2What is Immunity?Process by which our bodies protect themselves against:PathogensCancerForeign ObjectsInfectious AgentsCell surfaces are covered with messages that tell the body what is “self” and what is “foreign”
3Antigens Any “foreign” signal that induces an immune response Usually refers to the molecules on the cell surface that are recognized by immune system as foreignUsually made of:CarbohydratesProteinsForeign Cell
4AntibodiesProteins that recognize antigens and signal the “attack” against themControlled by immune systemBind to specific antigensPart of the immune system that allows body to “remember” a previous foreign pathogen
5Antigens and Antibodies YYAntigenYYAntibodyYYYForeign Cell
6Pathogens Organisms or infectious agents that cause disease Bacteria: Single celled prokaryotic organismsCan be treated with AntibioticsViruses:RNA or DNA wrapped in proteinsCannot be “cured” once infectedCan be vaccinated against
7How are genes involved? Any ideas? Developing Antibodies and other defense mechanismsGenes determine Antigen that is presentWhat would happen if genes aren’t functioning properly?Autoimmune disordersAllergiesInherited immune deficiencies
8Blood Types – ABO What is different between blood types? Different antigens on red blood cellsAntigens are complex sugarsTwo different types of antigens:A or BO means RBC have no sugarsAB RBC have both sugarsYour antibodies are only against the antigens that you DO NOT have
10Blood Types – ABO Individual is Type A: Individual is Type O Type AB What antibodies do they carry?What blood can they receive?What blood types can accept Type A blood?Individual is Type OType ABWhen you receive a blood transfusion your body will only recognize foreign antigens based on the antibodies it has and reject
11Blood Types – Rh Factor Blood is also either positive or negative This is referring to whether or not individual carries a second antigen known as “Rh”Positive – have Rh factorNegative – do not have Rh factorBlood types have to be matched for this, and other antigens, before transfusion
12Blood Types – Rh Factor Problem: Mother is Rh- and Father is Rh+ Baby may be Rh+Rh- mother may reject baby’s tissue as foreign:Baby’s blood supply is attackedSeems to get worse after one pregnancy with Rh+ babyWhy is that??
13HLA genes Human Leukocyte Antigens (HLA) Leukocyte = white blood cellsWBC are protective part of bloodAll cells with a nucleus have HLA antigens attached to their cell surfaceThis recognizes cells as “self” within bodyHLA encodes many genes all with many alleles – therefore many combinations of antigens
14HLA genesAbout 50 % of the genetic control of immunity is within the HLA genesOn Chromosome 6Therefore this region has been linked to autoimmune disorders:AsthmaDiabetesMultiple Sclerosis (MS)Arthritis and many others
15Immune Response Three levels of protection: Physical Barriers: Skin, mucous membranes, tears, saliva, etcInnate (nonspecific) immunityPhagocytosis, Antimicrobial proteins, feverAdaptive (specific) immunityB cells and T cellsAntibodies, Cytokines, etc
16First Line of Defense Unbroken skin Mucous membranes Earwax Cilia in respiratory tractStomach acidInfection fighting chemicals in tears and saliva
17Second Line – InnateInnate because these are general defenses we are born withNon-specificInflammation:Creating a hostile environmentFeverPhagocytosis:WBC that ingest foreign particles whole
18Second Line – Innate Three major classes of proteins: Collectins: Recognize foreign antigens and recruit othersComplement:Puncture or burst cells, release histamineHistamine – induces inflammation at siteCytokines:Interferon, Interleukins, and TNF
19CytokinesSmall secreted proteins that induce gene expression to trigger immune responsesInterferons – alert immune response to virusesStimulate macrophages and antibodiesInterleukins – induce feverFever makes environment hostileTumor Necrosis Factor (TNF)Destroys toxins and certain cancer cells
20Third Line – AdaptiveHighly specific to antigens and foreign agents that are attacking.Takes much longer than innate responseBut works better and without such severe side effectsB cellsProduce antibodiesT cellsProduce Cytokines
21Third Line – Adaptive Three basic characteristics: Diverse: Specific: Can handle many different types of pathogensSpecific:Distinguishes with great specificity between harmful and non-harmful antigensRemembers:Builds and keeps antibodies for a second attack
22B cells T cell stimulates B cells into action B cells “try on” the antigen until it finds one cell type that “matches” that antigenThat specific B cell type then:Makes tons of antibody against antigenAntibody speeds destruction of pathogenAlso, makes a “memory cell”Appropriate antibody will be ready for a secondary immune response
24Antibodies Constructed of several polypeptides: Heavy chains are constant – light chains are “variable” regions – matching to exact antigens – like very fast evolution
25Antibodies Antigen Binding Sites – specifically binding up antigens Mechanism of action:Kill pathogen directlyNeutralize toxin pathogen is producingClump pathogens together to be removed by macrophages (phagocytosis)Activate complement proteins
26T cells Both B and T cells are made in bone marrow T cells then move to Thymus glandWhere do B cells act?As T cells move through body those that attack “self” antigens are killed offTherefore the T cells that reach the Thymus are selected for and remain
27T cells Several types of T cells exist: Helper T cells: Stimulate B cells and cytokines to actionCytotoxic T cells:Directly bind and kill pathogensOr cancerous cellsAlso suppress immune system when response is finished or out of control
29Abnormal Immunity Inherited Immune Deficiencies: Very rareAcquired Immune Deficiency Syndrome:HIV virus induces AIDSAutoimmune Disorders:Very common – especially nowDiabetes, Arthritis, MS, AsthmaAllergies
30Inherited Immune Deficiency Can affect either Innate or Adaptive ImmunityGenetically inherited disordersUsually rare Mendelian disordersWhat genes could be involved?Treated with bone marrow transplantsWhy does that work?Think of the “Bubble Boy”
31AIDS Caused by the HIV virus All viruses have two choices: Human Immunodeficiency VirusAll viruses have two choices:Lysis – to immediately kill host cell after copying selves (by bursting)Lysogeny – to insert their viral RNA into the host DNAForce Host cell to copy their DNAWhile also Lysing majority of cells (same time)
32Viruses: Infectious agents that attack cells Can reproduce and mutate Cannot replicate on their own, they need the host cell’s proteins (machinery)
33A fraction of cells integrate, while most lysis at same time. Choice:Virus ReplicatesItself UntilCell BurstsLytic CycleUninfected CellVirus AttackingandInserting RNAViral RNAIntegrated IntoCellular DNALysogenic CycleA fraction of cells integrate, while most lysis at same time.
34HIV HIV choose Lysogenic Cycle Insert’s viral RNA into host cell’s DNA through a protein called:Reverse Transcriptase (RT)How do you imagine RT works?Reverse’s transcription by transcribing DNA from RNANow host cell produces HIV for the virus
36HIV What would the body’s normal response to the HIV virus be? Attack with:Fever, phagocytosisCytokines – especially InterferonsT cells and B cellsHIV is an incredibly well adapted virus because it uses T cells as it’s host cells
37AIDS As virus is being replicated by host cell It is also killing off T cellsThe very cells that are needed to activate the immune responseBody cannot fight off HIV virusAlso cannot fight off any infectionsEventually, will develop into AIDS – Acquired Immune Deficiency Syndrome
38Autoimmune Disorders When the immune system attacks body’s own cells Cells that are marked with “self”Produce Autoantibodies – Antibodies against your own cellsQ: How does it develop?A: We don’t really know yet:Self attacking T cells aren’t selected offSelf antigen looks very similar to foreign?
39Autoimmune Disorders Multiple Sclerosis (MS) Body attacks CNSColitis or Crohn’s DiseaseBody attacks colon or digestive trackArthritisBody attacks collagenDiabetesBody attacks beta-Islet cells
40Allergies Immune system is responding to a harmless particle Allergen B cells produce antibodies against allergenMast cells release histamineAsthmaContraction of airways because of inflammation – in response to allergensCan also be autoimmune
42Altering Immune Function VaccinesImmunotherapyEither amplify or redirect the immune responseAttacking cancer cellsWeakening autoimmune attacksDecreasing immune response for transplantationBioterrorism
43VaccinesInactive, or partial form of a pathogen, that stimulates B cells to develop antibodies against that pathogenProtection of having a previous attack without actually having the riskOnce some diseases have been removed with vaccines there is no longer any need to administer them:Polio, Smallpox
44Immunotherapy Amplifying or redirecting the immune response: Monoclonal antibody (MAb) treatment:Producing and administering antibodiesSome cancer treatments, to target drugsAdministering Cytokines:Various types of cancer treatmentsInterferon administered to prevent MS attacksWhy would that work?
45TransplantationReplacing a damaged organ (or tissue or blood) with one from a donorImmune system usually recognizes replacement as foreign (non-self)Attempts to destroy itClosely match HLA types and blood typeBetter chance of acceptanceImmunosuppressive drugsInhibit T cells or production of antibodies
46BioweaponsBiological weapons – use pathogens to intentionally harm individualsMedieval times – catapulted plague ridden bodies over city wallsModern times – weaponize a pathogenGenetically manipulate pathogenMake it stronger, more effective, concentratedWhat are your opinions about their use?
47Summary Antigen and Antibody Three levels of protection Innate vs. Adaptive Response and all the playersAbnormal ImmunityToo little or too muchAltering ImmunityVaccines, immunotherapy, transplants