Intro - Acquired/Specific Immunity, Theories of Ab Formation, Generation of Diversity Flashcards
What is Acquired Immunity?
It is also known as “Adaptive” or “Specific” immunity. It is characterized by a more rapid, stronger memory/secondary response (anamnestic).
(First exposure is usually slow. Second exposure is faster and stronger - the logic of vaccination.)
How is the response Specific?
Immune response must be able to detect subtle differences in proteins, carbs, and lipids.
- It must distinguish between self vs. non-self.
- It must distinguish between different forms of non-self (immune response to influenza virus will offer no protection against diphtheria). **Problem of specificity.
What is an Antigen?
The molecule or structure against which the immune response is directed.
The Antigen is defined as “non-self.”
Because the immune system evolved to protect us from invasion by other biological forms, the immune response only sees bio-organic Antigens (molecules based on C, and the atoms that form chemical bonds with C: H,O,N,P,S. It ignores sand or minerals or chemicals based on other atoms. It essentially detects molecules encoded or controlled by genes.
How does Antigenic diversity pose a problem to the immune system?
Antigenic universe is enormous - there are enormous numbers of different microbes.
However, the response is kept finite by the size of an antigenic determinant.
Additionally, bacteria replicate at a much faster rate than humans. Mutation frequencies are much higher and antigenic drift exceed the ability of human genes to mutate. Genetic changes made by the microbe are random and cannot be predicted by the vertebrate host. Thus, the antigenic universe is also constantly changing.
What are B and T cells?
They are cells that bear receptors to distinguish self from non-self.
Their function is to bind Antigen (like enzyme binds substrate), which leads to removal of the Antigen.
The particular configuration of CHONPS is the Antigenic determinant.
What is a B cell receptor?
B cell receptor: Antibody molecule (immunoglobulin). Activates B cells. Found on cell surface or in secreted forms. Antibodies can circulate throughout the body. These receptors/cells help remove Antigen from the body by binding to it and precipitating it, thereby destroying it.
What is a T cell receptor (TCR)?
TCRs have a completely different structure from Ab.
TCRs are only found on T cell surface; they are never secreted.
TCRs do not travel through the body like Ab; must be at site of infection.
They bind Ag on the surface of other cells, and must bind its Ag in a specific context - it must see it on the surface of a cell.
What is Robert Koch’s contribution to the theory of Antibody formation?
He discovered Antibody responses:
- He injected animals with bacteria/toxins.
- A transferable substance in the blood protected other animals against subsequent challenge.
What are the theories of Antibody formation?
- Instructional
- Selective
- Side Chain Theory
What is the Instructional Theory of Antibody formation?
The Antigen plays a central role in determining the specificity of the Antibody molecule.
Ex: Plastic clay rolls around Antigen.
BUT: Does not explain lack of reactivity to self nor secondary response.
What is the Selective Theory of Antibody formation?
The Antigen selectively reacts with a pre-made Antibody.
This theory appears to explain acquired immune responses.
BUT: Disproved by Karl Landsteiner, who made synthetic organic molecules and found that even these induced Ab responses.
What is the Side-Chain Theory of Antibody formation?
Formulated by Paul Ehrlich in 1900.
Antigen binds to side-chain receptors (Antibody), which results in the release of the receptor (gets secreted, like Antibody).
It induces production and release of more side-chain receptors (Antibodies) of same specificity.
Distinguishing aspect: The Antibody repertoire exists independently of exposure to Antigen. The repertoire is there, and Antigen selects out particular side chain (Antibodies) for production.
What is Karl Landsteiner’s contribution to the theory of Antibody formation?
Modified the Antigen structure - found that they all induced production of Antibodies.
Synthesized molecules that had never existed - found that they still induced production of Antibodies.
PROBLEM: This level of diversity caused loss of favor with selective theories (idea of premade Antibodies). Why would we have receptors for uptake of molecules that have never before been seen? How could this happen with limited numbers of genes?
What is Linus Pauling’s contribution to the theory of Antibody formation? (Instructional Theory)
Instructional Theory - Theory where Antigen encounters Antibody “blanks” or “templates.” They were thought to wrap around Ag, forming a complementary molecular structure which could neutralize all such Ag molecules in the future.
This theory satisfied Specificity and Inifinite Diversity issues.
BUT: It did not explain -
- Ability of immune system to distinguish between self and non-self (self-recognition).
- Memory - Secondary responses are 1-2 logs higiher and faster than primary responses. **This is the fundamental concept of immunity.
What is the Clonal Selection Theory? (Burnett, 1950s)
Applies to both T and B cells.
Assume that certain cells (B cells) are dedicated to only making Ab. These are the cells in which Ab diversity is generated, stored, and expressed.
- Every cell in this population makes a different Ab (in terms of Antigen specificity) from every other cell
- But each cell produces 1 and only 1 kind of Ab, specific for 1 and only 1 Antigen.
- A copy of the Ab the cell can make is displayed at the cell surface.
- Ab is generated randomly, with no knowledge of the Antigenic universe.
- any cell making an Ab reactive with self is eliminated.
*All Ab pre-exist. Repertoire is unaffected by the nature of Ag universe.
