Immune System Chapter 21
Dec 17, 2015
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 (non-
specific)– 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 B-
cells
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
Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com)
• 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
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– 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:– 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