Anticuerpos como Herramientas Terapéuticas e Hipersensibilidad IV PDF

# Anticuerpos como herramientas terapéuticas e Hipersensibilidad IV ## 12 Noviembre 2024 ### Introducción - Los anticuerpos son proteínas del sistema inmune adaptativo - No solo tienen actividad protectora - Diagnóstica - Terapéutica - Futuro de la terapéutica médica* > Corominas et al....

# Anticuerpos como herramientas terapéuticas e Hipersensibilidad IV ## 12 Noviembre 2024 ### Introducción - Los anticuerpos son proteínas del sistema inmune adaptativo - No solo tienen actividad protectora - Diagnóstica - Terapéutica - Futuro de la terapéutica médica* > Corominas et al. Hypersensitivity Reactions to Biological Drugs J Investig Allergol Clin Immunol 2014; Vol. 24(4): 212-225 ### Anticuerpos monoclonales (mAbs) > Buckley, R. H., et. al., (2014). Primary immunodeficiency diseases. In Middleton's Allergy ### Definición - Anticuerpo homogéneo producido por una célular híbrida producto de la fusión de un clon de linfocitos B descendiente de una sola y única célula madre y una célula plasmática tumoral. > Corominas et al. Hypersensitivity Reactions to Biological Drugs J Investig Allergol Clin Immunol 2014; Vol. 24(4): 212-225 ### Generalidades - El grado humanizado del anticuerpo se indica por la silaba que precede a la terminación "mab" > Corominas et al. Hypersensitivity Reactions to Biological Drugs J Investig Allergol Clin Immunol 2014; Vol. 24(4): 212-225 The image shows a diagram of an antibody, with labels for the following components: * VL, VH * CH1, CI * Bisagra * CH2 * Fc * CH3 * Fab * Cadenas pesadas * Cadenas ligeras * Regiones determinantes de complementariedad - **-zumab**: mAb humanizado, contiene 2-5% de la fracción múrida en regiones hipervariables del fragmento Fab. - **-ximab**: mAb quimérico, 25% fracción múrida en la fracción Fab + 75% fracción humana de IgG. - **-mumab**: mAb humano ### Sitios de acción The image shows a diagram of the different sites of action for different monoclonal antibodies used in the treatment of asthma. It includes details such as: * **Airway epithelial cells:** Tezepelumab, TSLP * **Dendritic cell and Th0 cell:** IL-4 * **Th2 cell:** Dupilumab, IL-4R * **ILC2 cell:** IL-5, IL-4 * **B cell:** Dupilumab, IL-4R * **Eosinophil:** Mepolizumab, Reslizumab, IL-5, IL-5R * **Mast cell:** Omalizumab, IgE * **Fibroblasts:** Tralokinumab, IL-13 * **Epithelial cells:** Tralokinumab, IL-13 * **Smooth muscle cells:** Benralizumab, IL-5 > Varricchi, G, Ferri, S, Pepys, J, et al. Biologics and airway remodeling in severe asthma. Allergy. 2022; 77: 3538- 3552. ### Omalizumab - Anticuerpo monoclonal recombinante humano que inhibe de manera selectiva la unión de IgE a los receptores de alta afinidad en los mastocitos y basófilos. - Omalizumab: 95% humano, 5% múrido > Boushey Jr HA. Experiences with monoclonal antibody therapy for allergic asthma. J Allergy Clin Immunol 2001; 108. S77-83 The image shows an antibody with labels for the following components: * Heavy chain * Light chain * Mouse CDR * Framework changes ### Omalizumab - **Asma**: Aprobado en > 6 años para asma alérgica moderado-grave - **Urticaria crónica**: Aprobado para > 12 años con UCE refractaria a antihistamínicos The image shows two images of the medication Xolair, and one of a syringe. > Corominas et al. Hypersensitivity Reactions to Biological Drugs J Investig Allergol Clin Immunol 2014; Vol. 24(4): 212-225 ### Dupilumab - Actúa sobre la subunidad alfa del receptor de la IL-4, bloqueando la IL-4 y la IL-13, los mediadores principales de la vía TH2. The image shows a diagram with details of how dupilumab blocks the action of IL-4 and IL-13. It includes labels such as: * Dupilumab * IL-4 * IL-13 * IL-4Ra * yC * IL-4Ra * IL-13R01 * JAK1 * JAK3 * JAK1/2 * TYK2 * Cytoplasm * STAT5 * STAT6 * Type I receptor * STAT5 * STAT6 * Type 2 receptor > Actas Dermosifiliogr. 2018;109:230-40 > Corominas et al. Hypersensitivity Reactions to Biological Drugs J Investig Allergol Clin Immunol 2014; Vol. 24(4): 212-225 ### Dupilumab: Mecanismo de acción The image shows a diagram that depicts the mechanism of action of dupilumab in relation to different types of cells involved in allergic response: * **Germinal Center:** Tfh, B-cell, IgE * **Eosinophils:** IL-5 * **APC:** IL-4 * **Basophils:** IL-4 * **Th0 cell:** TFGB * **Treg:** IL-4, IL-4/IL-13/IL-17 * **M2 Macrophages:** IL-4 * **ILC2 cell:** IL-4, IL-4/IL-13 * **ExTreg:** IL-4/IL-13/IL-17 > Harb, Hani, and Talal A. Chatila. "Mechanisms of dupilumab." Clinical & Experimental Allergy 50.1 (2020): 5- 14. ### Dupilumab - **Dermatitis atópica**: Aprobado para > 6 meses con formas graves o exacerbaciones frecuentes - **Asma**: > 6 años para asma moderada a grave - **RNSc con poliposis nasal**: > 12 años The image shows a picture of the medication DUPIXENT (dupilumab), along with a syringe. > Grey A, Katelaris CH. Dupilumab in the treatment of asthma. Immunotherapy. 2019 ### Mepolizumab, Reslizumab y Benralizumab - Anticuerpo anti-IL-5 - **Asma**: Aprobado en > 12 años para asma grave eosinofílica - **Nucala (Mepolizumab)**: Poliposis nasal The image shows a diagram with details on how Mepolizumab and Reslizumab bind to IL-5 and block its binding to IL-5R, and thus inhibits signal transduction in eosinophils. It includes details such as: * Reslizumab * Mepolizumab * IL-5 * Binding * No Binding * Eosinophil * IL-5R * Signal transduction * No Signal transduction > Corominas et al. Hypersensitivity Reactions to Biological Drugs J Investig Allergol Clin Immunol 2014; Vol. 24(4): 212-225 The image also shows 3 vials of Nucala (Mepolizumab), 2 vials of CINQAIR (Reslizumab), and a box of Fasenra (Benralizumab). > Corominas et al. Hypersensitivity Reactions to Biological Drugs J Investig Allergol Clin Immunol 2014; Vol. 24(4): 212-225 ### Tezepelumab - Unión especifica (antagonismo) a la TSLP - Reduce niveles de biomarcadores T2 - Disminuye eosinófilos e IgEt en sangre. - Disminuye óxido nítrico exhalado (FeNO). The image shows a diagram of the different ways tezepelumab can act on different cells involved in inflammatory response: * Allergens * Pollutants/smoke * Bacteria * Viruses * Physical Injury * Other External Stimuli * Epithelium * Dendritic cells * B cells * IgE * Mast cells * Airway smooth muscle cells * ILC2 * Dendritic cells * Neutrophils * Eosinophils * Leukotrienes * Th17 * Th0 * Th2 * Tfh * Treg * L-5R * IL-5 * IL-13 * IL-4 * IL-17 * IL-17A > Grey A, Katelaris CH. Dupilumab in the treatment of asthma. Immunotherapy. 2019 ### Tezepelumab - **Aprovación FDA (2021) / COFEPRIS (2023)** - Asma grave >12 años - sin importar fenotipo - Aplicación 1vez/mes - ¿más aprobaciones? The image shows a picture of the medication TEZSPIRE (tezepelumab-ekko), along with a syringe. > Grey A, Katelaris CH. Dupilumab in the treatment of asthma. Immunotherapy. 2019 ### Hipersensibilidad tipo IV (trasplante) ### Generalidades - Opción terapéutica de remplazo ampliamente utilizada - El trasplante de células/tejidos no idénticos genéticamente lleva a rechazo - El CMH o HLA son los responsables de las reacciones del rechazo. > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 The image shows two boxes, one labeled "Donador" and the other "Receptor u hospedero", connected by an arrow. ### Definiciones | Tipo de trasplante | Descripción | |---|---| | Autólogo | Mismo individuo | | Alogénico | Entre dos individuos relacionados genéticamente | | Singénico | Entre dos individuos idénticos genéticamente | | Xenogénico | Trasplante entre diferentes especies | > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Fisiopatología The image shows two diagrams depicting the different stages of the immune response after transplantation. The first diagram depicts the sensitization stage, which includes the process of T cell activation by direct and indirect antigen presentation. The second diagram shows the rejection stage, which details how effector T cells from the recipient migrate to the allograft and initiate the rejection process. It includes labels such as: * Sensitization * Donor dendritic cell * Allograft (kidney) * Afferent lymph vessel * Recipient dendritic cell * Donor alloantigen * Transport of alloantigens to lymph node * Recipient lymph node * Recipient CD8+ effector cells * Blood * Recipient CD4+ effector cells * Efferent lymph vessel * Rejection * Killing of target cell * Allograft (kidney) * Donor tissue cell * Recipient APC * Activation of effector T cells by alloantigen: graft rejection * Recipient effector T cell * Migration of effector T cells to allograft > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Tipos de rechazo | Tipo de rechazo | Duración | |---|---| | Hiperagudo | Minutos a horas | | Agudo | Días a semanas | | Crónico | Meses a años | (Mas común) > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Rechazo hiperagudo - Trombosis intravascular del tejido/órgano recibido The image shows a diagram with details on the hyperacute rejection involving the activation of complement, endothelial damage, inflammation, and thrombosis. It includes labels such as: * Hyperacute rejection * Endothelial cell * Blood vessel * Alloantigen (e.g., blood group antigen) * Circulating alloantigen-specific antibody * Complement activation, endothelial damage, inflammation and thrombosis > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Rechazo hiperagudo - Incompatibilidad sanguínea - IgM The image shows a table that compares the red blood cell types, antibodies present, and antigens present in four blood groups: A, B, AB, and O. It includes labels such as: * Group A * Group B * Group AB * Group O * Red blood cell type * Type A * Type B * Type AB * Type O * Antibodies present * Anti-B * Anti-A * None * Anti-A and Anti-B * Antigens present * A antigen * B antigen * A and B antigen * None > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Incompatibilidad RH - Caso de una paciente Rh (-) con producto Rh (+) - Sensibilizacion The image shows two red blood cells: one with a D antigen and the other without, representing Rh+ and Rh- blood types, respectively. - Profilaxis con Rhogam - Después del nacimiento de un bebé Rh positivo. - Prevención de rutina entre las semanas 26 y 28 del embarazo. - Sangrado materno o fetal durante el embarazo. - Aborto u amenza de aborto. - Embarazo ectópico. > Marcio Cesar Salinas, La Inmunología en la Salud y la Enfermedad, 2 edicion. Capitulos 19 y 24 ### Rechazo agudo - Lesión al parénquima y vasos sanguíneos The image shows a diagram depicting the acute rejection process, where T cells attack the allograft, leading to parenchymal cell damage, interstitial inflammation, and endothelialitis. It includes labels such as: * Acute rejection * Alloantigen-specific CD4+ and CD8+ T cells * Parenchymal cells * APC * Alloreactive antibody * Endothelial cell * Parenchymal cell damage, interstitial inflammation * Endothelialitis > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Prevención - Minimizar la variación aloantigenica entre donador y receptor. - Mayor número de alelos del MHC entre el donante y el receptor. - Evaluacion de anticuerpos anti MCH - Medicamentos inmunosupresores > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Manifestaciones clinicas - Cutáneas - Gastrointestinal - Hepatopatia The image shows three pictures: one of a person's back with skin lesions, one of a person's knee with skin lesions, and one of a person's hand with skin lesions. > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Rechazo crónico The image shows a diagram demonstrating the chronic rejection process, which involves inflammation in the vessel wall, intimal smooth muscle cell proliferation, and vessel occlusion. It includes labels such as: * Chronic rejection * Macrophage * Vascular smooth muscle cell * Cytokines * APC * Cytokines * Alloantigen-specific CD4+ T cell * Chronic inflammatory reaction in vessel wall, intimal smooth muscle cell proliferation, vessel occlusion > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Manifestaciones clínicas - poiquiloderma - Liquen plano - Esclerosis - Liquen esclerotico - Morfea The image shows five pictures of different skin lesions on human skin. > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Manifestaciones clínicas - Pulmonar: Bronquiolitis obliterante - Gastrointestinal: nausea, vómitos, diarrea - Hígado: Transaminasemia - Genitales: inflamación y estenosis - Ocular: deficiencia de capa acuosa lagrima, cataratas, hiperemia conjuntival > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17 ### Tratamiento - Inmunosupresor - Biológicos - Antimetabolitos - Inhibidores de calcinuerina - Corticoesteroides > Abbas, A. K.,. (2015). Transplantation immunology. Chapter 17