spleen
Secondary lymphoid organs: antigen processing
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Circulating lymphocytes encounter antigen in peripheral lymphoid organs(lymph node, spleen, Mucosal-Associated Lymphoid Tissue)
MALT
Secondary lymphoid organs: antigen processing
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Humoral component Plasma soluble protein
Complement system
Protein secreted by cells, complementary effect to antibody
Natural immune response
Acute phase protein
Protein secreted by cells, released due to immune response in early phase
Natural immune response
Antibody
Secreted by plasma cells, bind to antigen, first known has protective effect, various mechanism
Adaptive immune response
Cytokine
Soluble protein regulating other cell’s activity
Natural & Adaptive immune response
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Response against pathogen infection
Distinguish self vs non-self
Resulted in immunity (an immune condition)
Classification :
Innate immune response
Adaptive immune response
Immune response
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4 main tasks:
Immunological recognition
Immune effector function
Immune regulation
Immunological memory only in adaptive immune response
Immune response
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Innate/Natural/Native Adaptive /Acquired
Characteristics
Time Immediate (0-4 hours) Delayed (>96 hours)
Specificity Non-specific : Certain structure of all pathogens
Specific : Specific parts of the specific pathogen (antigen)
Diversity Limited Large range
Memory (-) (+)
Components
Cellular & chemical barriers
Skin, mucosal epithelia,Antimicrobial chemicals
Lymphocytes in epithelia,antibodies in epithelial surfaces
Humoral Complements, acute phase protein, cytokines
Antibodies , cytokines
Cellular Phagocytes, NK cell Lymphocytes (B & T)
Innate vs Adaptive
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Innate & adaptive immune response
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Innate immunity
May prevent
establishment of
infection?
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Immunological recognition
Innate
PAMPS (Pathogen-associated molecular patterns) Certain sugar residue
Anionic polymers
LPS
PRR (Pattern recognition receptors) MBL
Macrophage mannose receptor
TLRs, etc
Adaptive
Antigen: specific part of the specific pathogen with epitope (special site that can bound to its specific receptor)
Antigen receptors
T cell receptor MHC molecules
B cell receptor
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Examples of PRR: TLRs
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Antigen recognition by lymphocytes
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Actions of immune system to combat pathogen elimination of pathogen
Innate effector actions
Phagocytosis or other killing mechanisms
Inflammatory reactions
Cytokines release
Adaptive effector actions
T cell : Cellular-mediated mechanism
B cell :Antibody-mediated mechanism humoral
Cytokines release
Immunological effector phase
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Ability of immune system to self regulate
Mantain adequate response to dangerous agent & prevent excessive response that can damage the body
Failure in regultion: autoimmunity, allergy
T reg: regulatory T cell
Produce cytokines that regulate development & activity of other cells
Immunological regulation
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Immunological regulation
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Immunological regulation
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Specific feature of adaptive immune response
Protective immunity against reinfection against the same pathogen
Memory cells
Memory-associated immune response classification:
Primary immune response
Secondary immune response
Immunological memory
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Immunological memory
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Application of Immunological Memory
Immunization• Introduction of a pathogen, which allows are
body to do its primary immune response without the risk of actual sickness
• Active immunization• Passive immunization • Result in immunity of an immune person
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Infectious pathogen
Mechanical barriers
Tissue resident cells – pathogen
Elimination of pathogen
Inflammatory reaction
Chemokine & cytokine
Complement system
Inflammatory cells
Induction adaptive immune response
Activation of adaptive immune response
Effector phase of adaptive immune response
Interaction between innate & adaptive immune response
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Recognition by innate immune system
PAMPs - PRRs
Activation of cells in innate immunne response Pathogen killing
Release of cytokine & chemokine
Inflammatory process
Activation of complement system
Release of Acute Phase Protein
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Engulfing activity digestion
Large particles, ex: bacteria
Performed by phagocytes Macrophage
Neutrophil, eosinophil (little effect)
Receptor – Ligand
Engulfing phagosome formation fuse with lysosome
Digestion mechanism: O2 dependent
O2 independent
Opsonization by opsonins
Phagocytosis
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Phagocytes
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Phagocytosis
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Killing mechanism performed by NK cell
Viruses, tumor cell, intracellular bacteria
Recognition by NK cell Activating (NKARs) & inhibitory receptors (NKIRs)
Release granules that kills pathogen Perforin
Granzymes
Granulysin
(= Tcytotoxic cell)
Induce apoptosis of cell targets
ADCC
NK cell killing
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NK cell
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NK cell
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Inflammatory process
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Inflammation
Cardinal signs of inflammation
Rubor
Kalor
Tumor
Dolor
Functiolaesa
Organ + -”itis”
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Leucocyte migration to infection site: role of chemokine & cellular adhesion molecules
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MAC = Membrane attack complex
Formation of a hole in the membrane → cell lysis
Cell lysis by complement system
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Complement-Mediated Lysis of E. coli
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Feature Functional significance
Specificity Ensures distinct antigens elicit specific response
Diversity Enables immune system to respond to a large variety of antigens
Memory Lead to enhanced responses to repeated exposures to same antigens
Clonal expansion Increases number of antigen-specific lymphocytes
Specialization General responses that are optimal for defense against different pathogens
Contraction and homeostasis
Allows immune system to respond to newly encountered antigens
Adaptive immune response
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APC: Process & presents antigen to lymphocytes in secondary lymphoid organs
T cell activation
B cell activation
Proliferation Differentiation into effector cell
Cellular mechanism
Humoral mechanism
Immunological memory
Adaptive immune response
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Induction of adaptive response
Activation of specialized antigen-presenting cells (APC) is a necessary first
step for induction of adaptive immunity
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Induction of adaptive response
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Antigen: substances that specificly bound to lymphocytes
Recognized by:
Antibody/B cell receptor
T cell receptor
Major histocompatibility Complex (MHC)
Antigen recognition
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T cell & B cell activation
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Active lymphocyte Lymphoblast
T cell differentiation effector T cell
Th cell ( CD4+)
Tc cell : CTLs (CD8+)
Proliferate in T cell region of 2nd lymphoid organs
B cell differentiation
Naive B cell plasma cell (producing antibody)
B cell proliferation:
B cell region of 2nd lymphoid organs
Effector B & T cell exits from 2nd lymphoid organs
Proliferation & Differentiation of T cell & B cell
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Humoral
B cell antibody producing plasma cell
Neutralization
Opsonization
Complement activation
ADCC
Cellular
T cell
T cytotoxic/cytolitic : Destroy target cells
T helper:
Activate macrophages
Induce formation of cytotoxic T cells
Stimulate B cells to produce antibodies.
Effector mechanism of adaptive components
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Innate immunity Pathogen recognition non specific effector &
inflammation elimination of pathogen
Antigen Presenting Cells (APC) Antigen processing and presentation
Adaptive immunity Antigen recognition activation of T & B cell specific
effector cells elimination of pathogen memory
Summary
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Stop press
Active immunity vs passive immunity
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Active Immunity
Body produce antibodies after exposed to the antigen in the past either through:
- Exposure to the actual disease
- Planned exposure to a form of the antigen that has been killed or weakened(immunization/vaccination)
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How long does active immunity last?
Depends on the antigen Some pathogen develop
new forms of antigen body doesn’t recognize annual immunization
Some pathogen only induce low level of immunity booster/repeated immunization
Last for a lifetime
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Passive Immunity
Body doesn’t produce the antibodies A mother will pass
immunities on to her baby during pregnancy
Antibodies will protect the baby for a short period of time
Lasts until antibodies die
Why doesn’t the mother just pass on the WBCs that
“remember” the antigens?
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Stop press 2
CD molecules
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Surface markers
Indicate: functional properties, maturation stage, and lineage identity
Detected by panel of monoclonal antibodies:
well documented: CD1 – CD247examples:
- CD4+: TH; CD8+: CTL (cytolytic T lymphocyte)- CD19+: B cell- CD56+: NK cell; CD16+ Fcg receptor on NK cell- CD14+: macrophage
CD (cluster of differentiation/cluster designation) molecules
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CD molecules on B cell
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CD molecules on T cell
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Defects in immune system
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Immune Disorders~Hipersensitivites or Allergies~
- Immune system mistakenly recognizes harmless foreign particles as serious threats
- Launches immune response, which causes allergic symptoms
- Anti-histamines block effect of histamines and bring relief to allergy sufferers
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Aquired Immune Deficiency Syndrome
Caused by the Human Immunodeficiency Virus
Specifically targets and kills T-cells
- The HIV virus lowered immune system
- With immune system shutted down, common diseases that immune system normally could defeat become life-threatening
- No symptoms for several months all the way up to 10 years
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AIDS
Transmitted by sexual contact, blood transfusions, contaminated needles
As of 2007, it affects an estimated 33.2 million people
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Thank you very much….
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Murphy K, Travers P, Walport M, Janeway’sImmunobiology, 7th ed
Abbas AK dan Lichtman AH, Pillai S, Cellular & Molecular Immnunology, 6th ed
Roitt, IM., Delves, PJ, Roitt’s Essential Immunology
Burmester, Colour Atlas of Immunology
References