Immunology

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Immunology
By Wilairat Anurakolan
2
Immunology
????????????????/ Immunology ?????????????????????
?????????????????????????????????????????????????
????????????????????????????????????????????????
??????????????? ???????????????/ Immune system
?????????????????????????

• Defense against parasites
• Homeostasis
• Immunological surveillance

3
The immune response

• Natural (non-specific) immunity

• - cellular phagocytosis
• - humoral complement and other
• substances

• Acquired (specific) immunity

• - cellular regulatory and effector
• T lymphocytes, lymphokines
• - humoral B lymphocytes, antibodies,
• lymphokines

4
Natural Immunity
5
Natural/ Innate Immunity
1. External defense mechanism
????????????????????????????????????????
??? ???????????????????????????? (first line of
defense mechanism) ?????????????????????????????
(barrier)

• Physical barrier
• Chemical barrier

6

• Physical barrier

1. ??????? ???????????????????????
2. ??????????????????
3. ???????? ??? cilia ??????????????????
???????????? ??????????? ????????????????
4. Reflex ?????????????? ??????? ?????
?????? ?????????????? ?????
7

• Chemical barrier

Lactic acid ?????????????????????????
??????? ???????????????????
Lysozyme ?????? ????? ?????????
???????????? mucopeptide/ peptidoglycan
??????????????? ????????????????
Fatty acid ??????? ????????????????????
(???????? ??????????) ??????????
(???????????????)
8

• Chemical barrier

Glycolipid ?????? ????????????
Lactoferrin ??????????? ?????????????????? ????
??????????????????????????????????????
HCl ???????????? (pH 1.0) ?????
enveloped virus ????????????
Spermine ???????? ?????????????????????
9
Natural/ Innate Immunity
2. Internal defense mechanism
?????????????????????????????????????
?????????????????????? ???????????????????????????
? ???????????????????? ??????? 2 (second line of
defense) ??????????????
1. Phagocytosis 2. Complement system 3.
Interferon (IFN) 4. Inflammatory
10
Phagocytosis
?????????????????????????/ ???????????????????????
?????? ??? phagocytic cells/ phagocytes
?????????????? ?.?. 1883 ??? Elie Metchnikoff
??????????????????????
Phagocytes ????????????????????????? 2 ????

• Polymorphonuclear leucocytes (PMNs)

• Mononuclear leucocytes

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Polymorphonuclear leucocytes

• Phagocyte ???????????????????????? lobe
• ??????????????? granule ??????

• ??????????
• Neutrophil
• Eosinophil
• Basophil
• Mast cell

12
Mononuclear leucocytes

• Phagocyte ??????????????????? lobe ?????
• ???????????????? granule ??????

• ??????????
• Monocyte
• Macrophage

13
http//www.sc.edu/union/Sears/120.6.circ.htm
14
Macrophage

• ??????? monocyte
• ????????????

• ???????????????? ????
• ?????????????????????????

• ???????
• ????? antigen ???????? phagocytosis/ ADCC
• antigen presenting cell ?????? lymphocyte

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• antigen ???????? Foreign body giant cell/
• Multinucleated giant cell

• Macrophage ???????????????????????????
• ????? Küpffer cells
• ?????? Littoral cells
• ????? Alveolar dust cells
• ??????????????? Reticular cells
• ?????? Microglial cells

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Phagocytosis ???????? 5 ??????????
1. Chemotaxis phagocytes ??????????? ???????????
????????????? ????????????????????????
C5a/ ???????????????? endotoxin ??????????????????
2. Attachment ????????? phagocytes ?????????????
?? ????????????????? ???????????????????? opsonin
?????? C3b ???????????????? IgG
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Attachment
www.uoguelph.ca/mbnet/323IMMUN/
D2_COMPL/F13-12A.GIF
18
????? opsonin ????????????????????????????????????
?? phagocytosis ???????? opsonization
http//project.bio.iastate.edu/Courses/MIPM302/302
new/8_3abagrxn.html
19
Phagocytosis by Enhanced Attachment
(Opsonization)
http//www.cat.cc.md.us/courses/bio141/lecguide/un
it1/bacpath/phagsum.html
20
3. Ingestion phagocytes ???? pseudopodia ???????
????????????????????????????????
????????????????????? ??????????????????
phagosome ????? lysosome ???? granule
???????????????????????????????????
???????????????? phagolysosome
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4. Intracellular killing ????????????? anaerobic
glycolysis ??????????????? ?? lysosome
???????????????????? phagosome
http//project.bio.iastate.edu/Courses/MIPM302/302
new/7_2parasitism.html
22
Intracellular killing
1. Oxidative mechanism
????? phagocytes ?????????????????????????????????
?? oxidative metabolism ???????????????????
respiratory burst ??? ????????????????????????????
???? ??????? hexose monophosphate shunt (HMS)
??????????????? superoxide anion (O2-) ???
hydrogen peroxide (H2O2) ????????????
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Haber-Weiss reaction
hydrogen peroxide (H2O2) ??????????????
superoxide anion (O2-) ????????? hydroxyl radical
(OHº) ??? singlet oxygen (1O2)
24
Myeloperoxidase-hydrogen peroxide-halide system
hydrogen peroxide (H2O2) ?????????????? halide
(Cl-) ???????? ??????? myeloperoxidase ????
hypochlorous acid (HOCl)
25
???????????????????????????????????
?????????????????? ?? ????? ??? mycoplasma
?????????????????? lysosome fusion
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Intracellular killing
2. Non-oxidative mechanism
????????????????????? ????? granule ??? phagocytes
Gram (ve)
http//www.arches.uga.edu/emilyd/theory.html
27
http//www.arches.uga.edu/emilyd/theory.html
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• Lactoferrin ???????????????? (????????? ?????)

• Lysozyme mucopeptide ?????????????????????

???????????? granule ??? phagocytes
???????????? ????????????????????????????????
???? protein, lipid, nucleic acid, nucleotide,
glycan, proteoglycan, glycoprotein ???????
5. Release ????????????????????????????????? ???
??????????
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Phagocytosis
http//elmo.shore.ctc.edu/biotech/Immunology/notes
4-4.htm
30
Complement system

• ????????????????? ?????????
• ????????????????????????? (inactive form)
• ???????????????????????????????????????????
• ?????????????????????????????? (cascade)

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?????????????????????

• cytolysis ?????????????????????????????????
• opsonization ???????????????????????
  phagocytosis
• inflammation ?????????????????? histamine

http//www.uoguelph.ca/mbnet/323IMMUN/D2_COMPL/COM
PLEME.HTM
32
?????????? complement
http//www.montana.edu/wwwwami/523/Reading7b.htm
33
1. Classical pathway

• ????????????????????
• ?????????? antigen-antibody
• complex (IgG ???? IgM)
• ?????????????????????? Ab
• ???????????????????????????
• staphylococcal protein A,
• mycoplasma ??? RNA
• tumor virus

http//www-immuno.path.cam.ac.uk/immuno/part1/lec
15/lec15_97.html
34
2. Alternative pathway

• ???????????????????????
• ???????????? Ab
• ???????????????????????????
• ?????????????????????? Ab
• ???????????????????????
• ?????????????????? ???????
• ??????????????????????????

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3. MB Lectin pathway
MBL (family ???????? C1q) ?? ?????? mannose
?????????? ????????? ??????? MBL
???? ???????????? MASP-1, -2 (MBL associated
serine proteinase) ??????????????????????? C4
??? C2 ?????
http//nejm.org/teaching_tools/2janeway.asp
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A C T I V A T I O N
C O M P L E M E N T
http//www.socgenmicrobiol.org.uk/JGVDirect/18709/
Figs/F1_pg.htm
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http//www.sc.edu/union/Sears/120.6.circ.htm
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http//www.lifesci.utexas.edu/faculty/sjasper/bio3
01L/immune.html
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Classical Pathway
http//medtech.cls.msu.edu/ISL/immunology/comp1.ht
m
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Alternative Pathway
http//medtech.cls.msu.edu/ISL/immunology/comp2.ht
m
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The Membrane Attack Complex (MAC) Causing Cell
Lysis
http//www.cat.cc.md.us/courses/bio141/lecguide/un
it2/innate/mac.html
42
?????????? complement ???? classical ???
alternative pathway
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Acute phase protein
???????????????????????????????????????????????? ?
??????????????/ ??????????????????
???????????????????? C-reactive protein (CRP),
mannose binding protein (MBP)
CRP ??????????????????????????????
phospharylcholine ?? membrane ???????? Ca2 ion
????????????????????? ???????????????? complement
system ??? C3b ???????? ???????????????????????
(phagocytosis) ??????
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MBP ???????? mannose ????????? ?????????????????
???????????? ??????????? ????????? CRP
http//www-immuno.path.cam.ac.uk/immuno/part1/lec
15/lec15_97.html
46
Interferon (IFN)
????????????????????????? ???????????????????????
????? ????????????????????????????????????????????
??? IFN ???
?????????????????? IFN (IFN inducer)
- RNA viruses, DNA viruses - dsRNA, intracellular
bacteria (rickettsiae), bacterial endotoxin
??????????? ???????????????????????????????????
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Interferon inducer
http//gsbs.utmb.edu/microbook/ch049.htm
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Interferon (IFN) ??????????? 2 ????
1. Type I interferon
IFN-alpha (MNP) ??? IFN-beta (fibroblast) ??????
????????????????????????????
2. Type II interferon
IFN-gamma ???????? T cell ????????? Ag
?????????????? ???????????????????????
regulatory function ???IFN
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?????????????????? IFN
????????????????? receptor ???????? cell
membrane ??????????? transcription
???????????????????????? ?????????????????????????
??????????????????/ antiviral state ??????? IFN
???????????????????????????????????
???????? ?????????????????????? receptor
?????????????????
50
http//www.blc.arizona.edu/Marty/429/Lectures/429_
00lect5.html
51
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2,5-oligoA system ??????????????????????? IFN
???????????? proenzyme oligoisoadenylate (oligoA)
synthetase ???? ?????????? ??????????????????
dsRNA ?????????????????? dsRNA ??????? proenzyme
oligoA synthetase ???????????????????????? ???????
??? adenylic acid oligomers (2,5-oligoA) ??? ATP
??? ??????? 2,5-oligoA ??????????? proenzyme
RNase L ?????????? ???????????????????????????????
???????????????? RNA ???? ???????????????????
??????????????????????????????
53
2,5-oligoA system
http//www.blc.arizona.edu/Marty/429/Lectures/olig
oA.html
54
2,5-oligoA system
http//www.blc.arizona.edu/Marty/429/Lectures/olig
oA.html
55
Protein kinase system ???????????????????????????
???????? ???? translation ????????
???????????????????????? IFN ????? ???????
proenzyme ??? protein kinase P1
?????????????????? ?????????? dsRNA
??????????????? P1 ???????????????????? ??????????
?????????? phosphate (phosphorylation)
???????????? ?????? subunit ??? translation
initiation factor eIF-2 ???????? factor
?????????????????????? translation ????? eIF-2
??????? phosphate ???? ???????????????????????
?????????????? ???? translation ???
56
Protein kinase system
http//www.blc.arizona.edu/Marty/429/Lectures/P1.h
tml
57
Protein kinase system
http//www.blc.arizona.edu/Marty/429/Lectures/P1.h
tml
58

• ??????????????????????? IFN ???????????????????
  48 ???????
• ??????? Ab ???????????????? IFN
  ??????????????????????
• ??????????????????
• IFN ???????????????????????? ????????????????????
  ??????
• IFN ????????? species ??????????????? IFN
  ??????????
• IFN ????????????????????????? ???????????????????
  ?????????
• ???????????????????????????????????
  ????????????????????????
• ??????????????????????

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Inflammatory
????????? (inflammation) ?????????????????????
host ????? ???????????????????????????????????????
??????????????????? ??????????????
?????????????????????????????????????????????? ???
??? ????????????????????????????????????? ??????
?????????????????????????????????????
??????????????? ????????? (antibody, complement)
???????????????????????????? ?????????????????????
????????????????????????????????????
???????? ??????????????????????????????????????/
edema ????
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??????????????????????????????????? (capillary)
?? permeability ????????? ????????????????????????
??????????????????????????? ??????????????????????
???????????????????????????? ??????????????? ?????
????????????????????????????????????????????
(acute inflammation) ??? ??? ??? ??? ????
http//www.lifesci.utexas.edu/faculty/sjasper/bio3
01L/immune.html
61
Acute inflammation
??????????????????????????? ??????????????????????
?? ??????????????????? ??????????????????????????
? ?????????????????????????? ?????????????????????
?? ????????????????????????? ????????????????????
??????????????
62
?????????????????????????????????????????????????
????????? complement ??? alternative pathway ????
C3a ??? C5a (anaphylatoxin) ????????????? mast
cell ???????????????????? histamine,
prostaglandins ??? leukotrienes
??????????????????????????? ????? permeability
????????? ?????????? C5a ?????????????? chemotaxin
???????????????????? neutrophils (30-60 ????)
monocytes ??? lymphocyte (4-5 ???????)??????? ????
??????
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Chemotaxin/ Chemoattractant/ Chemotactic factor
??????????????????????????????????????????????? ??
??????????????????????????????????????????????

• N-formylated peptide ??????????????
• C3a ??? C5a complement system
• Leukotriene B4 (LTB4) neutrophil, monocyte ???
• macrophage
• chemokine inducible protein-10 (IP-10), RANTES
  
• ??? MIP-1alpha

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Specific Immunity
67
Specific Acquired Immunity/ Adaptive Immunity
????????????????????????????????????????????? ????
??????????????????????? (active)
?????????? ????????? (passive) ???????????????????
?? ??? 4 ???? ?????????
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1. Active naturally acquired immunity
????????????????????????????? ?????????????? Ab
??? ?????????? ????????????????????????????/
??????????????
2. Active artificially acquired immunity
???????????????????????/ toxoid
????????????? ??????????????? Ab
??????????????????????????? ????????
????????????????????
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3. Passive naturally acquired immunity
???????????????????????????????????????????? ?????
??????? ??????????????
4. Passive artificially acquired immunity
??????????????????????????????????????????/
??????? ??????????????????? ??????????????????????
????????????? ??? ???????????????????????????????
???
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???????????????????????????????????? ?????????????
???? 2 ??????

• Humoral (antibody-mediated) immunity

• ???????????????????? B lymphocyte ??? plasma cell

2. Cellular (cell-mediated) immunity

• ???????????????????? T lymphocyte ??? macrophage

72
Immune response
http//www.uta.edu/chagas/html/biolImS1.html
73
Humoral (antibody-mediated) immunity
Antigen (Ag)
Plasma cell
74
Immune Response
75
Types of immunoglobulin
http//www.emc.maricopa.edu/faculty/farabee/BIOBK/
BioBookIMMUN.html
76
Complementarity determining region
77
??????????????????????????? CDR ??? VL ??? VH
?????????????????????????????????? ???????????????
????
CDR ?????????????????/ ???????????????????????
????? 1 ?????????????? 1 ?????????????????? ?????
?????????????????????? (specificity) ??? ???????
(shape) ??? antigen-binding site
78
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http//project.bio.iastate.edu/Courses/MIPM302/302
new/8_3abagrxn.html
80
Antibody-dependent cell-mediated cytotoxicity
(ADCC)
http//www.cat.cc.md.us/courses/bio141/lecguide/un
it2/innate/exkill.html
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ADCC
82
Cellular (cell-mediated) immunity
83
Cellular (cell-mediated) immunity
http//www.lifesci.utexas.edu/faculty/sjasper/bio3
01L/immune.html
84
Antigen presenting cell (APC)
????????????????????? ??????????????????????? T
cell ??? MHC molecule ????????????????????????????
?????? peptide-MHC complex ???????????????????????
????????? ??????????? peptide ??????????????????
antigen processing ??????? peptide
??????????????? MHC molecule ?????????? ?????
peptide-MHC complex ??????????????????????????????
?? ??????????????? T cell ??????????????? antigen
presentation
85
http//www.lifesci.utexas.edu/faculty/sjasper/bio3
01L/immune.html
86
APC ??????????????????????????????????????

• ??????????????? class II MHC molecule ??????????
• ???????????????? class I MHC molecule
• ?? co-stimulatory molecule ??????????????????????
  ???? T cell
• ??????????????? ?????????????????????????????????
  ????

87
Effector cell ????????????????????????????
????????????? T lymphocyte ??????????? ???????????
?????????? (effector cell) ????????????? ?????????
???? ????????????????????

• Activated macrophage
• cytotoxic T lymphocyte
• Natural killer (NK) cell

88
http//www.pharmacology2000.com/Hemo/Immunosupress
ion/antibody1.htm
89
Activated macrophage
macrophage ??????????????????????
macrophage ????????????????? ???

• ??????????/ phagocytosis
• ingestion
• intracellular killing
• ???????? cytokine
• ????????????????? (APC)

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Cytotoxic (cytolytic) T lymphocyte

• ???????????????????????????
• ???????????????????????????????
• ???????????????????????????????????????

T cell receptor ?? pre-cytotoxic T lymphocyte
91
???????????? target cell
Granule ??? cytotoxic T lymphocyte
?????????????????????? TCR ????????? specific
epitope ????????? perforin/ cytolysin ??? granule
????????????????? perforin ????????????????? ?????
???? target cell ????????????????? ???????????????
????????????????????? ??? ion ????????-???
????????? ?????????????????????????? target cell
????????????? ???????????????? ????????????????
target cell ??? ????????????????
http//www.lifesci.utexas.edu/faculty/sjasper/bio3
01L/immune.html
92
???????????? infected cell ??? cytotoxic T cell
93
???????????????? perforin ???? ???????? cytotoxic
T lymphocyte ????????????????? (TNF)
????????????????? ?????????? target cell
??????????????? DNA ??????????? ???
?????????????? ??????????????? ????????????
target cell ??? apoptosis
94
Natural killer (NK) cell
???? cytotoxic lymphocyte ???????? target cell
???/ ???????????????????? cytotoxic T lymphocyte
??? NK cell ??????????????????? (Ag receptor)
??? ??????????????????????? class I MHC
molecule ?? target cell ??????????? NK cell
???????????? ???????? cytotoxic T lymphocyte
95
http//www.lifesci.utexas.edu/faculty/sjasper/bio3
01L/immune.html
96
http//www.people.virginia.edu/rjh9u/imsys.html
97
http//www.sc.edu/union/Sears/120.6.circ.htm
http//www.emc.maricopa.edu/faculty/farabee/BIOBK/
BioBookIMMUN.html
http//www.blc.arizona.edu/Marty/429/Lectures/429_
00lect7.html
http//project.bio.iastate.edu/Courses/MIPM302/302
new/7_2parasitism.html
http//www.sirinet.net/jgjohnso/immune.html
http//gsbs.utmb.edu/microbook/ch049.htm
http//www.lifesci.utexas.edu/faculty/sjasper/bio3
01L/immune.html
http//www-immuno.path.cam.ac.uk/immuno/part1/lec
15/lec15_97.html