Chapter 14. Part 2. An Introduction to Host Defenses Innate Immunities

Transcription

1 Chapter 14 Part 2 An Introduction to Host Defenses Innate Immunities

2 Host defense mechanisms To protect the body against pathogens, the immune system relies on a multilevel network of physical barriers, immunologically active cells, and a variety of chemicals First line of defense any barrier that blocks invasion at the portal of entry nonspecific Second line of defense protective cells and fluids; inflammation and phagocytosis nonspecific Third line of defense acquired with exposure to foreign substance; produces protective antibodies and creates memory cells specific

3 Recognition Actions of the second line of defense Inflammation Phagocytosis Interferon Complement

4 Function of the organs of defense Functions of a healthy functioning immune system: 1)Surveillance of the body 2)Recognition of foreign material 3)Destruction of entities deemed to be foreign Surveillance Body compartments are screened by circulating WBCs.

5 Body compartments participating in the immune system Immune system: Large, complex, and diffuse network of cells and fluids that penetrate into every organ and tissue The reticuloendothelial system The extracellular fluid The bloodstream The lymphatic system

6 Reticuloendothelial System (RES) Network of connective tissue fibers Interconnects other cells and meshes with the connective tissue network surrounding organs Dendritic cell Macrophage Neutrophil Inhabited by phagocytic cells Macrophages ready to attack and ingest microbes that passed the first line of defense Tissue cell (a) Reticular fibres (b)

7 Blood composition Whole blood consists of plasma and formed elements (blood cells) Serum is the liquid portion of the blood after a clot has formed minus clotting factors Plasma 92% water, metabolic proteins, globulins, clotting factors, hormones, and all other chemicals and gases to support normal physiological functions Buffy coat Plasma Red blood cells Serum Clot Unclotted Whole Blood Clotted Whole Blood

8 Whole blood = Cells + Plasma Serum = liquid portion of blood clotting factors Buffy coat Plasma Red blood cells Serum Clot (a) Unclotted Whole Blood (b) Clotted Whole Blood

9 Blood cells Hemopoiesis production of blood cells Stem cells undifferentiated cells, precursor of new blood cells Leukocytes White blood cells (WBCs) Granulocytes: lobed nucleus Agranulocytes: no lobes, rounded nucleus

10 Blood cells Neutrophil Basophil Eosinophil Monocyte Lymphocyte

11 CELLS FUNCTIONS Red blood cells Carry O 2 and CO 2 Platelets Neutrophils Basophils Eosinophils Monocytes Mast cells Dendritic cells Natural Killer (NK) cells Lymhocytes B cells T cells Involved in blood clotting and inflammation Phagocytes; active engulfers and killers of bacteria inflammatory events and allergies Active in worm and fungal infections, allergy, and inflammation Blood phagocytes that rapidly leave the circulation Tissue cells similar to basophills, trigger local inflammatory reactions and allergic symptoms Macrophages relatives; reside throughout the tissues and RES; involved in early immune reactions with foreign matter Related to T cells but displaying no specificity; active against cancerous and virally infected cells Primary cells involved in specific immune reactions to foreign matter Differentiate into plasma cells and form antibodies (humoral immunity) Perform a number of specific immune responses such as assisting B cells and cell- mediated immunity

12 Unique characteristics of Leukocytes Diapedesis migration of cells out of blood vessels into the tissues Chemotaxis migration in response to specific chemicals at the site of injury or infection Blood vessel Endothelial cell Margination Diapedesis Neutrophils Tissue space Chemotaxis Chemotactic factors

13 Granulocytes Neutrophils 55-90% - lobed nuclei with lavender granules; phagocytes Eosinophils 1-3% - orange granules and bilobed nucleus; destroy eukaryotic pathogens Basophils 0.5% - constricted nuclei, dark blue granules; release potent chemical mediators Mast cells: non-motile elements bound to connective tissue

14 Agranulocytes Lymphocytes 20-35%, specific immune response B (humoral immunity): activated B cells produce antibodies T cells (cell-mediated immunity): activated T cells modulate immune functions and kill foreign cells Monocytes, macrophages 3-7% - largest of WBCs, kidney-shaped nucleus; phagocytic Macrophages: final differentiation of monocytes Dendritic cells: trap pathogens and participate in immune reactions

15 Leukocytes

16 Erythrocytes and Platelets Erythrocytes: develop from bone marrow stem cells, lose nucleus, simple biconcave sacs of hemoglobin Platelets: formed elements in circulating blood that are not whole cells

17 1. Provides an auxiliary route for return of extracellular fluid to the circulatory system 2. Acts as a drain-off system for the inflammatory response Lymphatic system Tonsils (MALT) Thymus Axillary lymph node MALT in breast Spleen 3. Renders surveillance, recognition, and protection against foreign material Bone marrow GALT (Peyer s patches in small intestine) Inguinal lymph node MALT = mucosal-associated lymphoid tissue GALT = gut associated lymphoid tissue Lymphatic vessels

18 Lymphatic fluid Lymph is a plasma-like liquid carried by lymphatic circulation Formed when blood components move out of blood vessels into extracellular spaces Made up of water, dissolved salts, 2-5% proteins Transports white blood cells, fats, cellular debris, and infectious agents

19 Lymphatic vessels Lymphatic capillaries permeate all parts of the body except the CNS, bone, placenta, and thymus Thin walls easily permeated by extracellular fluid which is then moved through contraction of skeletal muscles Functions to return lymph to circulation; flow is one-direction toward the heart eventually returning to blood stream Lymphatic system Lymphatic capillaries Lymph nodes Lymphatic trunks Collecting ducts Collecting vessels Lymph flow Lymphatic capillaries Cardiovascular system Capillaries Subclavian vein Superior vena cava Blood flow Capillaries

20 Lymphoid organs and tissues Thymus gland Blood vessels Cortex Medulla

21 Lymphoid organs and tissues Primary lymphoid organs - Sites of lymphocytic origin and maturation - Thymus and bone marrow Secondary lymphoid organs and tissues - Circulatory-based locations such as spleen and lymph nodes - Collections of cells distributed throughout body tissues SALT, GALT, MALT SALT = skin associated lymphoid tissue MALT = mucosal-associated lymphoid tissue GALT = gut associated lymphoid tissue

22 Lymphoid organs Thymus high rate of growth and activity until puberty, then begins to shrink; site of T-cell maturation Lymph nodes small, encapsulated, bean-shaped organs stationed along lymphatic channels and large blood vessels of the thoracic and abdominal cavities Spleen structurally similar to lymph node; filters circulating blood to remove worn out RBCs and pathogens Miscellaneous GALT, Peyer s patch

23 Actions of the second line of defense Recognition Inflammation Phagocytosis Interferon Complement

24 Inflammatory response Classic signs and symptoms characterized by: Redness (rubor) increased circulation and vasodilation in injured tissues in response to chemical mediators Warmth (calor) heat given off by the increased blood flow Swelling increased fluid escaping into the tissue as blood vessels dilate edema; WBC s, microbes, debris, and fluid collect to form pus; prevents spread of infection Pain (dolor) stimulation of nerve endings Injury Rubor, calor Tumor Dolor, Loss of function

25 The major events in inflammation

26 The chemical mediators of the inflammatory response

27 Fever nitiated by circulating pyrogens which reset the hypothalamus to ncrease body temperature; signals muscles to increase heat roduction and vasoconstriction Exogenous pyrogens products of infectious agents Endogenous pyrogens liberated by monocytes, neutrophils, and macrophages during phagocytosis; interleukin-1 (IL-1) and tumor necrosis factor (TNF)

28 Benefits of fever 1) Inhibits multiplication of temperature-sensitive microorganisms 2) Impedes nutrition of bacteria by reducing the available iron 3) Increases metabolism and stimulates immune reactions and protective physiological processes

29 Phagocytosis General activities of phagocytes: 1. To survey tissue compartments and discover microbes, particulate matter, and dead or injured cells 2. To ingest and eliminate these materials 3. To extract immunogenic information from foreign matter

30 Phagocytes and Phagocytosis Neutrophils general-purpose; react early to bacteria and other foreign materials, and to damaged tissue Eosinophils attracted to sites of parasitic infections and antigenantibody reactions Macrophages derived from monocytes; scavenge and process foreign substances to prepare them for reactions with B and T lymphocytes

31 Recognition of foreign cells Protein receptors within cell membrane of macrophages, called Toll-like receptors Detect foreign molecules and signal the macrophage to produce chemicals to stimulate an immune response Toll-like receptor Foreign molecule Nucleus Macrophage Cytokines Interleukins Inflammatory mediators

32 Mechanisms of phagocytic recognition, engulfment, and killing Chemotaxis and ingestion: phagocytes migrate and recognize PAMPs Phagosome Phagolysosome: lysosome fused with phagosome (death ~30 minutes) Destruction and elimination Oxygen-dependent system (respiratory burst) Liberation of lactic acid, lysozyme, and nitric oxide

33 Phagocytosis How the Immune System Works- Sompayrac, 4 th edition

34 Interferon Small protein produced by certain WBCs and tissue cells Interferon alpha lymphocytes and macrophages Interferon beta fibroblasts and epithelial cells Interferon gamma T cells Produced in response to viruses, RNA, immune products, and various antigens, they bind to cell surfaces and induce expression of antiviral proteins and inhibit expression of cancer genes Virus infection Assembly Viral of viruses nucleic acid Virus release Degrades virus nucleic acid Blocks virus replication Synthesis of antiviral proteins IFN gene Synthesis of IFN Attachment of IFN to special receptor Signals activation of genes Infected cell Nearby cell

35 Complement Consists of 26 blood proteins that work in concert to destroy bacteria and viruses Complement proteins are activated by cleavage (cascade reaction) Liver is main source of complement proteins Pathways Classical: activated by the presence of antibody bound to microorganism Lectin pathway: nonspecific reaction of a host serum protein that binds mannan Alternative: begins when complement proteins bind to normal cell wall and surface components of microorganisms

36 4 Stages in the Complement Cascade 1) Initiation 2) Amplification and cascade 3) Polymerization 4) Membrane attack Jason R Dunkelberger and Wen-Chao Song. Cell Research (2010) 20:34 50.

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38 Effectors of complement system Jason R Dunkelberger and Wen-Chao Song. Cell Research (2010) 20:34 50.

39 Overview of the major host defenses