Ch 12. Host Defenses I: Nonspecific Defenses

Transcription

1 Ch 12 Host Defenses I: Nonspecific Defenses

2 SLOs Differentiate between innate and adaptive immunity. Define and explain PRRs and PAMPs Differentiate physical from chemical factors, and list examples of each. Describe the role of normal microbiota in innate resistance. Classify phagocytic cells, and describe the roles of granulocytes and monocytes. Define and explain phagocyte and phagocytosis. Explain the different stages of inflammation. Describe the cause and effects of fever. Describe the activativation of complement and describe the 3 outcomes. Explain the antiviral action of interferons Describe the role of transferrins and antimicrobial peptides in innate immunity.

3 12.1 Defense Mechanisms of the Host Immunity: Ability to. Susceptibility: Lack of to a disease. Innate immunity: Specific or not? Acquired immunity: Fig. 12.1

4 First Line of Defense: Physical Factors Skin & Mucous Membranes Epidermis Mucus of mucous membranes (Muco)-ciliary escalator Nose hairs Lacrimal apparatus Saliva Fig 16.3

5 Ciliary Defense Fig. 12.3

6 First Line of Defense: Nonspecific Chemical Factors Fungistatic fatty acids in sebum Skin ph and osmolarity Lysozyme in ph of gastric juice Transferrins in blood Also important: Antagonism and competitive exclusion of normal microbiota

7 Concept Check For each of the barriers below, state whether it is a physical, chemical, or genetic barrier. A. Hydrochloric acid of the stomach B. Sloughing of skin C. Lysozyme in saliva and tears D. Mutation in the gene for complement proteins E. Ciliary escalator

8 12.2 SECOND AND THIRD LINES OF DEFENSE: AN OVERVIEW Kick in if 1 st level of defense breached System of protective cells and fluids Includes inflammation and phagocytosis Rapid action at local and systemic levels Immune system responsible for: Body surveillance Recognition of foreign and abnormal material Destruction of these entities

9 The Body s Defensive Cells Can you name them? Host has PRRs (Pattern Recognition Receptors), e.g.: Toll-like receptors (TLRs). These attach to Pathogen-associated molecular patterns (PAMPs) Binding to PRRs induces release of cytokines that regulate the intensity and duration of immune responses

10 PRRs =? PAMP recognition

11 Formed Elements of Blood

12 Formed Elements in Blood Phagocytosis Phagocytosis Natural killer cells Destroy target cells Cell-mediated immunity Produce antibodies Blood clotting

13 Fig. 12.7

14 Fig Review Communicating Body Compartments on your own if necessary MPS Lymphatic system (Thymus, LNs, Spleen) Blood

15 12.3 The Second Line of Defense Generalized and nonspecific defenses that support and interact with specific immune responses: - Phagocytosis - Inflammation - Fever - Antimicrobial proteins

16 Phagocytosis: Cornerstone of Inflammation and Specific Immunity Neutrophils (part of PMNs): General purpose phagocytes Early inflammatory response to bacteria and other foreign materials and to damaged tissue Primary component of pus Monocytes and Macrophages Stationary Macrophages, e.g.: Fig. 12.8

17 Process/Phases of Phagocytosis Phagocytes engulf and kill microorganisms 1. Chemotaxis 2. Adherence: Recognition and attachment 3. Ingestion: Engulfment and creation of phagosome 4. Digestion: a. Fusion of phagosome with lysosome b. Destruction and digestion c. Residual body Exocytosis

18 Phagocytosis Various Mechanisms of Microbial Evasion of Phagocytosis!! Compare to Table 12.1

19 Inflammation Tissue damage leads to inflammatory response Purpose: Destroy pathogen limit spread of infection pave way for tissue repair Powerful defense mechanism but has potential to CAUSE disease. CVD due to chronic inflammation? Aging? Easily identifiable by 4 (5) cardinal signs: Rubor, Calor, Tumor, Dolor, and loss of function

20 The 3 Stages of Inflammation 1. Vascular Reaction: Vasodilation and increased vessel permeability due to histamine, chemokines, prostaglandins, and other cytokines 2. Pus Formation: Phagocyte migration and phagocytosis Margination and diapedesis (emigration) Chemotaxis(due to various cytokines and components of complement system) 3. Resulution: Tissue repair and scar formation. Depends on type of tissue

21 Diapedesis Margination Fig

22 Treatment of abscess? Inflammation review

23 Fever: An Adjunct to Inflammation Abnormally High Body Temperature. acts as body s thermostat. Normally set at? Exogenous vs. Endogenous pyrogens Endotoxin causes phagocytes to release interleukin 1 (IL 1). IL-1 acts on hypothalamus

24 Fever cont. Thermostat set to higher temp. Body reacts how? What happens when no more IL 1?

25 Beneficial effects of moderate fever: Inhibited pathogen growth Increased cellular metabolism e.g.: Increased transferrin production Increased T cell production Faster repair mechanisms Problematic effects of high fever: > 40.7 C (> 105 F) can be dangerous (Tachycardia, acidosis, dehydration, seizures) Death when > C

26 Antimicrobial Proteins 1. Interferons 2. Complement system 3. Antimicrobial peptides 4. Iron-binding proteins:

27 Interferons (IFNs) Family of small glycoproteins Not virus-specific -IFN and -IFN: Produced by virus infected cells. Mode of action is to induce uninfected cells to produce antiviral proteins (AVPs) that inhibit viral replication. -IFN: Produced by T- lymphocytes. Causes neutrophils and macrophages to phagocytize bacteria. Also involved in tumor immunology. Recombinant interferons have been produced. However short-acting and many side-effects. No effect on already infected cells.

28 Interferons (IFNs) Compare to Fig 12.11

29 Complement System Summary Series of >30 plasma (serum) proteins, activated in a cascade 3 outcomes of complement system: 1. Enhances inflammatory response, e.g.: attracts phagocytes 2. Increases phagocytosis through opsonization or immune adherence 3. Creates Membrane Attack Complexes (MACs) Cytolysis

30 The Complement System Compare to Fig Complement System Overview MAC

31 Opsonins (complement proteins or antibodies) coat bacteria and promote attachment of micro-organism to phagocyte Process is called Some bacteria evade complement system!!

32 Antimicrobial Peptides Produced by MM and phagocytes amino acids Cause bacterial cell lysis by inserting themselves into prokaryotic membranes Research looks for ways to turn them into therapeutic drugs Fig 12.13