3.1 Antigen structure and recognition
2 min read•july 25, 2024
Antigens are the key players in immune responses, with their structure and characteristics determining how effectively they trigger immunity. From size and complexity to foreignness and stability, various factors influence an antigen's ability to stimulate the immune system.
T-cell and B-cell epitopes differ in location, size, and recognition mechanisms. Understanding these differences is crucial for grasping how the immune system processes and presents antigens, leading to targeted responses against pathogens and other foreign substances.
Antigen Structure and Characteristics
Characteristics of immunogenic antigens
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- Size impacts immunogenicity with optimal molecular weight range 10,000 to 100,000 daltons enhances immune recognition (proteins)
- Complexity refers to chemical composition and structural features influencing antigen processing (carbohydrates, lipids)
- Foreignness determines immune response strength based on difference from self-molecules (bacterial cell wall components)
- Stability affects antigen persistence in body resisting degradation prolonging immune system exposure (viral capsid proteins)
- Repetitive structural motifs enhance immune cell recognition increasing binding avidity (bacterial flagella)
- Accessibility of exposed regions facilitates immune cell interaction crucial for effective response (surface glycoproteins)
T-cell vs B-cell epitopes
- B-cell epitopes located on intact antigen surfaces recognized by B-cell receptors and antibodies (hemagglutinin on influenza virus)
- T-cell epitopes are linear peptide fragments presented on MHC molecules recognized by T-cell receptors (internal viral proteins)
- size varies B-cell epitopes larger (5-15 amino acids) T-cell epitopes smaller (8-11 for MHC I, 13-17 for MHC II)
- B-cell epitopes often conformational depending on 3D structure while T-cell epitopes are linear sequences
- Recognition mechanisms differ B-cells directly bind epitopes T-cells require antigen processing and MHC presentation
Antigen processing and presentation
- Antigen uptake occurs through various mechanisms:
- Phagocytosis engulfs large particles (bacteria)
- Receptor-mediated endocytosis targets specific antigens (viruses)
- Pinocytosis captures soluble antigens (toxins)
- Intracellular processing involves:
- Endosomal pathway breaks down exogenous antigens (extracellular pathogens)
- Proteasomal pathway degrades endogenous antigens (intracellular pathogens, tumor antigens)
- MHC loading couples processed peptides with appropriate MHC molecules:
- presents exogenous antigens to CD4+ T cells
- presents endogenous antigens to CD8+ T cells
- Peptide-MHC complex transport moves assembled complexes to cell surface for T cell interaction
- Presentation to T cells involves TCR recognition and co-receptor engagement initiating immune response
Cross-reactivity in immune responses
- Cross-reactivity occurs when antibodies or T-cells recognize similar epitopes on different antigens (seasonal flu strains)
- Molecular basis stems from structural similarity between epitopes and flexibility in antigen-binding sites
- Positive implications include broader pathogen protection and potential for cross-protective vaccines (HPV types)
- Negative implications involve autoimmune reactions and allergic cross-reactions (pollen and fruit allergies)
- Factors influencing cross-reactivity include epitope similarity threshold and affinity of antibody or T-cell receptor
- Cross-reactivity plays role in vaccine design aiming for broad-spectrum protection (universal flu vaccine research)
Key Terms to Review (16)
Affinity Maturation: Affinity maturation is the process by which B cells increase the affinity of antibodies for their specific antigens during an immune response. This process occurs primarily in germinal centers within secondary lymphoid organs, where B cells undergo rapid proliferation and somatic hypermutation, leading to the selection of B cells that produce higher-affinity antibodies.
Antigenic Shift: Antigenic shift is a significant change in the antigens of a virus, particularly influenza viruses, that results from the reassortment of genetic material when two different strains infect the same host cell. This process can lead to the emergence of new viral strains that may not be recognized by the immune system, allowing them to evade immunity and potentially cause pandemics. Understanding antigenic shift is crucial for vaccine development and public health responses to viral outbreaks.
B lymphocytes: B lymphocytes, or B cells, are a type of white blood cell that play a vital role in the adaptive immune response by producing antibodies against specific antigens. They originate from hematopoietic stem cells in the bone marrow and mature there before migrating to peripheral tissues. Upon encountering an antigen, B cells can differentiate into plasma cells, which produce large amounts of antibodies, or memory B cells that provide long-lasting immunity.
B-cell antigen: A B-cell antigen is a substance that can bind to the B-cell receptor (BCR) on B cells, triggering their activation, proliferation, and differentiation into antibody-secreting plasma cells. These antigens are typically proteins, polysaccharides, or other large molecules that can elicit a specific immune response, highlighting the crucial role of B cells in the adaptive immune system's ability to recognize and respond to pathogens.
Cell-mediated response: The cell-mediated response is a crucial aspect of the adaptive immune system, primarily involving T lymphocytes (T cells) that target and eliminate infected or abnormal cells. This response is vital for combating intracellular pathogens, such as viruses, and plays a significant role in tumor surveillance. T cells recognize specific antigens presented by infected cells or antigen-presenting cells through major histocompatibility complex (MHC) molecules, leading to their activation and subsequent immune action.
Danger-Associated Molecular Patterns (DAMPs): Danger-Associated Molecular Patterns (DAMPs) are molecules that can initiate and perpetuate immune responses in the body following cellular damage or stress. These signals alert the immune system to potential threats, even in the absence of pathogens, by triggering inflammation and activating immune cells. DAMPs are crucial for recognizing tissue injury and promoting repair processes, as well as shaping adaptive immunity.
Epitope: An epitope is a specific part of an antigen that is recognized by the immune system, particularly by antibodies, B cells, and T cells. It plays a crucial role in the immune response as it is the precise site where these immune components bind, initiating a cascade of protective actions. Epitopes can be linear, consisting of a continuous sequence of amino acids, or conformational, formed by the three-dimensional structure of the antigen.
Hapten: A hapten is a small molecule that, when combined with a larger carrier protein, can elicit an immune response. Haptens by themselves are typically not immunogenic, but their association with proteins enables them to be recognized by antibodies, leading to the activation of the immune system. This property makes haptens significant in understanding how certain drugs and environmental chemicals can provoke allergic reactions and contribute to autoimmune diseases.
Humoral response: The humoral response is a type of adaptive immune response that involves the production of antibodies by B cells in response to specific antigens. This process is crucial for the identification and neutralization of pathogens, such as bacteria and viruses, that circulate in the body. The humoral response is initiated when B cells recognize an antigen, leading to their activation, proliferation, and differentiation into plasma cells that secrete antibodies, ultimately targeting the antigen for destruction.
MHC Class I: MHC Class I molecules are cell surface proteins that present endogenous antigens to CD8+ T cells, playing a crucial role in the immune system by enabling the recognition of infected or cancerous cells. These molecules are essential for distinguishing self from non-self, and their interactions with T cells are fundamental in the activation and differentiation of adaptive immune responses.
MHC Class II: MHC Class II molecules are proteins found on the surface of certain immune cells that play a crucial role in the adaptive immune response by presenting antigens to CD4+ T helper cells. These molecules specifically present processed extracellular antigens, enabling T cells to recognize and respond to pathogens such as bacteria and parasites, thus connecting them to the immune system's ability to differentiate between self and non-self.
Neutralization: Neutralization refers to the process by which antibodies bind to antigens, blocking their harmful effects, and preventing them from interacting with host cells. This action is critical in immune defense, as it directly relates to how the immune system recognizes foreign invaders, the generation of diverse antibodies, the specific structures and functions of antibodies, and the intricate interactions between antigens and antibodies.
Pathogen-associated molecular patterns (PAMPs): Pathogen-associated molecular patterns (PAMPs) are conserved molecular structures found on pathogens that are recognized by the innate immune system. They serve as signals that alert immune cells to the presence of infections, helping the body mount an immediate defense against various types of pathogens, including bacteria, viruses, and fungi. PAMPs play a crucial role in the activation of innate immune responses and are essential for the recognition of foreign invaders.
Specificity: Specificity refers to the ability of immune responses, particularly antibody-antigen interactions, to recognize and bind to particular molecules or structures, distinguishing them from others. This precision is crucial for the adaptive immune system, as it ensures that each immune response is tailored to specific pathogens, allowing for effective elimination while minimizing damage to host cells.
T Lymphocytes: T lymphocytes, or T cells, are a type of white blood cell that play a critical role in the immune response by recognizing and responding to antigens. These cells originate from stem cells in the bone marrow but mature in the thymus gland, where they acquire the ability to distinguish between self and non-self antigens. The recognition of antigens is facilitated by T cell receptors (TCRs) on their surface, which bind to specific antigens presented by Major Histocompatibility Complex (MHC) molecules on other cells.
T-cell antigen: A T-cell antigen is a molecule that is recognized by T cells, which are a type of white blood cell essential for the adaptive immune response. These antigens can be derived from pathogens, cancer cells, or even self-proteins, and they are presented to T cells by antigen-presenting cells (APCs) through major histocompatibility complex (MHC) molecules. The recognition of T-cell antigens is crucial for the activation and differentiation of T cells into effector and memory cells.