Notes (Page-by-Page)
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Course: Inflammation & Immunity
Authors/Presenters: Anne Collier, MSN, RN; Alysa Cummins, MSN, RN
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Topic: Innate Immunity
Focus: The body's non-specific first response to injury or invasion, operating without prior exposure to a pathogen.
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Unit Objectives
Explain the process of inflammation.
Describe the physiological process of normal tissue repair and wound healing.
Compare and contrast the innate and adaptive immune response, including the roles of cellular components and chemical mediators.
Describe differences between active and passive immunity.
Identify differences between primary and secondary immunodeficiency disorders.
Compare and contrast alterations in immune function associated with hypersensitivity and autoimmunity.
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Lines of Defense
1st line: natural barriers (physical/chemical barriers)
2nd line: inflammatory response
3rd line: immune response (adaptive immunity)
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1st Line of Defense
Physical barriers (Natural barriers)
Skin
Mucous membranes
Chemical barriers
Sweat and oils
Mucus
Tears
Saliva
Stomach acid
Urine
Interferons
Normal bacterial flora
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2nd Line of Defense: Inflammation
Triggered by tissue injury
Goals:
↑ blood flow to the site (vascular response)
↑ healing cells at the site (cellular response)
prepare for tissue repair
Note: the suffix -itis denotes inflammation
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Inflammation: Vascular Response
Facilitated by chemical mediators
Causes:
Vasodilation
Increased vascular permeability
Objective: increase blood flow to the injured area to deliver immune cells and mediators
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Inflammation: Cellular Response
Processes: margination, adhesion, transmigration
Chemotaxis: movement of leukocytes toward the site of injury
Leukocyte activation & phagocytosis
PHAGOCYTOSIS = RECOGNITION and REMOVAL of microbes
Key sequence: Blood flow → Endothelial cells → Chemotaxis → Cellular adherence → Cellular migration → PHAGOCYTOSIS
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Chemical Mediators (Table 5-1)
Histamine
Source: Mast cell granules
Major Action: Immediate vasodilation and increased capillary permeability to form exudate
Chemotactic factors
Source: Mast cell granules
Major Action: Attract neutrophils to the site
Platelet-activating factor (PAF)
Source: Cell membranes of platelets
Major Action: Activate neutrophils
Cytokines (interleukins, lymphokines)
Source: T lymphocytes, Macrophages
Major Action: Platelet aggregation
Leukotrienes
Source: Synthesis from arachidonic acid in mast cells
Major Action: Increase plasma proteins, ESR
Prostaglandins (PGs)
Source: Synthesis from arachidonic acid in mast cells
Major Action: Vasodilation, increased capillary permeability, pain, fever, potentiate histamine effect
Kinins (e.g., bradykinin)
Source: Activation of plasma protein (kinogen)
Major Action: Vasodilation; increased capillary permeability; pain; chemotaxis
Complement system
Source: Activation of plasma protein cascade
Major Action: Vasodilation and increased capillary permeability; chemotaxis; increased histamine release
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Initiation, Recruitment, and Debris Removal by Chemical Mediators
Initiate response: Histamine, C5a, Kinins, Leukotrienes, Prostaglandins, Neuropeptides, IL-1, TNF, IL-3, IL-6, CSFs, IL-8, Interferons, IL-2, FGF, PDGF, IL-4, IL-5, IL-6, TGF-β (and others)
Promote chemotaxis and leukocyte growth/proliferation
Invite neutrophils, macrophages, lymphocytes, platelets to the site
Modulate fever, acute-phase responses, and repair processes
CSF = Colony-stimulating factor; IL = Interleukin; TNF = Tumor necrosis factor; FGF = Fibroblast growth factor; PDGF = Platelet-derived growth factor; TGF-β = Transforming growth factor-beta
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Inflammation: Tissue Injury and Acute vs Chronic Inflammation
Tissue injury is regulated by plasma protein systems and the production/release of inflammatory mediators (mast cells, cytokines)
Vasoactive mediators include histamine, leukotrienes, prostaglandins
Chemotactic mediators (chemokines) stimulate cellular response (adherence, migration, phagocytosis)
Acute inflammation characteristics: redness, heat, swelling, pain, loss of function (local signs via vasodilation, permeability, and exudation)
Acute inflammatory cells: PMNs (polymorphonuclear leukocytes), Platelets, Mast cells
Chronic inflammation: macrophages and lymphocytes predominate
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Acute Inflammation: Timeline and Mechanisms
Tissue injury → Release of chemical mediators (histamine, kinins, prostaglandins)
Vasodilation and increased blood flow → Hot, red skin
Increased chemotaxis and capillary permeability → Edema, pain
Nerve irritation → Pain
Clot and fibrin mesh walls off the area
Phagocytosis removes cause and debris
Preparation for healing
If the cause persists, chronic inflammation ensues
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Acute Inflammation Diagram Notes
Wound exposure to histamines increases blood flow
Histamines cause capillary leakage, allowing phagocytes and clotting factors to reach the wound
Phagocytes engulf bacteria, dead cells, and debris
Platelets move out to form a clot to seal the area
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Local Manifestations of Inflammation
Redness (rubor)
Heat (calor)
Swelling (tumor/edema)
Pain (dolor)
Loss of function
The Five Cardinal Signs: Heat, Redness, Swelling, Pain, Loss of Function
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Exudates Types
Serous
Hemorrhagic
Fibrinous
Membranous
Purulent
Membranous conjunctivitis is an example mentioned
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Systemic Effects: Fever
Mechanism: Pyrogens reset the hypothalamic set point to a higher temperature
Stages:
Release of pyrogens into circulation
Fever onset: feeling warm
Body responses to increase heat: shivering, vasoconstriction, increased metabolic rate
Achieve new higher set point
Treatment to remove pyrogens
Hypothalamus resets to normal
Body responses to increase heat loss (vasodilation, sweating)
Return to normal temperature
Clinical notes: Fever is a systemic effect of inflammation
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Systemic Effects (Continued)
Sleepiness, lethargy, malaise
Anorexia, nausea, vomiting
Additional signs may accompany fever and systemic inflammatory response
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Chronic Inflammation
Recurrent or persistent inflammation lasting weeks to years
Monocytes, macrophages, and lymphocytes are more prominently involved
Formation of granulomas and scarring often occurs
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Acute vs Chronic Inflammation: Comparative Features
Onset: Acute = fast (minutes to hours); Chronic = slow (days to weeks)
Duration: Acute = usually < 2 weeks; Chronic = lasts at least 2 weeks, often longer
Cellular infiltrate: Acute = ↑ neutrophils; Chronic = ↑ monocytes, macrophages, lymphocytes
Tissue injury: Acute = usually mild and self-limiting; Chronic = persistent, progressive
Predominant processes: Acute = vascular and exudative; Chronic = new connective tissue formation
Local and systemic signs: Acute = prominent; Chronic = less severe
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Acute vs Chronic: Examples and Causes
Triggers/causes listed: irritants, infection, allergic reactions, trauma, burns, autoimmune diseases
Associated diseases: cancer, rheumatoid arthritis, lupus, fibromyalgia, chronic fatigue syndrome, etc.
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Tissue Repair: Outcomes
Resolution: cells return to normal in a short period
Regeneration: injured cells are replaced with cells of the same type
Repair by scar formation: necrotic cells replaced with collagen (scar tissue)
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Wound Healing: Primary vs Secondary Intention
Healing of incised wounds by first intention (primary)
Healing by second intention (secondary)
Phase I: Injury and inflammation; clotting, inflammation; scab formation
Phase II: Granulation tissue and epithelial growth; epithelial regeneration; macrophage involvement; fibroblasts; new capillaries
Phase III: More granulation tissue, collagen deposition, epithelial regeneration; macrophages; scar formation
Phase IV: Scar matures; possible small vs large scar remains; wound contraction
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Factors Affecting Wound Healing
Malnutrition
Blood flow and oxygen delivery
Impaired inflammatory and immune response
Infection, wound separation, foreign bodies
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Dysfunctional Wound Healing
Dysfunctional collagen synthesis
Wound disruption
Contracture
Dehiscence
Evisceration
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Adaptive Immunity
Third line of defense
Occurs after exposure to an antigen
Promotes processes against reinfection
Differences from inflammation:
Slower acting
Longer acting
Very specific response
Has memory
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Relationship: Barriers, Innate, and Adaptive Immunity
Nonspecific External Barriers: skin, mucous membranes, etc.
Innate Immune Response: phagocytic and natural killer cells, inflammation, fever
Adaptive Immune Response: cell-mediated immunity and humoral immunity
If barriers are penetrated, the body responds with innate immunity; if innate is insufficient, adaptive immunity provides a targeted response
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Adaptive Immunity Details
Third line of defense
Occurs after exposure to antigen; builds memory for reinfections
Differences from inflammation: slower to start, longer lasting, highly specific
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Antigen Recognition: Self vs Non-self
Self marker: Major Histocompatibility Complex (MHC) labels cells as 'self' and are tolerated by the immune system
Antigen: a molecule recognized as foreign (non-self) and treated as a foe
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Clonal Diversity and Selection; Cellular vs Humoral Immunity
CELL-MEDIATED IMMUNITY (T cells):
Lymphoblasts → Thymus → T cells → Migrate to lymph nodes
Processed antigen presented to T cells; results in sensitized T cell responses
Key cell types include Helper T cells, Cytotoxic T cells, Regulatory T cells
HUMORAL OR ANTIBODY-MEDIATED IMMUNITY (B cells):
Bone marrow maturation; B cells mature and migrate to lymph nodes
Antigen stimulation → Plasma cells + Memory B cells
Immunoglobulins produced by plasma cells neutralize pathogens
Visual: memory cells exist for faster future responses
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The Team (Lymphocytes): Major Players
CD8 T Cell: "The Killer" (cytotoxic T cell) – Seek and destroy virally infected and some cancerous cells; can proliferate to form memory cells
B Cell: Antibody-producing cells; can become plasma cells and memory B cells
Regulatory T Cell (T-reg): "I regulate or suppress other cells in the immune system"; helps maintain tolerance and prevent autoimmunity
CD4 T Cell: "The Helper" – Identifies foreign antigens and signals activation of B cells and killer T cells
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The Helper (CD4 T Cell)
Central role in adaptive immunity
Identifies foreign antigens and signals activation of:
B cells (humoral response)
Killer T cells (cell-mediated response)
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The Killer (CD8 Cytotoxic T Cell)
Purpose: Seek and destroy infected or abnormal cells
Capable of proliferation to form memory cells
Statement: "I'M READY TO FIND AND KILL THOSE INFECTED CELLS!" illustrating CTL readiness
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Regulatory T-Cell (T-reg)
Role: Regulate or suppress other immune cells to prevent overactivation and autoimmunity
Labeled as T-REG
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B-Cells and Antibody Production
Antigen binds to B cell receptor (membrane-bound antibody)
Activation leads to two fates:
Plasma cells (antibody-secreting)
Memory B cells (long-term protection)
Major function: production of antibodies to target pathogens
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Immunoglobulins (Antibodies) and Their Functions
IgM (pentamer, IgM):
First circulating antibodies in initial exposure
Large pentamer structure with many binding sites; effective at agglutination and complement activation
Too large to cross the placenta; does not confer maternal immunity
IgG (monomer, IgG):
Most abundant circulating antibody
Readily crosses vascular walls and tissue fluids; crosses the placenta to provide passive immunity to fetus
Protects against bacteria, viruses, toxins; activates complement
IgA (dimer, IgA):
Produced in mucosal surfaces; prevents attachment of pathogens to epithelial surfaces
Found in secretions: saliva, perspiration, tears; important in newborn GI protection via breast milk
IgD (monomer, IgD):
Does not activate complement; cannot cross placenta
Mostly on B cell surfaces; may function as an antigen receptor to help differentiation into plasma and memory B cells
IgE (monomer, IgE):
Small fraction of antibodies; binds to mast cells and basophils
Triggers release of histamine and other chemicals leading to allergic reactions
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Serology Example (Specimen Information)
Example: Varicella Zoster Virus IgG antibody testing (serology)
Interpretation highlights:
Positive IgG indicates past exposure or vaccination; does not distinguish active infection from past infection or vaccination
Negative IgG in a vaccinated individual does not necessarily indicate susceptibility
Note: Serology results require clinical correlation
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Acquiring Immunity: Primary and Secondary Antibody Response
Serum antibody titer dynamics over time after exposure
Naive B cell → Activated B cell → Primary anti-A response
After re-exposure: memory B cells mount a stronger, faster secondary anti-A response
Graphically: antigen A exposure leads to a rise in antibody titer after initial lag; secondary exposure shows a faster and higher titer
Concept: Immunological memory underlies faster secondary responses
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Passive vs Active Immunity
Passive immunity: immunity transferred from donor to recipient; immediate protection but temporary
Active immunity: immune response generated by the individual's own exposure to antigen; takes weeks to develop but provides long-lasting protection
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Alterations in Immunity
Focus: Changes in immune function that can be protective or harmful (e.g., hypersensitivity, immunodeficiency, autoimmunity)
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Immunodeficiency
Primary immunodeficiency: congenital, often due to single gene defects; usually diagnosed in infancy or childhood
Secondary immunodeficiency: acquired; more common; caused by disease or environmental factors (e.g., HIV, malnutrition, severe burns, medical treatments)
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Hypersensitivity Reactions
Definition: An inflated or inappropriate immune response to an antigen causing inflammation and tissue destruction
Features: typically occur after re-exposure to the antigen; can be immediate or delayed
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Type I: Immediate Hypersensitivity (Allergic Reactions)
Mechanism: IgE binds to mast cells and basophils → release of histamine and other mediators
Effects: Immediate inflammation and itching (pruritus)
Common triggers: allergens (insects, foods, medications, etc.)
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Anaphylactic Reactions (Type I) – Examples and Symptoms
Common triggers: insect stings (bee, wasp, ant), medication reactions, foods (peanuts, eggs, shellfish)
Rapid Onset symptoms: dyspnea, tight throat, bronchospasm, laryngeal edema; tingling/swelling in mouth, face, throat, and tongue; itching; hypotension; tachycardia; possible loss of consciousness
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Type II: Cytotoxic Hypersensitivity
Mechanism: IgG or IgM binds to antigen on the host's own cell; cell- or tissue-specific effects (often blood cells)
Outcomes: phagocytosis and/or cell lysis
Classic example: incompatible blood transfusion reactions
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Type II Milk-Case: Blood Transfusion Example (Table Illustration)
A, B, AB, O blood types and corresponding antibodies:
Type A: antigen A; Anti-B antibody
Type B: antigen B; Anti-A antibody
Type AB: antigens A and B; no anti-A or anti-B antibodies (universal recipient)
Type O: no antigens A or B; anti-A and anti-B antibodies (universal donor)
Concept: Type II reactions involve antibodies against donor antigens, leading to cell destruction
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Type III: Immune Complex Hypersensitivity
Mechanism: Antigen-antibody complexes form and circulate; complexes deposit in blood vessels or tissues; activate complement
Sequence: Antigen binds antibody → immune complexes form in circulation → deposits form at tissues → complement activation → inflammation
Effects: increased vascular permeability and inflammation; tissue damage at deposition sites
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Type IV: Cell-Mediated or Delayed Hypersensitivity
Mechanism: Delayed response mediated by sensitized T cells
Effects: delayed inflammation and tissue damage
Example: reaction to poison ivy
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Autoimmune Disorders
Concept: Immune system mistakenly targets self-antigens, leading to inflammation and tissue damage
Mechanism: autoantibodies or autoreactive T cells attack self-antigens and immune complexes deposit in tissues
Process (simplified):
1) Immune system forms antibodies to self-antigens
2) Autoantibodies attack self-antigens; immune complexes deposit
3) Inflammation and tissue damage occur
4) Autoantibody persistence provides some protection but with ongoing autoimmunity