Download immunology-introduction

GO Content Meeting
November 15 and 16, 2005
Improving the Representation of
Immunology in the Gene Ontology
Proposal List for GO Content Meeting
 A. Self and Non-Self Processes
 B. Reorganization of Cytokine Function Terms
 C. Adding CD antigen binding terms
 D. Improvements to T cell differentiation hierarchy
 E. Reorganization of immune response terms in several ways
1) Activation of the immune system vs. effector mechanisms
2) Improving representation of innate immunity
3) Improving representation of immune cell differentiation
4) Improving GO:0006954 inflammatory response
 F. The problem of regulation terms under immune response
 G. Tumor surveillance terms
Proposal List for GO Content Meeting
 A. Self and Non-Self Processes – Amelia and Jane
 B. Reorganization of Cytokine Function Terms
 C. Adding CD antigen binding terms
 D. Improvements to T cell differentiation hierarchy
 E. Reorganization of immune response terms in several ways
1) Activation of the immune system vs. effector mechanisms
2) Improving representation of innate immunity
3) Improving representation of immune cell differentiation
4) Improving GO:0006954 inflammatory response
 F. The problem of regulation terms under immune response
 G. Tumor surveillance terms
Proposal List for GO Content Meeting
 A. Self and Non-Self Processes – Amelia and Jane
 B. Reorganization of Cytokine Function Terms
 C. Adding CD antigen binding terms
 D. Improvements to T cell differentiation hierarchy
 E. Reorganization of immune response terms in several ways
1) Activation of the immune system vs. effector mechanisms
2) Improving representation of innate immunity
3) Improving representation of immune cell differentiation
4) Improving GO:0006954 inflammatory response
 F. The problem of regulation terms under immune response
 G. Tumor surveillance terms
Proposal List for GO Content Meeting
 A. Self and Non-Self Processes – Amelia and Jane
 B. Reorganization of Cytokine Function Terms
 C. Adding CD antigen binding terms
 D. Improvements to T cell differentiation hierarchy
 E. Reorganization of immune response terms in several ways
1) Activation of the immune system vs. effector mechanisms
2) Improving representation of innate immunity
3) Improving representation of immune cell differentiation
4) Improving GO:0006954 inflammatory response
 F. The problem of regulation terms under immune response
 G. Tumor surveillance terms
Proposal List for GO Content Meeting
 A. Self and Non-Self Processes – Amelia and Jane
 B. Reorganization of Cytokine Function Terms
 C. Adding CD antigen binding terms
 D. Improvements to T cell differentiation hierarchy
 E. Reorganization of immune response terms in several ways
1) Activation of the immune system vs. effector mechanisms
2) Improving representation of innate immunity
3) Improving representation of immune cell differentiation
4) Improving GO:0006954 inflammatory response
 F. The problem of regulation terms under immune response
 G. Tumor surveillance terms
Proposal List for GO Content Meeting
 A. Self and Non-Self Processes – Amelia and Jane
 B. Reorganization of Cytokine Function Terms
 C. Adding CD antigen binding terms
 D. Improvements to T cell differentiation hierarchy
 E. Reorganization of immune response terms in several ways
1) Activation of the immune system vs. effector mechanisms
2) Improving representation of innate immunity
3) Improving representation of immune cell differentiation
4) Improving GO:0006954 inflammatory response
 F. The problem of regulation terms under immune response
 G. Tumor surveillance terms
Problems for Immunology in the GO
 Incomplete Representation of Immunological Processes
 Conceptual Problems in Term Organization
 Poorly Formulated and Poorly Defined Terms
Incomplete Representation of
Immunological Processes
 Current GO lacks whole groups of terms for processes such as
mucosal immunity
tolerance induction
B cell differentiation
 And individual terms for important processes such as
granuloma formation
germinal center formation
affinity maturation
Conceptual Problems in Immunology
Term Organization in the GO
Terms describing the development of immune
system components are incorrectly placed
under GO:0006955 immune response, when
in fact many of the differentiation steps occur
prior to an immune response.
T cell differentiation (T cell development)
B cell differentiation (B cell development)
Conceptual Problems in Immunology
Term Organization in the GO (2)
The GO terms for cytokine metabolism and
cytokine production are children of immune
response, when in fact many cytokines are
produced independently of immune responses
and have non-immunological functions (EGF
or TGF-ß, for example).
Conceptual Problems in Immunology
Term Organization in the GO (3)
Separate GO terms for antigen processing and
antigen presentation exist, without recognition
of the relationship of these two concepts.
Furthermore, the children of these terms are
not well defined and important subprocesses
are missing from the GO. This has led to
confusion by annotators in the use of these
terms, and reflects poorly on the GO.
Conceptual Problems in Immunology
Term Organization in the GO (4)
GO:0006955 immune response is a child of
defense response in the current GO, yet
immune responses include tolerance induction
and regulatory processes that are not defense
responses.
GO:0006954 inflammatory response is a child
of immune response, yet inflammatory
responses include non-immunological
components.
Poorly Formulated and Poorly
Defined Terms
humoral immune response ; GO:0006959
--% humoral defense mechanism (sensu Vertebrata) ; GO:0016064
--% humoral defense mechanism (sensu Protostomia) ; GO:0016065
Poorly Formulated and Poorly
Defined Terms
humoral immune response ; GO:0006959
--% humoral defense mechanism (sensu Vertebrata) ; GO:0016064
--% humoral defense mechanism (sensu Protostomia) ; GO:0016065
An immune response mediated through a body fluid.
Poorly Formulated and Poorly
Defined Terms
humoral immune response ; GO:0006959
--% humoral defense mechanism (sensu Vertebrata) ; GO:0016064
--% humoral defense mechanism (sensu Protostomia) ; GO:0016065
The specific immune response mediated by antibodies,
as in, but not restricted to, the vertebrates (Vertebrata,
ncbi_taxonomy_id:7742).
Poorly Formulated and Poorly
Defined Terms
humoral immune response ; GO:0006959
--% humoral defense mechanism (sensu Vertebrata) ; GO:0016064
--% humoral defense mechanism (sensu Protostomia) ; GO:0016065
The specific immune response mediated by antibodies.
As in, but not restricted to, the taxon Protostomia
(Protostomia, ncbi_taxonomy_id:33317).
The Big Picture
The Big Picture
Assumptions Behind Changes to
Immune Response DAG
Current definition of GO:0006955 immune response:
Any process involved in the immunological reaction
of an organism to an immunogenic stimulus.
Assumptions Behind Changes to
Immune Response DAG
1. Immunological reactions involve largely, but not
solely, hematopoietically derived cell types,
commonly referred to as immune cells or
leukocytes in the GO, and may target any tissue or
cell type in the body as well as infecting organisms.
Assumptions Behind Changes to
Immune Response DAG
2. An “immunological stimulus” is any stimulus
capable of activating an immune response
activating cell surface receptor pathway. Such
pathways include:
BCR and TCR signaling pathways on mature B and T cells
C-type lectin receptor signaling pathways with activation activities
KIR signaling pathways with activation activities
Fc receptor signaling pathways with cellular activation activities
Toll-like receptor signaling pathways (and Toll in drosophila)
complement receptor signaling pathways with activation activities
certain other pathways (scavenger receptors etc.)
Assumptions Behind Changes to
Immune Response DAG
3. An immune response is considered to be the set of
physiological processes carried out by immune cell
types and certain additional cell types following an
immunological stimulus. Differentiation processes
for immune cell types (for instance thymic T cell
development) prior to an immunogenic stimulus
are not considered part of the immune response.
Assumptions Behind Changes to
Immune Response DAG
4. An immune response may be made against both
self and non-self determinants. Although the GO is
intended to cover "normal" processes, these
processes include immune responses against
microbes, pests and parasites of all types, whether
pathogenic or not, tolerance induction mechanisms
against peripheral antigens whether of self or nonself origin, anti-tumor immune responses, and even
beneficial autoimmune responses.
Changes to the GO:0006955
immune response hierarchy
Multiple Modes of Immune Response
1. Innate Immune Response
2. Adaptive Immune Response
3. Humoral Immune Response
4. Mucosal Immune Response
Changes to the GO:0006955
immune response hierarchy
Innate Immune Response
Adaptive Immune Response
Humoral Immune Response
Mucosal Immune Response
Activation of the Immune Response
Immune Effector Process
Immune Cell Mediated Immunity
Regulation of Immune Response
Problems with Regulation
 GO dogma: positive regulation of a child term is a
type of positive regulation of a parent term.
 However, this inference is not strictly true for many
processes in the immune system.
Problems with Regulation
Problems with Regulation
Problems with Regulation
Inflammatory Response
Tolerance Induction
Cell Activation
 The current paradigm in the biological_process ontology is that T cell
and B cell differentiation and proliferation are types of T cell and B cell
activation, respectively. This DAG structure has certain advantages in
annotation of things like T cell proliferation assays.
 T cell and B cell activation are defined in the GO to include any type of
activation of those cell types, not just activation through the TCR or
BCR, and included implicitly in activation are activation steps required
for differentiation.
 The big change now is that T and B cell differentiation processes prior
to an immune response (what immunologists know as T cell
development and B cell development) are no longer children of
GO:0006955 immune response.
Somatic Diversification of Immune
Receptors
Immunoglobulin Production
Outstanding Questions
1.
What other pathways of activation constitute immunological
stimuli?
2.
How should inhibitory pathways (ITIMs) be handled?
3.
Should plant innate immunity be included under innate
immunity?
4.
What other pathways of innate immunity, particularly for
invertebrates should be included?
Outstanding Questions
5.
What is the proper relationship of the inflammatory response
to the immune response?
6.
Is the cell activation/differentiation/proliferation structure
the best way to show the relationships of these terms?
7.
Is central tolerance to non-self antigens via upregulation of
CD4+CD25+ T regulatory cell differentiation an immune
response or not?