Table of Contents
Overview: What Makes the Specific Immune Response “Specific”?
The specific (also called adaptive or acquired) immune response is the part of the immune system that:
- Targets particular pathogens very precisely (e.g. one influenza strain, one bacterial toxin).
- “Learns” and remembers encounters, so responses become faster and stronger on repeat exposure.
- Is based on special white blood cells: lymphocytes (B cells and T cells).
It works in close cooperation with the nonspecific (innate) defenses but differs from them by:
- Specificity: each lymphocyte recognizes only one particular structure (antigen).
- Diversity: the body can generate receptors for millions of different antigens.
- Memory: after infection or vaccination, long-lived memory cells remain.
- Self–non-self discrimination: mechanisms reduce attacks on the body’s own tissues.
This chapter focuses on how this system is organized and how a specific response develops against a particular pathogen.
Antigens and Antigen Recognition
Antigens and Epitopes
A specific immune response is triggered by antigens. An antigen is usually:
- A foreign protein, polysaccharide, or sometimes lipid or nucleic acid.
- Part of a pathogen (e.g. viral coat protein, bacterial cell wall component) or a toxin.
- Sometimes a harmless substance (e.g. pollen, food proteins) in the case of allergies.
The immune system does not recognize whole pathogens all at once. Instead, it recognizes epitopes (antigenic determinants):
- Epitopes are small, specific parts of an antigen (e.g. a short amino acid sequence on a protein).
- One antigen has many epitopes.
- Different lymphocytes can recognize different epitopes on the same pathogen.
Antigen Receptors on Lymphocytes
Two main classes of receptors recognize antigens:
- B cell receptors (BCRs): membrane-bound antibody molecules on B cells.
- T cell receptors (TCRs): distinct receptors on T cells, recognizing antigen only when presented by other cells (see below).
Each individual B cell or T cell has many copies of one receptor type, specific for one epitope. As a whole, the lymphocyte population contains an enormous variety of different specificities.
B Lymphocytes and Antibody-Mediated (Humoral) Immunity
B Cells and Their Activation
B lymphocytes develop in the bone marrow. Each B cell:
- Rearranges its DNA to produce one unique BCR.
- Circulates through blood and lymphoid organs (e.g. lymph nodes, spleen) “searching” for its matching antigen.
Activation usually requires:
- Antigen binding
- The antigen (often a whole or soluble molecule) binds directly to the BCR.
- This binding is highly specific (lock-and-key-like).
- Help from T helper cells (for most protein antigens)
- B cells that have bound antigen internalize it, process it, and present peptide fragments on their surface in association with special presentation molecules (MHC class II).
- A matching T helper cell (see below) recognizes this complex and provides activation signals (cytokines and direct contact).
- This “two-signal” requirement helps prevent inappropriate activation.
Some special antigens (e.g. certain bacterial polysaccharides) can activate B cells with less or no T cell help, but such responses are often weaker and less able to form strong immunological memory.
Clonal Selection and Expansion
Once activated, a B cell undergoes:
- Clonal selection: the specific B cell with the matching receptor is “chosen.”
- Clonal expansion: it divides rapidly, forming a clone of many identical cells.
These cells then differentiate into:
- Plasma cells: short-lived, antibody-secreting factories.
- Memory B cells: long-lived cells that can respond rapidly upon re-exposure to the same antigen.
Antibodies: Structure and Main Functions
Secreted BCRs are called antibodies (immunoglobulins, Ig). Basic features:
- Shaped like a Y, with:
- Variable regions at the tips of the arms (bind the antigen).
- Constant region (determines class and effector functions).
- Each antibody binds a specific epitope.
Major functions of antibodies in specific immunity include:
- Neutralization: bind toxins or viruses to block their interaction with cells.
- Opsonization: “tag” pathogens to make them easier for phagocytes to ingest.
- Activation of complement system: triggers a cascade that can directly damage pathogens or enhance phagocytosis.
- Agglutination and precipitation: link multiple antigens together, forming clumps that are easier to clear.
Different antibody classes (e.g. IgM, IgG, IgA, IgE) have distinct distributions and roles, but their detailed properties are handled elsewhere.
T Lymphocytes and Cell-Mediated Immunity
Antigen Presentation and MHC
T cells cannot bind free antigen as B cells do. They recognize:
- Short peptide fragments derived from proteins.
- Only when these peptides are bound to major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells (APCs) or other body cells.
Two main MHC classes are involved:
- MHC class I: present on almost all nucleated body cells.
- MHC class II: present mainly on professional APCs (e.g. dendritic cells, macrophages, B cells).
This leads to two major functional groups of T cells.
T Helper Cells (CD4⁺ T Cells)
T helper cells recognize peptides on MHC class II:
- Mainly interact with APCs and B cells.
- Express the CD4 surface protein (hence CD4⁺ T cells).
After activation (requiring antigen recognition plus costimulatory signals):
- They proliferate (clonal expansion).
- Differentiate into subsets that secrete characteristic sets of cytokines (signaling molecules), such as:
- Subtypes that help B cells produce antibodies.
- Subtypes that support activation of macrophages and cytotoxic T cells.
- They coordinate and “direct” many specific immune responses.
Without functional T helper cells, antibody responses to most antigens are severely impaired and cellular immunity is weakened.
Cytotoxic T Cells (CD8⁺ T Cells)
Cytotoxic T cells recognize peptides on MHC class I:
- Target mainly virus-infected cells, some tumor cells, and transplanted tissue cells.
- Express CD8 (CD8⁺ T cells).
Upon activation:
- They clonally expand.
- They directly kill target cells displaying the matching antigen–MHC I combination by:
- Releasing perforin and granzymes (inducing apoptosis).
- Expressing molecules that trigger programmed cell death.
This is a key specific defense against intracellular pathogens that antibodies cannot reach.
Regulatory T Cells
A specialized subset, regulatory T cells (Tregs):
- Also mostly CD4⁺.
- Help limit immune responses and maintain self-tolerance.
- Produce inhibitory cytokines and directly suppress other lymphocytes.
They are essential in preventing excessive immune reactions and autoimmunity.
Clonal Selection Theory and Immune Memory
Clonal Selection: How Specificity Is Achieved
The principle of clonal selection explains the specificity and adaptability of the immune response:
- Before any infection, the body produces a huge variety of B and T cells, each with a unique receptor specificity (generated by gene rearrangements).
- An antigen selects only those lymphocytes whose receptors fit it.
- These selected cells proliferate and differentiate, forming a clone of effector and memory cells with the same specificity.
Thus, the immune system is prepared in advance with many potential specificities and “chooses” the right ones when needed.
Primary and Secondary Immune Response
When an antigen is first encountered:
- The response is called the primary response.
- It has a lag phase (days) before measurable antibodies or strong T cell activity appear.
- Antibody levels rise, then fall as the antigen is cleared.
- Memory B cells and memory T cells are generated.
Upon re-exposure to the same antigen:
- A secondary (memory) response occurs.
- It is faster (hours to a very few days), stronger (higher antibody levels), and often more specific (antibodies with higher affinity).
- Memory cells are rapidly reactivated and expand again.
Immunological memory is the basis for:
- Long-lasting protection after infection.
- The effectiveness of vaccination (artificially inducing a primary response without causing disease).
Cooperation Between Specific and Nonspecific Immunity
The specific immune response does not work in isolation:
- Innate mechanisms (e.g. phagocytes, complement) often control many pathogens before a strong specific response is needed.
- Antibody functions (opsonization, complement activation) rely on innate effector mechanisms to destroy targets.
- Antigen-presenting cells (like dendritic cells) are part of innate immunity but are essential for activating T cells.
- Cytokines produced by specific lymphocytes influence innate cell behavior (e.g. macrophage activation).
This close cooperation ensures both rapid initial defense and highly targeted, long-term protection.
Self–Non-Self Discrimination and Tolerance (Overview)
For a specific immune system to be useful, it must:
- Recognize and respond strongly to foreign antigens.
- Avoid attacking the body’s own components (self-antigens).
Mechanisms involved include:
- Selection during lymphocyte development: cells strongly reacting to self-antigens can be eliminated or inactivated.
- Regulatory T cells and other control mechanisms that dampen inappropriate responses.
- Dependence on the way antigens are presented and the presence of danger or inflammation signals.
Failures in these mechanisms contribute to autoimmune diseases, which are discussed separately.
Summary
- The specific immune response is based on antigen recognition by B and T lymphocytes with unique receptors.
- B cells mediate humoral immunity by producing antibodies that neutralize and mark pathogens.
- T cells mediate cellular immunity, with helper T cells orchestrating responses and cytotoxic T cells killing infected or abnormal cells.
- Clonal selection and the formation of memory cells ensure that responses are specific, adaptable, and faster upon re-exposure.
- Constant interaction with the nonspecific immune system and mechanisms of tolerance shapes effective yet controlled defense.