Immune Defence Mechanisms Specific Defence Inflammation lecture from Physiology and Pathophysiology I 12. 10. 2021 M. Chalupová Immune System • system of defence against pathogens (bacteria, viruses, fungi, parasites) and tumor cells Nonspecific vs. Specific Defence Congenital vs. Acquired Immunity Congenital/Nonspecific Immunity Acquired/Specific Immunity Congenital vs. Acquired Immunity Surface Coverage First Line of Defense PHYSICAL FACTORS • skin • mucous membranes with lysozymes • lacrimal apparatus • salivary glands • vaginal secretions • flow of urine CHEMICAL FACTORS • sebum • lysozyme • gastric juice • vaginal secretions • urine Nonspecific Immune System Second Line of Defense • generalized responses to pathogen infection – do not target a specific cell type Phagocytes • neutrophils • eosinophils • macrophages Non-phagocytic leucocytes • basophils • mast cells Complement proteins Complement Specific Immune System Third Line of Defense HUMORAL (Ab-MEDIATED) IMMUNE SYSTEM • antibodies • B-cells (lymphocytes) CELL-MEDIATED SYSTEM • T-cells (lymphocytes) • helper T lymphocytes (TH) – produce and secrete chemicals that promote large numbers of effector and memory cells • cytotoxic T lymphocytes (TC) – eliminate infected body cells and tumor cells PHAGOCYTIC COMPONENTS • macrophages, monocytes, neutrophils • engulf foreign objects and inform T lymphocytes that a specific antigen is present Lymphocytes Humoral (Antibody-Mediated) Immunity • production of antibodies by B-cells • B-cells migrate to the lymphoid organs (spleen, lymph nodes) after maturation Antibodies • synthesized by B-cells in soluble or cell-bound form • each antibody recognizes one specific antigen • immunoglobulins (5 classes) – glycoproteins • Ig G • Ig M • Ig A • Ig D • Ig E Antibodies Structure Antibodies Function Antibodies Production • polyclonal • monoclonal Primary and Secondary Antibody Response Antigen-Antibody Response Cell-Mediated Immunity T-cells Cell-Mediated Immunity T-cells • T-cells recognize antigen associated with MHC (major histocompatibility complex) molecules in the cells – MHC class I – MHC class II Cell-Mediated Immunity T-cells TH helper cells • TH cells receptors recognize antigen on the surface of APC (macrophages) • release of cytokines and activation of TC and B-cells • TC cells directly attack and destroy infected cells CELL IMMUNE RESPONSE • B-cells (plasma cells) produce antibodies HUMORAL IMMUNE RESPONSE Helper TH-cells Cytotoxic TC-cells • recognize the antigens on the surface of the cells • destroy infected cells (bacteria, viruses, fungi, parasites), tumour cells, transplanted tissue Cytokines • small proteins involved in cell signaling • amplify and regulate immune responses • interleukins (IL-1, IL-2…) • TNF-α (tumor necrosis factor alpha) • INF-γ (interferon beta) • colony-stimulating factors (G-CSF) Complex Immune Reaction • antigen ingested and presented by antigen presenting cells (APC), like macrophages • helper T-cells react with MHC-antigen complex • T-cell activation, proliferation and cytokine production • cytokines activate other cells (macrophages, NK cells, TC cells) • IL-2 stimulates B-cells to be developed to plasma cells with antibody production Complex Immune Reaction Inflammation • defense reaction of the organism to injurious stimuli MAIN AIMS • to neutralize and destroy invading and harmful agents • to limit the spread of harmful agents to other tissues • to prepare any damaged tissue for repair Inflammation Local Signs of Inflammation FIVE CARDINAL-LOCAL SIGNS OF INFLAMMATION: 1. RUBOR (REDNESS) 2. TUMOR (SWELLING) 3. CALOR (HEAT) 4. DOLOR (PAIN) 5. FUNCTIO LAESA (LOSS OF FUNCTION) …. - ITIS Inflammation Inflammation SYSTEMIC MANIFESTATION OF INFLAMMATION: • fever • Increased leukocyte counts (leukocytosis) • lethargy • muscle catabolism • increased acute phase proteins (CRP C-reactive protein) • increased erythrocyte sedimentation rate (ESR/FW) Inflammation INFLAMMATION AND INFECTION ARE COMMONLY CONFUSED BECAUSE THEY OFTEN COEXIST INFECTION IS ALWAYS ACCOMPANIED BY INFLAMMATION; HOWEVER, NOT ALL INFLAMMATION INVOLVES AN INFECTIOUS AGENT Inflammation TISSUE DAMAGE and RELEASE OF VASOACTIVE and CHEMOTACTIC FACTORS VASODILATATION INCREASED PERMEABILITY NEUTROPHIL EMIGRATION PAIN REDNESS HEAT SWELLING SWELLING Causes of Inflammation Biological • bacteria, viruses, fungi, parasites Physical • UV, temperature, X-rays Chemical • strong acids and alkalies Endogenous • autoimmune diseases, disintegrating tumor cells Surgery, trauma