Immune System Flashcards

Immune System & the Body's Defense

• Immune system protects from infectious agents and harmful substances without our awareness.
• It is composed of cellular and molecular structures that function together to provide immunity.
• Function depends on specific type of infectious agent.
• Infectious agents can damage or kill a host and pathogenic agents cause harm.
• Five major categories of infectious agents: bacteria, viruses, fungi, protozoans, and multicellular parasites.

Overview of Diseases Caused by Infectious Agents

• Bacteria:
  • Single-celled prokaryotes, small (1 to 2 µm) with a membrane and cell wall.
  • Varied types: spherical (cocci), rod-like (bacilli), or coiled (spirilla).
  • Most are harmless, some virulent (cause serious illness).
  • Virulent bacteria have external polysaccharide capsule or release toxins/damaging enzymes.
  • Examples: Clostridium tetani (tetanus), streptococcal bacteria (strep throat).
• Viruses:
  • Pieces of DNA or RNA in a protein shell; not cells, much smaller than bacteria (about one-hundredth of a micrometer).
  • Obligate intracellular parasites; must enter a cell to reproduce.
  • Direct infected cell to make copies of nucleic acid and capsid (shell).
  • The virus or immune response may kill the host cell.
  • Examples: common cold, Ebola, chickenpox.
• Fungi:
  • Eukaryotic cells with membrane and cell wall; include molds, yeasts, multicellular fungi that produce spores.
  • Release proteolytic enzymes inducing inflammation.
  • Cause superficial diseases in the integument (e.g., ringworm).
  • Can infect mucosal linings (e.g., vaginal yeast infections) or cause internal infections (e.g., histoplasmosis).
• Protozoans:
  • Eukaryotic cells without a cell wall.
  • Intracellular and extracellular parasites.
  • Disease examples: malaria and trichomoniasis.
• Multicellular parasites:
  • Nonmicroscopic.
  • Take nourishment from host they live in.
  • Example: tapeworm.
• Prions:
  • Fragments of infectious proteins; neither cells nor viruses.
  • Cause disease in nervous tissue.
  • Example: Variant Creutzfeldt-Jakob disease (“mad cow”), spread from cows to humans by consuming infected meat.

Immune Cells & Their Locations

• Leukocytes (formed in red bone marrow):
  • Granulocytes: neutrophils, eosinophils, basophils.
  • Monocytes: become macrophages when they leave blood & enter tissues.
  • Lymphocytes: B-lymphocytes, T-lymphocytes, NK (natural killer) cells.
• Structures housing immune system cells:
  • Most leukocytes are in body tissues (not blood).
  • Secondary lymphatic structures: T- & B-lymphocytes, macrophages, dendritic cells, & NK cells housed in lymph nodes, spleen, tonsils, MALT, lymphatic nodules.
  • Select organs house macrophages as permanent residents (e.g., alveolar macrophages) or migrating macrophages.
  • Epithelial layers of skin & mucosal membranes house dendritic cells (derived from monocytes), which engulf pathogens & migrate into lymph.
  • Connective tissue houses mast cells (typically in close proximity to small blood vessels), abundant in dermis & mucosa of respiratory, GI, & urogenital tracts; also found in connective tissue of organs (e.g., endomysium of muscle).

Cytokines

• Small proteins that regulate immune activity; produced by cells of both innate & adaptive immune system.
• Chemical messengers released from one cell that bind to receptors of target cells.
• Can act on cell that released it (autocrine), on local cells (paracrine), or on distant cells after circulating through blood (endocrine).
• Have short half-life.
• Effects:
  • Signaling cells (including non-immune cells, e.g., neurons).
  • Controlling development & behavior of immune cells.
  • Regulating inflammatory response.
  • Destroying cells.

Comparison of Innate Immunity & Adaptive Immunity

• Differ based on:

  • Cells involved.
  • Specificity of cell response.
  • Mechanisms of eliminating harmful substances.
  • Amount of time for response.

• Distinct but work together in body defense.

• Innate immunity:

  • Present at birth.
  • Protects against variety of different substances (nonspecific); no prior exposure necessary.
  • Includes barriers of skin & mucosal membranes, nonspecific cellular & molecular internal defenses.
  • Responds immediately to potentially harmful agents.

• Adaptive immunity:

  • Acquired immunity.
  • Response to antigen involves specific T- & B-lymphocytes; a particular cell responds to one foreign substance but not another.
  • Takes several days to be effective.

Innate Immunity

• Characteristics:
  • Prevents entry of potentially harmful substances.
  • Responds nonspecifically to a range of harmful substances.
  • First line of defense: skin & mucosal membrane.
  • Second line of defense: internal processes.
    • Activities of neutrophils, macrophages, dendritic cells, eosinophils, basophils, & NK cells.
    • Chemicals such as interferon & complement.
    • Physiological processes such as inflammation & fever.

Preventing Entry

• Skin:
  • Few microbes can penetrate intact skin (physical barrier of epidermis & dermis).
  • Releases antimicrobial substances (dermicidin, lysozyme, sebum, defensins).
  • Has normal nonpathogenic flora (microorganisms) to prevent growth of pathogenic microorganisms.
• Mucosal membranes:
  • Line body openings; produce mucin & release antimicrobial substances (defensins, lysozyme, IgA).
  • Lined by harmless bacteria that suppress growth of more virulent types.

Cellular Defenses

• Neutrophils, macrophages, & dendritic cells:
  • Cells of innate immunity that engulf unwanted substances by phagocytosis.
  • Neutrophils & macrophages destroy engulfed particles via phagolysosome (intake vesicle fuses with lysosome; digestive enzymes break down substances).
  • Dendritic cells destroy particles & then present fragments (antigens) on cell surface to T-lymphocytes for initiating adaptive immunity; macrophages can also perform antigen presentation.
• Basophils & mast cells:
  • Promote inflammation.
  • Basophils circulate in blood; mast cells reside in connective tissue, mucosa, internal organs.
  • Release granules containing chemicals that increase movement of fluid from blood to injured tissue & attract immune cells (chemotactic).
    • Histamine increases vasodilation & capillary permeability.
    • Heparin acts as an anticoagulant.
  • Eicosanoids released from plasma membrane also increase inflammation.
• Natural killer (NK) cells:
  • Destroy a variety of unwanted cells.
  • Form in bone marrow, circulate in blood, & accumulate in secondary lymphatic structures.
  • Perform immune surveillance (patrol the body detecting unhealthy cells).
  • Destroy virus-infected cells, bacteria-infected cells, tumor cells, cells of transplanted tissue.
  • Kill by releasing cytotoxic chemicals.
    • Perforin creates a transmembrane pore in unwanted cell.
    • Granzymes enter pore & cause apoptosis (cell death that causes shriveling rather than lysis) of cell.
• Eosinophils:
  • Attack multicellular parasites.
  • Degranulate, release enzymes & other toxic substances (can release proteins that form transmembrane pores in parasite’s cells).
  • Participate in immune responses of allergy & asthma.
  • Engage in phagocytosis of antigen-antibody complexes.
• Pattern recognition receptors (toll-like receptors):
  • Cells of innate immune system recognize microbes as foreign because of these receptors on cell surface that bind to patterns on microbe surface.

Antimicrobial Proteins

• Interferons:
  • A class of cytokines that nonspecifically impede viral spread.
  • IFN-γ produced by T-lymphocytes & NK cells stimulates macrophages to destroy virus-infected cells.
  • IFN-α & IFN-β produced by leukocytes & virus-infected cells bind to neighboring cells & prevent their infection; trigger synthesis of enzymes that destroy viral nucleic acids, inhibit synthesis of viral proteins.
• Complement system:
  • Group of over 30 plasma proteins that work along with (“complement”) antibodies; identified with letter “C” & number (e.g., C2).
  • Synthesized by liver, continuously released in inactive form; activation occurs by enzyme cascade.
  • Complement activation follows pathogen entry.
    • Classical pathway: Antibody attaches to foreign substance & then complement binds to antibody.
    • Alternative pathway: Complement binds to polysaccharides of bacterial or fungal cell wall.
  • Especially potent system against bacterial infections.
  • Opsonization: complement protein (opsonin) binds to pathogen, enhances likelihood of phagocytosis.
  • Inflammation is enhanced by complement (activates mast cells & basophils; attracts neutrophils & macrophages).
  • Cytolysis: complement triggers splitting of target cell; complement proteins form membrane attack complex (MAC) that creates channel in target cell’s membrane, fluid enters, causing cell lysis.
  • Elimination of immune complexes: complement links antigen-antibody complexes to erythrocytes, cells move to liver & spleen where complexes are stripped off.

Inflammation

• Immediate response to ward off unwanted substances; local, nonspecific response of vascularized tissue to injury; part of innate immunity.
• Events of inflammation:
  • Injured tissue, basophils, mast cells, & infectious organisms release chemicals (histamine, leukotrienes, prostaglandins, chemotactic factors) that initiate response.
  • Released chemicals cause vascular changes:
    • Vasodilation.
    • Increased capillary permeability.
    • Increased endothelial expression of molecules for leukocyte adhesion (cell-adhesion molecules, CAMs).
  • Recruitment of leukocytes:
    • Margination: adherence of leukocytes to endothelial CAMs.
    • Diapedesis: cells escape blood vessel walls.
    • Chemotaxis: leukocytes migrate toward chemicals released from damaged, dead, or pathogenic cells.
  • Leukocytes release cytokines stimulating leukopoiesis in marrow.
  • Macrophages may release pyrogens (fever-inducing molecules).
• Effects of inflammation:
  • Fluid (exudate) moves from blood to injured or infected area; exudate contains fluid, protein, & immune cells to eliminate pathogens & promote healing.
  • Vasodilation brings more blood to the area.
  • Contraction of vessel endothelial cells opens gaps between them, increasing capillary permeability.
  • Loss of plasma proteins decreases capillary osmotic pressure, thus decreasing fluid reabsorption into blood.
  • Extra fluid is taken up by lymphatic capillaries in the area (“washing”) - carries away debris & allows lymph node monitoring of its contents.
• Cardinal signs of inflammation:
  • Redness from increased blood flow.
  • Heat from increased blood flow & increased metabolic activity within the area.
  • Swelling from increase in fluid loss from capillaries.
  • Pain from stimulation of pain receptors (due to compression (extra fluid) & chemical irritants (kinins, prostaglandins, microbial secretions)).
  • Loss of function from pain & swelling in severe cases.
• Duration of acute inflammation: about 8 to 10 days; chronic inflammation has detrimental effects.

Fever

• Abnormal body temperature elevation - 1°C or more from normal (37°C).
• Results from the release of pyrogens (e.g., IL-1) from immune cells or infectious agents.
• Events of fever:
  • Pyrogens circulate through blood & target hypothalamus.
  • In response, hypothalamus releases prostaglandin E2.
  • Hypothalamus raises temperature set point leading to fever.
• Benefits of fever:
  • Inhibits reproduction of bacteria & viruses.
  • Promotes interferon activity.
  • Increases activity of adaptive immunity.
  • Accelerates tissue repair.
  • Increases CAMs on endothelium of capillaries in lymph nodes, which leads to additional immune cells migrating out of blood.
  • Recommended to leave a low fever untreated.
• Risks of a high fever:
  • High fevers potentially dangerous (103º F in children, slightly lower in adult).
  • Changes in metabolic pathways & denaturation of proteins pose risks.
  • Possible seizures.
  • Irreversible brain damage at greater than 106º F.
  • Death likely if temperature greater than 109º F.

Clinical View: Pus & Abscesses

• Pus: exudate containing destroyed pathogens, dead leukocytes, macrophages, cellular debris; removed by lymphatic system or through skin.
• If not completely cleared, may form abscess (pus walled off with collagen fibers), requires surgical intervention to remove.

Clinical View: Applying Ice for Acute Inflammation

• Ice recommended for acute inflammation; causes vasoconstriction of blood vessels (decreases inflammatory response), numbs area & makes less painful.

Clinical View: Chronic Inflammation

• Inflammation continuing for longer than two weeks; characterized by macrophages & lymphocytes (not neutrophils).
• Can occur from overuse injuries (e.g., tennis elbow or shin splints).
• May occur if acute inflammation unable to eliminate pathogen or due to autoimmune disorder.
• Can lead to tissue destruction & scar tissue formation.

Adaptive Immunity: An Introduction

• Involves specific lymphocyte responses to an antigen; contact with antigen causes lymphocyte proliferation.
• Immune response consists of lymphocytes & their products.
• Longer response time than innate immunity; considered the third line of body’s defense.
• Two branches:
  • Cell-mediated immunity involving T-lymphocytes.
  • Humoral immunity involving B-lymphocytes, plasma cells, & antibodies.

Antigens

• Pathogens are detected by lymphocytes because they contain antigens.
• Antigen: substance that binds a T-lymphocyte or antibody; usually a protein or large polysaccharide.
• Examples of antigens:
  • Protein capsid of viruses.
  • Cell wall of bacteria or fungi.
  • Bacterial toxins.
  • Abnormal proteins or tumor antigens.
• Foreign antigens differ from human body’s molecules and bind body’s immune components; self-antigens are body’s own molecules and typically do not bind immune components.
• Immune system generally able to distinguish, but in autoimmune disorders, the system reacts to self-antigens as if foreign.
• Antigenic determinant (epitope):
  • Specific site on antigen recognized by immune system; each has a different shape.
  • Pathogenic organisms can have multiple determinants.
• Immunogen:
  • Antigen that induces an immune response.
  • Immunogenicity: ability to trigger response (increases with antigen’s degree of foreignness, size, complexity, or quantity).
• Haptens:
  • Small foreign molecules that induce immune response when attached to a carrier molecule in host (e.g., toxin in poison ivy).
  • Account for hypersensitivity reactions (e.g., to drugs such as penicillin, pollen).

Clinical View: Autoimmune Disorders

• Immune system lacking tolerance for specific self-antigen and initiates immune response as if cells were foreign.
• Due to cross-reactivity, altered self-antigens, or entering areas of immune privilege.
• Examples: rheumatic heart disease, type 1 diabetes, multiple sclerosis (all affecting different body structures).

General Structure of Lymphocytes

• T- & B-lymphocytes have unique receptor complexes (about 100,000 per cell); each complex binds one specific antigen.
• TCR (T-cell receptor) is antigen receptor of T-lymphocyte; BCR (B-cell receptor) is antigen receptor of B-lymphocyte.
• Lymphocyte contact with antigen:
  • B-lymphocytes make direct contact with antigen.
  • T-lymphocytes have antigen presented by some other cell (antigen is processed & presented by another cell type).
  • T-lymphocyte coreceptors (e.g., CD proteins) facilitate the interaction.
• T-lymphocyte subtypes:
  • Helper T-lymphocytes are CD4+ cells that assist in cell-mediated, humoral, & innate immunity (e.g., activate NK cells & macrophages).
  • Cytotoxic T-lymphocytes are CD8+ cells that release chemicals that destroy other cells.
  • Other types include memory T-cells & regulatory T-cells.

Antigen-Presenting Cells & MHC Molecules

• Antigen presentation: cells display antigen on plasma membrane so T-cells can recognize it.
• Two categories of cells present antigens:
  • All nucleated cells of the body.
  • Antigen-presenting cells (APCs): Immune cells that present to both helper T-cells & cytotoxic T-cells (include: dendritic cells, macrophages, B-lymphocytes).
• Requires attachment of antigen to major histocompatibility complex (MHC), a group of transmembrane proteins.
  • MHC I is found on all nucleated cells.
  • MHC II is found on APCs (in addition to MHC I).
• Synthesis & display of MHC class I molecules on nucleated cells:
  • MHC class I molecules are glycoproteins with genetically determined structure unique to individual; continuously synthesized & modified by rough endoplasmic reticulum (RER); then inserted into cell membrane.
  • Display fragments of proteins that were bound in RER.
    • If fragments are from endogenous proteins, immune system recognizes them as “self ” & ignores them.
    • If fragments are from an infectious agent, immune system considers the antigen “nonself ” and communicates to cytotoxic T-cells that they should destroy cell.
• Display of MHC class II molecules on professional antigen-presenting cells:
  • MHC class II molecules are also glycoproteins; synthesized & modified by RER, sent to membrane.
  • Exogenous antigens brought into cell through endocytosis.
  • Phagosome merges with lysosome, forming phagolysosome.
  • Substance digested into peptide fragments.
  • Fragments “loaded” onto MHC class II molecules within vesicle.
  • Vesicle merges with plasma membrane with antigen bound to MHC molecule - provides means of communicating with helper T-lymphocytes.

Clinical View: Organ Transplants & MHC Molecules

• Transfer of organ from one individual to another (e.g., kidney, liver, heart).
• Individuals tested prior to donation for MHC antigens & ABO group; no two individuals with exactly same MHC molecules.
• Components of innate & adaptive immune system attempt to destroy transplanted tissue; recipient’s immune system suppressed with drugs.

Overview of Life Events of Lymphocytes

• Three main events in life of lymphocyte:
  • Formation & maturation of lymphocytes:
    • Occurs in primary lymphatic structures (red marrow & thymus).
    • Become able to recognize one specific foreign antigen.
  • Activation of lymphocytes:
    • In secondary lymphatic structures they are exposed to antigen & become activated.
    • Replicate to form identical lymphocytes.
  • Effector response: action of lymphocytes to eliminate antigen
    • T-lymphocytes migrate to site of infection
    • B-lymphocytes stay in secondary lymphatic structure (as plasma cells) - synthesize & release large quantities of antibodies, which are transported to infection site through blood & lymph.

Formation & Selection of Lymphocytes

• Lymphocytes are formed in red marrow and then tested for immunocompetence (cells bind & respond to antigen).
• Testing occurs during development & shortly after birth in primary lymphatic structures.

Formation of T-lymphocytes

• Originate in red bone marrow, migrate to thymus as pre-T-lymphocytes to complete maturation.
• Initially have both CD4 & CD8 proteins.
• Possess unique, randomly produced TCR receptor.
• Each cell has its TCR “tested” through a process of selection for:
  • Ability to bind MHC with antigen.
  • Binding only foreign (“nonself ”) antigen.

Selection of T-lymphocytes

• Thymic selection eliminates 98% of T-cells produced.
  • Positive selection: Selects for the ability of T-cells to bind thymic epithelial cells with MHC molecules (those that can bind survive).
  • Negative selection: Tests ability of T-lymphocyte to NOT bind self-antigens (self -tolerance). Thymic dendritic cells present self-antigens & T-cells that bind to them are destroyed.

Differentiation & Migration of T-Lymphocytes

• T-lymphocytes differentiate:
  • Helper T-lymphocytes lose CD8 protein.
  • Cytotoxic T-lymphocytes lose CD4 protein.
• T-lymphocytes migrate from thymus to secondary lymphatic structures.
  • They are immunocompetent - Naive T-lymphocyte: not yet exposed to antigens they recognize.
• Regulatory T-lymphocytes (Tregs):
  • They are CD4+.
  • Formed from T-cells that bind self-antigens moderately.
  • They migrate throughout body releasing chemicals that inhibit cell-mediated & humoral immune responses (function in peripheral tolerance, a form of self-tolerance).
  • Some tumors foster Tregs proliferation; some cancer treatments try to inhibit tumor Tregs.
• B-cells also undergo formation, selection, & migration to secondary lymphatic structures.
• New T- & B-cells form throughout one’s life.

Activation & Clonal Selection of Lymphocytes

• Clonal selection: forming clones in response to an antigen. All formed cells have same TCR or BCR that matches specific antigen.
• Antigen challenge: first encounter between antigen & lymphocyte, usually occurs in secondary lymphatic structures (antigen in blood taken to spleen; antigen penetrating skin transported to lymph node; antigen from respiratory, GI, urogenital tracts, in tonsils or MALT).

Activation of T-Lymphocytes

• Activation of helper T-lymphocytes:
  • First signal: direct contact with MHC molecule of APC. APC presents exogenous antigen with MHC class II molecules in secondary lymphatic structure. Specific TCR site of T-cell binds to antigen peptide fragment, interaction stabilized by CD4 molecule of helper T-lymphocyte. If it doesn’t recognize antigen, T-cell disengages quickly; if it does recognize antigen, contact lasts several hours.
  • Second signal: other receptors of APC & T-cell interact. Some cells become memory helper T-lymphocytes, available for future encounters. Lack of a second signal results in helper T-cells becoming Tregs. Helper T-cell secretes interleukin-2, stimulating itself and proliferates forming clones of helpers T-cells (with same TCR), some cells become activated helper T -lymphocytes that continue to produce IL-2.
• First signal: Direct contact between TCR of cytotoxic T-cell & peptide fragment with MCH I molecule (on APC or infected cell); interaction stabilized by CD8 of cytotoxic T- lymphocyte.
• Second signal: IL-2 released from helper T-cells binds to & stimulates cytotoxic T-lymphocytes.
• Activated cytotoxic T-cells proliferate & differentiate - Some become activated cytotoxic T-lymphocytes, others become memory cytotoxic T-lymphocytes activated upon re-exposure to same antigen.

Activation of B-Lymphocytes

• B-lymphocytes need to be activated, but can respond to antigens outside of cells.
• First signal: intact antigen binds to BCR, cross-linking 2 BCRs; stimulated B-cell engulfs, processes, & presents antigen to helper T-cell for recognition.
• Second signal: activated helper T-cell releases IL-4, stimulating B-lymphocyte.
• B-lymphocyte activation causes B-lymphocytes to proliferate & differentiate.
  • Most differentiate into plasma cells that produce antibodies; remainders become memory B-lymphocytes that retain BCRs & activate with re-exposure to same antigen & have much longer life span than plasma cells.
  • In some cases activation occurs without T-cells, but production of memory B-cells & various antibodies requires helper T- cell involvement in activation.

Lymphocyte Recirculation

• After several days, a lymphocyte exits secondary lymphatic structure. Circulates through blood & lymph; different lymphocytes delivered to secondary lymphatic structures, which makes it more likely lymphocyte will encounter specific antigen.

Effector Response at Infection Site

• Mechanism used by lymphocytes to help eliminate antigen; each lymphocyte type has its own.
  • Helper T-lymphocytes: Release IL-2 & other cytokines that regulate cells of adaptive & innate immunity.
  • Cytotoxic T-lymphocytes: Destroy unhealthy cells by apoptosis.
  • Plasma cells: Produce antibodies.

Effector Response of T-Lymphocytes

• Effector response of helper T- lymphocytes
  • After exposure to antigen (in secondary lymphatic structures), activated & memory helper T-cells migrate to infection site and continually release cytokines to regulate other immune cells.
  • Help activate B-lymphocytes, activate cytotoxic T-lymphocytes with cytokines, and stimulate activity of innate immune system cells.
• Effector response of cytotoxic T-lymphocytes
  • After exposure to antigen, activated & memory cytotoxic T-cells migrate to infection site and destroy infected cells that display the antigen (make physical contact with unhealthy or foreign cell).
  • After recognizing antigen, cytotoxic T-cell releases granules containing perforin & granzymes (cytotoxic chemicals).
  • Perforin forms channel in target cell membrane and granzymes enter channel & induce death by apoptosis.
  • Because this works against antigens associated with cells, the system is called cell-mediated immunity.

Effector Response of B-Lymphocytes

• Most activated B-lymphocytes become plasma cells, which synthesize & release antibodies and remain in the lymph nodes.
• Produce millions of antibodies during 5-day life span. Antibodies circulate through lymph & blood until encountering antigen.
• Antibody titer: circulating blood concentration of antibody against a specific antigen.

Structure of Immunoglobulins

• Antibodies: immunoglobulin proteins produced against a particular antigen; “tag” pathogens for destruction by immune cells, good defense against viruses, bacteria, toxins, yeast spores.
• Soluble antigens are combatted by “humoral immunity”.
• Structure: Y-shaped, soluble proteins composed of four polypeptide chains (two identical heavy chains & two identical light chains) with flexibility at hinge region of two heavy chains, held together by disulfide bonds to form antibody monomer.
• Two important functional areas: variable & constant regions.
• Constant region: Contains the Fc region, which determines biological function; same in structure for antibodies of a given class. Five major classes of immunoglobulins: IgG, IgM, IgA, IgD, IgE.
• Variable regions: Located at the ends of the antibody “arms”; contain antigen-binding site (most antibodies have two sites). Bind antigens through weak intermolecular forces (hydrogen bonds, ionic bonds, & hydrophobic interactions).

Actions of Antibodies

• Neutralization: Physically covers antigenic determinant of pathogen, makes it ineffective in establishing infection (e.g., covers region of virus used to bind cell receptor).
• Agglutination (clumping): Cross-links antigens of foreign cells causing clumping, especially effective against bacterial cells.
• Precipitation: Cross-links circulating antigens (e.g., viral particles). Forms antigen-antibody complex that becomes insoluble & precipitates out of body fluids. Precipitated complexes engulfed & eliminated by phagocytes.
• Fc region (of constant region) actions:
  • Complement fixation: Fc region of IgG & IgM can bind complement for activation (classical complement activation).
  • Opsonization: Fc region of certain antibody classes makes it more likely target cell will be “seen” by phagocytic cells. Some phagocytes have receptors for these Fc regions; bind to Fc region & engulf antigen & antibody.
  • Activation of NK cells: Fc region of some antibodies (IgG) trigger NK cells to release cytotoxins, which destroys abnormal cells through antibody-dependent cell-mediated cytotoxicity.

Classes of Immunoglobulins

• Five classes of immunoglobulins: IgG, IgM, IgA, IgD, & IgE.
• IgG: Make up 75–85% of antibodies in blood and also predominant antibody in other fluids (e.g., lymph, CSF); can participate in all types of antibody actions, can cross placenta & cause hemolytic disease of newborn.
• IgM: Found mostly in blood, normally has pentamer structure, most effective at agglutination & binding complement, responsible for rejection of mismatched transfusions.
• IgA: Found in areas exposed to environment, produced in mucus, saliva, tears, breastmilk, protects respiratory & GI tract. Dimer composed of two antibody molecules; helps prevent pathogens adhering to & penetrating epithelium and especially good at agglutination.
• IgD: Functions as antigen-specific B-lymphocyte receptor and identifies when immature B-lymphocytes ready for activation.
• IgE: Usually formed in response to parasites & in allergic reactions (otherwise low rate of synthesis), causes release of products from basophils & mast cells, and attracts eosinophils.
• Class switching: When a plasma cell changes the type of antibody it produces. Requires contact between helper T-cell & plasma cell, which must release particular cytokines to specify antibody class that will be formed.

Immunologic Memory

• Memory results from formation of a long-lived army of lymphocytes upon immune activation. Adaptive immunity activation requires contact between lymphocyte & antigen; there is lag time between first exposure & direct contact. Activation leads to formation of many memory cells against specific antigen.
  *Antibody titer - A measure of immunologic memory

Immunologic Memory

• With subsequent antigen exposure, many memory cells make contact with antigen more rapidly and produce powerful secondary response; pathogen typically eliminated before disease symptoms develop (e.g., person who develops measles will not have it again, even if exposed).
  Virus eliminated by memory T- & B-lymphocytes, antibodies before causing harm. Vaccines are typically effective in developing memory.

Measure of Immunologic Memory

• Initial exposure & the primary response: Initial exposure can be active infection or vaccine.
  • Primary response: antibody production to first exposure occurs.
    • Lag or latent phase: initial period of no detectable antibody that lasts 3 to 6 days including antigen detection, activation, proliferation, and differentiation.
    • Occurs within 1 to 2 weeks, production of antibody: plasma cells produce IgM & then IgG.
    • Antibody levels peak, then decline over time.
• Subsequent exposures & the secondary response:
  • Next exposure can occur after variable length of time.
  • Measurable response to subsequent exposure is the secondary response.
    • Lag or latent phase is much shorter than primary response due to memory lymphocytes.
    • Antibody levels rise rapidly and a large proportion of IgG antibodies is created.

Active & Passive Immunity

• Active immunity: build your own immunity results from direct encounter with pathogen, occurs naturally by direct exposure to antigen, and can occur artificially through exposure through vaccine.
  Memory cells against specific antigen are formed after using active immunity.
• Passive immunity: obtained from another individual.
  • Natural passive immunity arises from transfer of antibodies from mother to fetus (through placenta or milk).
  • Artificial passive immunity occurs when serum containing antibodies transferred from one person to another (e.g., antibodies to snake venom can be transferred this way).
    Neither form of passive immunity produces memory cells, and only lasts as long as antibody proteins present.

Clinical View: Vaccinations

• Vaccinations use weakened or dead microorganism or component to stimulate immune system to develop memory B-lymphocytes. Provides relatively safe means for initial exposure to microorganism.
• If later exposed, secondary response triggered with the immune system response predominantly from the humoral branch and may provide lifelong immunity or require booster shot.

Clinical View: Hypersensitivities

• Abnormal & exaggerated response of immune system to antigen.
  • Acute hypersensitivities occur within seconds after exposure.
  • Subacute hypersensitivities occurring within 1 to 3 hours after exposure. (Both involve humoral immunity).
  • Delayed hypersensitivities occur within 1 to 3 days after exposure (Involve cell-mediated immunity).
• Acute hypersensitivity: allergy
  • Overreaction of immune system to a noninfectious substance, allergen (e.g., pollen, latex, peanuts) that may cause multiple symptoms such as runny nose and watery eyes, red welts and itchy skin (hives), labored breathing and coughing (allergic asthma), vomiting and diarrhea, and systemic vasodilation & inflammation.
    May cause the carrier to go into anaphylactic shock.

Clinical View: HIV & AIDS

• Acquired immunodeficiency syndrome that is a life-threatening condition and the result of human immunodeficiency virus
• The virus infects & destroys helper T-lymphocytes then resides in body fluids of infected individuals and can be transmitted by intercourse, needle sharing, breastfeeding, or prevention through safe sex.
• HIV tests look for HIV antibodies in the blood.
• Becomes AIDS when helper T-lymphocytes drop below certain level - Individuals prey to opportunistic infections and may have CNS complications.
• No cure for HIV - Treatments alleviate symptoms & help prevent spread.