580 likes | 628 Views
Introduction to the immune system. Lisbeth N. Fink Nutritional Immunology Group – CBS - DTU. Protecting borders to the outside world. Challenges Discrimination between self and non-self bacteria fungi vira parasites (transplants) Evolution Dealing with non-pathogenic factors.
E N D
Introduction to the immune system Lisbeth N. Fink Nutritional Immunology Group – CBS - DTU
Protecting borders to the outside world • Challenges • Discrimination between self and non-self • bacteria • fungi • vira • parasites • (transplants) • Evolution • Dealing with non-pathogenic factors
Outline • Cells and tissues of the immune system • Innate and adaptive immunity • Antigen presentation • Immunity vs. tolerance
Hæmatopoesis = creation of blood cells Red blood cells Leukocytes/ White blood cells Lymphocytes Adaptivt/Specifikt Medfødt/Uspecifikt
Second line of defense: Humoral factors • Humor = liquid • (From greek, 4 humors controlling health and mood: blood, phlegm, yellow and black bile) • Antibodies – specific • pathogen recognition • Complement system • – non-specific recognition • Reactive oxygen species • (ROS) – bactericidal activity
Haematopoieisis Red blood cells Leukocytes/ White blood cells Lymphocytes Adaptive/Specific Innate/Non-specific
Outline • Cells and tissues of the immune system • Innate and adaptive immunity • Antigen presentation • Immunity vs. tolerance
T cells B cells Antibodies Memory MHC - HLA Diversity Somatic hypermutation Polymorphism Granulocytes Monocytes Macrophages Dendritic cells NK cells NK T cells Complement Pattern recognition Characteristics of the two parts Adaptive/Specific Innate/Non-specific
T cells B cellsAPC Antibodies Memory MHC - HLA Diversity Somatic hypermutation Polymorphism Granulocytes APC Monocytes APC Macrophages APC Dendritic cells APC NK cells NK T cells Complement Pattern recognition Characteristics of the two parts Adaptive/Specific Innate/Non-specific
Antigen uptake - phagocytosis Phagocytic cells: Granulocytes Monocytes Macrophages Dendritic cells
Pattern recognition in APC Takeda & Akira, Int. Immunol. 2005
Recognition of ”pathogenic” structures • Direct recognition of pathogens – ”danger signals” (viral, bacterial, fungal, parasitic) • Innate immune system alerts the adaptive immune system in parallel with antigen-presentation • Must recognize vital structures!
Outline • Cells and tissues of the immune system • Innate and adaptive immunity • Antigen presentation • Immunity vs. tolerance
T cells Recognizes MHC I on all cells Recognizes MHC II on APC Kills: Infected cells Tumour cells Helps: B-cells T cells Macrophages
MHC I and II Tc TH
Antigen presentation • 3. Signal • Cytokines ↔ Cytokine • receptors 2. 1. Activation Proliferation Help or Killing
Induction of immunity • Importance of CD4+ T cells: • CD4+ T cells are central in providing help for CD8+ T cell and B cell activation
Killing of virus-infected cells Apoptosis is induced due to the action of perforin (making pores), and the granule-containing granzyme B, a serine protease which activates a variety of caspases.
Second line of defense: Humoral factors • Humor = liquid • (From greek, 4 humors controlling health and mood: blood, phlegm, yellow and black bile) • Antibodies – specific • pathogen recognition • Complement system • – non-specific recognition • Reactive oxygen species • (ROS) – bactericidal activity
Preference for ”opsonized” bacteria Antigen uptake
Outline • Cells and tissues of the immune system • Innate and adaptive immunity • Antigen presentation • Immunity vs. tolerance
What about ’endogenous’ challenges? • Cancer cells – tumor antigens • Immune reactions within self-tissues: autoimmunity • Discontinuation of immune responses • …and reactions to harmless environmental factors: allergy (to food, pollen, fur etc.) • Immunity vs. Tolerance
The central issue: immunity versus tolerance • The immune system has the tremendous task to eliminate pathogens and eradicate arising tumours, while preventing auto-reactive responses that are harmful to the host. • In keeping with balancing this dual task, a complex interplay between immune cells exists and many stimulatory and inhibitory circuits are in place. • Deregulation of this intricate balance is directly associated with human diseases, ranging from inflammatory and autoimmune disorders to infection and cancer.
Definitions • Immunity: • Effective clearance of all infectious agents and tumours by immune cells • Tolerance: • Hindering of autoimmunity, and down-regulation of immune responses after clearing of pathogens
Discrimination between “self” and “non-self” Every immune response depends on regulation at the single-cell level
Different lines of tolerance induction • Regulation of tolerance is two-legged: • Central regulation (thymus, bone marrow) • Peripheral regulation
Central T cell tolerance Ideally, selected T cells contain TCRs with low affinity for self MHC in combination with “non-self” antigens, but usually auto-reactive T cells also exists in the periphery
Peripheral tolerance • Ways of down-regulating immune responses in the periphery: • Anergy – no co-stimulatory signal • Deletion - by apoptosis • Active suppression (by naturally-arising or peripherally induced Tregs)
Antigen presentation • 3. Signal • Cytokines ↔ Cytokine • receptors 2. 1. Activation Proliferation Help or Killing