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The Immune System

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pathogen
infectious agents that cause disease; mostly viruses, bacteria, protists, and fungi
immune system
system which enables an animal to avoid or limit many infections
innate immunity
active immediately upon infection and are same whether or not pathogen has been encountered previously; includes barrier defenses as well as defenses that combat pathogens after they enter the body
acquired immunity
aka adaptive immunity; activated after innate immune defenses take effect and develop more slowly; enhanced by previous exposure to the infecting pathogen; found only in vertebrates
lysozyme
enzyme that digests microbial cell walls
hemocyte
immune cells which circulate within hemolymph; some carry out phagocytosis; others trigger production of chemicals that kill microbes and help entrap multicellular parasites
hemolymph
insect equivalent of blood
phagocytosis
ingestion and digestion of bacteria and other foreign substances
antimicrobial peptides
secretion triggered by encounters with pathogens in hemolymph; circulate throughout body of insect and inactivate or kill fungi and bacteria by disrupting plasma membranes
events in phagocytic cell
1. pseudopodia surround microbes
2. microbes engulfed into cell
3. vacuole containing microbes forms
4. vacuole and lysosome fuse
5. toxic compounds and lysosomal enzymes destroy microbes
6. microbial debris released by exocytosis
barrier defenses
outer covering (such as skin or shell) which provides significant obstacle to invasion by microbes that are present on the body
barrier defenses in mammals
epithelial tissues block entry of many pathogens; include skin, mucous membranes, and secretions
mucus
viscous fluid that enhances defenses by trapping microbes and other particles
body secretions
create environment hostile to many microbes; lysozyme in saliva, mucous secretions, and tears; acidic environment of the stomach; acidic secretions from sebaceous (oil) and sweat glands
leukocytes
phagocytic white blood cells
protein Toll
receptor on surface of immune response cells in insects
Toll-like receptor (TLR)
receptors in vertebrates that recognize fragments of molecules characteristic of a set of pathogens; recognized marcomolecule normally absent from vertebrate body and is an essential component of a class of microbes
neutrophil
most abundant phagocytic cells in mammalian body; signals from infected tissues attract neutrophils which then engulf and destroy microbes
macrophages
"big eaters" provide more effective phagocyctic defense; some migrate throughout body; others reside permanently in various organs and tissues; those in spleen, lymph nodes, and other tissues of lymphatic system are particularly well positioned to combat pathogens; key role in initiating secondary immune response by presenting antigens to memory helper T cells
lymphatic system
consists of lymphatic vessels through which lymph travels and various structures that trap foreign molecules and particles
flow of lymph
1. interstitial fluid bathing tissues, along with white blood cells in it, continually enters lymphatic vessels
2. fluid inside lymphatic system, known as lymph, flows through lymphatic vessels throughout body
3. within lymph nodes, microbes and foreign particles present in circulating lymph encounters macrophages and other cells that carry out defensive actions
4. lymphatic vessels return lymph to the blood via two large ducts that drain into veins near the shoulders
eosinophils
low phagocytic activity but are important in defending against multicellular invaders such as parasitic worms; position themselves against parasite's body and discharge destructive enzymes that damage invader
dendritic cells
populate tissues that are in contact with the environment; stimulate development of acquired immunity against microbes they encounter; important in triggering primary immune response (serve as sentinels in epidermis and other tissues frequently exposed to foreign antigens; migrate from infection site to lymphoid tissues)
interferon
proteins that provide innate defense against viral infections; virus-infected body cells secret interferons, inducing nearby cells to produce substances that inhibit viral reproduction; limit cell-to-cell spread of viruses in the body; white blood cells may secret different type of interferon that helps activate macrophages
complement system
consists of roughly 30 proteins in blood plasma that function together to fight infections; proteins circulate in inactive state and are activated by substances on the surface of many microbes; activation results in cascade of biochemical reactions leading to lysis of invading cells; also functions in inflammation and acquired defenses
inflammatory response
changes brought about by signaling molecules released upon injury or infection; pain and swelling!
histamine
important inflammatory signaling molecule; stored in mast cells
mast cells
connective tissue cells that store chemicals in granules for secretion
progression of events in local inflammation
1. activated macrophages and mast cells at injury site release signaling molecules that act on nearby capillaries
2. capillaries widen and become more permeable, allowing fluid containing antimicrobial peptides to enter tissue; signaling molecules released by immune cells attract additional phagocytic cells
3. phagocytic cells digest pathogens and cell debris at the site and tissue heals
pus
fluid rich in white blood cells, dead microbes, and cell debris
systemic
throughout the body
fever
systemic inflammatory response; some toxins produced by pathogens, as well as substances called pyrogens released by activated macrophages, can reset body's thermostat to higher temperature
pyrogens
substance released by activated macrophages that reset body's thermostat to higher temperature
septic shock
overwhelming systemic inflammatory response; often life-threatening; characterized by very high fever, low blood flow, and low blood pressure
natural killer cells (NK cells)
help recognize and eliminate certain diseased cells in vertebrates; attach to stricken cells without class I MHC molecule and release chemicals that lead to cell death, inhibiting further spread of virus or cancer
lymphocytes
white blood cells critical for acquired immune defense; B cells and T cells are types of lymphocytes; originate from stem cells in bone marrow
T cells
lymphocytes that migrate from bone marrow to thymus and mature there; recognize and inactive foreign cells and molecules
thymus
organ in thoracic cavity above the heart
B cells
lymphocytes that mature in the bone marrow; recognize and inactive foreign cells and molecules; present antigens to helper T cells
immunological memory
enhanced response to a foreign molecule encountered previously
cytokines
proteins that help recruit and activate lymphocytes; secreted by macrophages and dendritic cells
antigen
any foreign molecule that is specifically recognized by lymphocytes and elicits a response from them; mostly proteins or polysaccharides; some released into extracellular fluid while others protrude from surface of pathogens or other foreign cells
antigen receptor
antigen-specific receptors on B and T cells that recognize antigens; bind to antigens via noncovalent bonds that stabilize interaction between epitope and binding surface
plasma cells
given rise by B cells; secrete soluble form of antigen receptor
antibody
secreted protein that is a soluble form of antigen receptor; also known as immunoglobulin (Ig)
epitope
antigenic determinant; small accessible portion of an antigen; single antigen generally has several different epitopes, each capable of inducing response from lymphocyte
specificity
lymphocyte recognize same epitope
B cell receptor
Y shaped molecule consisting of four polypeptide chains: two identical heavy chains and two identical light chains with disulfide bridges linking chains together; transmembrane region near one end of each heavy chain anchors receptor in cell's plasma membrane; short tail region at end of heavy chain extends into cytoplasm; recognize and bind to antigen regardless of whether antigen is free or on surface of pathogen
constant region (C region)
region in both light and heavy chains where amino acid sequences vary little among receptors present on different B cells; includes cytoplasmic tail and transmembrane region of heavy chain and all of disulfide bridges
variable region (V region)
within two tips of Y shape of both light and heavy chains; amino acid sequence varies extensively from one B cell to another; asymmetrical binding site for antigen
T cell receptor
two different polypeptide chains (alpha and Beta chain) linked by a disulfide bridge; transmembrane region, variable regions, constant regions; bind only to antigen fragements that are displayed or presented on surface of host cells
major histocompatability complex (MHC)
group of genes that produce a host cell protein that can present an antigen fragment to T cell receptors
antigen fragment
peptide antigens; smaller pieces of pathogen proteins that result when a pathogen is inside host cell and enzymes in cell cleave proteins; bind to MHC molecule inside cell
antigen presentation
display of an antigen fragment on the cell surface; movement of MHC molecule and bound fragment to cell surface
class I MHC molecules
found on almost all cells of body (excepted non-nucleated cells such as red blood cells); bind to peptide fragments of foreign antigens synthesized within cell; recognized by cytotoxic T cells
cytotoxic T cells
special group of T cells that recognize class I MHC molecules displaying bound antigen fragments
class II MHC molecules
made by few cell types, mainly dendritic cells, macrophages, and B cells; typically bind to antigen fragments derived from foreign materials that have been internalized through phagocytosis or endocytosis
antigen-presenting cells
dendritic cells, macrophages, and B cells; key role in displaying internalized antigens; display antigens for recognition by cytotoxic T cells and helper T cells
helper T cells
group of T cells that assist both B cells and cytotoxic T cells
3 major properties of acquired immune system
1. tremendous diversity of receptors ensures even pathogens never before encountered will be recognized as foreign
2. ability to recognize vast numbers of foreign molecules coexist with lack of reactivity against molecules that make up organism's own cells and tissues
3. response to an antigen that has been previously encountered is stronger and more rapid than initial response
immunoglobulin gene rearrangement
1. recombination deletes DNA between randomly selected V and J segments
2. transcription of permanently rearranged functional gene
3. RNA processing
4. Translation
effector cells
short-lived lymphocytes that attack antigen and any pathogens producing that antigen
memory cells
long-lived and less numerous; bear receptors specific for the antigen
clonal selection
proliferation of lymphocyte into clone of cells in response to binding an antigen
primary immune response
production of effector cells from a clone of lymphocytes during first exposure to an antigen
secondary immune response
secondary exposure to same antigen; response is faster, of greater magnitude, and more prolonged
humoral immune response
involves activation and clonal selection of effector B cells, which secrete antibodies that circulate in the blood and lymph
cell-meditated immune response
activation and clonal selection of cytotoxic T cells, which identify and destroy target cells
CD4
protein found on surface of most helper T cells that bind to class II MHC molecules; helps keep helper T cell and antigen-presenting cell joined
CD8
protein found on most cytotoxic T cells; enhances interaction between target cell and cytotoxic T cell; binding of CD8 to class I MHC molecule helps keep two cells in contact while cytotoxic T cell is activated
killing action of cytotoxic T cells
1. activated cytotoxic T cell binds to class I MHC-antigen fragment complex on targeted cell via its TCR and aid of CD8
2. T cell releases perforin molecules which form pores in target cell membrane, and granzymes, enzymes that break down proteins (enter cell by endocytosis
3. granzymes initiate apoptosis within target cell, leading to fragmentation of nucleus and cytoplasm and eventually cell death
B cell activation
1. after antigen-presenting cell enguls and degrade bacterium, displays an antigen fragment complex with class II molecule; helper T cell recognizes complex is activated with aid of cytokines secreted from antigen-presenting cell, forming clone of activated helper T cells
2. B cell with receptors for same peptide internalizes antigen and displays it on cell surface in complex with class II MHC protein; activated helper T cell bearing receptor specific for displayed antigen fragment binds to B cell
3. activated B cell proliferates and differentiates into antibody-secreting plasma cells and memory B cells; secreted antibodies are specific for the same bacterial antigen that initiated response
polyclonal
antibody tools that are the products of many different clones of B cells, each specific for a different epitope
monoclonal
antibody tools prepared from a single clone of B cells grown in culture
monoclonal antibodies
identical and specific for same epitope on an antigen; particularly useful for specific molecules
neutralization
antibodies bind to surface proteins of virus or bacterium, thereby blocking pathogen's ability to infect host cell; sometimes bind to and neutralize toxins released in body fluids
opsonization
antibodies bound to antigens present readily recognized structure for macrophages and thereby increase phagocytosis
activation of complement system and pore formation
binding of antibodies to antigens on surface of foreign cell activates complement system; membrane attack complex then forms pores in foreign cell's membrane, allowing water and ions to rush in, lysing the cell
membrane attack complex
complex that forms a pore in membrane of foreign cell
active immunity
immunity in response to infection; clones of memory cells form
passive immunity
transferred antibodies from pregnant woman to her fetus; through IgG antibodies that cross the placenta
IgA antibodies
passed from mother to infant in breast milk; provide additional protection against infections which infant's immune system develops
immunization
vaccination; induced active immunity; many use antigens to make vaccines
artificial passive immunization
antibodies from immune animal injected into nonimmune animal
immune rejection
cells from another person recognized and attacked by immune defenses
allergen
antigens that cause exaggerated or hypersensitive responses
IgE antibodies
involved in most common allergies
degranulation
release of histamine by mast cells and other inflammatory agents from granules
anaphylactic shock
whole-body, life-threatening reaction that can occur within seconds of exposure to an allergen; develops when widespread mast cell degranulation triggers abrupt dilation of peripheral blood vessels, causing precipitous drop in blood pressure
autoimmune disease
immune system turns against particular molecules of the body
systemic lupus erythematosus
immune system generates antibodies against histones and DNA released by normal breakdown of body cells
rheumatoid arthritis
damage and painful inflammation of cartilage and bone of joints
Type 1 diabetes mellitus
insulin-producing beta cells of pancreas are targets of autoimmune cytotoxic T cells
multiple sclerosis
T cells infiltrate central nervous system, leading to destruction of myelin sheath that surrounds many neurons
immunodeficiency
disorder in which ability of an immune system to protect against pathogens is defective or absent
inborn immunodeficiency
genetic or developmental defect in immune system (such as antibodies or proteins of complement system)
severe combined immunodeficiency (SCID)
functional lymphocytes are rare or absent
acquired immunodeficiency syndrome (AIDS)
caused by virus
antigenic variation
changes in epitope expression; regular events for some viruses and parasites
latency
viruses remain in host without activating immune defenses, ceasing production of viral products targeted by lymphocytes