The Immune System CAMPBELL and REECE Chapter 43 Innate Immunity nonspecific defense that is active immediately upon infection found in all animals amp plants includes outer covering skin or shell chemical secretions ID: 770382
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The Immune System CAMPBELL and REECE Chapter 43
Innate Immunity nonspecific defense that is active immediately upon infection found in all animals & plants includes: outer covering skin or shell chemical secretions @ openings to interior of body
Immune System must be able to identify nonself from self detection determined by molecular recognition of receptor molecules
Adaptive Immunity found only in vertebrates very specific aka acquired immune response activated after innate responses & develops more slowly
Innate Immunity of Insects only have innate immunity 1 st line of defense (barrier defenses) Exoskeletons: effective against most pathogens: made of polysaccharide, chitin
Innate Immunity in Insects: Barrier Defenses lining of intestine: has chitin where it blocks infection by pathogens ingested in food secretes lysozyme , enzyme that breaks down bacterial cell walls
Insect’s Internal Immune Responses if pathogen gets by barrier defenses: hemocytes : immune cells in hemolymph some can phagocytose others secrete chemicals that kill pathogens & help entrap large parasites (like Plasmodium ) interaction with pathogens some secrete antimicrobial peptides circulate in hemolymph
Phagocytosis
Insect Immune Cells bind to molecules unique to outer layers of fungi, or bacteria fungal cells: polysaccharides bacteria: combinations of sugars & a.a . not found in animal cells
Innate Responses unique for different classes of pathogens
Innate Immunity in Vertebrates coexists with adaptive immunity mechanisms 2 are strongly interdependent basis same as innate immunity in invertebrates but there are additions most research done on mammals
Barrier Defenses epithelial tissues block entry of many pathogens skin mucous membranes line organs that have opening to outside of body mucus: viscous fluid that blocks microbes & other particles saliva, tears have “washing” action keeping microbes from colonizing
Barrier Defenses cellular secretions lysozyme kills by breaking down cell walls saliva, tears dilute & prevent colonization sweat pH 3 – 4 stomach pH 2
Internal Innate Defenses 1. phagocytes cells that can detect fungi & bacteria use several types of receptors: Toll-like receptor (TLR) binds to fragments of molecules characteristic of set of pathogens similar mechanism used in insects
TLR Signaling Pathway
TLR TLR3 sensor for dsRNA (viral) TLR4 recognizes lipopolysaccharide (surface of many bacteria) TLR5 recognizes flagellin (bacterial flagella protein)
Types of Phagocytic Cells Neutrophils circulate in blood attracted by signals sent from infected cells Macrophages larger cells migrate thru tissues or reside permanently in organs/tissues likely to have invaders
Types of Phagocytic Cells 3. Dendritic cells mainly found in tissues that contact outside (skin) stimulate adaptive immunity after engulfing pathogen 4. Eosinophils found beneath mucous membranes low phagocytic activity speciality : able to defend against parasitic worms secrete enzymes
Natural Killer Cells circulate thru body detecting abnl surface proteins of cells infected with virus or cancer cells on detection secrete chemicals that kill affected cell
Lymphatic System network of vessels that connect lymphatic tissues thru out body ICF lymph vessels venous drainage some macrophages in lymph nodes
Lymphatic System dendritic cells migrate to lymph node after interacting with pathogen interact with other immune cells stimulating adaptive immunity attack aka APCs: Antigen-Presenting Cells
Lymphatic System
Pathogen Recognition Triggers: release of peptides & proteins attack pathogens or impede their reproduction
Interferons proteins released in response to viral infection vertebrates only now used in early treatment
Complement System ~30 proteins in plasma circulate in inactive state activated by substances on surfaces of some microbes activation starts cascade of reactions lysis of invading cells
Inflammatory Response innate immune defense triggered by physical injury or infection of tissue involving the release of substances that promote swelling, enhance the infiltration of WBCs, & aid in tissue repair & destruction of invading pathogens
Histamine 1 of inflammatory signaling molecules stored in granules of mast cells (in CT)
Cytokines group of small protein secreted by # of cell types: macrophages helper T cells regulate function of other cells to enhance immune response promote increased blood flow to injured area causes redness & increased skin temp engorged capillaries leak fluid localized swelling
Inflammatory Response
Some Pathogens Evade Innate Immunity Bacteria: some have outer capsule that interferes with recognition & phagocytosis Streptococcus pneumoniae
Adaptive Immunity unique to vertebrates relies on lymphocytes
Thymus organ in thoracic cavity some new lymphocytes travel from bone marrow thymus & are “taught” how to respond in immune attack mature into T cells
B Cells lymphocytes that stay in bone marrow to mature become effector cells for humoral immune response
Antigen (agn ) substance that elicits an immune response by binding to receptors of B cells, antibodies, or of T cells example: bacterial or viral protein agn receptor: general term for a surface protein, on B or T cells, that binds to agns , initiating adaptive immune responses
agn receptors specific enough to bind to just one part of 1 molecule from particular pathogen 1 B cell or 1 T cell makes only 1 specific receptor ~ 100,000 agn receptors on 1 B or T cell
B Cell or T Cell Receptors
agns usually large foreign molecules (proteins or polysaccharides most often) stick out surface of foreign cells or virus molecule of toxin secreted by bacteria
Epitopes small, accesible region of agn to which an agn receptor or antibody ( aby ) binds aka: agn determinant
Epitopes single agn typically has several different epitopes each will bind to receptor with different specificity agn receptors of B & T cells encounter agns differently
Recognition of agn by B Cells B cell agn receptors “Y” shaped made of 4 polypeptide chains 2 identical heavy chains 2 identical light chains disulfide bridges link them
B Cell Antigen Receptor heavy chains extend into cytoplasm anchor receptor light & heavy chains have “constant”(C) region (nearly same on all B cells) & “variable” (V) regions (great amt variation from 1 B cell to another) includes tail (heavy chain only)that extends thru membrane & into cytoplasm and all disulfide bridges
B Cell Activation starts when agn binds to a B cell agn receptor ends with B cell secreting soluble form of its agn receptor = antibody ( aby ) or immunoglobulin ( Ig ) abys have same “Y” shaped organization as the B cell agn receptor
B Cell recognition of agn
T Cell Recognition of agn agn receptors made of 2 chains: α chain & a β chain linked by disulfide bridges both chains pass thru plasma membrane & into cytoplasm both have C regions & V regions
T Cell Antigen Receptors fundamentally different from B Cell these bind only to fragments of agns displayed or presented on surface of host cells host protein that displays the fragment called MHC (major histocampatibility ) molecule
T Cell Recognition of agns begins when pathogen or part of one either infects or is taken in by a host cell enzymes in host cell break pathogen smaller peptides (each 1 called agn fragment) which bind to MHC molecule combination moves to cell membrane outer surface = agn presentation
agn presentation advertises fact that this cell has been invaded by foreign substance when presenting cell meets T cell with compatible agn receptor it will bind to the agn fragment & the MHC molecule
4 Major Characteristics of Adaptive Immunity immense diversity of lymphocytes & receptors enables immune system to detect pathogens never before encountered adaptive immunity normally has “self” tolerance arises as B cell matures
4 Major Characteristics of Adaptive Immunity cell proliferation triggered by activation greatly increases the # of B and T cells there is a stronger & more rapid response to agn previously encountered immunological memory occurs after mature lymphocyte encounters & binds to a specific agn
B & T Cell Diversity everyone has ~ 20,000 protein-coding genes but has ~1 million different B cell agn receptors & ~ 10 million T cell agn receptors manage this by making different combinations
B Cell Diversity 3 genes code for light chain V segment J segment (joins) C segment V + J = variable region light chain gene contains 1 C segment, 40 different V segments & 5 different J segments: these pieces can be combined in 200 different ways heavy chain segments have even more combinations possible
Enzyme complex called recombinase links 1 light chain gene segment to 1 J gene segment forming single exon that is part V & part J
Recombinase acts randomly linking any 1 of 40 V gene segments with any 1 of 5 J segments same random connections made in heavy chains once rearrangements complete agn receptors can be built
Origin of Self - Tolerance because combinations are random sometimes receptors will be made that are specific for epitopes on own cells/molecules as lymphocytes mature in bone marrow or thymus their agn receptors are tested for self reactivity when discovered are destroyed by apoptosis or rendered nonfunctional
Proliferation of B & T Cells successful match between epitope with an agn receptor triggers a # of changes in cell # & activity changes “activate” the lymphocyte # of cell divisions producing a clone population some become effector cells Helper T Cells Cytotoxic T Cells rest become memory cells long-lived cells effector cells should same agn be encountered any time in animal’s life
Immunological Memory gives individual long term protection from an infection or vaccination Primary Immune Response produces effector cells from a clone of lymphocytes peaks 10 -17 days after initial exposure
Immunological Memory Secondary Immune Response if individual exposed again to same agn there is a faster, larger & longer response peaks 2- 7 days after exposure is hallmark of adaptive (acquired) immunity
Humoral Immune Response occurs in blood & lymph abys neutralize or eliminate toxins & pathogen in blood or lymph includes a primary & secondary immune response
Cell-Mediated Immune Response specialized T cells destroy infected host cells includes primary & secondary immune responses
Helper T Cells triggers both humoral & cell-mediated immune responses but does not directly carry out these responses signals from helper Ts initiate production of abys that neutralize pathogens activate T killers
T Helper Cells need 2 things to activate adaptive immune responses foreign molecule must bind to agn receptor of T cell agn must be displayed on surface of an Agn -Presenting Cell (APC) APC must be a dendritic cell, macrophage, or B cell
APCs have a 2 nd class of MHC molecules most body cells have Class I MHC molecules APCs also have Class II MHC molecules
Class II MHC Molecules provide molecular signature by which APC is recognized complex interaction between T cell & APC
T Cell Proliferation follows agn presentation by dendritic cell or macrophage forms clone of helper Ts
B cells present agn to activated helper T cells these T cells then stimulate activate B cells & cytotoxic T cells
Cytotoxic T Cells in cell-mediated immune response role: effector cells synthesize toxic gene products that kill infected cells activated by signaling molecules from helper T cells + interaction with APC
Activation of B Cells when stimulated by both an agn & cytokines secreted from helper Ts B cell differentiates into an aby -secreting plasma cell
Activation of B Cells
Activated B Cells give rise to thousands of plasma cells 1 plasma cell secretes ~2,000 aby /s plasma cell lives 4 – 5 days
Antibody Function do not kill pathogens bind to agns inactivation or destruction
Antibody-Mediated Mechanisms of Antigen Disposal
Active Immunity defenses that arise when a pathogen infects the body & prompts a primary or secondary immune response
Passive Immunity pregnant mom’s IgG abys cross placenta & protect fetus last few wks few mos newborn receives IgA abys in breast milk give boost to baby’s immune system until it fully develops Adults: IgA in tears, saliva, mucus
Artificial Active Immunity Immunizations: introduce agns to body abys develop giving immunity to person receiving vaccination Jenner: took cowpox virus to induce adaptive immunity against small pox (closely related viruses)
Small Pox Vaccination
Antibodies as Tools Monoclonal Antibodies: made by clone of B cells in reaction to single epitope used in medical diagnosis & treatment: Home pregnancy tests genetically engineered to use as immunotherapy
Blood Groups
Tissue & Organ Transplants MHC molecules stimulate the immune response that rejection MHC molecules have many alleles and any 1 individual has many that vary in shape & charge for most transplant recipients there will be some MHC molecules seen as foreign
Tissue & Organ Transplants to decrease the chance of rejection the donor & recipient are “matched” = MHC molecules same is both as much as possible also, recipient takes meds to suppress immune response makes recipient more vulnerable to infections
Moon Face
Graft Versus Host Rejection seen in bone marrow transplants recipient’s bone marrow radiated b/4 to get rid of abnl cells also wipes out their immune system lymphocytes in donor’s marrow react to “foreign” recipients tissues and cells
Allergies exaggerated hypersensitivity reactions to allergens : agn that triggers exaggerated immune response most involve aby of IgE class example: hayfever agn on surface of pollen grains
Allergic Response agn attaches to IgE abys on mast cells when cross linked release of histamine typical allergic symptoms of itchy eyes, sneezing, runny nose, teary eyes, smooth muscle contraction constriction of airways
Anaphylactic Shock whole-body, life-threatening reaction in response to allergen due to widespread release of histamine by mast cells: abrupt dilation of peripheral blood vessels quick drop in BP & constriction of bronchioles (smaller airways) death can occur w/in minutes due to decreased blood flow and inability to breathe
Autoimmune Diseases Immune system reacts to some molecules of self
Autoimmune Diseases
Exercise & the Immune System moderate exercise boosts the immune system & significantly reduces susceptibility to colds & other URTI exercise to pt. of exhaustion more frequent infections psychological stress disrupts immune system by altering interplay of
Stress & the Immune System psychological stress disrupts immune system by altering interplay of the nervous system endocrine system & immune system rest important for immunity adults with < 7 hrs sleep/ nite : 3x more likely to get sick when exposed to cold virus as those who average 8 hrs sleep/ nite
Immunodeficiency Diseases immune response to agns deficient or absent frequent infections & increased risk of certain cancers Inborn Immunodeficiency: genetic or developmental defect in immune system Acquired Immunodeficiency: follows exposure to chemical or biological agents
SCID Severe Combines ImmunoDeficiency : missing one or more immune cells freq. die in infancy due to infections treatment: bone marrow transplant stem cell transplantation gene therapy
Immundeficiency Disease Caused by Drugs drugs used to fight against autoimmune diseases or prevent transplant rejection suppress immune system immunodeficiency state
Immunodeficiency Disease Caused by Cancer Hodgkins Lymphoma best known for this possible genetic predisposition
AIDS Acquired ImmunoDeficiency Syndrome caused by HIV (Human Immunodeficiency Virus)
HIV escapes & attacks adaptive immune response infects helper Ts virus binds specifically to the CD4 accessory protein
HIV also infects cells with low levels of CD4: macrophages brain cells
HIV RNA Genome reverse transcribed product DNA inserted into host genome directs production of new virus
Immune Response to HIV immune system does respond to HIV attack but some escape: the virus has high rate of mutation during its replication so has high agn variation (each infected individual’s population of the virus is evolving w/in that individual) viral DNA w/in host genome it is protected from immune system (some latent for period of time then activate)
Latent HIV also protected from any anti- virals used to treat patient
HIV over time avoids adaptive immune system & destroys it viral reproduction ( lytic cycle) & cell death loss of helper T cells loss of humoral & cell-mediated immune responses progresses to AIDS
2º Infections Pneumocystis carinii fungal pneumonia Kaposi’s Sarcoma herpesvirus rare cancer except in AIDS Candida fungal infection rare except in babies
Progress of Untreated HIV
Treatment Strategy use combinations of anti- virals since each round of HIV has mutations still get drug-resistant strains
Transmission of HIV virus particles or infected cells person to person in any body fluid semen blood breatmilk most infections from unprotected sex or tainted needles having another STD or some break in mucous membranes increases likelihood of HIV
Transmission of HIV newly infected person can pass it on even b/4 their blood test (+) for HIV blood test measures HIV abys 10 – 50% new cases got it from another newly infected person
Evolutionary Adaptations of Pathogens that Avoid Immune Responses 1. antigenic variation immunologic memory is a record of previous epitopes encountered pathogen may no longer express those agns viruses parasites
Antigenic Variation in Trypanosoma bruceii
Influenza Virus mutates as spreads person to person exchanges genes with pigs, chickens Influenza outbreak 1918-1919: >20 million died worldwide
Latency 2 nd way pathogens can change to avoid immune system a largely inactive state dormant viruses quit making most viral proteins and no free virus particles so do not trigger adaptive immune response viral genome still in host nuclei
Latency typically persists until conditions arise that are favorable for viral transmission or unfavorable for host survival or defense (currently fighting another infection
Herpes Simplex Viruses establish home in sensory neurons after initial infection Type I: mostly oral herpes infections Type II: mostly genital herpes stimuli likely to cause recurrences: fever emotional stress menstruation
Cancer & Immunity when adaptive immunity inactive, incidence of certain cancers increases 15 – 20% of human cancers involve viruses
6 Viruses Known to Cause Cancer Herpesvirus Hepatitis B Human Papilloma Virus (HPV) Hepatits C Human T cell lymphotropic virus Epstein-Barr virus
Vaccinations Hepatitis B HPV