Download - Immunology in Haematology (part 1)
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Dr C G Lopez
Ex Transfusion Medicine Unit
University Malaya Medical Centre
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Protects body from infectionAllows recovery from infectious disease
Comprises - Leucocytes
Organs thymus, spleen, lymph nodes ,lymphatic channels
Complex interaction between cells located in blood,lymph nodes , body tissues
Recognition of non self in any potential pathogen orforeign cells - e.g. red cells when transfused, transplanttissue
Capacity to produce a highly specific response to
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Immune Bo
IMMUNE
SYSTEM
Protects body
from infections
Infections
andotherharmfulagents
http://d/AppData/Roaming/Microsoft/Windows/Recent/Immune%20Body.lnkhttp://d/AppData/Roaming/Microsoft/Windows/Recent/Immune%20Body.lnk -
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INDUCERS OF THE IMMUME RESPONSE
Only large molecules, infectious agents, or insoluble
foreign matter can elicit an immune response in the
body.)
A small molecule hapten - can elicit an immune
response but only when attached to a large carrier such
as a protein
Once antibodies are generated to a hapten-carriermolecule the small hapten can also bind antibody, but by
itself does not initiate an immune response
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Immunogen: substance that causes derectableimmune response. Mol wt ususally > 10,0000daltons. If less than 5000 daltons seldom causes
antibody formation
Antigen: a substance that is capable of reactingwith a product of an immune response e .g antigen
combines with antibody ( product of immuneresponse )
Hapten: Small molecules if coupled with largercarrier moleclules can become immunogenic .Once immune response initiated by the complex ,
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Small part of the immunogen that isrecognised by the cells ( antigenic determinant) may comprise as few as 5 6 amino acids orsugars.
Small epitopic region responsible forspecificity i.e contains the molecular
configuration that allows recognition bycorresponding A/B
Many epitopes present on single large
immunogen can produce many antibodies with
Definitions ----continuedEpitopes
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Epitopes
Antigens
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Type of Defences
Non specificResponse
Surface barrier
Innate immunityPrimitive
Non-specific
No memory
Specific ImmuneResponse
Response specificallyinduced towards the agentwhich stimulated it
Mechanism : Humoral andCell-mediated immuneresponse
Memory: Previousencounters
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Antigen presenting cell
Helper T 4Cytotoxic T 8
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Structural barriers Skin, mucosal membranes
Acidity Lactic acid in sweat, HCl in
stomach
Proteins Complement, lysozyme,interferons
Phagocytic cells Monocytes, macrophages,
neutrophils, eosinophils
Non-phagocytic cells NK cells, basophilsPhysiological responses Inflammation, the acute
phase response
Non-specific immunological response
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Specific immunological response
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Specific Immune Response
involvesLeucocytesB cells derived from bone marrow stemcells
T cells also derived from bone marrowstem cells but undergoes processing in
Thymus where self reacting T cells areeliminated by contact with epithelial anddendritic cells
The immune system must distinguish
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Immune Competance
By 4 6 months after birth external
substances encountered in the bodyby leucocytes will be regarded as nonself
Before this period the Immune Systemis immature unresponsive toantigens
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Antigen binding to- structures on lymphocytes or- A/B
Each antigen has specific receptor onlymphocyte or antibody molecule
Receptors will bind only specific set ofantigens
Clones then induced to proliferate and
Specific Immune Responseinvolves
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Foreign particles are engulfed and degradedby phagocytic cells such as macrophages,neutrophils and monocytes = phagocytosis
Degraded particles i.e. nonself antigens arepresented on MHC Class II molecules
If host cell was infected by a bacterium or
virus, or was cancerous, antigens displayed onsurface of cells with a Class I MHC molecule.
Specific immunological response
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Role of MacrophagesSpecialised macrophages (Antigen Presenting
Cells, or
APCs )phagocytose A/B or complement coated
particles ,
processes particles - enzymes degrade
particlespresent antigens to T and B lymphocytes as
peptides
( degraded proteins )or polysaccharides in
association with molecules of Major
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Stimulation through CD28 in addition to
the TCR provides a potent co-stimulatory
signal to T cells for the production of
various interleukins (IL-2 and IL-6 in
particular).
CD28
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Killer cellsLarge granular Lymphocytes with no T or Bcell markersCytotoxic activity against tumour cells
Have Fc receptors . Can therefore bind Ab alreadybound to tumour cells and destroy them usingperforin mechanism
Cytokines activate and release granules in CTLscytoplasm which contain protein Perforin
Perforin kills virus infected cells by establishing
channels in virus infected cell ; rapid influx ofCa++ prevents viral replication
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NK (Natural Killer )CellsLarge granular Lymphocytes with no
T or B cell markers
Cytotoxic activity against variety ofvirally infected and tumour cells
Activated by - Inteferon and IL- 2
Do not have specific receptors butrecognise target structures.
Attack & kill atypical cells e.g tumour orvirus infected cells using perforin
mechanism
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LargegranularKiller Cellswith no T or Bmarkers
Killer Cells haveFc receptors . Canbind Ab alreadybound to tumourtargetProbably perforin
release mechanismkills cells
NK Cells bindtumour targets
NK Cells bind targetsby unknown mechanism. Kill cells thru perforin
release mechanism
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Function of T and B cells
Origin
Blood
Bone marrow
Function
Surfacemarkers
Gene rearranged
Growth & differentiation
factors
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Helper T40 60%
Cytotoxic /Suppressor T49 50 %
Recognises Class IIHLA
on macrophageAmplifies immuneresponse by producingcytokinesHelps activate B cellsproduce antibodies
Recognises Class 1 HLA oninfected body cell surfaceDown regulates immuneresponsesKills virus infected cellstumour cells , transplantedtissue
Has CD 4 Surface
protein
CD4 protein assistsHelper T bind itsspecific Ag receptorto Ag presented with
HLA Class II protein byMacrophage
Has CD8 Surface
protein
CD8 protein stabilisesinteraction of Ag receptorand viral Ag with HLA Class Imol on surface of infected
cell surface
Peripheral Blood Lymphocytes
BLymphocytes
20 30%
T Lymphocytes 70
80%
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T Lymphocytes
CD 4 T Helper CD 8 Cytotoxic /
Supressor T
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Originate in bone marrow
ThymusLymph nodes / spleenBlood stream ( 70 -80 % of all lymphocytes )
Half life > 2 years some live as long as 20 years
T cells protect against infection by viruses , fungi,
facultative microorganisms
Helper T CD 4 protein binds specific Ag receptor to Agpresented by macrophage in combination with MHC( HLA Class II molecules )
T Lymphocytes
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CD4 + T Helper Cell
ActivationAg displayed by macrophage with HLAclass II self protein
Helper T binds to specific Ag ; receivessignal from macrophage Together amplifies immune response by
producing a mixture of cytokines ( act asgrowth factors )
Hel s to activate other immune cells
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T Helper CD4 + Cell
cific Immune Response CD4 + T cell activat
Macrophage
Ag displayed by macrophage withHLA class II self protein
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T Cell Activation :Mounting the immune response
Cytokine
generation
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Th I Secrete mainly IL 2, IFN- Activates B cells - but no significant heavy chain
() IgM switching to () IgG heavy chain Participates in delayed hypersensitivity reaction
Th2
Secrete mainly IL 4, IL-5, IL- 10, IFN- Activates B cells maturation and antibodyproduction - switching from IgM to IgG Found in chronic inflammatory lesions
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Specific Ag receptor binds to specifictarget e.g.
viral Ag by recognizing HLA class I
molecules onsurface of infected cells
Cytokines activate and release granulesin CTLs
cytoplasm which contain protein Perforin
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Cytotoxic T Cells
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Cytotoxic T Cells
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B Lymphocytes and B cellImmune Response
How T Cells Help ToGenerate Antibodies
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Humoral Immune Response
B cells and Antibody Production
B lymphocyte recognises foreign Ag throughits specific surface Ag receptor ( antibody
molecule )
B lymphocyte receives cytokine signal fromhelper T cell
Divides and differentiates to become plasmacells which produce antibodies - large
amounts over 3- 4 days
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Each
antibodymolecule hasspecific Agbinding site
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Tetramer : 2 identical heavy and 2 identical light chains
Fab: variable region Ag binding
Fc : constant region effector function
Antigen binds to Fab and triggers effector function thro Fc portion
Fc
Fab
B cell
in
Plasma
Macrophage with Ag
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p g gpresentedto T helper lymphocyte
B CELLB CELL
Activated bycytokines
More Helper T cellsMore Cytotoxic T clls( CTLs)B cells to Plasma cells
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Humoral Immune ResponsePlasma cells secrete specific antibodies i. e
glycoproteins (protein - carbohydrate moieties) - into extracellular space
Antibodies bind to antigens with highspecificity
Initial production - IgM antibodies
Heterogenous group of antibodies collectivelycalled Immunoglobulins
IgG Immunoglobulins divided into 5 classes IgG ,
IgM , IgA, IgD , IgE
IgG Subclasses
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IgG Subclasses
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Primary Immune Response
First time T cell interacts with Ag response isslow may take 5 7 days to generateantibodies and activate a number of cells
Secondary Immune Response
If challenged by same Ag again, antibodiesare rapidly generated within 48 hourspredominantly IgG , peaks in out 6 days mayprevent occurrence of disease
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Primary and secondary immune response
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T-cell independent immune
response
Antigen can initiate B cell proliferation and A/Bsecretion without action of T helper cell
Always IgM; isotype switch does not occur
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A and B antigen is composed ofcarbohydratestructures that attach to cell surfaceglycolipids
Binding ofB lymphocyte SIg receptor torepetitive carbohydrate antigens on surface ofRBC - triggers proliferation of B cells
Natural occuring IgM antibodies foundagainst A & B antigens of red cells probablyantibody production is independent of T
helper cell activity ( T independent immune
Blood Group Antigens
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Summary of the main Specific
Immune Response activities
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Macrophage
Helper T cell CD 4
Macrophagepresentsantigen to Tcell
T c cell
Thcell
B cell
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To be continued
The complement system
Antigenantibody reaction