Transcript Immune System - Georgia Highlands College

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)
– Adaptive immunity (specific)
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
• 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
• 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
• 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 defensins to pierce PM
• Exocytosis
• Fig 21.2
Natural Killer (NK) Cells
• Large, granular lymphocytes
• Recognize and attack any ‘non-self’ cells (nonspecific)
– Cancer and viral cells
• Perforins secreted to puncture PM
• Induce apoptosis, programmed cell death
• Enhance 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
• 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
• 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
• Synthesized by infected cells
– Enter neighboring cells to
‘interfere’ w/ viral reproduction
• Not virus specific
• Activate macrophages and NK
cells too
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
• 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
• 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
• 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 Bcells
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)
• 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
• 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
• Primary
immune
response
– Antigen
challenge
• Secondary
immune
response
– Stronger,
faster, &
longer
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
• 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
• 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
• 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
• 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
• 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
• 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
• Key is to maximize match while reducing rejection
– Blood type (ABO and Rh) AND MHC protein
• Grafts exchange tissues b/w recipient and donor
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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
• 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
• Immune response to harmless antigens that result in tissue
damage
• Immediate occur w/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
• 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
• Body recognizes ‘self’ selves as ‘non-self’ and
attacks
• Examples:
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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
Immune Response Summary