UNIT 4: Overview of the Immune System, Immune Components, and B-cell Activation

Exam Focus: Distinguish between Innate and Adaptive Immunity. The structure of **Immunoglobulins** (Heavy/Light chains, variable/constant regions) and the processes of **Class Switching** and **Affinity Maturation** are central topics in B-cell biology.

Overview of the Immune System
- Innate and Adaptive Immunity
- Humoral and Cellular Immune Responses
Immune Components
B-cell Activation: Antibody Production

1. Overview of the Immune System

The immune system is a complex network of cells and organs that protects the body from disease-causing pathogens and abnormal cells.

Innate and Adaptive Immunity

Feature	Innate (Natural) Immunity	Adaptive (Acquired) Immunity
Specificity	Non-specific (reacts the same way to all threats).	Highly specific (targets particular antigens).
Response Time	Immediate (minutes/hours).	Slow (days/weeks) on first exposure.
Memory	No immunological memory.	Has immunological memory (faster, stronger response upon re-exposure).
Components	Phagocytes, Natural Killer (NK) cells, Complement, Physical barriers.	B Lymphocytes and T Lymphocytes.

Humoral and Cellular Immune Responses

These are the two main arms of the adaptive immune system.

**Humoral Immune Response:** Mediated by **B lymphocytes** and the production of **antibodies (Immunoglobulins)**. Effective against extracellular pathogens (bacteria, toxins).
**Cellular Immune Response:** Mediated by **T lymphocytes** (especially cytotoxic T cells). Effective against intracellular pathogens (viruses) and cancer cells.

2. Immune Components

B Lymphocytes and T Lymphocytes

Both are lymphocytes, but they differ in maturation site and function:

**B Lymphocytes:** Mature in the **Bone marrow**. Differentiate into **Plasma Cells** (antibody secretors) and memory B cells. They recognize soluble antigen via their B Cell Receptor (BCR).
**T Lymphocytes:** Mature in the **Thymus**. Types include:
- **Helper T cells (T_H):** Secrete cytokines to activate other cells (B cells, macrophages).
- **Cytotoxic T cells (T_C):** Directly kill infected or cancerous cells.

Structure of Immunoglobulins (Antibodies)

Antibodies are Y-shaped proteins produced by plasma cells.

**Structure:** Composed of **four polypeptide chains**—two identical **Heavy (H) chains** and two identical **Light (L) chains**, held together by disulfide bonds.
**Regions:** Each chain has **Variable (V)** regions (which form the antigen-binding site) and **Constant (C)** regions (which determine the antibody class/isotype, e.g., IgG, IgM).

T Cell Receptors (TCR)

Receptors found on the surface of T lymphocytes that recognize antigens.

**Structure:** Typically composed of two chains (α and β). Unlike B cells, **TCRs only recognize antigens presented on MHC molecules** (discussed in Unit 5).

3. B-cell Activation: Antibody Production

B-cell activation occurs when the B cell binds to its specific antigen and receives signals from Helper T cells, leading to proliferation and differentiation into plasma cells.

Class Switching (Isotype Switching)

A genetic recombination mechanism that changes the **Constant (C)** region of the Heavy chain gene.

**Mechanism:** Allows a plasma cell, which initially secreted IgM, to switch to producing IgG, IgA, or IgE, while retaining the same antigen specificity (Variable region). This switch is directed by **cytokines** secreted by T_H cells.

Affinity Maturation

The process by which the **affinity** (binding strength) of antibodies for their antigen **increases** during a prolonged immune response.

**Mechanism:** Occurs in the germinal centers of lymphoid organs via **somatic hypermutation** (high rate of point mutations in the V region gene segments) followed by selection of B cells that produce higher-affinity antibodies.

Heavy Chain Gene Transcription

The gene segments encoding the Heavy chain (V (Variable), D (Diversity), and J (Joining) segments, plus the C (Constant) segment) undergo **V(D)J recombination** during B cell development. This process shuffles and splices these segments, leading to the immense **diversity** of antibody variable regions. The final V(D)J exon is transcribed along with the C segment to produce the H chain mRNA.