Pharma Change Room Lockers, Pharma Work Tables , Pharma Trolleys
Pharma-6-immuno.pptx
-
Upload
nicole-dela-rosa -
Category
Documents
-
view
215 -
download
0
Transcript of Pharma-6-immuno.pptx
-
8/19/2019 Pharma-6-immuno.pptx
1/48
IMMUNOLOGY
-
8/19/2019 Pharma-6-immuno.pptx
2/48
Definitions and outline structure of
the immune system
• Primary function of the immune system is to defend against and
eliminate ‘ foreign ’ material, and to minimize any damage that may
be caused as a result of the presence of such material
• Pathogen - organism which has the ability to cause disease
• Virulence - used to indicate the degree of pathogenicity of a given
strain of microorganism
• Attenuation - Reduction in the virulence of a pathogen
• Antigen - gives rise to the primary interaction with the body’s immune
system
• Immunogen an antigen that elicits an immune response
-
8/19/2019 Pharma-6-immuno.pptx
3/48
Definitions and outline structure of
the immune system
• !ithin a given antigen, e"g" a protein, there will be antigenic
determinants or epitopes , which actually represent the antigen
recognition sites for our adaptive immune system
• monoclonal antibody - antibody nominally recognizing only a single
antigen and within which only a single common epitope is recognized
• polyclonal antibody - an antibody nominally recognizing only a single
antigen but within which a number of different epitopes are
recognized
-
8/19/2019 Pharma-6-immuno.pptx
4/48
Definitions and outline structure of
the immune system
• #he immune system is broadly considered to e$hibit two forms of
response%
• #he innate immune response, which is non - specific, displays no
time lag in responsiveness, and is not intrinsically affected by prior
contact with infectious agent
• #he adaptive immune response , which displays a time lag in
response, involves highly specific recognition of antigen and affords
the generation of immunological memory
-
8/19/2019 Pharma-6-immuno.pptx
5/48
Definitions and outline structure of
the immune system
• #he adaptive immune system is further subdivided into%
• Humoral immunity - the effector cells are B- lymphocytes and where
antigen recognition occurs through interactions with antibodies"
• Cell - mediated immunity - the effector cells are T - lymphocytes
• &n cell - mediated immunity the peptide antigen must be presented to# - lymphocytes by other cell types 'antigen-presenting cells or (P)s%
macrophages* in association with a class of plasma membrane
molecules termed major histocompatibility complex !HC" proteins
-
8/19/2019 Pharma-6-immuno.pptx
6/48
)ells of the immune system
• !ononuclear phagocytic cells monocytes to macrophages
• #ranulocyte cell - neutrophil, basophil and eosinophil
• !ast cell $ release numerous initiating factors leading to aninflammatory response
• %atural &iller '+* - elicit cytoto$ic actions against host cells infected
with virus and those host cells that have acuired tumour cell
characteristics
• B $ lymphocytes - mature or differentiate in the bone marrow
• T $ lymphocytes - undergo maturation in the thymus
-
8/19/2019 Pharma-6-immuno.pptx
7/48
#he innate immune system
• &nnate barriers at epidermal and mucosal surfaces
• &nnate defence once epidermal or mucosal barriers have been
compromised
-
8/19/2019 Pharma-6-immuno.pptx
8/48
&nnate barriers at epidermal and mucosal surfaces
• &nvolves a range of non - specific mechanisms
• &ntact s.in• /low of fluid secretions from tear ducts, the urogenital tract and the
s.in 'sweat*
• 0any of these secretions possess bacteriostatic or bactericidal
activity
-
8/19/2019 Pharma-6-immuno.pptx
9/48
&nnate defence once epidermal or
mucosal barriers have been
compromised
• 0ononuclear phagocytic cells
• 1ranulocyte cell populations
• Phagocytosis
• (lternative complement pathway
-
8/19/2019 Pharma-6-immuno.pptx
10/48
0ononuclear phagocytic cells
• &nclude monocytes and macrophages
• #he mononuclear phagocytic cells secrete a wide range of molecules%
• lysozyme or cathepsin 1
• Cyto&ines - provide innate protective antiviral 'e"g" interferon '&/+*
- 2 or - 3 * and antitumour 'e"g" #+/ - 2 * activity against other host
cells
• Bioactive lipids - promote the inflammatory response
-
8/19/2019 Pharma-6-immuno.pptx
11/48
1ranulocyte cell populations
• &nclude the neutrophils, basophils and eosinophils
• +eutrophil - the most abundant granulocyte and is the most important
in terms of phagocytosis
• 4osinophils - have a specialized role in the e$tracellular .illing of
parasites
-
8/19/2019 Pharma-6-immuno.pptx
12/48
Phagocytosis
-
8/19/2019 Pharma-6-immuno.pptx
13/48
)50P6404+# P(#7!(89
i" )6(99&) P(#7!(8
ii" (6#4R+(#4 P(#7!(8
-
8/19/2019 Pharma-6-immuno.pptx
14/48
-
8/19/2019 Pharma-6-immuno.pptx
15/48
)lassic Pathway
• &nitiation
• :inding of ); comple$ to (b’s bound to (g
• )omponents
• ); to )<
• 9tages
i" Recognition
ii" (mplificationiii" 0()
-
8/19/2019 Pharma-6-immuno.pptx
16/48
Mg++
7undreds of )= and )>
molecules
7ighest conc than any
other complement)?b% opsonin
-
8/19/2019 Pharma-6-immuno.pptx
17/48
&ntermediate
comple$
';>-;@*
-
8/19/2019 Pharma-6-immuno.pptx
18/48
(lternate Pathway
• &nitiation
• +on-(b-initiated pathways
• )omponents
• /actor : and /actor D
• )?, )@ - )<
-
8/19/2019 Pharma-6-immuno.pptx
19/48
(lternate Pathway
9tablized by 0gAA
B mins ?C mins
-
8/19/2019 Pharma-6-immuno.pptx
20/48
#he humoral adaptive immune system
• : - lymphocyte antigens
• :asic structure of antibody molecule
• )lonal selection and e$pansion
• 7umoral immune effector functions
-
8/19/2019 Pharma-6-immuno.pptx
21/48
: - lymphocyte antigens
• ( substance or molecule specifically interacting with an antibody, and
which may lead to the further production of antibody and an
immunological response
Molecules Characteristic Immunogenicity
Protein 7igh 0!, )omple$structure
4$cellent AAAA
Polysaccharides'blood grp (gs*
6arge, lac. comple$ity 0ust be lin.ed to aprotein or lipid
AA
6ipid 9imple structure and low
stability
0ust be lin.ed to a
protein orpolysaccharide
A
+ucleic acid 9imple, fle$ible, degradesrapidly
poor A
-
8/19/2019 Pharma-6-immuno.pptx
22/48
14+4R(6 )7(R()#4R&9#&)9 5/ (+#&:5D&49
• (ntibodies
• &mmunoglobulins
• 9pecific glycoproteins
• 0ost 'not all* are found in the gamma-region inelectrophoresis• 7ence immunoglobulinE
• Present in plasma and body fluids 'tears, saliva, colostrum*
-
8/19/2019 Pharma-6-immuno.pptx
23/48
(+#&:5D8 9#RF)#FR4 (+D&00F+5165:F6&+ )6(9949
• /ive )lasses
• Differ in 0! and sedimentation coefficients
;" &g0
>" &g1?" &g(
=" &g4
@" &gD
-
8/19/2019 Pharma-6-immuno.pptx
24/48
(+#&:5D8 9#RF)#FR4 (+D&00F+5165:F6&+ )6(9949
• (ntibodies
• (ll have a common, basic polypeptide structure
• /our polypeptide chains lin.ed together by covalent andnoncovalent bonds• wG identical heavy and light chains
• 0onomers% &g1, &gD, &g4
• 0onomer and polymer% &g(
• Pentamer% &g0 '@ four-chain subunits*
-
8/19/2019 Pharma-6-immuno.pptx
25/48
(+#&:5D8 9#RF)#FR4 (+D&00F+5165:F6&+ )6(9949
• (ntibody 0olecule
• 8E shaped
• Domain• :asic unit ';>*
• )hains 'lin.ed by disulfide bonds*• 7eavy chain '>*
• 6ight chain '>*
• Hariable 'H* region
• )onstant ')* region
-
8/19/2019 Pharma-6-immuno.pptx
26/48
(+#&:5D8 9#RF)#FR4 (+D&00F+5165:F6&+ )6(9949
• &g1
• 7as = subclasses determined by thehinge region
• /ab region
• 0obile and can swing freelyaround the hinge region
-
8/19/2019 Pharma-6-immuno.pptx
27/48
(+#&:5D8 9#RF)#FR4 (+D&00F+5165:F6&+ )6(9949
IgG
CHARACTERISTICS INCREASE ECREASE
-0aIor &g in normal serum 'JC
J@K*-)rosses the placenta-0!% ;@C,CCC D-9)% J9-+H% LCC-;LCC mgGd6
&nfectious diseases-
hepatitis, rubella, &0
7ematologic disorders-Polyclonal gammopathies,monoclonal gammopathies,06, 7odg.in’s Disease
Primary and
secondary &gdisorders
-
8/19/2019 Pharma-6-immuno.pptx
28/48
(+#&:5D8 9#RF)#FR4 (+D&00F+5165:F6&+ )6(9949
• &g0
• Pentamer
• M-chain 'disulfide bond*• 6in.s the @ subunits in a circular
fashion
-
8/19/2019 Pharma-6-immuno.pptx
29/48
(+#&:5D8 9#RF)#FR4 (+D&00F+5165:F6&+ )6(9949
IgM
CHARACTERISTICS INCREASE ECREASE
-;C K of &g pool-
Produced early 'first* inimmune response-0!%
-
8/19/2019 Pharma-6-immuno.pptx
30/48
(+#&:5D8 9#RF)#FR4 (+D&00F+5165:F6&+ )6(9949
• &g(
• Dimer
• > &g( mols Ioined by M-chain at the /c portion
-
8/19/2019 Pharma-6-immuno.pptx
31/48
(+#&:5D8 9#RF)#FR4 (+D&00F+5165:F6&+ )6(9949
IgA
CHARACTERISTICS INCREASE ECREASE
-;@ >CK in &g pool-
Predominant &g insecretions 'tears, saliva,colostrum, mil., intestinalfluids*-0!% 'dimer* ?L@,CCC D-9)% 'dimer* ;;9-+H%
-
8/19/2019 Pharma-6-immuno.pptx
32/48
(+#&:5D8 9#RF)#FR4 (+D&00F+5165:F6&+ )6(9949
Ig IgE
-6ess than ;K of &g pool-4$tremely susceptible to proteolysis dueto e$posed hinge region and lac. of
interchain disulfide bonds bet 7)s
-)an mediate hypersensitivity 'allergic*reactions- &mmunity to invading parasites
- #riggers the release of histamines and
heparin from mast cells and basophils
-
8/19/2019 Pharma-6-immuno.pptx
33/48
(+#&:5D8 98+#749&9
• )lonal selection
• (ctivation and proliferation of : lymphocytes in response to an
antigen
• Production of (b specifically for that (g• ?-@ days
• (ntigenicity
• Related to portal of entry• &H, intraperitoneal N subcuataneous, &ntramascular
-
8/19/2019 Pharma-6-immuno.pptx
34/48
(+#&:5D8 98+#749&9
• Primary (ntibody Response
• /our Phases
;" 6ag% no (b detectable
>" 6og% inc in (b titer ?" Plateau% (b titer stabalizes
=" Decline% (b is catabolizes
-
8/19/2019 Pharma-6-immuno.pptx
35/48
(+#&:5D8 98+#749&9
• 9econdary '(namnestic* Response
• 0emory response due to subseuent e$posure to same (g
• Differs from Primary
• #ime% shorter lag phase, longer plateau 'tenfold*, more gradualdecline
• #ype of (b• Primary% &g0 9econdary% &g1
• (b titer% higher titer
-
8/19/2019 Pharma-6-immuno.pptx
36/48
(+#&:5D8 98+#749&9
-
8/19/2019 Pharma-6-immuno.pptx
37/48
-
8/19/2019 Pharma-6-immuno.pptx
38/48
)ell - mediated adaptive
immune system
• #-6ymphocytes 9ubsets
)D=A subset
• helper-inducerE # cell
)DLA subset
• suppressor-cytoto$icE # cell
i" 7elper # 6ymphocytes
ii" )ytoto$ic # 6ymphocytes
-
8/19/2019 Pharma-6-immuno.pptx
39/48
# 6ymphocyte 9ubsets
• 746P4R # 680P75)8#49
• #-helper '#h* cells
• 9ubsets
i" 7elper # type ; '#h;*N for cell-mediated effector mechs
ii" 7elper # type > '#h>*
N regulation of (b production
iii" Regulatory # '#reg*
N immunoregulatory type of #h cells
-
8/19/2019 Pharma-6-immuno.pptx
40/48
# 6ymphocyte 9ubsets
• 746P4R # 680P75)8#49
• /unction mainly in cyto.ine production
• #h;
• &/+O% direct and inderect activation of phagos to .ill ingested microbes• #h>
• &6-=% stimulates &g4 production
• &6-@% activates eosinophils
• 9timulates &g1= production
-
8/19/2019 Pharma-6-immuno.pptx
41/48
# 6ymphocyte 9ubsets
• 746P4R # 680P75)8#49
• Reacts w (g-07) && comple$ on (P)
• 6eads to cyto.ine production
• )D=A #)R
-
8/19/2019 Pharma-6-immuno.pptx
42/48
# 6ymphocyte 9ubsets
• )8#5#5&) # 680P75)8#49
• #-cytoto$ic '#c* cells
• Direct destruction of virally infected target cells
• )DLA• &nteracts w (g-07) & comple$ or 07)-& alone
• Hirus infected cells or tumor cells
• 0aIor effector in allograft organ reIection
-
8/19/2019 Pharma-6-immuno.pptx
43/48
(ntigen Processing and (ntigen Presentation to #
cells
• (ntigen-Presenting )ells '(P)s*
• )ells capable of ta.ing up (gs and presenting them to lymphocytes
• Dendritic cells, macrophages, : cells, tissue cells
• (g processing pathwaysi" 4ndogenous - #c
ii" 4$ogenous - #h
-
8/19/2019 Pharma-6-immuno.pptx
44/48
(ntigen Processing and (ntigen Presentation to #
cells
-
8/19/2019 Pharma-6-immuno.pptx
45/48
#ransplantation reIection
• #ransplantation is the process of transferring cells, tissues or organs
Q termed a graft Q from one location to another
• (n autologous graft is a transplant between two sites within the sameindividual, e"g" s.in graft from the thigh to the hand
• (n allogeneic graft is a transplant between two genetically different
individuals of the same species
• ( xenogenic graft is a transplant across different species, e"g" pig to
human
-
8/19/2019 Pharma-6-immuno.pptx
46/48
#ransplantation reIection
• Hyperacute rejection occurs within minutes to hours" #his should now
be a rare event clinically as recipients are tested 'cross - matched*
before transplantation for the presence of antibodies reactive with
cells of the donor
• Acute rejection occurs within wee.s to months following
transplantation and involves humoral 'antibody* and cell - mediated
induced cytoto$icity" Damage may be reversed with early diagnosis
and more aggressive immunosuppressive therapy
• Chronic rejection occurs many months or even years following
transplantation"
-
8/19/2019 Pharma-6-immuno.pptx
47/48
7ypersensitivity
• Defined as an e$aggerated response of the immune system leading
to host tissue damage
• Type I Q immediate hypersensitivity " #his is also called anaphylactic
or acute hypersensitivity" &t involves &g4 antibody and is mediated via
degranulation of mast cells for rapid inflammatory reaction
• Type II hypersensitivity Q antibody- mediated cytotoxicity " #his is
caused by antibodies that are directed against cell surface antigens"
&g1 and &g0 are the .ey antibodies involved that direct cytoto$icevents against the cell surface with which they interact
#ype && hypersensitivity disorders include blood transfusion reactions
arising from mismatch of the blood (:5 antigens
-
8/19/2019 Pharma-6-immuno.pptx
48/48
7ypersensitivity
• Type III hypersensitivity Q complex - mediated " #his involves the
formation of large antigen antibody comple$es that circulate in the
blood
• &f this process is compromised for any reason then the antigen
antibody comple$es will be deposited in tissue capillary beds that can
lead to a condition termed glomerulonephritis in .idney
• Type IV hypersensitivity Q cell - mediated " #his results frominappropriate accumulation of macrophages at a localized site, and
may or may not involve the presence of antigen