Example questions by Tier
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Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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Acquired immunodeficiency syndrome (AIDS) is an advanced form of HIV infection in which the patient has developed opportunistic infections or certain types of cancer and/or the CD4+ T cell count has dropped below 200/μL. More than 40 million persons around the world are infected with HIV, with approximately 14,000 new infections every day. The disease causes 3 million deaths worldwide each year, 95% of them in developing countries. Optimal management of human immunodeficiency virus requires strict adherence to highly active antiretroviral treatment (HAART) regimens, but the complexity of these regimens (e.g., pill burden, food requirements, drug interactions, and severe adverse effects) limits effective treatment. However, more patients with HIV are surviving longer today because of these drugs. This allows further study of commonly associated adverse effects. These may affect all body systems and range from serious toxicities to uncomfortable but manageable events. 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She is also an Affiliated Scientist at the Women’s College Research Institute, a Registered Dietitian and a Senior Scientific Associate at The University Health Network. Dr. Aghdassi obtained a doctoral degree in Nutritional Sciences from The University of Toronto in 1995. She has then immediately started her research and been actively involved in research related to Nutrition, Metabolism and Quality of Life in the field of chronic diseases in Canada. She has brought a unique and original contribution to research in HIV using her skills as a translational researcher and nutritionist. 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Risk management is concerned with the identification of risks, the avoidance, mitigation, transference, or sharing of unacceptable risks, and the acceptance of risks that are within an organization’s risk tolerance. However, just as with information system controls within NIST’s RMF, it is necessary to monitor the risk posture of systems, maintaining an ongoing assessment of the level of risk they represent within and to an organization. This risk posture changes with changes to the hardware and software employed by the organization, as well as when patches and updates are released that are intended to be applied to deployed software. Changes can also occur from vulnerabilities identified with no patch available, or when new types of information are allowed on a previously authorized or accredited information system. Different types of information are of varying interest to an organization or adversary. More valuable information generally has a higher impact on the organization when it is compromised Compromise is used in this chapter to indicate a loss of confidentiality, integrity, or availability of the information.
The IA OM® metric is a good choice for use as an enterprise risk management metric, as described in this chapter, due to its versatility as a management metric. This metric:
Measures information security risk management activities within an organization;
Shows organizational senior management where their organization currently stands with respect to its risk management strategy, and its monitoring plan; and
Demonstrates to senior management how such metrics can be used over time to track and improve their organization’s ability to meet its overall risk management strategy and risk monitoring plan.
Risk management focuses on understanding and managing risks to an organization. This chapter focuses on information security (also referred to as information assurance (IA)) risks. Wheeler [3] in his book on risk management stated that “The goal of risk management is to maximize the output of the organization (in terms of services, products, revenue, [mission accomplishment], and so on), while minimizing the chance for unexpected outcomes”. This goal is best accomplished through the use of an established, proven framework for managing information security risks to organizations. This chapter proposes an approach based on the structure provided by the NIST.
The approach described by the NIST is used in this chapter due to several factors. First, the NIST approach has been developed to be consistent with and harmonize with international standards to the extent appropriate. These international standards include those of the International Organization for Standardization (ISO) and the International Electrotechnical Commission (IEC) The NIST risk management structure is aligned with ISO/IEC 3100, Risk Management – Principles and Guidelines; 31010, Risk Management – Risk Assessment Techniques; 27001, Information technology – Security techniques – Information Security Management Systems – Requirements; and 27005, Information Technology – Security Techniques – Information Security Risk Management Systems.
The approach described by the NIST is based on a 4-step process, used within a 3-tiered structure. The 3-tiered structure is used to depict the principal functional areas within an organization as they relate to risk management decision-making – the organization, mission/business process, and information systems Tiers – described in Section 2.2. The risk management process and the 4-steps in the process – frame, assess, respond, and monitor – are described in Section 2.3.
Information security practitioners are transitioning from a compliance-based, checklist type of approach to a more risk managed approach to security [3]. This is being done largely due to practicality and resource constraints [3]. It is not possible to eliminate risk in an information system, and is resource intensive to try [3, 4]. In order to effectively manage resources and maintain usability of the system, it is necessary to implement a risk managed approach to securing Information Technology (IT) systems.
To understand this change, it is important to start with a good definition of risk. A good definition in this case is one that can be understood operationally and can be easily used to clarify the process. Not surprisingly, there are many different definitions of risk. Wheeler [3] defines risk as: “the probable frequency and probable magnitude of future loss of confidentiality, integrity, availability or accountability”. Accountability is not commonly accepted as being a part of the definition of risk, is not included in the definition of risk used by the NIST The definition of risk provided by the NIST is: “A measure of the extent to which an entity is threatened by a potential circumstance or event, and typically a function of: (i) the adverse impacts that would arise if the circumstance or event occurs; and (ii) the likelihood of occurrence. [Note: Information system-related security risks are those risks that arise from the loss of confidentiality, integrity, or availability of information or information systems and reflect the potential adverse impacts to organizational operations (including mission, functions, image, or reputation), organizational assets, individuals, other organizations, and the Nation]” [17].
Risk: The probable frequency and probable magnitude of future loss of an organization’s operations (including mission, functions, image, or reputation), organizational assets, individuals, other organizations, and the Nation resulting from a loss of confidentiality, integrity, or availability.
There are two fundamentally different approaches to Information security risk management activities used by organizations:
Compliance-based; and
Risk management-based.
Each of these approaches, while working toward the overall objective of ensuring the confidentiality, integrity, and availability of the organization’s information and information systems, attempts to meet that objective in a fundamentally different way. Compliance-based approaches default to including controls from the best practice or other framework they are implementing – not including a prescribed control is the exception [5]. On the other hand, risk management-based approaches default to not including a control unless its need and utility can be justified by a risk analysis [5].
Failure to comply with the legal and regulatory structures confronting an organization can result in penalties, loss of contracts, loss of confidence, loss of business, and stock price declines [6]. Some of the requirements that organizations may need to maintain compliance with include:
U.S. Legal requirements (e.g., the Sarbanes-Oxley Act, the Health Insurance Portability and Accountability Act (HIPAA), Gramm-Leach-Bliley Act (GLBA);
Non-U.S. Legal requirements for organizations operating outside the United States;
International frameworks (e.g., Basel, Basel II); and
Industry standards (e.g., the Payment Card Industry Data Security Standard (PCI or PCI-DSS)).
Compliance with these requirements is often a part of an organization’s due diligence [7]. The focus on best practice frameworks frequently focuses on satisfying the auditor/examiner, helping to meet compliance requirements rather than the organizations genuine information security needs [8, 9]. Unfortunately, these checklist or compliance-based approaches to information security risk management provide static, “one-size-fits-all” information security “solutions” [3]. One result of this approach is the common perception among information security practitioners that “if you are secure you
There are a number of best practice frameworks for information security, including the Information Technology Infrastructure Library (ITIL) [10], COBIT [11], and the ISO/IEC 27001 [12], 27002 [13], and 27005 [14]. Unfortunately, these approaches are dated almost as soon as they are published due to the speed of change on the Internet and within the IT security arena [15]. Attackers are very adaptable, and change their tactics quickly. In addition, a checklist or compliance-based approach assumes that every system requires the same protection as every other system, without regard for cost, information sensitivity, and mission or business impact [3]. However, there are often considerable differences in the types of systems deployed in an enterprise, and the information they contain. Since the information contained in the IT system is normally the critical asset requiring protection, the protective mechanisms that should be implemented will depend largely on the sensitivity of the information processed, stored, or transmitted by the system [8].
However, best practice frameworks do provide a useful method for ensuring that all aspects of an IT information security program are considered when using a risk managed approach to IT information security requirements development. Due to the need of organizations to remain compliant with respect to specific legal requirements and industry frameworks some form of compliance-based approach is likely to remain necessary.
Risk-based approaches to securing information systems allow organizations to customize their information security protections, based in the needs of their organization. Using a risk-based approach requires consideration of the information processed, stored, or transmitted by the information system, as well as consideration of the IT system’s environment, connectivity, and threat environment [7, 16]. Other considerations include the cost of implementing security controls weighted against the impact on the mission and business operations of the organization should a loss of confidentiality, integrity, or availability of the information occur [7].
A risk-based approach to information security is what the U.S. government is transitioning to with the release of the NIST Special Publication (SP) 800-37 [2] and SP 800-39 [3, 17]. The NIST has developed a series of SPs to focus on information security risk management, starting with an enterprise view in SP 800-39 [17], an information system view in SP 800-37 [2], and by providing an approach for performing risk assessments in SP 800-30 [18]. NIST SP 800-53 [19] provides a catalog of security controls, and recommends “baselines” of security controls based on the sensitivity of the information on the system. These baselines are intended to be customized, or “tailored” to meet the needs of the information and the information system when consideration of the system’s environment, connectivity, and threats are considered [19].
When addressing information security risk management activities, the NIST and other authors divide organizations into three levels [17, 20]. The NIST [17] identifies these tiers as the:
Organization;
Mission/Business Process; and
Information Systems.
Each tier has different organizational risk management responsibilities. However, despite their different perspectives and roles, they all use the same 4-step risk management process described in Section 2.3 for risk management actives within their Tier. This 3-tiered structure is depicted in Figure 1.
Risk Management Tiers This figure is adapted from
At the organization tier, risk to the entire organization is considered and managed. Part of the responsibility for managing risk throughout the organization is the process of “risk framing”, establishing the context within which all organizational risk management activities will be conducted [17]. Risk framing establishes the governance framework from which are derived the risk management activities and the risk tolerance of the organization. Other activities occurring at Tier 1 include:
Establishment and prioritization of activities and programs at the Mission/Business Tier;
Determination of organization-wide common controls Common controls are security controls implemented in a way that they are available to information systems across the organization. Common controls can be “inherited” by a system, meaning that the system itself does not need to implement the control the system can leverage/use the control as implemented by the organization.
The Risk Executive (Function) The Risk Executive (Function) is an individual or office responsible for considering risk across the organization, to include mission, business, and security risks, balancing them appropriately for the organization, and making recommendations to decision-makers within the organization based on their risk determinations.
The Risk Executive (Function) (REF) is an individual or group within the organization that serves in an advisory role to organizational decision makers at all 3-tiers. The REF does not make decisions for the organization; rather it informs decision makers about the risks to the system, network, and the organization that may result from a particular risk decision. The REF considers risk from a holistic perspective, considering mission and business risks, in addition to security risks. This risk consideration is done with an organization-wide perspective, allowing the REF’s recommendations to evaluate the potential impact of accepting risks in one area or system on other systems or the organization.
Tier 2 is where the mission/business processes necessary to implement the strategic goals and objectives established at Tier 1 are defined and prioritized [17]. This is also where the types of information required, the information sensitivity, and information flows necessary to support the Tier 1 goals and objectives is determined [17]. The IT enterprise architecture is defined and established at this tier, to include the implementation of the common controls identified in Tier 1. The decisions and activities at this tier have a direct effect on the activities undertaken at Tier 3.
Tier 3 is where the information systems that support the organization reside. The decisions and prioritizations established in Tiers 1 and 2 are implemented in information systems at this tier. The activities required for each of the steps in the Risk Management Framework (RMF) The RMF is described in detail in NIST Special Publication (SP) 800-37, available from: The system development life cycle established by the NIST is described in NIST SP 800-64, Security Considerations in the System Development Life Cycle, Oct. 2008 [23].
The risk management process is comprised of a number of discrete steps. These steps take place at different times within the process, and possibly at multiple times in the process due the iterative nature of risk management activities. It is important that all of the steps are completed for a risk management program to be fully effective. These steps apply to risk management activities taking place at each tier within the organization, so this process is equally applicable to risk management activities taking place at Tier 1 as it is at Tier 2 or 3.
NIST describes four distinct steps in the risk management process. These steps are:
Risk Framing
Risk Assessment
Risk Response
Risk Monitoring
Risk framing is a governance activity that is performed at Tier 1. Its principal output is a risk management strategy “that addresses how organizations intend to assess risk, respond to risk, and monitor risk” [17]. The risk management strategy is created as a joint effort between an organization’s senior management and/or executives in conjunction with the risk executive (function) [17]. The risk management strategy explicitly states the assumptions, constraints, risk tolerances, and priorities or trade-offs used in making investment and operational decisions for the organization [17]. It also details what types of risk responses are supported, how risk is assessed, and how risk is monitored for the organization [17].
Risk assessment is the process of:
Identifying risks (threats and associated vulnerabilities) to an organizational asset, activity, or operation;
Estimating the potential impact and likelihood of the risk materializing, and
Prioritizing the identified risks according to their severity to the organization [3, 17].
Risk assessments can and should be conducted at every Tier of the organization. However, the objectives of risk assessments conducted at different Tiers will reflect the differences in responsibility and objectives for the Tier being assessed [17]. For example, a risk assessment at Tier 3, the Information Systems Tier, will go into considerable technical detail on a specific information system and the risks involved in its operation. Whereas a risk assessment at Tier 1, the Organization Tier, may address information systems from the perspective of the organization’s enterprise architecture or common control framework, but will not go into significant technical detail, nor will it address a specific information system. However, a Tier 1 risk assessment will address business risks, and the risks involved in investing in particular missions or business areas.
Responding to risk involves deciding on and implementing a course of action to address the risk within the organization. The options available to the organization for risk response are defined in the organization’s risk management strategy. The courses of action available to address risk as identified in NIST SP 800-39 [17] are:
Accept – take no action when the risk is within the organization’s risk tolerance;
Avoid – eliminate the activities or technologies resulting in risk that exceeds the organization’s risk tolerance, or reposition the activities or technologies into areas or positions where the risk is avoided;
Mitigate – apply security controls, safeguards, or process re-engineering to reduce the risk to a level acceptable to the organization;
Transfer or Share – shifting all or part of the liability for risk, respectively, to another organization.
Risk monitoring is conducted on an ongoing basis to ensure that the organization’s risk posture remains within the organization’s risk tolerance. The risk monitoring process allows an organization to:
Ensure compliance with national laws, regulations, organizational policies, and mission/business functions;
Determine how effective its risk response measures are;
Identify changes to organizational assets or their operating environments that result in changes their risk postures [17].
Risk monitoring activities are normally conducted on a periodic basis, with the period determined in accordance with the organization’s risk management strategy and the sensitivity of the information or business process being protected [16, 17]. Monitoring risk and changes to operating environments includes identifying changes to the threat environment, and determining whether a change in the threat environment requires a reassessment of the risk posture of an organizational asset, activity, or operation earlier than normally scheduled [3].
These risk monitoring activities can be implemented at any tier in the organization [17]. The objectives and process for each tier will differ according to their respective needs, and, particularly at Tiers 1 and 2, are likely to involve cross-tier monitoring – as the upper tiers are directly affected by operational or process-level changes to the organization’s risk posture at the lower levels [17]. An example of cross-tier monitoring would involve the monitoring of the risk posture of an information system authorized to operate within an organization. The organizational official responsible for the authorization decision will want to monitor the risk posture of the information system to ensure it continues to operate within an acceptable level of risk, and that any changes to the risk posture of the system or its environment are properly evaluated and addressed.
The metrics or results derived from the IA OM® methodology are meaningful to the organization because the measurements themselves are “tied directly to questions that are important to the organization”[21]. The results are also useful to organizational management since they indicate the degree to which specific information security risk management goals are being met as action is taken to improve an organization’s overall information security posture in terms of its information security objectives [1]. In this instance IA OM® can be conceptually expressed as providing a measure of the degree to which the organization’s information security risk management objectives are being met [1].
The creators of the OM® methodology, Donaldson and Siegel [21, 22], have 20+ years of professional software engineering experience at Science Applications International Corporation (SAIC) and in the Department of Defense (DoD). The OM® methodology enables one “to measure software products and software systems development processes in everyday terms familiar and – therefore meaningful – to your organization” [21]. The OM® methodology measures software products and software systems development processes as part of a continual process improvement exercise. The OM® framework derives its effectiveness as a “management process” tool in that the OM® Index, akin to the Consumer Price Index, folds in a number of individual measurements into a single overall value [1, 22]. The OM® Index can also be deconstructed to gain insight into the elements comprising the index value. By looking at trends in the index values, it is possible to determine the effect or outcome of changes within the organization.
The OM® quantifies software
The IA OM® metric can be used with existing organizational objectives or industry best practices. However, industry best practices are not appropriate for many organizations, and as described in Section 2.1.1, are often not sufficient in and of themselves to meet the an organization’s requirements. Each organization must determine what is most appropriate for its needs. This is best accomplished when requirements are evaluated in the context of their budget and a thorough risk analysis [7]. Evaluating an organization’s information security risk management posture, based on how well its systems comply with the organization’s information security risk management objectives, provides a metric with greater versatility and applicability across a wider range of organizations [1].
Implementing IA OM® at an organizational level provides Senior Management with a high-level or strategic-level view of where its organization’s risk management program stands and how well it is meeting its stated information security risk management objectives. IA OM® is the OM® OM® was developed by Donaldson and Siegel, SAIC, [21] to evaluate system development life cycle (SDLC) processes.\n\t\t\t\t\t See Ting and Comings [1] for a complete description of IA OM®.
Quantitatively determine the degree of risk identified within an organization’s information security risk management program;
Characterize the organization’s risk management policy elements as they are applied to its information security risk management program for IA OM® evaluation;
Determine the weighting factors, based on a determination of the relative importance of each component, for the identified characteristics of the organization’s risk management strategy and policy;
Periodically present the results of the evaluation, the current risk management posture of the enterprise, in a balanced scorecard-like format that is familiar and easy to understand and interpret by Senior Management;
Analyze the metrics data, identify the strengths and weaknesses of proposed metrics approaches; and
Suggest areas for future assessment and evaluation.
IA OM® will help answer Senior Management’s questions regarding the state of their organization’s information security risk management program enabling them to determine their organization’s current risk posture, identify areas needing improvement, and prioritize the allocation of organizational resources in addressing identified risks.
Any effective risk management program requires periodic monitoring and re-assessment, including risk monitoring at the organization, mission/business process, and, information systems Tiers. The components of risk management at these multiple-tier levels are specifically identified NIST SP 800-39 [17], Managing Information Security Risk, describes the fundamentals of risk management in Chapter 2 and the process for framing, assessing, responding and monitoring risk in Chapter 3.
Tier 1 – Addresses risk from an organizational perspective by establishing and implementing governance structures including: 1) Establishment and implementation of a risk executive (function); 2) Establishment of a risk management strategy including a determination of organizational risk tolerance; and 3) Development of organization-wide investment strategies for information resources and information security.
Tier 2 – Addresses risk from mission/business process perspective by designing, developing, and implementing the processes supporting the mission/business functions defined at Tier 1 including: 1) Risk aware processes designed to manage risk according to the risk management strategy defined at Tier 1 and explicitly accounting for risk in evaluating the mission/business activities and decisions at Tier 2; 2) Implementing an enterprise architecture, and, 3) Establishing an information security architecture as an integral part of the organization’s enterprise architecture.
Tier 3 – Addresses risk from an information system perspective, guided by risk context, risk decisions and risk activities at Tiers 1 and 2, risk management activities (i.e. activities at each step of the Risk Management Framework (NIST SP 800-37 [2]) and in the systems development life cycle (NIST SP 800-64 [23])
These three Tiers, properly integrated, provide the capability to establish a strong, risk-based security infrastructure for an organization.
Risk management monitoring must be conducted at all three Tiers, making sure that all key activities are performed properly within each Tier and across Tiers [17]. Monitoring at the information systems level must take into account those controls that are “common” to an organization or enterprise [2]. Common controls are those controls that are established by an organization itself, or an element within an organization, and are made available for use by other elements and information systems within the organization. It is often not possible for an individual system owner to monitor common controls – such monitoring must be provided by the Common Control Provider.
With monitoring taking place at many levels within the organization, the need for an enterprise-wide risk management solution is even greater. Without a big-picture view of the information security risk posture of the systems within an organization, there may be systems operating that are creating significant risks to the organization without anyone in a position to address the problems realizing a problem exists.
At the Tier 1 and 2 levels, the concept of common controls is not the same as at Tier 3, however, there is still the need to ensure that organizational guidance and organizational functions remain aligned. When strategies, policies, and other organization-level guidance changes, the changes need to ripple through the organization – updating policies, programs, investments, etc. to ensure they remain in alignment with the top-level guidance.
IA OM® addresses these needs by aggregating the results of risk monitoring programs occurring throughout the organization, rolling them up, and presenting them as a set of summary statistics indicating where an organization stands with respect to remaining within its:
Overall risk tolerance
Risk tolerance within organizational elements
Risk tolerance for individual systems
Applied this way, IA OM® allows Senior Management to readily assess their current information security risk management posture and determine whether it fits within their risk tolerance. It also identifies those areas, programs, and systems of greatest risk to the organization – allowing Senior Management to quickly and easily prioritize their remediation efforts.
The process for using IA OM® as an enterprise risk management metric involves a number of steps. The overall steps in the process, as adapted from the OM® process, are:
Decide what questions you need or want answers to regarding your organization’s risk management program;
Identify the organizational assets, processes, or operations that need to be measured to answer the questions from step 1;
Identify any characteristics and sub-activities of the organizational assets, processes, or operations to be measured from step 2;
Define an activity value scale for each activity or sub-activity in terms that make sense within the organization;
Determine the current value (or location along the value scale) for each activity or sub-activity being measured;
Calculate the value for each asset, process, or operation identified in Step 2 using the formulas provided in Section 4.4 and the activity (or sub-activity) values from step 5. Weighting factors are selected based on the organization’s determination of the relative importance of the activities;
Combine the values for each activity (asset, process, or operation) into an overall IA OM® index value to be reported and analyzed.
These steps and activities are applied to organizational risk management using IA OM®, resulting in a metric that provides:
The ability to evaluate the risk posture of a specific organizational asset, process, or operation;
A set of organizational assets;
All activities within a risk management tier; or
Risk management activities across tiers.
This process is shown in Figure 2 [24] using an activity from an organization’s personnel security process as an example. The individual process steps are examined in more detail in Sections 4.1 – 4.7.
IA OM Process with Personnel Security Process Example
IA OM® is like other investigative ventures – the first step in the process is determining what you want or need to know. This chapter focuses on evaluating and understanding the ongoing risk management activities within an organization. As a result, the questions framed for use with IA OM® in this chapter focus on what the organization’s executives, program managers, or system-level managers want or need to know about the risk posture of the portion of the organization they are responsible for. As such, the questions to be addressed by IA OM® need not to be restricted to Tier 1 – they can, and ultimately should, be spread across all three tiers so that the managers at each tier have the answers they need to be successful in the organization’s risk management program.
Examples of questions that might be asked at each Tier are presented in Table 1:
Is our risk management strategy aligned with our organizational goals and objectives? | How well do our mission/business processes align with our organization’s risk management strategy? | Are our information systems properly operating within the risk tolerance of our organization’s mission/business processes? |
How well aligned is our risk management strategy with our mission and business programs? | How well does my mission program align with our organization’s risk management strategy? | Is the risk posture of this system within established boundaries to support this mission? |
Is our common control strategy effective? | Which common controls are cost effective? | How fully am I using the common controls available to me? |
Example questions by Tier
Now that the questions to be answered have been identified, the next step is to identify the assets, processes, or operations that can be measured to obtain answers to those questions. For example, to determine the effectiveness of an organization’s common control strategy, you could examine:
The common controls called for in the common controls strategy/policy;
Their alignment with current organizational goals and objectives; and
Their utilization.
An example analysis of Tier 1 risk monitoring activities, their components, and their subcomponents is provided in Figure 3. The common controls assets are presented as Characteristicn in the right hand branch of the figure. These characteristics and subcharacteristics will also be referred to as diagnostic areas, where diagnostic area 1 (da1) is equivalent to characteristic1; da2 is equivalent to characteristic2; and so forth. The subcharacteristics for each area follow a similar numbering scheme where, for example, subcharacteristic11 is equivalent to da11 and so forth. This is done to simplify the abbreviations used in the equations in Steps 6 and 7.
It is important to remember that the identification of organizational assets, processes, and operations are organization-specific. This is one of the strengths of the IA OM® process, since it enables the abstraction of these key activities – specifically identified by the organization as being of interest – into a metric that shows Senior Management where their organization stands with respect to its risk management strategy and policies. If low level technical metrics exist, they can be combined and abstracted into the IA OM® process. Metrics produced through the use of the IA OM® process can be deconstructed into their component areas, allowing Senior Management to identify the areas needing attention. If further improvement in their risk management program is required, the IA OM® and its component measures can be used to track and improve the organization’s risk posture over time.
Example analysis of risk monitoring activities and their subcomponents
Activity value scales used for IA OM® activities are normally scoped to range between 0 and 1. This makes comparison easy and allows them to be aggregated and rolled-up into measures that are easy to use and understand. Also, these values can be readily seen as percentages to further enhance their understanding. However it is perfectly acceptable to have more important characteristics have values greater than 1 if desired to indicate their relative importance to the organization. Alternatively, the relative importance of different characteristics/subcharacteristics can be accounted for using the weighting factors discussed in Steps 6 and 7.
For activities that can only assume a specific set of values (e.g., Yes/No, or high, moderate, and low), the value scales can be adapted to accommodate them. For example, with a binary set, like Yes and No, it is common to use Yes = 1, and No = 0. Sets like high, moderate, and low could be represented with high = 1, moderate = 0.5, and low = 0. It would also be possible to decide that high = 0.9 (since even high is not definite like “yes”), moderate = 0.5, and low = 0.1 (since low is also not definite like “no”). The decision on value scales is made by the organization and is made to maximize the utility and understandability of the measurements in the context of their organization.
Continuing with the example of the effectiveness of an organization’s common controls strategy, value scales for each of the three subcomponents can be defined, and values determined for each of the subcharacteristics assigned as shown in Figure 4. Each subcharacteristic/diagnostic area (daij) will be evaluated separately and then combined in Step 6 to provide an overall value for each characteristic or top-level diagnostic area (dai). These values are then combined in Step 7 to provide an overall IA OM Index Value.
Common Control Value Scales Example
Steps 3 through 5 have shown how to derive values for each of the assets, processes, and operations identified in Step 2. Each of these values represents a characteristic or subcharacteristic for an asset, process or operation. In this step, any values for subcharacteristics (daij) will be combined with weighting factors and aggregated to provide values for each characteristic (dai).
The weighting factor value (wij) for each subcharacteristic (daij) is assigned by organizational management to represent the organization’s determination of the relative importance of each subcharacteristic to the characteristic being evaluated.
Equation 1 – Calculating diagnostic area (characteristic) values:
Where:
wij = weighting factor for diagnostic daij of diagnostic area
max [
For the common control example, using organizationally determined weightings and subcharacteristics/diagnostic areas values provided in Table 2:
Weightings | Subcharacteristics/diagnostic areas |
w31 = 1 | da31 = 0.42 |
w32 = 1 | da32 = 0.94 |
w33 = 2 | da33 = 0.61 |
Weightings and Subcharacteristics Values
The equation works out to:
Thus:
Characteristic3 =
Inserting values for the other characteristics, and arranging all of the values into a fishbone diagram for clarity of presentation provides breakdown of the process as shown in Figure 5.
Calculating an IA OM® index provides a concise, high-level assessment of the enterprise risk management posture of the organization. The IA OM index, in this case referred to as the IA risk management index, or IARMIndex, is defined in terms of:
Diagnostic areas
Diagnostic criteria for each diagnostic area
Diagnostic criterion value scales
Fishbone Diagram with All Risk Monitoring Characteristics and Subcharacteristics Values
All of these items are provided in the fishbone diagram provided as Figure 5. A weighting factor can be applied to each characteristic/diagnostic area. As noted above, the weighting factor is an organizationally defined value indicating the relative importance to the organization of the particular characteristic. In this example the IARMIndex is normalized to one (i.e., ranges between zero and one). In all cases, value scales are defined in terms familiar to corporate management.
The process for calculating the IARMIndex is shown in Equation 2. For activity element characteristics, the IARMIndex Taken and adapted from Donaldson & Siegel [22] (p. 420).
Equation 2 – Calculating the IARMIndex value:
Where:
max [
Using the values from above and the organizationally defined weightings as shown in Table 3:
Weightings | Characteristics/ diagnostic areas |
w1 = 2 | da1 = 0.25 |
w2 = 1 | da2 = 0.25 |
w3 = 1 | da3 = 0.65 |
Weightings and Characteristics Values
Results in a value for IARMIndex = 0.35
The following steps describe the analysis process allowing organizational management to quickly uncover areas needing attention and prioritize which area(s) to address first to obtain the greatest benefit:
The IARMIndex value is examined to determine whether it is within the range determined by the organization to correspond to its risk tolerance;
If the IARMIndex value is within the risk tolerance of the organization, the current values are included in the trending information and no further action is required until the next review cycle is initiated.
If the IARMIndex value is not within the risk tolerance of the organization:
The individual component index values that were aggregated to derive the IARMIndex value are examined and the value(s) furthest from the normalized value of 1.0 (the values closest to 0) is singled out for further analysis;
The selected component index value(s) is then unfolded (if applicable) to find the subcomponent(s) with the lowest value(s);
The component(s)/subcomponent(s) with the lowest value(s) is analyzed and a method for improving it is identified and implemented;
At management’s discretion, reassess and recalculate the characteristic(s) (and any applicable subcharacteristic(s)) value(s) for the component(s) that was addressed and update the IARMIndex value to assess the impact of the changes made.
By looking at trends in the IARMIndex values, and the component index values compiled over time, the organization may determine the overall improvement resulting from addressing these components.
By looking at the IA OM® mapping and measurement trends in the component values, leadership or management can see which areas have had the greatest improvement, and which areas are most in need of attention.
Continuing with the example from above, the IARMIndex value = 0.35. Assuming the organization has determined that any value under 0.70 is outside of its risk tolerance, the next step is to determine which component(s) to single out for further analysis. Using the values in Table 4, we find that characteristics da1 and da2 have the lowest values. However, if we also consider the weightings we see that w1 = 1.0 indicates that it is a higher priority item to the organization than w2, suggesting that if we cannot address both areas, priority should be given to characteristic1, reviewing and updating the organization’s risk management strategy.
Component Values and Their Weightings
The need to initially assess, and then conduct ongoing monitoring of an organization’s overall risk posture, the risk posture of its assets, processes, and systems has been clearly established. The more valuable the information, asset, activity, or operation, the greater the need to increase the frequency of monitoring activities to ensure these resources are not compromised, or to identify and respond to any compromises as quickly as possible. This chapter shows how the IA OM® metric herein described provides an enterprise-wide risk management metric that can integrate synergistically with other risk management tools and efforts within an organization to provide monitoring personnel and decision-makers with the timely, accurate, and useful information they need to perform their functions and ensure their organization’s mission and business functions are protected. IA OM® not only provides a metric targeted to organizational senior management, but one that can be used by decision-makers at all levels in the organization to ensure the processes and assets they are responsible for are protected in a way that aligns with the risk management strategy of the organization.
David R. Comings, Ph.D., CISSP, CRISC,
Wendy W. Ting, Ph.D., CISSP, CISM,
The human immune system has two major divisions: innate and acquired. We will talk about innate immunity. Innate immunity can be defined as the first line of defense against pathogens, which represents a great machinery to create an adequate and definitive systemic response to prevent infections and maintain homeostasis of the organism. The elements of innate immunity include external physical barriers, humoral and cellular effector mechanisms. This type of immunity recognizes pathogens such as bacteria and viruses. This works thanks to the phagocytosis of the pathogens with the consequent induction of inflammatory reactions. It also has a critical role in the activation and regulation of adaptive immunity. This immunity has the ability to develop an induced response during primoinfection. This response is specific due to the expression of cell surface pattern recognition (PRR) receptors, which are capable of recognizing complex polysaccharides, glycolipids, lipoproteins, and nucleic acids. We know that pathogens contain in their structure various components that act as substances strange (antigens) and this in turn will induce an innate immune response that will subsequently activate the adaptive response. It is imperative to recognize that the important exploration of these innate mechanisms is essential for the understanding of the complex events involved in human innate immunity and is also crucial for the discovery of new antimicrobials, antitumor drugs, and immunomodulators with therapeutic applications [1]. Innate immunity, which is considered a simple immune system, is essential for the onset of acquired immunity and has been found to play an important role in the pathogenesis of the disease age [2]. Among them, it recognizes nucleic acids derived from pathogens. The innate immune pattern recognition (PRR) receptor recognizes self-derived nucleic acids. Innate pattern recognition receptors regulate antigens for the presentation and subsequent responses of B cells and T cells, for example, physiological management of autoantigens, induction of immature dendritic cells to detect tolerant signals to T cells. The activation of toll-like receptors (TLR), NOD type receptors (NLR) or Helicases similar to RIG (RLH) by molecular agents associated with pathogens where the patterns will induce dendritic cell maturation, costimulation.
\nT cell activation and production of antibodies by B cells. Therefore, recognition of innate patterns is now being considered as a central element of immunity modulation. There are at least 80 different autoimmune diseases discovered so far, which in the US alone, affect 20 million people [3]. These pathologies are established systemically or in a specific organ, but require for their expression certain conditions that are the result of multifactorial processes that involve a deregulation of the innate immune system and therefore adaptive that lead the body to erroneous responses with the subsequent attack itself of their own tissues. The innate immune system as discussed above is the first line of immediate defense against invading microorganisms that links to the adaptive response. Specific cells of the innate immune system, which are dendritic cells (DC) (antigen presenting), which are cells with an important and critical role in promoting the responses of B and T cells. This type of immunity is critical to maintain homeostasis and prevent microbial invasion, eliminating a wide variety of pathogens and contributing to the activation of the adaptive immune response.
\nIt is the control point. A dendritic type receptor that bears the title of “access gate” for innate cellular immunity: this basically consists of a type of toll-like receptor. It has been found that it plays a fundamental role as a sensor in the recognition of pathogens in the innate immune system [4].
\nThis pattern recognition receptor acts on bacteria and viruses (PAMP) [5]. The innate immune response in immunological terms controls the infection and prevents its spread. And more recently it is known that to induce this series of reactions against pathogens, in addition to the existence of antigens, another series of molecules in the pathogens is required. These molecules are known as pathogen-associated molecular patterns (PAMPs). PAMPs play and interact with a series of receptors that are mainly present in phagocytic cells (macrophages), and these “gate” receptors have been called recognition patterns to pathogen-associated molecular patterns (PRRs). These receptors contain other subfamilies where we can find toll type receptors (TLRs), NOD type receptors (NLRs), RIG-1 type receptors (RLRs), and lectin C type (CLRs). This molecular pattern related to the associated damage known as DAMP comes to behave as a type of alert that recognizes signals and most importantly this does not involve pathogen detection. The main molecular recognition patterns (PRRs) include TLR and NLR receptors, also known as nucleotide binding oligomerization domains. TLR is the homologous receptor that has already been identified in the Drosophila genetic code, and that to date some TLRs have been found in humans mainly in the cell surface, membrane, and lipids [6]. Types 1, 2, 4, 5, and 6 are those that recognize proteins, nucleic acids located in the endoplasmic reticulum and those that are found in the endosomal membranes. 3, 7, 8, and 9 detect lipopolysaccharides in the outer membrane of gram-negative bacteria (endotoxins). The TLR4 type, which transmits inflammatory signals, is the best known in general and the most studied of the TLR. This receptor responds to MyD88, which becomes a station at the central point of the inflammation signal, and corresponds to the first phase of activation of the transcription factor NF-κB pathway (nuclear factor-kappa B), which a In turn, production begins and a kind of “chain reaction” of inflammatory cytokines to eliminate pathogens [7]. Meanwhile, these TLR receptors are incorporated into PAMPs, which by recognizing nucleic acids act as an inflammatory cytokine. Receptors that mediate innate immune responses, such as toll-like receptors (TLR) and specific C-type lectin receptors (CLR) that recognize associated molecular patterns (PAMP), have been implicated in autoimmune disease mechanisms, both directly through self-recognition ligands and indirectly through the regulation of immune homeostasis [8, 9].
\nIn intracellular infections, in addition to antigens and PAMPs, the participation of another series of molecules that participate in the activation of the immune response is necessary. Recently, some studies have shown that cells can die from a type of immunogenic “apoptosis” and thus expose their nuclear or cytoplasmic molecules to their membrane. These have a way of stimulating the immune response, thanks to their activity. They are also released during the process of necrosis and have been given the name of molecular patterns associated with damage or warning signs, the famous DAMPs. The NLR receptor is present in the cytoplasm. It has the particularity of recognizing not only PAMP but also several DAMP among them [uric acid, cholesterol, sterols crystals, extracellular ATP (adenosine triphosphate), silica] or even recognizing exogenous DAMP such as asbestos, origin of aseptic inflammation, such as gout, arteriosclerosis, and silicosis [10]. It is clear that it is a cause and attracts attention. The abnormalities in the immune system that are the basis and fertilizer for autoimmune diseases are mainly caused by an abnormal acquired immunity [11]. In recent years, in contrast to the concept that autoimmune or auto-inflammatory diseases are mainly due to abnormal innate immunity, it is attracting more attention.
\nDendritic cells, macrophages, and other myeloid cells also play an important role in the innate immune response, both as antigen presenting cells as effector cells that mediate the tissue damage [12, 13, 14]. Therefore, they are fundamental and will be as in conflicts, “the first line of defense” in the face of a bacterial or other stimulus. We will also take them into account in relation to autoimmune diseases, because of their responsiveness and because they are important mediators of innate immunity, an interest has arisen in this potential to contribute to the pathology of these diseases. Proinflammatory cytokines: mainly TNFa (tumor necrosis factor alpha), induce the activation of endothelial cells, resulting in an increase in the expression of different adhesion molecules (CD62E, CD62P, ICAM-1, and VCAM-1). This causes the leukocytes to roll over them, and during this bearing, they are activated by the intracellular signals that are generated through their adhesion molecules and different chemokine receptors, which interact with the ligands found on the surface of the cells endothelial. Subsequently, these activated leukocytes adhere firmly to the endothelium, change their morphology (cell polarization) and carry out their transendothelial migration, and then migrate to the inflammatory focus, guided by the gradient of chemotactic substances that are released. Macrophages are multifunctional antigen presenting cells, with an important role in innate immunity and, therefore, in the inflammation process [15]. Macrophages are found in almost all organs, and recent studies have demonstrated their multifunctionality and heterogeneous capacities established by their numerous subpopulations, adaptation in specific tissue microenvironments and different stages of maturation. For example, during a bacterial infection, classically activated macrophages show inflammatory functions (type 1 or M1 macrophages), while with alternative activation (by Th2 type cytokines, such as IL-4 or IL-13), macrophages acquire anti-inflammatory functions (type 2 macrophages or M2). In addition to depletion or inhibition of macrophage function, reprogramming of M2 has also been explored. Recently, it has been shown that paracoccin, a protein contained in a fungal human pathogen, induces the repolarization of M1 macrophages through interaction with toll as a receptor (TLR) 4, being a new possible immunotherapeutic agent for pathologies related to M2 macrophages. Macrophage-related therapies have been proposed for various autoimmune and inflammatory pathologies. In the case of PPARγ and PPARδ, which are nuclear receptors that control different genes associated with M2 macrophages, and their agonists have been proposed as a therapy directed at macrophages to induce M2 pathways. In addition, the demonstration that TLR9 receptor signaling can reverse the aberrant M2 macrophage phenotype.
\nDendritic cells (DC) are professional antigen presenting cells (APC), often referred to as “orchestra directors of the innate immune response” due to their ability to capture, process, and present antigens to T cells. Depending on the nature of the antigen may exhibit an immunogenic or tolerogenic effect, which will be defined by cytokine secretion. They are often considered tolerogenic, because they have autoantigens in the absence of costimulation and, together with anti-inflammatory stimuli, (TGF-β), can promote the induction of regulatory T cells and/or induce anergy of T cells [16]. After activation by proinflammatory stimuli, they mature and generate an expression of costimulatory molecules and the major histocompatibility complex (HCM) class II, which causes a potent response of specific T cells to the antigens. Therefore, they play a fundamental role in maintaining self-tolerance, and on the other hand, they initiate the response against foreign antigens for their subsequent elimination by effector immune cells. In a state of aberrant hyperreactivity, they could contribute to perpetuating immune responses, backed by evidence of a high frequency of immunogenic infiltration [17]. Due to their ability to modulate the cellular response, they have been considered a powerful target for immune modulation. Strategies such as pharmacological modulation to affect their maturation status and genetic engineering to improve their tolerance or immunogenic properties for the treatment of autoimmune diseases have been studied. In several murine models, they were transduced to express IL-4 and were able to prevent disease in 12-week NOD mice. In a murine model of collagen-induced arthritis (CIA), it was shown that the injection of dendritic cells with tolerogenic activity improves the clinical and the outcome of the disease. Although the treatment was found to be safe and feasible, other studies are needed to evaluate the efficacy of cellular treatment in autoimmunity.
\nThey are a growing family of immune cells that reflect the phenotypes and functions of T cells. Natural killer cells (NK) can be considered innate homologs of cytotoxic CD8 + T cells, while ILC1, ILC2, and ILC3 correspond to innate homologs of T cells CD4 + (TH1), TH2, and TH17. However, in contrast to T cells, they do not express antigen receptors or undergo clonal selection and expansion when stimulated [4]. The ILCs react and respond to the signs of tissue damage and produce a series of cytokines, which direct the immune response and this adapts to contain the lesion. Therefore, these cells can control or unleash the immune response. As with B cells and T cells, these also originate from the common lymphoid lineage but the specific transcription factors of these suppress and modify their development until the generation of the different types of ILC. The precursors of these can migrate from their primary production site in infected and injured tissues, where they complete their maturation, in a process very similar to the differentiation of virgin T cells into TH effectors. The cytokines produced by local cells, as well as some trauma and stress response ligands as well as bacterial and dietary compounds regulate the maturation and activation of ILC in effectors that play an important role in early immune responses to pathogens in particular has been found relationship with symbionts, helminths, and allergens. The cytokines they produce induce innate responses in stromal, epithelial, and myeloid cells that in turn will regulate the activity of dendritic cells and will also play a central role in the transfer of information between ILC and T cells. ILCs by activating DC found in tissues to migrate to the lymph nodes, where they cause specific T-type cellular responses. ILCs also regulate T cells directly through the presentation of peptide antigens through CMH type II. However, ILCs are also involved in autoimmunity, because their cytokine production can exacerbate and exaggerate the inflammatory process.
\nRecent research has revealed new knowledge about the respective roles of these cells in relation to cellular and humoral immunity as well as the extension to adaptive immunity [18]. There is talk of a recent study in which a genetically modified mouse prototype model was developed with an autoimmune disease similar to lupus that does not require to express the adaptive immune system machinery, but is triggered directly by the innate immune response [19]. For many autoimmune diseases, we largely know the roles that key cells (T cells and B cells) play and for example are evident in the success of existing therapies (anti-CD3 and anti-CD20). Then knowing this, each of the functions of myeloid cells, and in general of the innate immune response cells, can “autoimmune” disease occur in the absence of adaptive immunity and these cells act as effectors in disease progression? The answer to this could be yes [20]. The most recent example is the study of mice eaten by moths that have been genetically modified to have deficiencies in hematopoietic cells, and to express an autoimmune disease characterized by alopecia (giving a “peeled or eaten by moths”) and edema in their legs. These were also accompanied by high antibody titers, with renal and pulmonary functions being compromised due to immune complex deposits [21, 22]. However, in another study, mice with deficiency in hematopoietic cell phosphatase were crossed with mice that lack the recombinase-1 activator gene (RAG-1) that caused a subsequent deficiency in the production of T and B cells and found that the disease autoimmune had progressed normally in the absence of an adaptive immune response [22, 23] even though these mice lacked high antibody titers and immune complex deposits, and they exhibited all other symptoms of the disease. Subsequently, although the onset and progression of the disease could not be defined, it was concluded that the autoimmune disease of this type of mice was mediated by an aggressive response of macrophages and other myeloid cells. Now, a study with murine models is also described, with mice with a genetic alteration associated with the deficiency in the enzyme α-mannosidase type II (αM-II) where there is premature aging with the clinical expression and the characteristic symptoms of SLE and Lupus nephritis (high titers of anti-DNA antibodies, glomerulonephritis, and renal compromise due to deposition of immunoglobulins in the kidney) that seems to be driven by a mechanism that also seems to involve the innate immune system [12, 24, 25]. In the case of the murine model, evidence was provided that the abnormal presence of hybrid glycoprotein structures acts as a trigger for the induction of an innate immune response mediated by members of the C-type lectin family that is specific for mannose. Serum mannose-binding lectins (MBL-A and MBL-B) are soluble lectins that mediate innate immunity to pathogenic bacteria and fungi that express glucans (mannose). It is also believed that the macrophage of the mannose receptor cell surface (MMR) participates in innate immune responses, and its expression has been documented in mesangial renal cells [26, 27]. In mice with αM-II deficiency, MBL lectins are deposited in renal glomeruli which, when they express high levels of mannose glucans in mesangial cells, also express higher levels of MMR, which can bind mannose ligands in the serum. Monocyte chemoattractant protein 1 (MCP-1) levels, produced by activated mesangial cells, represent the entry of activated macrophages. By aberrantly expressing mannose-containing glucans in mice with αMII deficiency, they act as triggers for an innate immune response mediated by mannose-specific C-type lectins programmed to recognize mannose glucans as PAMP.
\nThe second point in importance is the role of antibodies in stimulating the innate immune response. How can this be to the production of autoantibodies in autoimmune diseases, such as our old friend, lupus? Systemic lupus erythematosus (SLE) is an autoimmune disease that translates inflammation and exaggerated immune responses and thus with a large generalized associated tissue damage. We are clear that innate immunity plays a great role in its development and sequentially its clinical expression, and it has been shown that defects found in any of the immune recognition pathways will promote autoimmunity. First, dendritic cells and macrophages activated by TLR receptors can regulate the differentiation of self-reactive B cells through the expression of CD40 and the action of IL-6. Second, by nucleic acids. These can activate and in a powerful and disorderly way certain TLR and RLH receptors; therefore, these are normally protected from immune recognition by multiple mechanisms (epigenetic modifications, nuclear compartmentalization, and the rapid elimination of cells that have entered apoptosis and extracellular compartments by a type of DNase and RNAse enzymes). These immune complexes containing chromatin or circulating RNA particles can avoid being “digested” by these enzymes in the extracellular space and facilitate the uptake of the complex in intracellular compartments through Fc receptor-mediated endocytosis (FcR) in dendritic cell-mediated uptake or by B cell receptor (BCR) in B cells. And it has also been confirmed by studies with lupus-prone mice deficient in TLR receptors and their respective signaling molecules. As an exception, mice with TLR-9 deficiency with a predisposition to lupus produce more autoantibodies against it, indicating that TLR-9s have additional functions in the regulation of systemic autoimmunity. Innate pattern recognition (PRR) receptors regulate the production of autoantibodies associated with lupus and self-reactive T cells by modulating the presentation of autoantigens and also contribute directly to the end result that is tissue or organ injury secondary to autoimmunity. In general, it is believed that this “injury” or tissue damage is generated from the deposition of the immune complex, complement activation, and subsequent release of cytokines and chemokines to trigger local inflammation. This concept has been redefined. For example in glomerulonephritis, in the glomerular immune complex, deposits are not always associated with innate and adaptive immune responses. These are traditionally seen as separated from each other, but emerging evidence suggests that they overlap and interact with each other. Recently discovered cell types, particularly innate lymphoid cells and myeloid cell-derived suppressors that are gaining increasing attention. It is a rapidly evolving field with molecular pathways and new types of discovered cells and multiple constantly changing paradigms. In general, it is believed that many autoimmune diseases are triggered by aggressive responses of adaptive immunity by an automatic antigen system, resulting in tissue damage and pathological sequelae.
\nThe third point is undoubtedly the role of infectious agents, which have the potential to trigger an exaggerated immune response, through molecular imitation, polyclonal activation or antigen release. For example, there are certain diseases that respond to certain infectious autoantigen peptides. This is the case of multiple sclerosis, where T cells are activated by Epstein-Barr virus peptides, type A flu, and human papilloma and that react with the myelin autoantigen peptide [28]. In this case, the viral infection could cause the activation of the lymphocytes, and the autoantigen could maintain this activation, even after the eradication of the infectious agent. Microbial infection can also cause polyclonal activation of lymphocytes, and this is the underlying mechanism in increasing the incidence of autoimmunity in murine models exposed to microbial pathogens [29]. Microbes (viruses or bacteria) that destroy cells also cause an inflammatory response and also the release of antigens that have been previously captured and this could also result in autoimmunity. There is another important point. Inflammation, even in the absence of infection, can trigger polyclonal activation and self-activity. This is that through the activation of annergic cells, by inflammatory mediators or the activation of new self-reactive cells in an inflammatory environment for example in the context of ischemia of any tissue, tissue autoreactivity could be caused and because not at a systematic level [3]. Within non-infectious detonators, we have those of the hormonal type that in many autoimmune diseases are more common in women than in men. Drugs can also alter the immune repertoire. One of the most common and studied procainamide induces antinuclear antibodies and sometimes induces a lupus-like syndrome. And even some substances produced by the same cells can act as haptens and make autoantigens immunogenic, for example, CD1 T cells, with receptors (gamma/delta), CD4+, CD25+, and cytokine-producing agents that monitor activity, reduce, and control self-reactive cells, and they can become pathogenic. As some must complete their maturation in the thymus, and others the activation of autoantigens in the periphery, in these processes alterations in the number and function of regulatory cells that can contribute to autoimmunization can be generated.
\nUpon contact with the stimulus, whether microbial or of any substance, the recruitment and activation of macrophages will begin. The macrophages will serve as the primary effector cells that cause tissue damage and loss. And it has been concluded that the vast majority of autoimmune diseases could be explained by an aberrant adaptation as an immune response to the antigens themselves. On the other hand, autoimmunity as a disease contrasts with innate immunity. The first in which the term autoinflammatory was used was the periodic fever syndrome related to the TNF receptor (tumor necrosis factor), whose causative gene is TRAPS 4 and which was directly related to the presence of genetic abnormalities associated with innate immunity autoinflammatory diseases that are generally considered as a group of diseases where we can find an active responsibility for aberrant innate immunity and in which T cells are not detected and include TRAPS, cryopyrine-associated syndrome (secondary to mutations in the NLRP3 gene in children) (CAPS), Familial Mediterranean Fever (FMF), Bechet’s disease, Still’s disease in adults, Crohn’s disease, Gout, Type 2 diabetes, and various metabolic disorders [30]. The mechanism of its many initiation is still unclear, but the symptoms and diseases themselves are caused by the collapse of immune tolerance. Thymus autoreactivity and subsequent and completely abnormal inactivation of receptive and regulatory (Th) T cells suppress the reaction to the foreign antigen. The other part of the aberrant response of the innate immune response is carried out in the recipients of recognition of autoimmune patterns and diseases recognized by nucleic acids (PRR). This recognition is transmembrane due to its location in the cell and is divided into two general and cytoplasmic phases. This receptor is found in the endoplasmic reticulum or endosome and is directly related to autoimmune diseases (SLE = TLR7/9). When comparing the sequence of own nucleic acids and pathogen derivatives by means of the TLR7/9TLR9 receptors, it is noted that it contains unmethylated CpG sequences, and these are derived from pathogens that in turn recognize a type of single stranded DNA. TLR7 on the other hand recognizes single stranded RNA derived from viruses and other types, as well as messenger RNA (mRNA). From this, TLR7/9 is self-sufficient, and this receptor can strictly distinguish between conventional nucleic acids and pathogen derivatives. Stimulates an immune response in response to auto-nucleic acid. In other words, viruses and infected cells are captured by endosomes, and these nucleic acids are recognized by TLR7/9. In the case of SLE, the TLR7/9 receptor, due to the genetic modification secondary to the aberrant response to the own nucleic acids that were released and transferred to the endosome and therefore increases the genetic expression of the type I IFN and is known as the “IFN signature.” This signature of IFN is directly related to SLE, rheumatoid arthritis (RA), and systemic sclerosis (SSc) and its effects, suggesting the importance of type I IFN in autoimmune disease [31]. It also activates and stimulates plasma cells that in turn produce large amounts of type I IFN.
\nThe TLR7/9 receptor also mediates the response of plasmacytoid cells and is considered an IFN type I producing cell, which through the TLR7/9 Fc receptor activates the signal to induce the production of non-protein IFN type I histone in the core (HMGB1), to subsequently activate DAMP. The balance between TLR7 and TLR9 is also considered important for inflammation and immune response. The other transmembrane PRR receptors TLR3 and TLR8 also recognize double stranded and single stranded RNA. On the other hand, the cytoplasmic PRR receptor, type RIG-I, and MDA-5 normally identifies a specific structure of single stranded RNA. By recognizing double-stranded RNA, the specific proteins of these DAI, IFI16, and DDX41 receptors induce the production of IFN and inflamasome and, in turn, the production of IL-1β and IL-18.
\n“The authors declare no conflict of interest.”
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',metaTitle:"Horizon 2020 Compliance",metaDescription:"General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed. ",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
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\n\nMetadata for all publications is also automatically deposited in IntechOpen's OAI repository, making them available through the Open Access Infrastructure for Research in Europe's (OpenAIRE) search interface further establishing our compliance.
\n\nIn other words, publishing with IntechOpen guarantees compliance.
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I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. 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After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). 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I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). 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