Microbiology: Basic and Clinical Principles Chapter 11 PDF

Microbiology: Basic and Clinical Principles Second Edition Chapter 11 Innate Immunity Presented by Janet Dowding, Ph.D....

Microbiology: Basic and Clinical Principles Second Edition Chapter 11 Innate Immunity Presented by Janet Dowding, Ph.D. St. Petersburg College Copyright © 2023 Pearson Education, Inc. All Rights Reserved Clinical Case Copyright © 2023 Pearson Education, Inc. All Rights Reserved Overview of the Immune System and Responses After reading this section, you should be able to: Describe the general features of innate and adaptive immunity. Describe how normal microbiota may impact immune responses and limit pathogens. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Immune Responses Are Classified as Either Innate or Adaptive (1 of 5) An immune response is a physiological process coordinated by the immune system to eliminate antigens Our immune system includes two key branches: innate and adaptive immunity The common features of both are that they: 1) recognize diverse pathogens 2) eliminate identified invaders 3) discriminate between self and foreign antigens Copyright © 2023 Pearson Education, Inc. All Rights Reserved Immune Responses Are Classified as Either Innate or Adaptive (2 of 5) Innate immunity – Inborn, ancient protection existing in one form or another in all eukaryotic organisms – Generalized responses – Nonspecific immunity Copyright © 2023 Pearson Education, Inc. All Rights Reserved Immune Responses Are Classified as Either Innate or Adaptive (3 of 5) Adaptive immunity – Only in vertebrate animals – Matures over time – Responses tailor to pathogens (specific) – Typically requires 4–7 days to fully activate (longer than innate immunity) – Exhibits memory Copyright © 2023 Pearson Education, Inc. All Rights Reserved Immune Responses Are Classified as Either Innate or Adaptive (4 of 5) Immune – Specific protection conferred by adaptive immune responses Susceptible – Not immune to a given pathogen and it may cause infection Copyright © 2023 Pearson Education, Inc. All Rights Reserved Immune Responses Are Classified as Either Innate or Adaptive (5 of 5) Table 11.1 Comparing Innate and Adaptive Immunity Feature Innate Immunity Tools Adaptive Immunity Tools Response time Immediate 4–7 days (after innate) Organisms that have it All eukaryotes (multicellular and Only vertebrates unicellular eukaryotic organisms) Distinguishes self from Yes Yes foreign Kills invaders Yes Yes Effective against diverse Yes Yes threats Tailors response to specific No Yes antigen Remembers antigen and No Yes amplifies response upon later exposure Copyright © 2023 Pearson Education, Inc. All Rights Reserved Collaboration Between Innate and Adaptive Immunity Immunity is three collaborating lines of defense IMMUNE SYSTEM INNATE ADAPTIVE IMMUNITY IMMUNITY Barrier Cellular and Adaptive defenses molecular defenses defenses Chapter 11 Chapter 12 Copyright © 2023 Pearson Education, Inc. All Rights Reserved Normal Microbiota Has a Role in Shaping Immune Responses and Conferring Protection (1 of 4) A wide collection of microbes live as symbiotic partners in and on our bodies while excluding others These microbes fine-tune our immune system to fight pathogens while training immune system to tolerate nonpathogens, food, and self-tissues Copyright © 2023 Pearson Education, Inc. All Rights Reserved Normal Microbiota Has a Role in Shaping Immune Responses and Conferring Protection (2 of 4) When our normal microbiota community changes, our immune system may become confused – overreact against harmless agents Some scientists suggest that these shifts could be linked to the rising incidence of allergy and autoimmunity Copyright © 2023 Pearson Education, Inc. All Rights Reserved Normal Microbiota Has a Role in Shaping Immune Responses and Conferring Protection (3 of 4) Hygiene hypothesis – Proposes a decrease in diversity and levels of microbes in our normal microbiota may negatively affect immune responses Understanding of how normal microbiota impacts our immune responses is in its infancy Copyright © 2023 Pearson Education, Inc. All Rights Reserved Normal Microbiota Has a Role in Shaping Immune Responses and Conferring Protection (4 of 4) Studies of germ-free animals has shown: – Microbe-free environments lead to underdeveloped immune systems – Normal microbiota have a direct role in immune system development Copyright © 2023 Pearson Education, Inc. All Rights Reserved Introduction to First-Line Defenses After reading this section, you should be able to: State the general function of first-line defenses. Describe mechanical, chemical, and physical barriers, and provide examples of each. Discuss the features that make skin a useful barrier. Explain what lysozyme is, what it does, and where it is found. Describe antimicrobial peptides and review their basic role. Copyright © 2023 Pearson Education, Inc. All Rights Reserved First-Line Defenses Aim to Prevent Pathogen Entry (1 of 2) First-line defenses – Attempt to prevent pathogen entry – Subcategorized as: ▪ Mechanical ▪ Chemical ▪ Physical barriers Copyright © 2023 Pearson Education, Inc. All Rights Reserved First-Line Defenses Aim to Prevent Pathogen Entry (2 of 2) MECHANICAL CHEMICAL Molecules that directly attack microbes Flushing, rinsing, and trapping actions or generate an environment that limits their survival Lysozyme in Tears rinse tears, mucus, microbes saliva, and away breast milk kills bacteria In the respiratory tract, Stomach acid limits mucus traps invaders and pathogens cilia sweep them away PHYSICAL A structural Skin blockade to entry (throughout body) Microbe blocked by skinAMPs destroy pathogens Copyright © 2023 Pearson Education, Inc. All Rights Reserved Mechanical Barriers Mechanical barriers rinse, flush, or trap pathogens to limit their spread into the body Examples include: – Tears washing debris/pathogens from eyes – Urine flushing microbes out of the body – Saliva limits what microbes adhere – Mucus membranes trap microbes ▪ line all body entrances as well as the stomach, intestines, lungs, and bladder – Mucociliary escalator sweeps away from the lungs and toward the mouth by ciliated cells Copyright © 2023 Pearson Education, Inc. All Rights Reserved Chemical Barriers (1 of 4) Chemical barriers may directly attack invaders or establish environments that limit pathogen survival in or on a particular tissue Examples: – Lysozyme—found in secretions (e.g., tears, breast milk) and breaks down bacterial cell walls – Hydrochloric acid in the stomach – Skin is relatively dry, salty, and slightly acidic – Fatty acids in sweat and earwax Copyright © 2023 Pearson Education, Inc. All Rights Reserved Chemical Barriers (2 of 4) Antimicrobial peptides (AMPs) – Proteins that destroy Stimulate AMPs Directly target a wide spectrum of leukocytes pathogen viruses, parasites, Cell wall bacteria, and fungi DNA Leukocytes will Plasma membrane Protein Modulate Inflammation Clear pathogens Disrupt plasma Target intracellular by phagocytosis membrane components and/or cell wall and/or processes Copyright © 2023 Pearson Education, Inc. All Rights Reserved Chemical Barriers (3 of 4) Antimicrobial peptides 1. Stimulate leukocytes ▪ Modulate inflammation ▪ Clear pathogens by phagocytosis 2. Directly target pathogens ▪ Disrupt plasma membrane and/or cell wall ▪ Target intracellular components and/or processes Copyright © 2023 Pearson Education, Inc. All Rights Reserved Chemical Barriers (4 of 4) Defensins are an important class of mammalian AMPs that rapidly kill invaders by inserting themselves into target cell membranes Copyright © 2023 Pearson Education, Inc. All Rights Reserved Physical Barriers Physical barriers include structures that physically block pathogen entry Examples: – Epithelial tissue is a main physical barrier in animals ▪ Lines every body cavity and body entrance – Skin is one of our most important physical barriers – Epidermis is made up of tightly compacted dead epithelial cells (enriched with proteins and lipids to serve as a water-resistant layer) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Introduction to Second-Line Defenses and the Lymphatic System After reading this section, you should be able to: Name the two categories of second-line defenses. Describe lymph, and how it is collected and filtered. Name the primary and secondary lymphoid tissues and describe their basic roles. Name the two main categories of leukocytes and describe how they differ. Explain several roles of molecular second-line defenses in innate immunity. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Second-Line Defenses Kick in When First-Line Defenses Are Breached Despite the general effectiveness of our first-line barriers, occasionally microbes still gain entry to the body Encounter the second-line defenses Consist of assorted molecular factors and leukocytes (white blood cells) Copyright © 2023 Pearson Education, Inc. All Rights Reserved The lymphatic System Collects, Circulates, and Filters Body Fluids Our immune system is interconnected with and dependent upon the lymphatic system Lymphatic system – Collection of tissues and organs – Collect, circulate, and filter fluid in body tissues before it is returned to the blood Copyright © 2023 Pearson Education, Inc. All Rights Reserved Lymph and Lymphatic Vessels (1 of 2) As blood is delivered to our tissues, some plasma exits the capillaries – Seeps into the small spaces becoming interstitial fluid – Lymphatic capillaries take up interstitial fluid and is then called lymph – Lymph travels to lymph nodes – It is screened for pathogens and filtered – Fluid is eventually channeled into veins – Returns to circulatory system Copyright © 2023 Pearson Education, Inc. All Rights Reserved Lymph and Lymphatic Vessels (2 of 2) Veins Heart Arteries After filtration at a lymph node, lymph Lymphatic trunk rejoins blood via veins and is again Lymph plasma. node Lymphatic vessels Plasma exits capillaries into the space between cells and is renamed interstitial fluid. Lymph Tissue Interstitial fluid from tissues enters lymphatic Plasma capillary and is renamed Interstitial fluid lymph. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Primary and Secondary Lymphoid Tissues (1 of 6) Primary lymphoid tissues – Site of production and maturation of leukocytes – Thymus and bone marrow Secondary lymphoid tissues – Filter lymph – Sample body sites for antigens – Lymph nodes, spleen, and mucosa-associated lymphoid tissue (MALT) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Primary and Secondary Lymphoid Tissues (2 of 6) PRIMARY LYMPHOID SECONDARY LYMPHOID TISSUES TISSUES Adenoids MALT Thymus Tonsils Lymph nodes Bone marrow Spleen Peyer’s patchesMALT Appendix Lymph nodes Copyright © 2023 Pearson Education, Inc. All Rights Reserved Primary and Secondary Lymphoid Tissues (3 of 6) Thymus – Butterfly-shaped organ located just behind the sternum (breastbone) near the heart – Site of T cell maturation Bone marrow – Spongy tissue located inside bones – Site for red and white blood cell production – Long bones of the arms and legs and pelvis are rich in bone marrow – Site of B cell maturation Copyright © 2023 Pearson Education, Inc. All Rights Reserved Primary and Secondary Lymphoid Tissues (4 of 6) Lymph nodes – Humans have 500–700 lymph nodes – Clustered in neck, underarm, and groin – Serve as filtering and screening centers for lymph before returning it to the bloodstream Upon detecting an invading microbe… – Leukocytes in a node rapidly multiply – Nodes become swollen – Swollen nodes are an indicator of infection Copyright © 2023 Pearson Education, Inc. All Rights Reserved Primary and Secondary Lymphoid Tissues (5 of 6) Spleen – Located in the upper left part of the abdomen, just under the diaphragm – Place where leukocytes look for invaders – Filters blood rather than lymph – Damaged erythrocytes removed Copyright © 2023 Pearson Education, Inc. All Rights Reserved Primary and Secondary Lymphoid Tissues (6 of 6) Mucosa-associated lymphoid tissue (MALT) – Diffuse system of lymphoid tissue – Found in all mucosal linings ▪ Play a key role in finding and fighting harmful microbes – Examples: ▪ Tonsils, appendix, and Peyer’s patches – MALT is often more specifically named based on its location in the body: ▪ GALT—gut-associated lymphoid tissue Copyright © 2023 Pearson Education, Inc. All Rights Reserved Leukocytes Are Essential in All Immune Responses (1 of 2) Leukocytes have diverse functions and are classified as: – Granulocytes—cells with granules in their cytoplasm that are visible when stained – Agranulocytes—lack granules in cytoplasm Copyright © 2023 Pearson Education, Inc. All Rights Reserved  Leukocytes Are Essential in All Immune Responses (2 of 2) Granulocytes Agranulocytes Neutrophils Eosinophils Basophils Mast cells Monocytes Dendritic cells Lymphocytes NK cells B cells T cells Appearance Multilobed Bilobed Bilobed nucleus Circular nucleus; Large horseshoe- Ruffled Small cells with a nucleus nucleus; obscured by dark dark staining shaped nucleus membrane with large rounded red-orange purple granules granules around long cytoplasmic nucleus and staining nucleus extensions limited cytoplasm granules Notes Highly phagocytic; Moderately Attack allergens Moderately Highly phagocytic Highly NK cells: innate fight many invaders, phagocytic; and parasites phagocytic; once they mature phagocytic; immunity to especially bacteria attack allergens attack bacteria, into macrophages activate adaptive viruses, bacteria, and viruses and parasites allergens, and (which can be fixed immune parasites, and parasites; reside or wandering); responses tumor cells in tissues activate adaptive B and T cells: immune responses adaptive immunity Copyright © 2023 Pearson Education, Inc. All Rights Reserved White Blood Counts as a Clinical Measure (1 of 2) Differential white blood cell (WBC) count – WBC differential – Rapid, inexpensive test used in diagnosis – Determines if any leukocytes are over- or underrepresented in a patient’s blood – Leukocytosis—increase in leukocytes Copyright © 2023 Pearson Education, Inc. All Rights Reserved White Blood Counts as a Clinical Measure (2 of 2) Table 11.2 Examples of Leukocytoses Name Leukocyte Increased Typical Noncancerous Causes Neutrophilic Neutrophils Acute (sudden onset) bacterial leukocytosis infections Eosinophilia Eosinophils Allergy, asthma, parasitic infections Basophilia Basophils Usually only occurs with certain rare blood cancers Monocytosis Monocytes Chronic infections/inflammation Lymphocytosis Lymphocytes (usually T or B Chronic infections/ inflammation; viral cells) Infections Copyright © 2023 Pearson Education, Inc. All Rights Reserved Cooperation Between Leukocytes and Molecular Factors After leukocyte activation, active molecules are released into the local environment These molecules have diverse functions such as: – Recruiting other leukocytes to the site of infection – Restricting pathogen growth – Triggering fever – Stimulating inflammation Copyright © 2023 Pearson Education, Inc. All Rights Reserved Cellular Second-Line Defenses After reading this section, you should be able to: Describe structural and functional features of neutrophils, eosinophils, basophils, and mast cells. Discuss the features of monocytes, macrophages, and dendritic cells. Name the three main categories of lymphocytes and discuss their general features. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Granulocytes Include Neutrophils, Eosinophils, Basophils, and Mast Cells Most granulocytes and agranulocytes exhibit some degree of phagocytosis Phagocytes (macrophages, dendritic cells, and neutrophils) target bacterial cells, viral particles, or general debris Enzymes of the lysosome typically destroy the targeted material Some microbes have virulence factors to help them avoid or thwart steps in phagocytosis Copyright © 2023 Pearson Education, Inc. All Rights Reserved Neutrophils Neutrophils – Most numerous white blood cells in circulation – Contain multilobed segmented nucleus – First leukocytes recruited to injured tissues – Release potent antimicrobial peptides (AMPs) – Phagocytize foreign cells and viruses – Elevated neutrophil count may indicate an acute bacterial infection – Neutropenia—low neutrophil count ▪ Caused by certain viral infections Copyright © 2023 Pearson Education, Inc. All Rights Reserved Eosinophils Eosinophils – Account for 30 different proteins that work together in a cascade fashion – Mostly made by the liver – Circulate in the blood in an inactive form – When activated, a cascade of events result in a boost to the immune defenses Copyright © 2023 Pearson Education, Inc. All Rights Reserved Complement Cascades Boost the Effectiveness of Innate Immune Responses (2 of 3) Complement proteins are activated by three main pathways: – Classical pathway – Alternative pathway – Lectin pathway Copyright © 2023 Pearson Education, Inc. All Rights Reserved Figure 11.11 Complement Cascades and Outcomes Activation CLASSICAL PATHWAY ALTERNATIVE PATHWAY LECTIN PATHWAY Complement proteins Complement proteins Complement proteins activated when activated by directly activated when mannose- antibodies bind to a interacting with binding lectin (MBL) pathogen. pathogen. Complementbinds to pathogen. Antibody MBL protein C3 Pathogen Direct activation Multiple steps Multiple steps C3 Outcomes of activation Proinflammatory factors C3b C3a Leukocyte C3b cleaves C5 C5 Blood C5b vessel MAC C5a Water Inflammation Opsonization Complement proteins Complement Cell lyses C3a and C5a protein C3b Cytolysis Complement protein C5b (along with C6, C7,recruit leukocytes tags pathogen from blood vessels C8, and for phagocytosis. C9) form membrane attack complex (MAC) in pathogen’s plasma membrane. to tissue. Leukocytes release factors that Water and ions rush through MAC and lyse cell. promote inflammation. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Complement Cascades Boost the Effectiveness of Innate Immune Responses (3 of 3) All three of these complement pathways have the same three outcomes: – Opsonization—tags the invader with complement proteins; more readily cleared by phagocytic cells – Formation of a membrane attack complex (MAC), which causes cytolysis – Inflammation Copyright © 2023 Pearson Education, Inc. All Rights Reserved Classical Pathway Classical complement cascade – Triggered by antibodies bound to an invading agent Copyright © 2023 Pearson Education, Inc. All Rights Reserved Alternative Pathway Alternative pathway – Complement proteins activate by directly interacting with the invading agent – No need for an intermediary antibody Copyright © 2023 Pearson Education, Inc. All Rights Reserved Lectin Pathway Lectin pathway – Independent of antibodies – Becomes activated when mannose-binding lectin associates with certain sugars on a microbe’s surface – Other than how it is initiated, this pathway is identical to the classical pathway Copyright © 2023 Pearson Education, Inc. All Rights Reserved Complement Evasion and Regulation Complement proteins will damage our own tissues if they are not properly regulated Regulation methods: – “Self-destruct feature”—complement proteins are highly unstable and deteriorate if not stabilized by other activated proteins – Regulators of complement activation (RCAs)— collection of proteins that turn off complement cascades after a threat passes Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation and Fever (1 of 2) After reading this section, you should be able to: List the three primary functions of inflammation and describe its three phases. State the four cardinal signs of inflammation and describe how they come about. Discuss roles of several key chemical mediators in inflammation. Describe the features of chronic inflammation. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation and Fever (2 of 2) After reading this section, you should be able to: State what fever is, list its potentially useful effects, and describe how it is generated and treated. Correctly use clinical terminology to describe different fever patterns. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation and Fever are Key Protective Innate Immune Responses When a threat is detected… – Tissue cells and local leukocytes release chemical mediators – Cellular defenses converge on the scene (triggered by chemokines) – Cytokines, complement proteins, and other pro- inflammatory factors coordinate defense efforts – Inflammation and sometimes fever are triggered Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Is Essential to Healing and Immunity, but if Unregulated It Damages Our Own Tissues (1 of 3) Inflammation – Important part of our innate immune defense and is essential to healing – Innate immune response that tends to develop when our tissues are damaged – Tissue injury initiates blood-clotting cascades – Blood clots curb blood loss and limit pathogen spread Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Is Essential to Healing and Immunity, but if Unregulated It Damages Our Own Tissues (2 of 3) The three main goals of inflammation are: 1. Recruit immune defenses to the injured tissue 2. Limit the spread of infectious agents 3. Deliver oxygen, nutrients, and chemical factors essential for tissue recovery Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Is Essential to Healing and Immunity, but if Unregulated It Damages Our Own Tissues (3 of 3) Cardinal signs of inflammation 1. Redness 2. Pain 3. Localized heat (not fever) 4. Swelling ▪ Loss of function Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (1 of 12) Inflammation occurs in three general phases: 1. Vascular changes 2. Leukocyte recruitment 3. Resolution INJURY INFLAMMATION Skin VASCULAR LEUKOCYTE RESOLUTION CHANGES RECRUITMENT Chemical alarm signals Cytokines recruit Inflammation signals Tissue damage released by damaged cellsleukocytes. Neutrophils decrease; tissue repair from trauma and/or Blood vessel and leukocytes increase arrive first, followed by initiated. infectious agents blood flow and vessel monocytes, which mature permeability. into macrophages. Neutrophils and macrophages phagocytize invaders and recruit other leukocytes. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (2 of 12) Vascular changes phase – Undamaged blood vessels increase in diameter – Vasodilatation (more blood flows to injured tissues) – Vessel permeability increases, which causes vessels to be slightly “leaky” – Exudate accumulates in the tissues – Proteins of exudate help finalize blood clot formation Copyright © 2023 Pearson Education, Inc. All Rights Reserved  Inflammation Phases (3 of 12) INFLAMMATION VASCULAR CHANGES LEUKOCYTE RECRUITMENT RESOLUTION Summary Details An Injury or infection triggers the Damaged tissue Pathogen release of vasoactive molecules from damaged tissue cells and resident leukocytes such as mast cells. Vasoactive molecules induce nearby, undamaged vessels to dilate and become more permeable. Complement Increased blood flow and vessel Mast cell proteins permeability promote swelling as Vasoactive plasma seeps into the tissues. molecules Complement proteins also move into the tissues from the blood. Key players Mast cells Vessel diameter widens Vasoactive molecules (mainly kinins, eicosanoids, and histamines) Exudate (fluid and associated plasma proteins, such as complement proteins) Vessel becomes Exudate seeps more permeable into tissues Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (4 of 12) Histamine – Vasoactive molecule – Made by mast cells, basophils, eosinophils, and platelets – Mast cells are one of the most important histamine releasers early in inflammation process Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (5 of 12) Kinins – Pro-inflammatory, vasoactive factors – Induce vascular changes, stimulate pain receptors, and assist in blood-clotting cascades – Amplify inflammation by triggering the production of numerous downstream signaling molecules (e.g., eicosanoids) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (6 of 12) Eicosanoids – Vasoactive signaling molecules – Promote many physiological events (e.g., inducing uterine contractions in childbirth to regulating stomach acid secretions) – During inflammation, they induce vascular changes and stimulate pain receptors – Certain eicosanoids generate fever when released in the hypothalamus of the brain Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (7 of 12) Examples of eicosanoids include: – Prostaglandins – Leukotrienes – Thromboxanes Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (8 of 12) Nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., aspirin, ibuprofen, naproxen) and steroidal anti- inflammatory drugs (SAIDs) (e.g., cortisone, prednisolone) reduce eicosanoid production Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (9 of 12) Leukocyte Recruitment phase – Relies on chemoattractants – Increased blood flow conveys more leukocytes to the vicinity – Increased vessel permeability makes it easier for the leukocytes to escape blood vessels – Cells exit blood vessels in two steps ▪ Margination—leukocytes slow and adhere to the vessel Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (10 of 12) Dipedesis (also called transmigration or extravasation) – Leukocyte changes shape and squeezes out of the blood vessel Cytokines released by injured or infected cells guide recruited leukocytes to the site Neutrophils are the first leukocytes to exit vessels; followed by monocytes Neutrophils release substances and act as phagocytes to eliminate invaders Copyright © 2023 Pearson Education, Inc. All Rights Reserved Figure 11.14 Leukocyte Recruitment Phase of Inflammation INFLAMMATION VASCULAR CHANGES LEUKOCYTE RECRUITMENT RESOLUTION Summary Details Damaged and inflamed tissue Pathogen Chemoattractants recruit leukocytes to the inflamed tissue. Neutrophils and monocytes are the first recruits. Leukocytes undergo margination and diapedesis to exit capillaries. Monocytes mature into macrophages as they migrate Macrophage through the tissue. Chemoattractants As neutrophils and macrophages carry out phagocytosis they release cytokines to recruit other leukocytes. Key players Monocyte Chemoattractants (cytokines and other signaling molecules released Neutrophil by local tissues and leukocytes such as mast cells) Adhesion Rolling Leukocytes: Neutro- Mono- Macro- phils cytes phages Margination Diapedesis Leukocytes slow as they Leukocytes change shape roll along vessel wall Leukocytes squeeze out of vessel Eventually leukocytes mature into adhere to vessel wall Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (11 of 12) Resolution phase – Tones down inflammation – Organized by assorted chemical signals released by leukocytes and tissue cells – Activated leukocytes in the tissue decrease – Blood vessels begin to revert to normal – Exudate in the tissues is collected – Swelling decreases Copyright © 2023 Pearson Education, Inc. All Rights Reserved Figure 11.15 Resolution Phase of Inflammation INFLAMMATION VASCULAR CHANGES LEUKOCYTE RECRUITMENT RESOLUTION Summary Details The resolution phase begins as Pus Scab Exudate the threat passes. Local returns to capillaries return to normal while lymphatic leukocytes and tissue cells in the vessels area release chemical signals that reduce inflammation and promote healing. Leukocytes that are no longer needed die off through apoptosis, contributing to the pus that may form in this stage. Swelling is reduced as exudate is collected by nearby lymphatic capillaries. Key players Cytokines and growth factors (reduce inflammation and encourage healing) Leukocytes (especially neutrophils and macrophages) Blood vessel Pus (dead cells in fluid exudate) returns to normal Copyright © 2023 Pearson Education, Inc. All Rights Reserved Inflammation Phases (12 of 12) Late resolution phase—wound healing begins – Damaged tissues are repaired – Angiogenesis builds new blood vessels – Blood clots dissolve – Leukocytes undergo apoptosis – Pus (dead tissue cells and leukocytes) may form Complete healing can take days to years, depending on the location and severity Copyright © 2023 Pearson Education, Inc. All Rights Reserved Chronic Inflammation Chronic inflammation – May develop when an inflammatory response goes on too long – Not useful or protective – Exacerbates tissue injury – Promotes atherosclerosis, certain cancers, and progressive neurodegenerative disorders Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fever Is a Systemic Innate Immune Response (1 of 7) Fever (pyrexia) – Abnormally high systemic body temperature – Pyrogens—fever-inducing agents ▪ Bacterial toxins (e.g., endotoxin, LPS) ▪ Trigger the release of cytokines (e.g., IL - 1, TNF - , IFN -  ) ▪ Signal the hypothalamus to raise the body’s baseline temperature Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fever Is a Systemic Innate Immune Response (2 of 7) Hypothalamus Signal received by the hypothalamus causes body’s thermostat to be set to a temperature above 37°C (98.6°F). Fever: Hormone level changes, shivering, and increased metabolism raise body temperature––also, blood vessels constrict such that heat loss through the skin is reduced. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fever Is a Systemic Innate Immune Response (3 of 7) Studies suggest fever: – Enhances antiviral effects of interferons – Increases phagocyte efficiency – Enhances leukocyte production – Limits growth of certain pathogens – Promotes tissue repair Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fever Is a Systemic Innate Immune Response (4 of 7) Low-grade fever – 37.5°C to 38.3°C (99.5 - 101°F) – Considered protective Some healthcare providers argue that a low-grade fever should be allowed to run its course Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fever Is a Systemic Innate Immune Response (5 of 7) If the patient is uncomfortable and not resting much, it makes sense to treat fever with an antipyretic (fever- reducing drug) – Examples include aspirin, ibuprofen (Advil/ Motrin) and acetaminophen (Tylenol) – Work by limiting the production of prostaglandins in the hypothalamus Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fever Is a Systemic Innate Immune Response (6 of 7) A fever that reaches 40.5 oC (105 oF) and does not decrease with treatment is a life-threatening – Considered a medical emergency – Essential cellular enzymes and proteins will begin to denature and stop working A body temperature above 43 oC (109.4 oF) is fatal Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fever Is a Systemic Innate Immune Response (7 of 7) Table 11.5 Fever Classifications Term Description Fever of undetermined origin (F UO) Fever of at least 38.3°C (101°F) that persists more than 3 weeks and isn’t 38.3 degrees Celsius, 101 degrees Fahrenheit linked to a specific cause within a week of inpatient study; usually due to infections or neoplasms (malignant cancers or benign growths) Intermittent fever Body temperature elevates, but falls to normal at some point in the day Pel–Ebstein fever Fever lasting 3–10 days followed by nonfever state of similar length; characteristic of Hodgkin’s disease and certain other lymphomas Relapsing fever Recurrent episodes spaced by days or weeks of normal body temperature; characteristic of certain tick-transmitted bacteria such as Borrelia species Remittent fever Elevated body temperature that fluctuates, but doesn’t reach normal in the course of the fluctuations Sustained fever Consistently elevated body temperature with limited fluctuation (0.3°C or 0.3 degrees Celsius less) during a 24-hour period Tertian fever Fever that occurs on 1st and 3rd days; common in malaria caused by Plasmodium vivax Quartan fever Fever that occurs on 1st and 4th days; common in malaria caused by Plasmodium malariae Copyright © 2023 Pearson Education, Inc. All Rights Reserved Visual Summary: Innate Immunity and Adaptive Immunity (1 of 2) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Visual Summary: Innate Immunity and Adaptive Immunity (2 of 2) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (1 of 5) Summary of the case: – 5-year-old Jackson presented with an ear infection on Saturday – Symptoms included ear drainage and fever – Jackson had a history of chronic illness – 10 days prior he finished a course of amoxicillin to treat otitis media – Jackson’s oral temperature was 102°F (38.9°C), despite taking Advil – Erin, his mother, called the pediatrician and was prescribed a new antibiotic course that day – The pediatrician advised Erin to start the medication, keep Jackson on Advil, bring him on Monday, and mentioned that if he got worse they should take him to the emergency room Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (2 of 5) Summary of the case: – By Sunday afternoon Jackson complained of a stiff neck (nuchal rigidity) and was increasingly disoriented – His parents drove him to the hospital – Laboratory tests on Jackson’s CSF and fluid drained from his ear revealed Gram-positive, encapsulated cocci in chains – Jackson was diagnosed with bacterial meningitis – Streptococcus pneumoniae was cultured from the ear fluid and C SF samples, confirming diagnosis – Nia asked how Jackson developed a S. pneumoniae infection when he was up to date on all routine vaccines, and had been vaccinated against this bacterium – The physician explained the vaccine works against the most invasive strains of the bacterium, but not all of them Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (3 of 5) Summary of the case: – Jackson spent three weeks in the hospital for treatment – Fully recovered – Over the next few years Jackson continued to suffer from pyrogenic bacterial infections – Doctors to checked for an immune deficiency and hemochromatosis – Doctors discovered Jackson had abnormally low levels of mannose- binding lectin (MBL) – There is currently no therapy for MBL deficiencies – The family can only be vigilant about early infection symptoms and seek immediate treatment – It was recommended that he receive the meningococcal vaccine earlier than most children Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (4 of 5) 1. What do you predict a differential white blood cell count on Jackson’s blood would reveal? Be sure to support your conclusion with information from the chapter. 2. Given Jackson’s diagnosis of MBL deficiency, what do you think his prognosis (forecast) is for a normal life? Consider what immune system defenses would be most directly affected in Jackson versus defenses that are less directly impacted. 3. Despite Jackson’s MBL deficiency, his pediatrician is convinced that Jackson’s immune system will respond to the meningococcal vaccine and provide protection against N. meningitidis. Why? Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (5 of 5) 4. Describe the general molecular mechanism by which Jackson developed a fever and explain why Advil was expected to help manage Jackson’s discomfort and fever. Also, explain why the doctor recommended emergency care if the Advil didn’t limit the child’s fever. 5. Describe some first-line defenses that were likely overcome by the pathogen to successfully invade Jackson’s body and explain what second-line defenses were likely called to action to help fight the infection. 6. Why did Jackson’s doctors check for hemochromatosis? 7. What leukocyte(s) would you expect would be increased in Jackson’s cerebrospinal fluid sample? Explain your reasoning. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Copyright This work is protected by United States copyright laws and is provided solely for the use of instructors in teaching their courses and assessing student learning. Dissemination or sale of any part of this work (including on the World Wide Web) will destroy the integrity of the work and is not permitted. The work and materials from it should never be made available to students except by instructors using the accompanying text in their classes. All recipients of this work are expected to abide by these restrictions and to honor the intended pedagogical purposes and the needs of other instructors who rely on these materials. Copyright © 2023 Pearson Education, Inc. All Rights Reserved