UNIT 5: Antigen Recognition and Presentation, Autoimmune Diseases, Immunodeficiency, and Immunodiagnostics
Exam Focus: The comparison table for **MHC Class I vs. Class II** is essential (which T cell interacts, which cells express it, source of antigen). Be prepared to describe the basic principles of **ELISA** and **RIA** and list examples of autoimmune diseases.
Table of Contents
- Antigen Recognition and Processing
- Autoimmune Diseases
- Immunodeficiency: HIV and AIDS
- Introduction to Immunodiagnostics
1. Antigen Recognition and Processing
T cells cannot directly recognize soluble antigens. They require antigens to be processed and presented on the surface of other cells by Major Histocompatibility Complex (MHC) molecules.
Class I & Class II MHC Molecules
| Feature |
MHC Class I (HLA-A, B, C) |
MHC Class II (HLA-DP, DQ, DR) |
| **Expression** |
Expressed on **all nucleated cells**. |
Expressed primarily on **Antigen Presenting Cells (APCs)** (Dendritic cells, Macrophages, B cells). |
| **Source of Antigen** |
Endogenous (intracellular, e.g., viral proteins, cancer proteins). |
Exogenous (extracellular, e.g., bacteria, toxins). |
| **T cell Interaction** |
Interacts with **Cytotoxic T cells (TC)** via CD8 coreceptor. |
Interacts with **Helper T cells (TH)** via CD4 coreceptor. |
Antigen Processing and Presentation by MHC Molecule
The pathway by which antigens are degraded into peptides and complexed with MHC molecules.
- **MHC Class I Pathway:** Antigen (e.g., viral protein) is produced in the cytoplasm, degraded by the **proteasome**, transported into the ER, loaded onto nascent MHC-I molecules, and presented on the cell surface.
- **MHC Class II Pathway:** Antigen (e.g., bacteria) is taken up by the APC via endocytosis, degraded in endosomes/lysosomes, loaded onto MHC-II molecules in a specialized vesicle, and presented on the cell surface.
2. Autoimmune Diseases
These diseases result from the failure of the immune system to distinguish between self and non-self, leading to an immune response that targets and damages the body's own tissues (loss of **self-tolerance**).
Organ-specific Autoimmune Diseases
The immune response is primarily directed against antigens restricted to a single organ.
- **Hashimoto's Disease:** Targets the **thyroid gland** cells, leading to hypothyroidism (underactive thyroid).
- **Myasthenia Gravis:** Targets acetylcholine receptors at the neuromuscular junction, leading to muscle weakness.
Systemic Autoimmune Diseases
The immune response is directed against antigens that are broadly distributed throughout the body.
- **Systemic Lupus Erythematosus (SLE):** Produces autoantibodies against common cellular components (e.g., DNA, nuclear proteins), causing inflammation and damage to multiple organs (skin, joints, kidneys).
- **Rheumatoid Arthritis (RA):** Targets the lining of the joints (synovium), causing chronic inflammation, pain, and joint deformation.
3. Immunodeficiency: HIV and AIDS
A state where the immune system's ability to fight infectious diseases and cancer is compromised.
- **HIV (Human Immunodeficiency Virus):** A retrovirus that primarily targets and destroys CD4+ **Helper T cells**, which are crucial coordinators of the adaptive immune response.
- **AIDS (Acquired Immunodeficiency Syndrome):** The final stage of HIV infection, characterized by a severely depleted CD4+ T cell count and the onset of opportunistic infections and unusual cancers. The destruction of CD4+ cells causes a catastrophic collapse of both humoral and cell-mediated immunity.
4. Introduction to Immunodiagnostics
Techniques utilizing the highly specific nature of antigen-antibody binding to detect and measure antigens (pathogens, hormones) or antibodies (indicative of infection or immunity) in a sample.
ELISA (Enzyme-Linked Immunosorbent Assay)
A plate-based assay technique designed for detecting and quantifying peptides, proteins, antibodies, and hormones.
- **Principle:** Uses an enzyme (linked to an antibody) that produces a color change when a substrate is added, indicating the presence of the target molecule.
- **Types:** Direct, Indirect, Sandwich, and Competitive.
RIA (Radioimmunoassay)
A highly sensitive technique used to measure concentrations of substances, usually antigens or antibodies, by employing **radioactive isotopes** (tracers).
- **Principle:** Involves the competitive binding of a known amount of radioactively labeled antigen with the unknown, unlabeled antigen in the sample to a limited amount of antibody. The amount of radioactivity measured is inversely proportional to the amount of unlabeled antigen in the sample.
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