Professional Documents
Culture Documents
Plan de la presentacion
Nomenclatura Componentes del sistema de defensas Las respuestas defensivas Control del sistema Alteraciones del sistema
Definitions
Immune system = cells, tissues, and molecules that mediate resistance to infections Immunology = study of structure and function of the immune system Immunity = resistance of a host to pathogens and their toxic effects Immune response = collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system
Homeostasis
destruction of abnormal or dead cells (e.g. dead red or white blood cells, antigenantibody complex) Other unknown functions?
Progenitor B
Clula pre-B
Clula NK
Progenitor T
Pre-Timocito Timocito inmaduro Timocito maduro Linfocito T Linfocitos Th y Tc Linfoquinas
Memoria
IgM
IgG IgA IgE IgD
Th1
IL-2 IL-3
Th2
IL-4
LINFOCITOS T
Representan el 60-70% de los linfocitos perifricos.
LINFOCITOS T
Marcadores comunes: CD2, CD7, CD3, CD28 CD4+: linfocitos T cooperadores/inductores CD8+: linfocitos T citotxicos/supresores CD4 y CD8 son mutuamente excluyentes Relacin CD4 : CD8 = 2 : 1
LINFOCITOS T
Molculas de Superficie de las Th y Tc
Linfocito T
10 Figure 21.7
LINFOCITOS T
Complejo Receptor de las Clulas T (TCR)
Sitio de unin del antgeno
LINFOCITOS B
Representan el 10- 20% de linfocitos circulantes Ubicados en centros germinales y folculos linfoides de ganglios, bazo, amgdalas y tejido linfoide asociado a mucosas Se transforman en clulas plasmticas para la secrecin de inmunoglobulinas Reconocen especficamente a los antgenos mediante su complejo receptor especfico BCR compuesto por cadenas y cadenas Ig Marcadores especficos: CD19, CD21.
LINFOCITOS B
Marcadores de superficie
CLULA PLASMTICA
Immunocompetent B or T cells
Display a unique type of receptor that responds to a distinct antigen Become immunocompetent before they encounter antigens they may later attack Are exported to secondary lymphoid tissue where encounters with antigens occur Mature into fully functional antigen-activated cells upon binding with their recognized antigen It is genes, not antigens, that determine which foreign substances our immune system will recognize and resist
14
Immunocompetent B or T cells
Red bone marrow
Key:
= Site of lymphocyte origin = Site of development of immunocompetence as B or T cells; primary lymphoid organs = Site of antigen challenge and final differentiation to activated B and T cells
Circulation in blood
1 Thymus
Immature lymphocytes
1
1 Lymphocytes destined to become T
Bone marrow
2
cells migrate to the thymus and develop immunocompetence there. B cells develop immunocompetence in red bone marrow.
2
Lymph nodes, spleen, and other lymphoid tissues
marrow as naive immunocompetent cells, lymphocytes seed the lymph nodes, spleen, and other lymphoid tissues where the antigen challenge occurs.
3 Mature (antigen-activated)
immunocompetent lymphocytes circulate continuously in the bloodstream and lymph and throughout the lymphoid organs of the body.
15
Figure 21.8
Reconocen las clulas propias a travs de un receptor que se une a molculas clase I (C) del MHC para inhibir sus accin citoltica
GRANULOCITOS
Fagocitos PMN Primera respuesta inflamatoria Secretan enzimas proteolticas (mieoloperoxidasa)
Migran de la sangre a los tejidos por factores quimiotcticos Sobrevida y proliferacin inducida por IL-5
Clulas circulante que, junto con los MASTOCITOS tisulares, secretan mediadores qumicos (Histamina) en las reacciones alrgicas tipo I mediadas por el entrecruzamiento de molculas IgE adheridas a los receptores de memebrana
Presentadoras de antgenos profesionales Se encuentran en superficies tisulares mucosos y cutneas. Captan los antgenos y migran a los ganglios linfticos
presentadores de
antgenos Poca o ninguna capacidad fagoctica.
CITOQUINAS
Molculas que inducen y regulan la respuesta inmunitaria mediante el establecimiento de interacciones con receptores especficos presentes en linfocitos, monocitos, clulas inflamatorias y clulas endoteliales.
24
Innate immunity
Based on genetic make-up Relies on already formed components Rapid response: within minutes of infection Not specific
same molecules / cells respond to a range of pathogens
Has no memory
same response after repeated exposure
NK Cell
Eosinophils
Neutrophil
Monocyte Macrophage
Mechanism of Phagocytosis
Microbes adhere to the phagocyte Pseudopods engulf the particle (antigen) into a phagosome Phagosomes fuse with a lysosome to form a phagolysosome Invaders in the phagolysosome are digested by proteolytic enzymes Indigestible and residual material is removed by exocytosis Chapter 21, Immune System 27
Mechanism of Phagocytosis
28
Figure 21.1a, b
The four cardinal signs of acute inflammation are redness, heat, swelling, and pain
Chapter 21, Immune System 29
4 Positive
chemotaxis Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents
3 Diapedesis 2 Margination
1 Neutrophils
Capillary wall
30 Figure 21.3
4. Antimicrobial Proteins
Enhance the innate defenses by:
Attacking microorganisms directly Hindering microorganisms ability to reproduce
Interferon Family
Interferons are a family of related proteins each with slightly different physiological effects Lymphocytes secrete gamma () interferon, but most other WBCs secrete alpha () interferon Fibroblasts secrete beta () interferon Interferons also activate macrophages and mobilize NKs FDA-approved alpha IFN is used: As an antiviral drug against hepatitis C virus To treat genital warts caused by the herpes virus
Chapter 21, Immune System 32
4 b. Complement
20 or so proteins that circulate in the blood in an inactive form Proteins include C1 through C9, factors B, D, and P, and regulatory proteins
Complement Pathways
34 Figure 21.5
35
36
Antigen is taken from site of infection to the lymph node either by the flow of lymph or is carried by a maturing dendritic cell that migrates along the lymphatics.
The dendritic cell presents antigen to nave T cells in the lymph node to initiate the T cell immune response.
Activated T cells, after they have expanded in number, leave the lymph node and go via the blood to sites of inflammation, where they look for their antigen to mediate cell-mediated immunity.
40
41
42
Passive Immunity
via breast milk, placenta
Artificial
Vaccination:
Live, killed, purified antigen vaccine
Antigens
Substances that can mobilize the immune system and provoke an immune response The ultimate targets of all immune responses are mostly large, complex molecules not normally found in the body (nonself)
48
Complete Antigens
Important functional properties:
Immunogenicity the ability to stimulate proliferation of specific lymphocytes and antibody production Reactivity the ability to react with the products of the activated lymphocytes and the antibodies released in response to them
Complete antigens include foreign protein, nucleic acid, some lipids, and large polysaccharides Chapter 21, Immune System 49
If they link up with the bodys proteins, the adaptive immune system may recognize them as foreign and mount a harmful attack (allergy)
Chapter 21, Immune System 50
Antigenic Determinants
Only certain parts of an entire antigen are immunogenic Antibodies and activated lymphocytes bind to these antigenic determinants Most naturally occurring antigens have numerous antigenic determinants that: Mobilize several different lymphocyte populations Form different kinds of antibodies against it Large, chemically simple molecules (e.g., plastics) have little or no immunogenicity
Chapter 21, Immune System 51
Antigenic Determinants
52 Figure 21.6
MOLCULAS DE HISTOCOMPATIBILIDAD
Molculas glucoproteicas de la superficie de las clulas que se unen a fragmentos peptdicos, a fin de presentarlos a las clulas T especficas
Complemento
TNF
B C
CLASE II
CLASE III
CITOQUINAS
CLASE I
CITOQUINAS
Molculas que inducen y regulan la respuesta inmunitaria mediante el establecimiento de interacciones con receptores especficos presentes en linfocitos, monocitos, clulas inflamatorias y clulas endoteliales.
CITOQUINAS Clasificacin
Citoquinas pro-inflamatorias que median la inmunidad natural: (IL-1, TNF-alfa, IFN-gamma, IL-8). Citoquinas que regulan el crecimiento, activacin y diferenciacin de los linfocitos (IL-2, IL-4, IL-10, IL-12 y TGF-beta). Ciroquinas que estimulan a otras clulas (IL-13 a linfocitos B, IL-5 a eosinfilos) Citoquinas que estimulan la hematopoyesis (GM-CSF, M-CSF, IL-3).
Clonal Selection
59
Figure 21.9
60
Clones that do not become plasma cells become memory cells that can mount an immediate response to subsequent exposures of the same antigen
Chapter 21, Immune System 61
Immunological Memory
Primary immune response cellular differentiation and proliferation, which occurs on the first exposure to a specific antigen
Lag period: 3 to 6 days after antigen challenge Peak levels of plasma antibody are achieved in 10 days Antibody levels then decline
Chapter 21, Immune System 62
Immunological Memory
Secondary immune response reexposure to the same antigen
Sensitized memory cells respond within hours Antibody levels peak in 2 to 3 days at much higher levels than in the primary response Antibodies bind with greater affinity, and their levels in the blood can remain high for weeks to months
63
Figure64 21.19
65
Figure 21.10
67
Figure68 21.11
RESPUESTA INMUNE
RECONOCIMIENTO DE ANTGENOS
Presentacin del pptido antignico en la fosa o canal de la molcula MHC clase I a un linfocito T CD8+ o citotxico
RESPUESTA INMUNE
PRESENTACIN DEL ANTGENO
Presentacin del pptido antignico por molculas MHC clase II a las clulas T CD4+ (helper). Importancia de las molculas co-estimulatorias CD28 y B7
CLULA T CD4*
Th 1
Th 0
Th 2
Alergeno
El tipo de anticuerpo resultante depende del perfil de citoquinas secretado por las clulas Th en respuesta a la presentacin del Ag
Antibodies
Also called immunoglobulins Constitute the gamma globulin portion of blood proteins Are soluble proteins secreted by activated B cells and plasma cells in response to an antigen Are capable of binding specifically with that antigen There are five classes of antibodies: IgD, IgM, IgG, IgA, and IgE
73
Inmunoglobulinas
Cada monmero se forma por la unin no covalente de dos cadenas livianas (kappa o lambda) y dos cadenas pesadas especficas de cada isotipo de inmunoglobulina: IgM cadenas IgG cadenas IgA cadenas IgE cadenas IgD cadenas Sus funciones biolgicas dependen del fragmento Fc: Fijacin de complemento (IgM e IgG) Unin a receptores celulares (IgG, IgM, IgE) Pasaje placentario (IgG) Pasaje a mucosas (IgA)
Antibody Targets
Antibodies themselves do not destroy antigen; they inactivate and tag it for destruction All antibodies form an antigen-antibody (immune) complex Defensive mechanisms used by antibodies are neutralization, agglutination, precipitation, and complement fixation
Chapter 21, Immune System 75
76
Figure 21.13
Figure80 21.14
81
83 Figure 21.15a
Figure 21.15b
84
Figure85 21.16
86 Figure 21.17a
Helper T Cells
87 Figure 21.17b
Mechanisms of Tc Action
89
Figure 21.18a, b