Cellular Immunology Short Answer Questions

## Mechanisms of Autoimmunity Autoimmunity arises from a breakdown in the immune system's ability to distinguish self from non-self. Several mechanisms contribute to the development of autoimmune diseases. One primary cause is the **loss of self-tolerance**, where failures in central (thymus/bone marrow) or peripheral tolerance mechanisms allow **autoreactive lymphocytes** to survive and become active. Another mechanism is **molecular mimicry**, where pathogens express antigens that closely resemble **self-antigens**. This similarity can trigger cross-reactive immune responses, leading the immune system to attack the body's own tissues. **Epitope spreading** describes a process where an initial immune response to a specific antigen broadens over time, leading to responses against other self-antigens. The **release of sequestered antigens** can also initiate autoimmunity. Normally hidden self-antigens, such as those found in the eye or brain, can become exposed due to tissue damage or infection, subsequently being recognized as foreign by the immune system. Lastly, **aberrant expression of MHC molecules**, particularly the upregulation of **MHC class II** on cells that are not typical antigen-presenting cells (non-APCs), can lead to the presentation of self-antigens to T cells, thereby initiating an autoimmune response. ## Alternative Complement Pathway The **alternative complement pathway** is an important component of innate immunity, activated independently of antibodies. It begins with **initiation** through the spontaneous hydrolysis of **C3**, producing **C3(H2O)**, which then binds to **factor B**. This binding leads to the **formation of C3 convertase**: **factor D** cleaves factor B, resulting in the complex **C3bBb**, which serves as the alternative pathway's C3 convertase. An **amplification loop** quickly ensues, where C3bBb cleaves more C3, generating additional **C3b** and thereby amplifying the complement response. **Properdin** plays a crucial role in stabilizing the C3bBb complex, particularly on microbial surfaces, enhancing its activity. The pathway culminates in the **terminal pathway**, where C3b joins the C3bBb complex to form **C5 convertase (C3bBbC3b)**. This C5 convertase then initiates the formation of the **membrane attack complex (MAC)**, a pore-forming structure that can lyse target cells. ## T-Cell Receptor (TCR) Characteristics The **T-cell receptor (TCR)** is a crucial molecule on the surface of T cells, responsible for recognizing specific antigens. Its **structure** typically consists of two polypeptide chains, either **α and β chains** or, less commonly, **γ and δ chains**. Each chain possesses both **variable (V)** and **constant (C) regions**, contributing to its antigen-binding specificity and structural integrity. For **antigen recognition**, the TCR does not bind directly to free antigens. Instead, it specifically binds to **peptide-MHC complexes** presented on the surface of **antigen-presenting cells (APCs)**. Each TCR is **monovalent**, meaning it recognizes a single, specific antigenic peptide presented in the context of an MHC molecule. A key distinction from antibodies is that TCRs have **no soluble form**; they are exclusively membrane-bound and are not secreted by T cells. Upon antigen binding, the TCR itself does not directly transmit signals into the T cell. Instead, it **requires the CD3 complex** to transduce these signals, initiating the intracellular cascade necessary for T cell activation and function. ## Classification of Immunodeficiencies Immunodeficiencies are conditions where the immune system's ability to fight infectious diseases is compromised. They can be broadly classified based on the primary component of the immune system affected: * **B cell (Humoral) Deficiencies** involve impaired antibody production, leading to increased susceptibility to bacterial infections. An example is **X-linked agammaglobulinemia (Bruton’s disease)**. * **T cell (Cellular) Deficiencies** compromise cell-mediated immunity, often resulting in susceptibility to viral, fungal, and intracellular bacterial infections. **DiGeorge syndrome**, characterized by thymic hypoplasia, is a notable example. * **Combined Immunodeficiencies** involve defects in both B and T cell arms of the adaptive immune system, leading to severe and life-threatening infections. **Severe Combined Immunodeficiency (SCID)** is a classic example. * **Phagocytic Defects** compromise the function of phagocytic cells like neutrophils and macrophages, making individuals vulnerable to bacterial and fungal infections. **Chronic Granulomatous Disease (CGD)** is an example. * **Complement Deficiencies** involve defects in components of the complement system, which can impair host defense against certain pathogens and immune complex clearance. A **C3 deficiency**, for instance, can lead to recurrent bacterial infections. ## Tissue-Specific Macrophages Macrophages are versatile immune