Diapositiva 1

INMUNIDAD A INFECCIONESDra. M Isabel Oliver

1

Los mecanismos de defensa contra un germen estn mediados por los mecanismos efectores tanto de la I Natural como de la I Especfica.

El SI responde de diferentes formas a los diferentes tipos de grmenes, generalmente de la forma ms efectiva para combatir o eliminar al agente infeccioso.

Generalidades

GeneralidadesOrganismos Extracelulares bacteria Helmintos (eucariontes multicelulares)

Organismos Intracelulares bacteria protozoo (eucariontes unicelulares) virus hongos

Generalidades

La sobrevivencia y patogenicidad de los grmenes en el huesped estn influenciados por la habilidad del germen para evadir o resistir los mecanismos efectores de la RI.

En muchas infecciones el dao tisular y la enfermedad son causados por la respuesta del huesped al germen ms que por el germen mismo.

Bacterias Extracelulares

Mechanisms of pathogenicityExamples of human diseasesMicrobe

Skin infections; acute inflammation induced by toxins; cell death caused by pore-forming toxinsSystemic: enterotoxin ("superantigen")-induced cytokine production by T cells causing skin necrosis, shock, diarrheaSkin and soft tissue infections, lung abscess; systemic: toxic shock syndrome, food poisoningStaphylococcus aureus

Acute inflammation induced by various toxins, e.g., streptolysin O damages cell membranes (antiphagocytic action of capsular polysaccharides)PharyngitisSkin infections: impetigo, erysipelas; cellulitisSystemic: scarlet feverStreptococcus pyogenes (group A)

Acute inflammation induced by cell wall constituents; pneumolysin is similar to streptolysin OPneumonia, meningitisStreptococcus pyogenes (pneumococcus)

Son capaces de proliferar en : Circulacin Tejido conectivo Lumen respiratorio y gastrointestinal

Principal mecanismo patognico: Inflamacin y destruccin tisular (pigenas) Produccin de toxinas (LPS)

Bacterias ExtracelularesRI Natural: Fagocitosis Complemento R Inflamatoria

C3bBb

C4b2b

Bacterias Extracelulares

RI Natural: Fagocitosis Complemento R Inflamatoria

Bacterias ExtracelularesRI AdquiridaIgG e IgAIgGIgM / IgG

IL 17

Bacterias IntracelularesCytotoxin lyses cells and causes lung injury and inflammationLegionnaires' diseaseLegionella pneumophila

Listeriolysin damages cell membranesListeriosisListeria monocytogenes

Macrophage activation resulting in granulomatous inflammation and tissue destructionTuberculosis, leprosyMycobacteria

MicrobeExamples of human diseasesMechanisms of pathogenicity

Pathogenic microorganisms occupy various niches in host cells. Mycoplasmae adhere to the host-cell membrane to access nutrients from the cell.Other intracellular pathogens either associate with distinct stages of the phagosomalendosomal system or escape from the phagosome into the cytoplasm (for example, listeriae and rickettsiae). Mycobacteria, ehrlichiae, salmonellae and histoplasmae inhibit the maturation of phagosomes. Coxiellae and leishmaniae prefer acidic, hydrolase-rich late endosomal/lysosomal compartments, and leishmania vacuoles interact with autophagosomes the recycling system of the host cell. Legionellae and brucellae associate with membranes of the endoplasmic reticulum (ER) and chlamydiae and toxoplasmae associate with mitochondria.

Bacterias Intracelulares

LTh1

RI Innata y Adquirida Activacin de macrfagos Lisis celular por LTC

Rol del INF gama y la IL-12 en la RI a Bacterias Intracelulares

Bacterias Intracelulares

Bacterias IntracelularesBacteria intracelular citoplasmticaCooperacin CD4 y CD8 en RI a bacterias intracelulares

Bacterias Intracelulares

Restringe y previene la diseminacin bacteriana. Fibrosis y necrosis tisular.

VIRUS

Clula infectadaIFN a (fagocitos mononucleares)IFN b (fibroblast y otras clulas infectadas)

inh. replicacin viral (+) NK (+) expresin de MHC I en cl. Infectadas. (+) LTh1

VIRUS

VIRUS

DEFENSA ANTIVIRAL

VIRUS

Inhibicin del procesamiento antignico por algunos virusVIRUS

Mecanismos de evasin inmunolgica : Variacin antignica (mutacin). Inhibicin de la presentacin antignica. Produccin de molculas inmunosupresoras (protenas de unin a citoquinas) Infeccin y lisis de clulas inmunocompetentes.

PARSITOS Helmintos ProtozoosRI InnataProtozoos:Amebiasis Enf de ChagasMalariaLeishmaniasisToxoplasmosis. Fagocitosis

RI Adaptativa El principal mecanismo de defensa contra protozoos que sobreviven en macrfagos es la RI celular mediada por macrfagos activados por LTh1.

Ciclo de vida de Plasmodium (Malaria)

PARSITOSRI Adaptativaanopheles Dependiente del estado del ciclo de vida del parsito.

LTc

RI humoral

RI humoralProtozoos:

Helmintos

PARSITOS El principal mecanismo de defensa contra helmintos es la RI mediada por LTh2.

Anticuerpos Mastocitos (IgE) Eosinfilos (IgG, IgA) peristaltismo

Helmintos

PARSITOS El principal mecanismo de defensa contra helmintos es la RI mediada por LTh2. Anticuerpos Mastocitos (IgE) Eosinfilos (IgG, IgA)

Hongos

Micosis principalmente oportunistas en individuos inmunodeficientes o inmunodeprimidos por tratamientos anti cancergenos o transplantados.

Role of TLRs as activators of innate and adaptive immunity to fungi.The recognition of fungi and fungal pathogen-associated molecular patterns (PAMPs), mainly associated with fungal cell walls, leads to the activation of antifungal effector functions in phagocytes, such as respiratory burst and degranulation, and production of interleukin-12 by dendritic cells. This leads to inflammatory and protective antifungal T helper 1 (TH1)-cell responses.. GXM, glucoronoxylomannan from Cryptococcus neoformans; PLM, phospholipomannan from Candida albicans; Aspergillus fumigatus; Pneumocystis carinii.

HongosBalancing protection and immunopathology in fungal infections: a cooperative effort of the innate and adaptive immune systems.

Balancing protection and immunopathology in fungal infections: a cooperative effort of the innate and adaptiveimmune systems. Most fungi are detected and destroyed within hours by innate defence mechanisms mediated by phagocytes andopsonins through the involvement of distinct pattern-recognition receptors (PRRs). These mechanisms act immediately and arefollowed some hours later by an early induced inflammatory response, which must be activated by infection but does not generatelasting protective immunity. These early phases help to keep infection under control. In vertebrates, however, if the infectious organismcan breach these early lines of defence, an adaptive immune response will ensue, with the generation of antigen-specific T helper (TH)effector cells, regulatory T (TReg) cells and B cells that specifically target the pathogen and induce memory cells that prevent subsequent infection with the same microorganism. Dendritic cells sample fungi at the site of colonization/infection, transport them to the draining lymph nodes and activate disparate TH and TReg cells in a morphotype- and tissue-dependent manner. As the different TH-cell subsets release a distinct panel of cytokines, capable of delivering activating and inhibitory feedback signals to effector phagocytes, the activation of the appropriate TH-cell subset is instrumental in the generation of a successful immune response to fungi. Counterregulatory TReg cells might serve to dampen the excessive inflammatory reactions and contribute to the development of memory antifungal immunity. Solid and broken lines refer to positive and negative signals, respectively. IFN-, interferon-; IL, interleukin; TCR, T-cell receptor; TGF-, transforming growth factor-; TNF, tumour-necrosis factor.

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