Natural History of Immunity (Phylogeny)
The phylogenetic development of the immune system is inextricably linked with a major evolutionary leap: the emergence of multicellular organisms, or Metazoa.
The appearance of the first autonomous organisms required the creation of their own internal environment, reliably separated by a barrier from the external environment. This separation became critically important because the external surroundings are a priori hostile to the organism and serve as a constant source of aggression and fierce competition.
The evolution of defense mechanisms was a response to various types of biological aggression:
- Penetration of foreign unicellular organisms into the isolated internal environment.
- Continuous competition for living space and food resources.
- Active damage to own cells by external agents.
- Intoxication of the organism by foreign toxins and metabolic products (metabolites).
Under these harsh conditions, the precursor of the immune system arose as a vital internal «service». Its main task became the maintenance of cellular and molecular constancy (homeostasis) within the isolated community of cells of the multicellular organism.
Basic Conditions for the Formation of Immunity
For immunity to form as a fully functional defense system, two fundamental conditions historically had to be met simultaneously.
- Territorial condition. It consists in the presence of a strictly defined, «guarded», and enclosed territory. This territory must necessarily be demarcated from the aggressive external environment by robust barriers.
- Functional condition. It implies the appearance of specialized factors and mechanisms capable of ensuring the constancy of this internal environment. Their work boils down to the active cleansing of the organism from any penetrating foreign agents.
It is within the functional condition that the original, historical meaning of the very term «immunity» lies, which was initially interpreted as exemption or deliverance from something foreign.
Immunology as an Independent Science
Modern immunology is extremely closely tied to molecular biology. Nevertheless, it firmly retains the status of an absolute independent scientific discipline. This is due to the fact that immunology possesses its own completely unique object of study.
The object of research in immunology is the specific interactions occurring between antigens and their receptors.
It is these interactions that form the fundamental principle of the science: they underlie the subtlest discrimination and infallible recognition of any structures based on the core «self–nonself» principle.
Modern Concepts and Development Vectors
In the 21st century, immunology continues to develop rapidly, leading to the revision of many established dogmas. For instance, an important revision of terminology took place: cells previously known as suppressor T cells were rediscovered at a new methodological level and are currently classified exclusively as regulatory T lymphocytes.
The major theoretical generalization that defined the entire vector of development of modern immunology was the doctrine of Charles Janeway. His concept deeply reveals the nature of recognition in innate immunity and the strict hierarchy of immune system interactions.
Janeway's doctrine relies on two key postulates:
- Specificity of innate immunity. Janeway discovered a completely new type of immunological recognition. This discovery completely refuted previously existing notions that innate immunity is entirely nonspecific.
- Hierarchy of activation. The fundamental impossibility of triggering adaptive (acquired) immunity mechanisms without prior activation of the innate immune systems was scientifically substantiated.
Briefly: answers to topical questions
What are the main differences between innate and adaptive immunity according to Janeway's doctrine?
The main differences between innate and adaptive immunity according to Ch. Janeway lie in the features of recognition and the hierarchy of activation.
| Characteristic | Innate immunity | Adaptive immunity |
|---|---|---|
| Recognition specificity | Innate immunity is capable of specific recognition of pathogen-associated molecular patterns, which refutes the notion of its absolute non-specificity | Adaptive immunity performs individualized recognition of antigens |
| Activation hierarchy | Prior activation of innate immunity is necessary to trigger adaptive immunity | Cannot be triggered without prior activation of innate immunity |
What are the main stages and cells involved in the activation of adaptive immunity by the innate immune system?
The activation of adaptive immunity by the innate immune system is based on antigen presentation and costimulation processes.
Main steps:
- Antigen processing — stimulated under the action of interferon gamma.
- Antigen presentation — the initiating event of the adaptive immune response.
- Costimulation — a process critically necessary to initiate the adaptive response.
Cells involved in activation:
- Dendritic cells — act as antigen-presenting cells (APCs), expressing MHC-I and MHC-II molecules.
- Macrophages — also function as APCs for efficient antigen presentation.
What are the mechanisms for maintaining cellular and molecular constancy (homeostasis) of the internal environment in multicellular organisms?
The maintenance of cellular and molecular constancy of the internal environment is ensured by immune mechanisms that maintain homeostasis.
The main mechanisms include:
- Removal of foreign molecules — cleansing the internal environment of foreign agents to maintain the constancy of the macromolecular composition.
- «Self–nonself» recognition — a mechanism that allows defense cells to distinguish foreign cells and molecules from their own.
- Phagocytosis — a mechanism for eliminating potentially aggressive cells from the organism's internal environment.
- Regulation by the metasympathetic division of the ANS — participation in mechanisms ensuring relative dynamic constancy of the internal environment and stability of basic physiological functions.
The two historical conditions for the emergence of immunity are easy to remember via the «Border and Customs» association: The territorial condition is the state border separating the country from the outside world, while the functional condition is the customs service clearing the internal territory of unwanted elements.
Class and exam questions
What is the revolutionary nature of Charles Janeway's doctrine?
He proved that innate immunity has its own recognition specificity, and established that without its activation, it is impossible to trigger adaptive (acquired) immunity.
What are former "suppressor T cells" called in modern immunology?
Following rediscovery and terminology revision, they are currently classified as regulatory T lymphocytes.
What evolutionary prerequisites led to the emergence of immunity?
The emergence of multicellular organisms (Metazoa) with an isolated internal environment that required protection from a hostile external environment, penetrating unicellular organisms, competition, and toxins.
What else to study on this topic
- Mechanisms of specific recognition in innate immunity (according to Ch. Janeway)
- Hierarchy of activation: how innate immunity triggers adaptive immunity
- Functions and biological role of regulatory T lymphocytes
- Structural basis of antigen-receptor interactions
- Evolution of defense barriers in Metazoa
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