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Immune System . Chapter 21. Immune System. Functional body system Structures are cells not organs Provides immunity Recognizes ‘self’ from ‘non-self’ Fights pathogens and infections Destroy cancer cells Isolate and remove foreign substances Divisions Innate immunity (non-specific)

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immune system

Immune System

Chapter 21

immune system1
Immune System
  • Functional body system
    • Structures are cells not organs
    • Provides immunity
  • Recognizes ‘self’ from ‘non-self’
    • Fights pathogens and infections
    • Destroy cancer cells
    • Isolate and remove foreign substances
  • Divisions
    • Innate immunity (non-specific)
    • Adaptive immunity (specific)
innate immunity
Innate Immunity
  • External defenses prevent entry
    • Skin
    • Mucous membranes
  • Internal defenses prevent/inhibit spread
    • Identified by surface carbs or proteins
    • Types
      • Phagocytes and natural killer (NK) cells
      • Inflammation (chemicals) and fever
      • Antimicrobial proteins
external defenses
External Defenses
  • Most efficient when unbroken/uninjured
  • Skin
    • Keratinized stratified squamous
  • Mucous membranes (chemical barriers)
    • Lines body cavities w/external openings
    • Produce wide range of chemicals
      • Sebaceous and sweat glands
      • Gastric juices, urine, and vaginal secretions
      • Salivary and lacrimal lysozyme secretions
      • Nasal cilia
  • Table 21.2
phagocytes
Phagocytes
  • Macrophages (monocytes)
    • Wander through tissues (free)
    • Kupffer cells in liver and microglia in brain (fixed)
    • Resilient fighters
  • Neutrophils
    • Need exposure to infectious substances
    • Self sacrifice fighters
  • Eosinophils
    • Against parasitic worms
  • Mast cells
    • Local inflammatory response w/ pathogen exposure (allergies)
    • Release histamine, heparin, and proteases
phagocytosis
Phagocytosis
  • Microbe is engulfed  phagosome
    • Phagocyte adheres to PM identifiers
    • Complement proteins and antibodies assist  opsonization
  • Phagosome fuses to lysosome  phagolysosome
  • Digestion
    • Respiratory burst needed for complex microbes
      • Helper T cells stimulate macrophages to produce
      • Increase pH to activate additional enzymes
    • Neutrophils produce defensinsto pierce PM
  • Exocytosis
  • Fig 21.2
natural killer nk cells
Natural Killer (NK) Cells
  • Large, granular lymphocytes
  • Recognize and attack any ‘non-self’ cells (non-specific)
    • Cancer and viral cells
  • Perforins secreted to puncture PM
  • Induce apoptosis, programmed cell death
  • Enhance inflammatory response
inflammatory response
Inflammatory Response
  • Clean up area and isolate/stop spread
  • Process
    • Histamine released by damaged tissues
    • Local vessel(s) vasodilation and permeability increase
      • Hyperema from increased blood flow (Redness and heat)
      • Clotting factors & antibodies (exudate) into tissues (edema)
        • Swelling presses on nerves  releasing prostoglandins (pain)
        • Antihistamines and aspirin/acetaminophen reduces
    • Phagocytes attracted
    • Fig 21.3
phagocyte attraction
Phagocyte Attraction
  • Leukocytosis
    • Chemical signals increase neutrophil number
  • Margination
    • Neutrophils cling to capillary walls in injured area
    • Cell adhesion molecules (CAM’s) signal location and facilitate attachment
  • Diapedesis
    • Neutrophils move from blood to tissue
  • Chemotaxis
    • Attracts WBC’s to area  phagocytosis
      • Monocytes follow neutrophils  macrophages
      • Pus with bad infections
fever
Fever
  • Systemic response to pathogen invasion
  • Leukocytes & macrophages release pyrogens to signal hypothalamus
  • High is dangerous
    • Denaturation of proteins (enzymes)
  • Moderate can be beneficial
    • Metabolic rate up = tissue repair rate up
    • Liver & spleen withhold iron & zinc = starves microbe
antimicrobial proteins interferons
Antimicrobial Proteins: Interferons
  • Synthesized by infected cells
    • Enter neighboring cells to ‘interfere’ w/ viral reproduction
  • Not virus specific
  • Activate macrophages and NK cells too
antimicrobial proteins complement
Antimicrobial Proteins: Complement
  • ‘Complements’ innate and adaptive defenses
  • 20+ inactive blood proteins
  • Activation
    • Classical pathway: activates through antigen/antibody binding
    • Alternate pathway: proteins directly attach to antigen
  • Result
    • Lyse many cell types (‘self’ are protected)
      • Protein complex produces a pore in PM
      • H2O floods in
    • Amplifies inflammatory response
    • Opsonization
adaptive defenses
Adaptive Defenses
  • Attacks specific foreign substances
    • Longer reaction (antigen exposure)
    • Systemic protection (blood stream residence)
    • Permanent protection (‘memory’)
  • Mechanisms
    • Humoral immunity utilizes antibodies
    • Cellular immunity utilizes lymphocytes and other phagocytes
antigens
Antigens
  • Molecules/cells eliciting adaptive immune response
    • Antigenic determinants provide signal
      • Immunogenicity: stimulates lymphocyte and antibody production
      • Reactivity: react with lymphocytes and antibodies
  • Types
    • Complete
      • Biological macromolecules, pollen, and microorganisms
    • Incomplete (haptens)
      • Smaller molecules that bind to ‘self’ selves
      • Cause hypersensitivity or allergies
mhc proteins
MHC Proteins
  • Basis for ‘self’ and ‘non-self’ identification
    • Major histocompatibility complex genes encode
    • Unique to all individuals
  • Synthesized in the ER and transported to the PM for display
    • Class I on all body cells
    • Class II on dendritic cells, macrophages, and B-cells
lymphocytes revisited
Lymphocytes (revisited)
  • Produced in red bone marrow from hemocytoblasts
  • Develop immunocompetence in primary lymphoid organs
    • B-cells in bone marrow and T-cells in thymus
    • Multiple antigen receptors
  • Migrate to secondary lymphatic organs
    • Antigen binding completes differentiation
      • Learn self-tolerance through positive & negative selection
  • Effector or memory cells free to wander
antigen presenting cells apcs
Antigen-Presenting Cells (APCs)
  • Dendritic cells, macrophages, and B-cells
  • Functions
    • Engulf antigens for T-cell presentation
      • Fragments join MHC proteins on PM surface
      • Enables visualization of antigen by T-cell
    • Self/non-self complex recognized by T-cell
      • Binding signals differentiation
  • Key to initiating adaptive immunity
humoral immune response
Humoral Immune Response
  • Antigen challenge when B-cell first meets antigen
  • Clonal selection forms …
    • Plasma cells  antibodies circulate to ‘flag’ antigens
    • Memory cells  quicker repeat response
  • Occurs in spleen or lymph nodes
immunological memory
Immunological Memory
  • Primary immune response
    • Antigen challenge
  • Secondary immune response
    • Stronger, faster, & longer
humoral immunity 2 0
Humoral Immunity 2.0
  • Active immunity
    • B-cells encounter antigens and MAKES antibodies
      • Natural exposure causes symptoms & suffering
      • Artificial exposure from dead or attenuated (vaccines)
    • Examples of each?
  • Passive immunity
    • Antibodies WITHOUT antigen exposure
      • Naturally b/w mother and fetus/infant
      • Artificially through pre- or post-injection
    • Examples of each?
antibodies
Antibodies
  • Produce by B-cells AFTER antigen challenge
    • Also known as immunoglobins (Igs)
  • 4 looping polypeptides
    • Identical light (2) and heavy (2) chains
    • Variable regions (2 per)
      • Bind antigen
    • Constant regions
      • Basis for class distinction (5)
      • Determine functioning
  • Functions
    • Recognize and bind antigens
    • Inactivation of antigens

Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com)

antibody classes
Antibody Classes
  • IgM
    • Produced 1st by plasma cells; activates complement
  • IgA
    • Prevents pathogen attachment in mucus membranes
  • IgD
    • B-cell surface receptor to activate other B-cells
  • IgG
    • Most abundant for 1° and 2° responses; fetal immunity, activates complement
  • IgE
    • Responsible for allergies due to histamine release
targeting antigens
Targeting Antigens
  • Precipitation
    • Phagocyte accessibility increase due to weight increase
  • Lysis (by complement)
    • Antibodies (which?) insert MAC into PM (earlier)
    • Enhance inflammatory response and opsonization
  • Agglutination
    • Clumps antigens for phagocytes
  • Neutralization
    • Bind/block attachment and exotoxin sites on antigen
    • Slows until phagocytosis
cell mediated immune response
Cell-Mediated Immune Response
  • Works when cells are infected w/antigen
    • Requires ‘visualization’ of antigen for T-cell
  • T-cells distinguished by glycoprotein receptors
    • CD8 cells
      • Recognize class I MHC proteins (all body cells)
      • Become cytotoxic/killer T-cells (TC)
    • CD4 cells
      • Recognize class II MHC proteins (APCs)
      • Become helper T-cells (TH) or memory T-cells
t cell types
T-Cell Types
  • Cytotoxic T-cells directly attacks and kills
    • Perforins or apoptosis signal to ‘non-self’ cells
  • Helper T-cells elicit immune responses
    • Stimulate B-cells to proliferate
    • Activate CD8 cells w/ co-stimulatory chemicals
    • Increase macrophage strength, cytokine release, & amplify innate defenses
  • Memory T-cells remain to prepare for future exposure
  • Regulatory T-cells (TReg) inhibit immune response
    • Stops once unnecessary
    • Autoimmune disease protection
t cell differentiation and cloning
T-Cell Differentiation and Cloning
  • Differentiation requires double recognition
    • Self and non-self
      • Class I MHC proteins with endogenous antigens
      • Class II MHC proteins with exogenous antigens
    • CD8 and CD4 recognize and bind accordingly
  • Co-stimulation signals clones to be produced
    • Additional T-cell binding or cytokine/interleuken release
    • Lack of causes T-cell tolerance and prevents mitosis
organ transplants
Organ Transplants
  • Key is to maximize match while reducing rejection
    • Blood type (ABO and Rh) AND MHC protein
  • Grafts exchange tissues b/w recipient and donor
    • Autografts: same person, different site
    • Isografts: genetically identical donor
    • Allografts: not genetically identical, but same species
    • Zenografts : different species
  • Post - immunosuppressive therapy lessons the rejection
    • Drugs to suppress inflammation response and mitosis
    • Increases chance of secondary infection
allergies
Allergies
  • Hypersensitivity to otherwise harmless antigens (allergens)
    • Animal dander (skin cells) and saliva proteins
    • Dust (mite feces) and pollen
  • 2 stage reaction
    • Sensitization: IgE produced but no response
    • Allergic response: antigen binds IgE mast cells and histamine released
  • Triggers inflammatory response = symptoms
hypersensitivities
Hypersensitivities
  • Immune response to harmless antigens that result in tissue damage
  • Immediate occurw/i seconds of exposure (IgE)
    • Atopy: allergic reaction not in direct allergen contact
    • Anaphylactic shock: system wide inflammatory response
  • Subacute occur 1 - 3 hours after exposure (IgG and IgM)
    • Cytotoxic (type II): binding signals phagocytosis and lysis (mismatched blood)
    • Immune complex (type III): antigen-antibody complex can’t be removed
  • Delayed occur 1 – 3 days after exposure
    • Contact dermatitis: hapten (incomplete antigen) exposure
    • Tuberculosis skin test: hardened lesion post-injection if sensitization had occurred
immunodeficiences
Immunodeficiences
  • Reductions of immune system cell numbers
  • Examples
    • Severe Combined Immunodificiency(SCID): genetic abnormality that reduces B-cell number
    • Hodgkin’s disease: B-cell cancer that depresses lymph nodes
    • Acquired Immune Disease (AIDS): destroys CD4 receptor cells (helper T-cells primarily)
      • Caused by human immunodeficiency virus (HIV)
autoimmune disease
Autoimmune Disease
  • Body recognizes ‘self’ selves as ‘non-self’ and attacks
  • Examples:
    • Multiple sclerosis: white matter (myelin) in CNS
    • Myasthenia gravis: skeletal muscle ACh receptors
    • Graves’ disease: excessive amounts of fluid by thyroid
    • Type I diabetes: pancreatic insulin producing cells
    • Systemic lupus erythematosus(SLE): chronic system inflammation (kidneys, heart, lungs, and skin common)
    • Rhematoid arthritis: bones and cartilage of joints
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