Lesson_01_Introd_Estela_19_20.pdf

Lesson 1: introduction 1.- Definitions 2.- Innate and adaptive immunity 3.- Humoral and cellular responses 4.- Primary and secondary responses 5.- Phylogeny of the Immune system  First historical data Greece. (464-404 b.C.) Tucídides reports that in an epidemy during...

Lesson 1: introduction 1.- Definitions 2.- Innate and adaptive immunity 3.- Humoral and cellular responses 4.- Primary and secondary responses 5.- Phylogeny of the Immune system  First historical data Greece. (464-404 b.C.) Tucídides reports that in an epidemy during the Peloponeso war, only people that had already been infected and survived the disease took care of new patients. It had been observed that those people would not suffer the disease again: they were immune. China. (XI century b. C) People that had smallpox in childhood would not suffer it again. They tried to induce protection by a mild form of infection caused by inhalation of smallpox dust.  Century XVIII: smallpox was a very severe disease in Europe; causing the death of 10% of the population.  Morbimortality was even worse in places of recent European colonisation, America in particular. Jenner and smallpox vaccine Main vaccines introduction Efficacy of vaccination against frequent diseases 1.- Definitions  Immunology: Discipline that studies the system of defense against organisms or potentially harmful substances that try to penetrate into the body and modify the homeostasis Immune system (IS): Cells and organs committed to the defense of the body. Together with the nervous and endocrine systems, IS functioning is based on cellular communication. Immune response: Coordinated action of the IS against the entrance of non-self substances into the body. 2.- Innate and adaptive immune response (or immunity) 2.1. – Innate (or natural) immunity 1. CELLS  Innate Immunity Cells Neutrophils: Phagocytosis of opsonized microorganisms (Complement, IgG, IgM) Eosinophils: Defense against helmints (IgE) Basophils/Mast cells: IgE receptors. Degranulation→ Mediators release (histamine) Immediate hypersensitivity (= allergy): Vasodilation Smooth muscle contraction Inflammation Monocytes/Macrophages: Phagocytosis and antigen presentation NK cells: destruction of malignant and virus-infected cells Dendritic cells  INNATE IMMUNE RESPONSES A) Local inflammation – Immune cells accumulation – Modification of tissue microenvironment B) Systemic modifications - Hyperthermia – Blood chemistry changes (Acute phase molecules) – Neutrophilia : Modification of systemic cellular profile  LOCAL INFLAMMATION Macrophages are activated. This implies the liberation of cytokines that modify the microenvironment around: Endothelium: Increment of permeability and expression of adhesion molecules Mast cells: degranulation and histamine release, leukotriene, cytokines and chemokines production Neutrophils: activation of microbicide mechanisms Dendritic cells: migration to secondary organs and maduration NK cells: recruiting and increment of cytotoxic capacity  Systemic modifications: 1. Acute phase proteins A) They function as microbistatics or microbicides. B) They protect from harmful effects associated to inflammation Humoral factors: complement α-1 antitripsin. activation and phagocytosis enhancement. Complement factors: Anti-oxidant compounds Factor B,C3 and C5. Hepatocyte Ions sequesters: Transferrin, Ceruloplasmin. Coagulation factors: Fibrinogen, Enzymes: Prothrombin, Plasminogen. Phospholipase A2.  Systemic modifications: 2. Body temperature augmentation Characteristic of acute phase response in infections, mainly from bacterial origin. Caused by action of cytokines (IL-1,IL-6,TNF-α) on hypothalamus. Effects of temperature augmentation: Microbistatic against pathogens, microbial proliferation inhibitor Neutrophilia  Systemic modifications: 3. Neutrophilia Neutrophilia: on bone marrow, temperature augments production of mature neutrophils and accelerates differentiation. Increases peripheral number of neutrophils, even immature forms. 2.2. - Adaptive (acquired) Immunity CELLULAR COMPONENTS Adaptive immune response phases  Innate – Adaptive Immunity connection Innate immunity is not only a first line defense, but it also plays a role in initiating the adaptive response. Example: Macrophages and antigen presentation Both responses are complementary. Example: complement and antibodies 3.- Humoral and Cellular Immunity 4.- Primary and secondary responses  Primary and secondary responses Concept: In a second exposition to antigen, the response is stronger and more effective: suffering the infection confers immunity. Mechanisms: Memory lymphocytes: remain after clonal amplification. When a lymphocyte encounters its specific antigen, it proliferates and gives rise to a progeny of identical antigeneic specificity (CLONE). Some of these lymphocytes survive for a long time and in a second encounter with antigen they proliferate again and amplify the response. Secondary response: advantages over primary Cellular immunity: Earlier and amplified response. Humoral immunity (antibodies production) : More intense More rapid Longer time Class switch (IgM to IgG, IgA o IgE) Stronger antigen affinity 5.- Immune system phylogeny  All pluricelular organisms have defense tools against microbes Most ancient system is innate immunity, already present in invertebrates Adaptive immunity only appears in vertebrates: expression of antigen receptors submitted to somatic recombination