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 (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

Immune Response Summary