Biology (9700) | Antibodies and vaccination

Welcome to Immunity: Antibodies and Vaccination!

Hi there! If you’ve ever wondered how your body fights off a cold or why vaccines are so important, this chapter is for you. We're diving into the amazing world of the immune system's ultimate weapons: **antibodies**.
Don't worry if immunity seemed complex before—we will break down the structures, the methods, and the biology behind long-term protection against disease!

1. The Molecular Structure and Function of Antibodies

Antibodies are specialized proteins produced by **plasma cells** (which are mature B-lymphocytes) in response to the presence of an antigen. They are also known as **immunoglobulins** (Ig).

1.1 Antibody Structure: The Y-Shaped Weapon

Think of an antibody as a Y-shaped molecule, perfectly designed to recognize and neutralize specific targets.

• Polypeptide Chains: Each antibody is made up of four polypeptide chains:
  • Two identical **heavy chains** (long chains).
  • Two identical **light chains** (short chains).
  These chains are held together securely by strong chemical links called **disulfide bonds**.
• Variable Region: Located at the tips of the 'Y' arms. This region has a unique shape specific to one type of **antigen**. This area is known as the **antigen-binding site**.
  Analogy: If an antigen is a specific lock, the variable region is the key designed only for that lock.
• Constant Region: The stem and lower parts of the 'Y'. This region is the same within a class of antibodies and determines how the antibody will perform its action (e.g., whether it will activate phagocytes).

Key Takeaway Structure: Y-shape, 4 chains (2 heavy, 2 light), held by disulfide bonds. The **variable region** gives the antibody its **specificity**.

1.2 How Antibodies Fight Infection (Functions)

The structure of the antibody directly relates to its function. Once the variable regions bind to the antigen, they can neutralize the pathogen in several ways:

1. Agglutination (Clumping): Because antibodies have two binding sites, they can link multiple pathogens (like bacteria or viruses) together, forming large clumps.
   Why is this helpful? The clumps are too large to infect cells and are easier for **phagocytes** (like macrophages) to find and destroy in one go.
2. Neutralisation: Antibodies bind to the toxins or the surface antigens of pathogens, effectively blocking their ability to bind to and enter host cells.
3. Opsonisation: The stem (constant region) of the antibody acts as a signal flag, making the pathogen more recognizable to phagocytes, promoting engulfment and destruction.

2. Understanding Immunity: Active vs. Passive

Immunity refers to the ability of an organism to resist infection. We classify immunity based on two main criteria: whether the body *made* the antibodies (Active vs. Passive) and whether it happened *by chance* or *by intervention* (Natural vs. Artificial).

2.1 Active Immunity

Definition: Active immunity occurs when the body's own immune system is stimulated to produce its own antibodies and **memory cells**.

• Timeframe: Slow acting (takes days for B cells to proliferate and make antibodies).
• Duration: Long-term (thanks to memory cells).
• Natural Active Immunity: Immunity achieved after catching a disease and recovering from it (e.g., getting the chickenpox virus).
• Artificial Active Immunity: Immunity achieved through vaccination (e.g., receiving a measles jab).

2.2 Passive Immunity

Definition: Passive immunity occurs when an individual is given (receives) antibodies from an external source. The body does not produce them itself, and thus, no memory cells are formed.

• Timeframe: Fast acting (immediate protection).
• Duration: Short-term (the transferred antibodies eventually break down).
• Natural Passive Immunity: Antibodies passed from mother to baby. This happens across the placenta (IgG) or through breast milk (IgA).
• Artificial Passive Immunity: Antibodies injected into the body to provide quick, temporary protection (e.g., an antitoxin injection for tetanus or rabies).

3. Vaccination Programmes and Herd Immunity

3.1 How Vaccines Work (Artificial Active Immunity)

Vaccination is the deliberate introduction of **antigens** into the body to trigger a primary immune response and establish long-term immunity without causing the full symptoms of the disease.

Vaccines contain modified pathogens, such as:

• Weakened (attenuated) pathogens.
• Dead pathogens.
• Harmless parts of the pathogen (antigen fragments or protein coats).
• mRNA instructions for making the antigen (modern vaccines).

The Immune Response Pathway (Review of 11.1):

1. The vaccine is injected, introducing the antigen.
2. Macrophages engulf the antigens and present them on their surface.
3. T-helper cells bind to the presented antigen.
4. T-helper cells activate specific B-lymphocytes and T-killer cells.
5. B-lymphocytes divide rapidly via mitosis to form clones (clonal selection). Most clones become **plasma cells** (producing antibodies), and some become **memory cells**.
6. If the real pathogen is encountered later, the abundant memory cells quickly launch a massive, rapid **Secondary Immune Response**, preventing disease.

3.2 The Importance of Herd Immunity

Vaccination programmes are designed not just to protect the individual, but to protect the entire population—a concept known as **herd immunity**.

Herd Immunity Explained:

• Herd immunity occurs when a sufficiently large proportion of the population is immune to a disease (usually 80-95%).
• This high level of immunity makes the likelihood of a susceptible person meeting an infected person very low.
• This interrupts the chain of transmission, effectively protecting the small number of people who cannot be vaccinated (e.g., the very young, the elderly, or those with compromised immune systems).

Controlling Disease Spread: High participation in vaccination programmes is crucial for controlling infectious diseases because it reduces the number of 'reservoirs' (infected individuals) from which the disease can spread, potentially leading to the eradication of the disease (as seen with smallpox).

4. Monoclonal Antibodies (Mabs)

Monoclonal antibodies are antibodies that are **identical** because they are all produced by clones of a single plasma cell. They are highly valued because they target one specific antigen site with incredible precision.

4.1 The Hybridoma Method (Production)

Since normal plasma cells die quickly outside the body, scientists developed a technique to fuse antibody-producing B-cells with cancer cells, creating a cell line that produces specific antibodies forever.

Here is the outline of the hybridoma method:

1. Antigen Injection: A mouse (or other mammal) is injected with the specific antigen to stimulate an immune response, producing plasma cells.
2. Cell Extraction: Antibody-producing plasma cells are extracted from the mouse's spleen.
3. Fusion: These plasma cells are fused with fast-dividing **myeloma cells** (a type of tumour/cancer cell).
4. Hybridoma Formation: The resulting fused cells are called **hybridomas**. They possess two key traits: the ability to produce a specific antibody (from the plasma cell) and the ability to divide indefinitely (from the myeloma cell).
5. Selection and Cloning: The hybridomas are selected and cultured to form clones, allowing the mass production of the desired monoclonal antibody.

4.2 Uses of Monoclonal Antibodies (Mabs)

Mabs are utilized in both the diagnosis and treatment of various diseases due to their precise targeting ability.

Diagnosis of Disease

• Pregnancy Tests: Mabs are used to detect the hormone human chorionic gonadotropin (hCG) in urine. A Mab specific to hCG is often attached to an enzyme or dye; when hCG is present, the complex binds and triggers a visible colour change.
• Blood Typing: Mabs can be used to quickly and accurately identify specific antigens on red blood cells.
• Disease Detection: Mabs are used in tests to detect low concentrations of disease antigens (e.g., certain cancer markers or viral proteins) in patient samples.

Treatment of Disease

• Cancer Treatment: Mabs can be used as "biological missiles."
  A Mab is engineered to be specific to an antigen found only on the surface of tumour cells. The Mab is then attached to a drug, toxin, or radioactive substance.
  When injected, the Mab travels through the body, binds precisely to the cancer cell, and delivers the toxic payload directly to the tumour, minimizing damage to healthy cells.
• Autoimmune Diseases: Mabs can block the action of specific signalling molecules (like certain cytokines) that trigger harmful inflammation in conditions such as rheumatoid arthritis.

Key Takeaway Mabs: Mabs are highly specific, uniform antibodies produced using the **hybridoma technique** (fusing plasma cells and myeloma cells). They are essential tools for targeted diagnosis and treatment.