17:
252:
Whereas the danger model proposes non-silent cell death releasing intracellular contents and/or expressing unique signalling proteins to stimulate an immune response, the damage-associated molecular pattern (DAMP) model theorizes that the immune system responds to exposed hydrophobic regions of
257:
and
Matzinger argued that as cellular damage causes denaturing and protein misfolding, exposed hydrophobic regions aggregate into clumps for improved binding to immune receptors.
210:
Matzinger's work emphasizes that bodily tissues are the drivers of immunity, providing alarm signals on the location and extent of damage to minimize collateral damage. The
147:
based on the presence of pathogens and/or alarm signals from cells under stress. When injured or stressed, tissues typically undergo non-silent types of cell death, such as
84:
distinguishes between self, which is tolerated, and non-self, which is attacked and destroyed. According to this theory, the chief cell of the immune system is the
852:"The Hunt for the Source of Primary Interleukin-4: How We Discovered That Natural Killer T Cells and Basophils Determine T Helper Type 2 Cell Differentiation
218:
using its antigen-presenting cells to activate B and T lymphocytes for specific antibodies, exemplified by low dendritic cell counts resulting in
116:(PAMPs) as infectious non-self, whereas PRRs are not activated by non-infectious self. However, neither of these models are sufficient to explain
113:
60:
proposes that it differentiates between components that are capable of causing damage, rather than distinguishing between self and non-self.
32:. The activation of a resting helper T cell causes it to release cytokines and other signals (green arrows) that stimulate the activity of
247:
905:
Seong S, Matzinger P (2004). "Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses".
219:
223:
1104:
109:
278:
238:
for an organ-specific response of driving naïve CD4+ T cells to become Type 2 Helper T cells, as opposed to Type 1.
517:"Recognition of damage-associated molecular patterns related to nucleic acids during inflammation and vaccination"
265:
Pattern
Recognition Receptors (PRRs) are a family of surface receptors on antigen-presenting cells that includes
88:, activated by recognizing non-self structures. Later research showed that B cell activation is reliant on CD4+
711:
Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Galicier L, Lepelletier Y, Webster D, et al. (October 2004).
93:
21:
382:
211:
176:
231:
468:"Immunomodulation strategies for preventing vascular disease of the brain and heart: workshop summary"
754:"Transforming growth factor β: a master regulator of the gut microbiota and immune cell interactions"
374:
215:
387:
274:
930:
832:
693:
646:
408:
266:
203:. In comparison, neoplastic tumors do not induce significant immune responses because controlled
164:
143:
formulated the danger model, theorizing that the immune system identifies threats to initiate an
1001:"Conformational rearrangements og RIG-I receptor on formation of a multiprotein: dsRNA assembly"
16:
1081:
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981:
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887:
824:
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734:
685:
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548:
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443:
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344:
331:
Janeway CA (1989-01-01). "Approaching the asymptote? Evolution and revolution in immunology".
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73:
1071:
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1020:
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971:
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713:"Common variable immunodeficiency is associated with defective functions of dendritic cells"
677:
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281:. They recognize alarmins, a category that includes both DAMPs and PAMPs, to process their
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degrades most danger signals, preventing the detection and destruction of malignant cells.
172:
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124:
101:
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Hallenbeck J, Del Zoppo G, Jacobs T, Hakim A, Goldman S, Utz U, Hasan A (December 2006).
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950:"Implication of inflammatory signaling pathways in obesity-induced insulin resistance"
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48:. The proliferation of Helper T cells stimulates B cells and macrophages.
769:
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Matzinger P (April 2002). "The danger model: a renewed sense of self".
282:
97:
41:
819:
802:
634:
85:
918:
681:
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618:
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Matzinger P (1994). "Tolerance, danger, and the extended family".
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120:
15:
1050:"Molecular recognition of paired receptors in the immune system"
192:
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in 1949 with later refinement by Burnet. It theorizes that the
160:
156:
29:
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during bacterial invasions to stimulate B cell production of
999:
Beckham SA, Brouwer J, Roth A, Wang D, et al. (2012).
619:"Friendly and dangerous signals: is the tissue in control?"
108:
in 1989. Janeway's theory involved APCs being activated by
666:"Tissue-based class control: the other side of tolerance"
271:
nucleotide oligomerization domain (NOD)-like receptors
20:
Function of T helper cells: Antigen-presenting cells (
275:
retinoic acid inducible gene-I (RIG-I)-like receptors
515:
Jounai N, Kobiyama K, Takeshita F, Ishii KJ (2012).
28:). Helper T cells recognize these by expressing the
24:) present antigens on their Class II MHC molecules (
333:
Cold Spring Harbor
Symposia on Quantitative Biology
803:"Liver: An organ with predominant innate immunity"
100:-specific, capable of processing self structures,
521:Frontiers in Cellular and Infection Microbiology
242:Damage-associated molecular pattern (DAMP) model
230:. Similarly, 30-40% of the liver's T cells are
112:(PRRs) that recognize evolutionarily conserved
948:Tanti JF, Ceppo F, Jager J, Berthou F (2012).
8:
461:
459:
457:
360:
358:
68:The first major immunologic model was the
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1024:
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881:
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818:
801:Gao B, Jeong WI, Tian Z (February 2008).
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728:
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491:
386:
1048:Kuroki K, Furukawa A, Maenaka K (2012).
320:. Cambridge: Cambridge University Press.
758:Clinical & Translational Immunology
293:
224:transforming growth factor beta (TGF-β)
220:common variable immunodeficiency (CVID)
114:pathogen-associated molecular patterns
318:Cellular Immunology: Self and Notself
305:(2nd ed.). Melbourne: Macmillan.
7:
664:Matzinger P, Kamala T (March 2011).
285:for presentation to T helper cells.
261:Pattern Recognition Receptors (PRRs)
92:and a co-stimulatory signal from an
568:"The danger theory: 20 years later"
440:10.1146/annurev.iy.12.040194.005015
279:C-type lectin-like receptors (CLRs)
248:Damage-associated molecular pattern
566:Pradeu T, Cooper EL (2012-01-01).
484:10.1161/01.STR.0000248836.82538.ee
14:
752:Bauché D, Marie JC (April 2017).
222:. For example, gut cells secrete
155:, releasing danger signals like
253:biological molecules. In 2004,
1:
232:Type I Natural Killer T (NTK)
110:pattern recognition receptors
64:History of immunologic models
44:, the last of which produces
617:Matzinger P (January 2007).
303:The Production of Antibodies
301:Burnet FM, Fenner F (1949).
96:(APC). Because APCs are not
954:Front Endocrinol (Lausanne)
428:Annual Review of Immunology
341:10.1101/sqb.1989.054.01.003
1121:
730:10.1182/blood-2004-04-1325
670:Nature Reviews. Immunology
267:toll-like receptors (TLRs)
245:
907:Nature Reviews Immunology
106:Infectious Non-self Model
1067:10.3389/fmicb.2012.00429
967:10.3389/fendo.2012.00181
873:10.3389/fimmu.2018.00716
585:10.3389/fimmu.2012.00287
534:10.3389/fcimb.2012.00168
860:Frontiers in Immunology
572:Frontiers in Immunology
397:10.1126/science.1071059
94:antigen-presenting cell
228:Immunoglobulin A (IgA)
212:adaptive immune system
49:
335:. 54 Pt 1 (1): 1–13.
19:
850:Yoshimoto T (2018).
236:Interleukin 4 (IL-4)
216:innate immune system
1105:Immunology theories
1017:10.1093/nar/gks1477
379:2002Sci...296..301M
165:heat shock proteins
129:anti-tumor immunity
70:Self/Non-self Model
770:10.1038/cti.2017.9
316:Burnet FM (1969).
50:
1005:Nucleic Acids Res
820:10.1002/hep.22034
635:10.1038/ni0107-11
623:Nature Immunology
478:(12): 3035–3042.
373:(5566): 301–305.
283:antigenic regions
234:cells, providing
199:for detection by
74:Macfarlane Burnet
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201:dendritic cells
173:serum amyloid A
169:hyaluronic acid
145:immune response
141:Polly Matzinger
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125:graft rejection
102:Charles Janeway
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30:CD4 co-receptor
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214:relies on the
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90:T helper cells
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38:killer T cells
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58:immune system
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629:(1): 11–13.
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251:
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189:interferon-α
138:
135:Danger model
123:infections,
105:
78:Frank Fenner
72:proposed by
69:
67:
54:danger model
53:
51:
764:(4): e136.
34:macrophages
807:Hepatology
289:References
246:See also:
153:pyroptosis
46:antibodies
383:CiteSeerX
205:apoptosis
185:cytokines
181:uric acid
175:protein,
139:In 1994,
1099:Category
1086:23293633
1035:23325848
986:23316186
935:13336660
927:15173835
892:29740428
829:18167066
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739:15226176
698:10809131
690:21350581
643:17179963
604:23060876
553:23316484
502:17082471
413:13615808
405:11951032
167:(Hsps),
149:necrosis
1077:3533184
1060:: 429.
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977:3539134
960:: 181.
883:5924770
866:: 716.
854:In Vivo
837:5441697
779:5418590
651:6448542
595:3443751
578:: 287.
544:3539075
527:: 168.
493:1853372
448:8011301
375:Bibcode
367:Science
349:2700931
98:antigen
56:of the
42:B cells
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183:, and
86:B cell
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833:S2CID
717:Blood
694:S2CID
647:S2CID
409:S2CID
197:CD40L
187:like
127:, or
121:viral
1082:PMID
1031:PMID
982:PMID
923:PMID
888:PMID
825:PMID
784:PMID
735:PMID
686:PMID
639:PMID
600:PMID
549:PMID
498:PMID
444:PMID
401:PMID
345:PMID
277:and
76:and
52:The
26:MHC2
22:APCs
1072:PMC
1062:doi
1021:PMC
1013:doi
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962:doi
915:doi
878:PMC
868:doi
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774:PMC
766:doi
725:doi
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678:doi
631:doi
590:PMC
580:doi
539:PMC
529:doi
488:PMC
480:doi
436:doi
393:doi
371:296
337:doi
177:ATP
161:RNA
157:DNA
151:or
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