6 - Homeostasis y tolerancia
New Section
In this section, the speaker introduces the topic of maintaining homeostasis in the immune response and discusses mechanisms related to innate and adaptive immunity, antimicrobial responses, anti-tumor responses, and tolerance towards self-antigens.
Mechanisms for Maintaining Homeostasis in Immune Responses
- The discussion delves into how the immune system learns to recognize self-antigens and distinguish them from foreign antigens to prevent autoimmunity.
- Focus shifts towards the regulation of innate antimicrobial immune responses, specifically looking at the complement system, neutrophils, and macrophages.
- The cascade activation of the complement system is highlighted as a crucial component contributing to inflammatory responses and amplification through various mediators.
- Key points regarding regulating complement system activation in cascades are discussed to prevent excessive inflammation and control inflammatory mediator generation.
- Soluble mediators involved in inhibiting the complement system are explored, including factors like S1 inhibitor and factor H that regulate C3 convertase activity.
Regulation of Complement System Activation
- Factor I inhibitor's role in blocking C4 cleavage by C1 esterase inhibitor is detailed along with its impact on preventing C3 convertase formation.
- Factor H's ability to bind host cell surfaces rich in sialic acid aids in distinguishing self-cells from pathogens by inhibiting alternative pathway C3 convertase formation.
- Factor H's dual function as a surface binder and enhancer for factor I activity underscores its significance in regulating complement activation pathways.
Additional Factors Influencing Complement System Regulation
- Factor Y's interaction with factor H facilitates proper C3b binding for downstream complement cascade modulation.
- Various regulators like CR1, MCP, CD46 play roles in controlling C3 convertase assembly or accelerating its degradation to maintain immune balance.
Detailed Overview of Immune Response Mechanisms
In this section, the importance of complement system regulation and the role of neutrophils in the innate immune response are discussed.
Regulation of Complement System
- The significance of regulating the complement system is highlighted to emphasize its impact on immune responses.
Role of Neutrophils in Innate Immunity
- Neutrophils play a crucial role in innate immunity by being recruited to sites of infection due to their destructive potential.
- They are efficiently removed from inflamed tissues as over 70 billion neutrophils are released daily from the bone marrow into circulation.
- Neutrophils exhibit potent microbicidal capabilities, especially in inflamed joints where their numbers can reach significant levels.
- This high microbicidal potential necessitates efficient clearance mechanisms to prevent collateral damage.
Neutrophil Apoptosis and Macrophage Clearance
The process of neutrophil apoptosis, macrophage-mediated clearance, and its implications for inflammation control are discussed.
Neutrophil Apoptosis
- Neutrophils undergo apoptosis as a crucial mechanism for controlling inflammation.
- Apoptosis leads to a unique form of cell death called "apoptotic bodies" characterized by intact cytoplasmic membranes that retain cellular contents internally.
- This containment within apoptotic bodies facilitates rapid removal by macrophages, particularly through phagocytosis.
Macrophage-Mediated Clearance
- Macrophages play a pivotal role in clearing apoptotic cells, acting as essential components of the immune system's waste disposal system.
- Phagocytosis of apoptotic bodies triggers an anti-inflammatory response in macrophages, leading to cytokine production like interleukin-17 for inflammation resolution.
- This dual strategy involves effective removal of apoptotic cells and macrophage activation towards an anti-inflammatory profile.
Fagocitosis Signaling Pathways and Autoimmune Implications
The signaling pathways involved in phagocytosis, autoimmune associations due to defective cell clearance, and macrophage differentiation profiles are explored.
Phagocytosis Signaling Pathways
- Specific molecules and receptors participate in forming phagocytic portals for engulfing apoptotic bodies by macrophages.
- Recognition signals such as phosphatidylserine facilitate efficient identification and clearance processes.
- Defects in phagocytosing apoptotic cells may lead to secondary necrosis triggering inflammatory responses perpetuating tissue damage.
Autoimmune Implications
- Dysfunctions in apoptotic cell clearance could contribute to autoimmune conditions like systemic lupus erythematosus (SLE) due to secondary necrosis effects on extracellular content release.
- Altered fagocitosis efficiency may sustain inflammatory processes exacerbating tissue damage characteristic of autoimmune disorders.
Understanding the Process of Tissue Repair
In this section, the speaker discusses the tissue repair process, focusing on factors involved in scar formation and extracellular matrix components.
Factors in Tissue Repair
- The tissue repair process involves a pattern known as tissue repairer, crucial for scar formation.
- Components of the extracellular matrix play a significant role in scar formation and have been extensively studied recently.
Homeostasis Control Points
- Key control points include homeostasis regulation, complement system regulation, removal of apoptotic bodies from neutrophils, and macrophage activation.
Immune Response Activation and Regulation
This part delves into the adaptive immune response activation, focusing on regulatory cell receptors and dendritic cells' role in antigen presentation.
Adaptive Immune Response Activation
- Activation of naive lymphocytes occurs following an injury where bacteria access the dermis and interact with immature dendritic cells.
- Dendritic cells play a crucial role as a link between innate and adaptive immune responses during migration to regional lymph nodes.
Antigen Presentation by Dendritic Cells
- Mature dendritic cells increase MHC expression, enhancing antigen presentation to T cells in regional lymph nodes.
- Dendritic cells encounter naive T lymphocytes in cortical zones of lymph nodes for specific antigen recognition.
Lymphocyte Activation Mechanisms
This segment explores the activation mechanisms of T lymphocytes through antigen recognition signals and co-stimulatory molecules.
Lymphocyte Activation Process
- Naive T lymphocytes require two signals for activation: antigen recognition via MHC molecules and co-stimulation through CD28 binding to stimulatory molecules on mature dendritic cells.
- Clonal expansion post-activation leads to rapid proliferation generating effector cell populations with specific functions.
Regulation of Clonal Expansion
The discussion shifts towards regulating clonal expansion through effector cell differentiation and inhibitory signals.
Clonal Expansion Control
- Effector cells modulate clonal expansion through cytokine production while expressing molecules that regulate proliferation.
New Section
This section discusses the expression of molecules on T lymphocytes and their interaction with ligands to regulate signaling pathways, proliferation, cytokine production, and cell survival.
Expression and Function of Molecules on T Lymphocytes
- The molecule PD-1 is expressed on the surface of T lymphocytes.
- Interaction with ligands such as PDL-1 or PDL-2 inhibits signaling through the TCR and CD28 pathways.
- PD-1 controls T cell proliferation, cytokine production, and affects cell survival.
New Section
This part explores how mutations in PD-1 can lead to autoimmune manifestations in chronic infections and cancer due to its impact on lymphocyte survival.
Impact of Mutations in PD-1
- Mutations in PD-1 can result in autoimmune manifestations.
- High and sustained expression of PD-1 is observed in chronic infections and cancer.
- Increased PD-1 expression is linked to senescence in memory T cells.
New Section
The discussion shifts towards therapeutic opportunities by targeting the interaction between PD-L1 and PD-L2 using monoclonal antibodies.
Therapeutic Potential of Blocking PD-L1 Interaction
- Blocking the interaction between PD-L1 and its receptors presents a therapeutic opportunity.
- Monoclonal antibodies are currently used for therapeutic purposes to target various diseases.
New Section
The use of monoclonal antibodies as biological agents for treating diseases by inhibiting immune checkpoints is highlighted.
Role of Monoclonal Antibodies in Disease Treatment
- Monoclonal antibodies revolutionized disease treatment by targeting cytokines or immune checkpoint inhibitors like PD-L1.
New Section
A dual strategy involving lymph node level intervention and tumor microenvironment modulation through immune checkpoint inhibition is discussed.
Dual Strategy Utilizing Immune Checkpoint Inhibition
- Immune checkpoint inhibition involves strategies at both lymph node level (inhibiting CTLA4) and tumor microenvironment (blocking PDL1).
New Section
The revolutionary impact of monoclonal antibodies as therapeutic agents for various diseases is emphasized.
Revolutionary Impact of Monoclonal Antibodies
- Original technique developed by Köhler & Milstein led to significant advancements in antibody design for therapeutic treatments.
New Section
A study from 2015 showcasing the efficacy of pembrolizumab in melanoma treatment is presented along with impressive results after 18 months.
Efficacy of Pembrolizumab in Melanoma Treatment
- Pembrolizumab demonstrated significant improvement in survival rates compared to traditional therapies after 18 months.
New Section
This section discusses the control points for the proliferation of lymphocytes, focusing on regulatory T cells and their role in controlling auto-reactive clones.
Regulatory T Cells
- Regulatory T cells play a crucial role in controlling the proliferation of auto-reactive clones.
- Two main types of regulatory T cells are natural and inducible.
- Natural regulatory T cells receive specific signals in the thymus, expressing CD4, Foxp3 transcription factor, and CD25 receptor.
- Inducible regulatory T cells are induced peripherally under different circumstances.
New Section
This part delves into various subtypes of regulatory T cells based on their characteristics and functions.
Subtypes of Regulatory T Cells
- Different subtypes include Tr1 (producing high levels of IL-10), Th3 (associated with high beta production), and inducible invisible regulatory T cells.
- Both inducible and natural regulatory T cells share some characteristic markers like Foxp3 positivity.
New Section
The mechanisms of action of regulatory T cells are discussed here, emphasizing how they suppress immune responses.
Mechanisms of Action
- Interaction between CTLA-4 and CD80/86 on dendritic cells leads to decreased co-stimulation and increased indoleamine 2,3-dioxygenase (IDO) expression.
- Production of granzyme induces apoptosis in dendritic cells, further suppressing adaptive immune responses.
New Section
The significance of interleukin 2 consumption by regulatory T cells is highlighted as a key mechanism for inhibiting lymphocyte differentiation and proliferation.
Interleukin 2 Consumption
- Regulatory T cells consume interleukin 2 to inhibit lymphocyte differentiation and proliferation.
- Initially challenging to identify due to cell death without interleukin 2; its consumption inhibits lymphocyte activation.
New Section
The impact and relevance of regulatory T cells in various diseases are explored, emphasizing their role in immune regulation.
Role in Diseases
- Mutations in FOXP3 lead to fatal conditions characterized by polyendocrinopathy, inflammatory bowel diseases, diabetes mellitus, splenomegaly, lymphadenopathy, cytokine storms.
New Section
Activation mechanisms and antigen-specific suppression by regulatory T cells are discussed here.
Antigen-Specific Suppression
Induction of Tolerogenic Cells
The discussion revolves around the induction of tolerogenic cells through various mechanisms involving cytokines, chemical agents, and molecules like vitamin D3.
Mechanisms of Inducing Tolerogenic Cells
- Production of immunoglobulin intravenously can induce tolerogenic cells with significant relevance in regulating effector responses.
- Focus shifts to points of control in the adaptive immune response leading to immune tolerance and mechanisms towards self-antigens.
- Mechanisms inducing tolerance occur centrally in primary organs like bone marrow and thymus, crucial for preventing autoimmunity.
- Understanding central tolerance mechanisms in T lymphocytes involves the generation of diverse clones during ontogeny forming the T cell repertoire.
T Cell Ontogeny and Repertoire Formation
Delving into T cell development, focusing on gene rearrangements, segmental genes, and somatic recombination processes.
Gene Rearrangement and Repertoire Formation
- Genes undergo rearrangement sequentially starting with beta chain followed by gamma chain rearrangements crucial for successful TCR formation.
- Recombination process involves specific recombination sequences facilitated by RAG complex enzymes ensuring proper gene arrangement.
- RAG complex initiates gene rearrangement by cutting DNA strands allowing segments to join leading to irreversible changes in gene configuration.
T Cell Maturation and Selection Process
Detailing maturation stages involving constant region arrangement, translation to protein level, and association with alpha chain.
Maturation and Selection Process
- After constant region arrangement, translation occurs followed by association with alpha chain forming pre-T cell receptor expressed on cell surface undergoing proliferation cycles.
- Alpha chain encoding involves somatic recombination driven by two gene families resulting in alpha-beta or gamma-delta TCR expression based on successful somatic recombination.
Thymic Development and Positive Selection
Exploring thymic development stages including CD4/CD8 expression marking double-positive stage crucial for positive selection processes.
Thymic Development Phases
- Thymus structure overview highlights cortex, medullary zones where immature cells differentiate migrating towards medulla for further differentiation processes.
Intercellular Interactions in Thymus Development
In this section, the discussion revolves around the interactions between thymocytes and their fate based on these interactions during thymus development.
Intercellular Signaling and Cell Fate
- Positive selection ensures the survival of thymocytes capable of interacting appropriately with signals. This process determines double-positive cells to single-positive cells.
- Some thymocytes die due to negative selection triggered by intense signals, potentially from self-reactive clones.
- Thymocytes that overcome central tolerance mechanisms differentiate into mature T CD4 and CD8 lymphocytes.
- Double-positive thymocytes learn to recognize self-major histocompatibility complex (MHC) molecules, becoming self-tolerant.
- Cortical zone presentation of a diverse range of peptides by stromal cells is crucial for positive selection in thymocyte maturation.
Thymocyte Selection Processes
This section delves into the processes involved in presenting peptides to developing thymocytes for their selection and maturation.
Peptide Presentation Mechanisms
- Thymic stromal cells express unique machinery facilitating peptide presentation to double-positive thymocytes for MHC class 1 and 2 molecules.
- Double-positive thymocytes primarily recognize MHC molecules on cortical epithelial cells during selection processes.
Positive and Negative Selection Mechanisms
The discussion focuses on how positive and negative selections determine the fate of developing thymocytes through signaling intensity.
Cellular Fate Determination
- Most thymocytes undergo apoptosis due to inadequate recognition of self-MHC molecules, termed death by neglect.
- Positive selection ensures survival of thymocytes recognizing self-peptides, while negative selection eliminates potentially harmful clones through apoptosis.
Understanding Central and Peripheral Tolerance Mechanisms
In this section, the discussion revolves around the mechanisms of central and peripheral tolerance in the immune system, focusing on how certain clones are selected for survival or elimination based on signal intensity.
Clonal Selection and Survival
- Central tolerance mechanisms involve selecting potentially self-reactive clones during positive selection with low-intensity signals to survive.
- Escape of some auto-reactive clones to the periphery leads to peripheral tolerance induction through pathways involving regulatory cells.
Signal Intensity in Tolerance Induction
- CD4+ Foxp3+ regulatory cells entering from the thymus receive different signal intensities through their TCR during positive selection compared to natural regulatory cells.
- The intensity of signals received by cells during selection determines their fate, with an intermediate signal required for positive selection.
Role of Natural Regulatory Cells
- Natural regulatory cells from the thymus can induce peripheral tolerance by controlling auto-reactive clones that escaped central tolerance mechanisms.
Insights into Negative Selection Process
This part delves into the negative selection process following positive selection, highlighting how epithelial cells play a crucial role in presenting self-proteins and inducing apoptosis in autoreactive clones.
Epithelial Cell Mediation
- Epithelial cells in the thymus play a vital role in negative selection by presenting numerous self-proteins, including those expressed in other tissues.
- Auto-tolerant CD4+ single-positive cells emerge post-selection due to recognizing MHC molecules as self, leading to apoptosis if they recognize self-proteins excessively.
Implications of AIRE Gene Mutations
The focus shifts towards discussing how mutations in the AIRE gene can lead to autoimmune syndromes due to failed negative selection processes allowing autoreactive clones to escape into the periphery.
Autoimmune Syndromes
- Mutations in the AIRE gene result in autoimmune syndromes as antigens fail recognition as self during negative selection, enabling autoreactive clones' escape.
Peripheral Tolerance Control Mechanisms
Exploring mechanisms governing peripheral tolerance control, emphasizing factors preventing autoimmunity by regulating autoreactive lymphocytes effectively.
Preventing Autoimmunity
- Various mechanisms prevent autoimmune responses by ensuring autoreactive lymphocytes do not trigger immune reactions through effective control measures.
Desarrollo y Maduración de Linfocitos T
This section discusses the development and maturation of T lymphocytes, focusing on various mechanisms that impact their activation and function.
Mechanisms Affecting Activation of Auto-Reactive Naive T Lymphocytes
- Auto-reactive naive T lymphocytes may fail to find the necessary conditions for activation in the periphery due to:
- Absence of the second signal required for activation.
- Personal ignorance leading to inadequate density of antigen-presenting complexes.
Impact of Signals on Activation
- The first signal for activation involves recognition by the T cell receptor (TCR) and CD28 interaction, crucial for specific recognition in class 2 context.
- Failure in this interaction leads to anergy (lack of response), followed by induction of tolerogenic dendritic cells with low stimulatory molecule levels.
Factors Influencing Control of Auto-Reactive Clones
- Various factors contribute to controlling auto-reactive clones in the periphery:
- Failure to find necessary conditions in the periphery.
- Personal ignorance.
Activation Mechanisms in Periphery
- Auto-reactive clones may activate but remain ignorant individuals through mechanisms like regulatory cells or final selection via FasL system.
- Regulatory cells, including natural and induced regulatory cells, play a role in controlling auto-reactive clones.
Ontogeny and Selection Process
This section delves into central and peripheral tolerance mechanisms within lymphoid organs during ontogeny and selection processes.
Central and Peripheral Tolerance Mechanisms
- During ontogeny, hundreds of millions of different clones are generated in the bone marrow, undergoing selection processes both there and in lymph nodes.
- Heavy chain genes rearrange during early stages, followed by light chain rearrangements. Germinal center configurations influence B cell development similarly to what occurs with heavy chains.
Rearrangement Processes
- Gene segments rearrange to express immunoglobulins. The process is guided by recognition signal sequences but lacks precise cuts at junction points.
- After initial heavy chain rearrangement, a new recombination event occurs involving variable regions. This results in membrane expression of rearranged proteins along with alpha chains forming BCR complexes.
Maturation Processes
- Following BCR expression on B cells' surface, replication cycles occur before light chain rearrangements take place within germinal center configurations.
Desarrollo del Sistema Inmune
This section discusses the maturation process of immune cells in the bone marrow and lymphoid tissues, emphasizing the importance of selection processes for cell development.
Maturation Process in Bone Marrow
- The factor 10 plays a crucial role in the maturation of immune cells in the bone marrow.
- Cells undergo negative selection to recognize self-antigens before moving to lymphoid tissues.
- Cells experience further negative selection processes in lymphoid tissues, ensuring proper maturation stages.
Cell Signaling and Maturation
- Cells receive signals through their B-cell receptors (BCR), leading to editing if successful or cell death if unsuccessful.
- Different outcomes occur based on the type of antigen encounter, influencing cell maturation or elimination.
Migration and Activation
- Mature cells migrate to lymph nodes as mature antigen-presenting cells for immune surveillance.
- Specific antigen recognition triggers activation signals requiring collaboration with T-cells for further differentiation.
Control Mechanisms in Immune Response
This segment explores control mechanisms regulating auto-reactive clones and tolerance levels within peripheral immune responses.
Plasma Cell Generation
- Plasma cells are produced from mature B-cells, aiding antibody production and long-term immunity maintenance.
Auto-Reactive Clones Control
- Mechanisms exist to control auto-reactive clones at peripheral sites like spleen and bone marrow.
Peripheral Tolerance Mechanisms
- Lack of necessary signals prevents activation of auto-reactive clones, maintaining peripheral tolerance levels.
Peripheral Immune Response Regulation
Examining additional mechanisms controlling peripheral immune responses through receptor interactions and signal modulation.
Receptor Interactions
- Inefficient receptor cross-linking can prevent full activation, impacting cellular responses significantly.
Inhibitory Receptors Role
- Inhibitory receptors like CD32b play a crucial role in modulating immune responses by preventing overactivation.
Regulation of Immune Responses
Exploring how specific receptor interactions regulate immune responses by balancing activation signals effectively.
Signal Modulation
Detailed Analysis of Immunological Concepts
This section delves into the importance of immune functions in various tissues and their role in species preservation. It discusses barriers that trigger immune responses, induction of tolerance towards local antigens, and the presence of anti-inflammatory microenvironments.
Immune Functions in Tissues
- The immune functions in different tissues are crucial for species preservation.
- Barriers play a significant role in generating an immunological response.
- Induction of tolerance towards local antigens is a common phenomenon.
- Tissues often have anti-inflammatory microenvironments to regulate immune responses.
Mechanisms of Antigen Secrestration
This part explores how certain antigens are sequestered, preventing their recognition and leading to potential autoimmune responses.
Antigen Secrestration Mechanisms
- Some antigens are sequestered to avoid recognition and subsequent immune reactions.
- Low exposure of specific antigens can lead to the activation of auto-reactive clones.
Autoimmunity and Tolerance Mechanisms
The discussion shifts towards mechanisms regulating tolerance and autoimmunity, emphasizing the importance of maintaining balance within the immune system.
Autoimmunity and Tolerance
- Mechanisms inducing tolerance play a vital role post-infection or when there is a breakdown in self-tolerance.
- Imbalance in these mechanisms can lead to autoimmune diseases with varying incidences across populations.
Types and Examples of Autoimmune Diseases
Different types of autoimmune diseases are highlighted along with specific examples showcasing organ-specific and systemic conditions.
Classification of Autoimmune Diseases
- Autoimmune diseases can be organ-specific or systemic, affecting various body systems such as skin, thyroid, or adrenal glands.
- Some autoimmune disorders are linked to genetic defects that impact immune function but are relatively rare.
Role of Regulatory T Cells in Autoimmunity
The significance of regulatory T cells (Tregs) in controlling autoimmunity is discussed through examples like IPEX syndrome.
Regulatory T Cells' Role
Autoimmune Diseases: Factors and Mechanisms
The discussion delves into the multifactorial nature of autoimmune diseases, exploring the role of genetic factors, environmental influences, and specific examples like arthritis and type 1 diabetes.
Genetic and Environmental Factors
- Autoimmune diseases are often multifactorial, involving a combination of genetic predisposition and environmental triggers such as infections or drug treatments.
- Specific alleles like class 2 MHC alleles are associated with autoimmune diseases, influencing antigen presentation.
- Examples include arthritis where certain genes like PTPN22 are highly expressed due to their ability to present collagen epitopes effectively.
Disease Specific Associations
- Diseases like celiac disease show strong associations with specific alleles such as HLA-DQ2 and HLA-DQ8, indicating a genetic susceptibility.
- Not all individuals with these alleles develop the disease; other factors like breastfeeding, infections, or frequency play a role in disease development.
Mechanisms of Autoimmunity: Molecular Mimicry and Drug-induced Responses
This segment explores mechanisms behind autoimmunity including molecular mimicry where pathogens resemble self-antigens leading to immune responses. Additionally, drug-induced autoimmunity is discussed with examples like heparin-induced thrombocytopenia.
Molecular Mimicry
- Molecular mimicry occurs when pathogen antigens resemble self-antigens, leading to immune system confusion and potential tissue damage.
- Examples include streptococcal infections triggering immune responses against heart antigens due to molecular similarities.
Drug-induced Autoimmunity
- Certain drugs can induce autoantibody production by binding to platelet membrane proteins, causing immune reactions against newly formed antigens.
- Heparin-induced thrombocytopenia is a common example where heparin binds to platelet factor 4 (PF4), inducing an immune response that leads to thrombosis.
Pathophysiology of Thrombocytopenia in Drug-induced Reactions
This part focuses on the pathophysiology of drug-induced thrombocytopenia elucidating how drug interactions lead to platelet destruction through complex immune responses.
Platelet Destruction Mechanism
- In drug-induced reactions like heparin-PF4 complex formation, antibodies bind to platelets via Fc receptors leading to platelet activation, aggregation, release of pro-inflammatory substances causing thrombosis.
Infections as Triggers for Autoimmune Responses
The discussion highlights how infections can trigger autoimmune processes by attracting autoreactive clones or increasing inflammatory cytokines at infection sites.
Infection-triggered Autoimmunity
- Infections can attract autoreactive clones through chemotactic gradients or increase pro-inflammatory cytokines at infection sites activating autoreactive clones.
Autoimmune Disorders: Multiple Sclerosis Pathogenesis
Understanding Multiple Sclerosis and Psoriasis
In this section, the speaker discusses the pathophysiology of multiple sclerosis and psoriasis, highlighting key mechanisms and characteristics of these autoimmune diseases.
Damage in Multiple Sclerosis
- The damage in multiple sclerosis can be visualized through MRI scans, showing scarring and plaques that reflect irreparable damage to myelin.
- Autoimmune clones attacking myelin sheaths lead to a sequence of damage, ultimately resulting in axonal loss.
- Early treatment with disease-modifying medications is crucial upon multiple sclerosis diagnosis to prevent further damage.
Role of Myelin Repair Potential
- Myelin repair potential remains an intense area of research interest due to its implications for self-repair capabilities.
- Once axons are damaged in multiple sclerosis, they cannot be repaired due to zone-specific damage that occurs even in early disease stages.
Immune Response Mechanisms in Multiple Sclerosis
This section delves into the immune response mechanisms involved in multiple sclerosis, focusing on experimental models and cellular interactions contributing to neuroinflammation.
Activation of Effector Cells
- Experimental models using encephalomyelitis induction show how dendritic cells become activated by myelin antigens and adjuvants.
- Effector cells, including Th1 and Th17 types, enter the bloodstream from lymph nodes and breach the blood-brain barrier to reach the central nervous system.
Inflammatory Cascade
- Infiltration of effector cells leads to reactivation upon encountering myelin substances or via antigen-presenting cells.
- This recruitment triggers the production of reactive oxygen species and cytotoxic molecules that contribute to myelin sheath damage and subsequent neurological deterioration.
Pathogenesis of Psoriasis
The discussion shifts towards psoriasis, an autoimmune skin condition characterized by plaque formation and inflammation.
Psoriasis Characteristics
- Psoriasis affects 1% to 3% of the population, manifesting as thickened red plaques with well-defined borders on the skin.
- Histological analysis reveals acanthosis (skin thickening) and leukocyte infiltration as hallmarks of psoriatic lesions.
Role of Th17 Cells
- Th17 cells play a central role in psoriasis pathogenesis by responding to specific antigens along with triggers like trauma or infections.