*Biology 318: Immunology

Dr. Janet Kluftinger

Office: SCI 164Telephone Number: (250) 807-8870E-mail: janet.kluftinger@ubc.ca

*Introduction and A Brief Historical Perspective Non-Specific Surface Defenses

*Immunology = branch of science that deals with the immune system and attempts to understand the many phenomena that are responsible for both acquired (specific) and innate immunity (also includes use of antibody-antigen interaction in diagnostic and experimental laboratory work)

Serum = liquid, non-cellular component recovered from coagulated blood

Serology = branch of immunology concerned with in vitro reactions involving one or more serum constituents (ex. antibodies, complement)

*Immunity = state of protection from infectious disease (from Latin term immunis meaning exempt)Immune System = remarkably adaptive defense system that has evolved in vertebrates to protect from invading pathogenic microorganisms and cancer. (Its not a linear system i.e. like a soccer team)Pathogen = any virus, bacterium or other agent that causes diseasePathogenesis = the means by which a pathogen causes disease

*Discipline of immunology grew from observation that individuals who had recovered from certain infectious disease were thereafter protected from that diseaseEarliest written reference to phenomenon of immunity: Athens, 430 BC (only those who had recovered from the plague could nurse the sick because they would not contract the disease a second time)

*Early Vaccination Studies:15th Century: Chinese and Turks use dried crusts derived from smallpox pustules (inhale into nostrils or insert into small cut in skin)1798: Edward Jenner notices that milkmaids who had contracted cowpox (relatively mild disease) are subsequently immune to smallpox inoculates eight-year-old boy (James Phipps) with fluid from cowpox pustule and later intentionally infects child with smallpox (he was then immune due to the cowpox inoculation)

*~ 1880: Louis Pasteur studied chicken cholera and developed procedure for attenuating (weakening) organisms for use as vaccinePasteur also developed rabies vaccine made of dried spinal cord from rabbits infected with rabiesJoseph Meister = first person to be immunized against rabies (1885)

*1977: Last known case of naturally acquired smallpox (Somalia) see Table 1-1

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*Early Studies of Humoral and Cellular Immunity:1890: Emil von Behring and Shibasaburo Kitasato demonstrate that serum from animals immunized to diphtheria transfers immunity to un-immunized animals1930s: Elvin Kabat shows that the active fraction of serum is gamma globulin (now called immunoglobulin)Because this type of immunity is mediated by antibodies contained in body fluids (known at the time as humors), it was called humoral immunity

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*1883: Elie Metchnikoff observes that certain white blood cells (he called them phagocytes) ingested microorganisms or other foreign material discovery of cell-mediated immunity

*Infection and ImmunityMost human pathogens can be grouped into four major categories:VirusesBacteriaFungiParasites -- range in size from tiny protozoa (1-2 m in diameter) to arthropods and tapeworms (up to several meters in length)More rare pathogenic entities: Prions and AlgaePathogenesis varies from microorganism to microorganism

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*Elephantiasis of the Leg

*Prions:Associated with spongiform encephalopathies (degenerative changes in brain)Lack nucleic acid genomeHighly resistant to all conventional disinfectionProteinaceousThought to be modified forms of a normal cellular protein, and cause disease by converting normal protein into further abnormal formsKuru, Creutzfeldt-Jakob disease, bovine spongiform encephalopathy

*Effective defense relies on the nature of the individual microorganismViruses require mammalian cells for replication and multiplication, so effective defense may involve recognition and killing of infected cellsSome bacteria, fungi and parasites replicate outside host cells, so effective defense may involve prompt recognition by antibodies or soluble molecule, followed by cellular and molecular immune mechanismsOpportunistic pathogens are usually ubiquitous microorganisms that become pathogenic under certain circumstances, such as when the immune system is compromised

*Immune system must deal with all types of pathogens and has evolved multiple strategies for dealing with invasion by almost any given pathogen!

*The Bodys 3 Lines of Defense Against Infection:

Non-specific (innate) surface defenses (entry barriers)

Non-specific (innate) interior defenses

Specific (adaptive) interior defenses

*Non-specific (Innate) Surface Defenses:

Structural: Epithelial (skin and mucosal membrane) surfaces relatively impermeable barrierSloughing of dead skin cells sloughing of adherent bacteria

Mechanical:Movement of underlying muscles (intestine)Mucociliary system: ciliated epithelial cells move mucus and adhering bacteria toward mouth swallowed and eliminatedBathing action of fluids (urine, tears)

*Biochemical: substances produced by the body that inhibit microbial growth

Substances that lower pH (fatty acids in skin, acidic perspiration, HCl in stomach) newborns have less acidic stomach contents and are thus susceptible to some pathogens that dont infect adultsKeratin-packed skin cells have low water content = inhospitable to many microorganismsSubstances with microbiocidal effects (bile disrupts bacterial cell envelopes; lysozyme in secretions disrupts peptidoglycan of gram +; psoriasin produced by skin kills E. coli)

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*Microbial:Nonpathogenic organisms colonize epithelial cells of mucosal surfaces (normal flora)Normal flora out-compete pathogens for attachment sites on epithelial cell surface and for nutrients Note: In addition, many species of animal are not susceptible to certain diseases simply because their normal body temp. inhibits growth of the pathogen (ex. Chickens have innate immunity to anthrax because of high body temp)

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*Non-specific (Innate) Interior Defenses:Once pathogen surmounts surface barriers, non-specific interior defenses come into action

InflammationPhagocytosisComplementInterferon

*Specific (Adaptive) Immune Defenses:SPECIFIC because they act against ONE PARTICULAR TYPE OF ANTIGENImmune system recognizes pathogens by markers on their surface called antigens (~ immunogens)*ANTIGENS (abbrev. Ag): Markers on surface of cells, viruses and large molecules that provoke a response from the immune system -- may be protein, protein-carbohydrate, lipid, nucleic acid, or complex polysaccharide (best protein)ANTIBODY (abbrev. Ab): Defensive protein made in response to exposure to an Ag that can recognize and bind to that Ag

Two Branches of the Specific Immune ResponseHumoral Response: Involves interaction of B cells with foreign proteins (antigens), and B cell differentiation into antibody-secreting cellsAntibody binds to foreign proteins or infectious agents and helps to clear them from the body

Cell-Mediated Response: Involves various subpopulations of T cells performing many functionsSecretion of soluble messengers that help direct other cells of the immune system (Helper T cells = TH)Direct killing of infected cells (Cytotoxic T cells = TC)*

*INNATE RESISTANCE Genetically pre-determined resistance to certain diseases (i.e. canine distemper)

INDIVIDUAL RESISTANCEAffected by age, sex, nutritional status, and general health

IMMUNITYAbility of the body to SPECIFICALLY counteract foreign substances or organisms

Tues: 9- 10:30 am, 2:00 3:00 pm**Why immune system has to be so complex?

*-Never remember dates.

***Know the last and what they did.*Know the names

****What does that do?*What does that do?*What does it do?*What does that do?It goes into your lipfatix and block them.Kuru was caused by cannabalism.Creutzfeldt-Jakob disease is like mad men cow disease.

**Defined each?

****Know lysozymes and lactoferrin (sequester iron) is in secretion, psoriasin, cathellidin, surfactant protein (no need to be specific)*Just review!**