micro biology

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kevin34669  on November 5, 2010

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micro biology

Pathogenicity
The ability to cause disease
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Terms

Definitions

Pathogenicity The ability to cause disease
Virulence The extent of pathogenicity
ID50: Infectious dose for 50% of the test population
LD50 Lethal dose (of a toxin) for 50% of the test population
Portal of entry - Skin ID50 : 10-50* endospores, "woolsorters disease"
Portal of entry - Inhalation 10,000-20,000, * endospores, pulmonary anthrax
Portal of entry Botulinum, Shiga toxin, some Shigella,some E. coli from plasmid
Adhesins/ligands bind to receptors on host cells : Form biofilms for transportation, nutrient transport and protection.
Glycocalyx: Streptococcus mutans, others
Fimbriae: Escherichia coli, many others
M protein: Streptococcus pyogenes, toxic : resists phagocytosis
Capsules Prevent phagocytosis and immune recognition.
Opa protein inhibits T helper cells
Neisseria gonorrhoeae
Mycolic acid (waxy lipid) resists digestion by macrophages
Mycobacterium tuberculosis
Coagulase Coagulates fibrinogen, prevents clots from containing pathogen
Kinases Digest fibrin clots, allowing spreading.
Hyaluronidase: Hydrolyzes hyaluronic acid, increasing host cell penetration
Collagenase Hydrolyzes collagen, reducing host cell interconnectivity
IgA proteases Destroy IgA antibodies, adversely affecting host defense
Toxin Substance that contributes to pathogenicity eg. endo or exotoxins
Toxigenicity Ability to produce a toxin
Toxemia Presence of toxin in the host's blood
Toxoid Inactivated toxin used in a vaccine eg. tetanus vaccine
Antitoxin Antibodies against a specific toxin, eg. rattlesnake antivenin
Membrane-Disrupting Toxins Lyse host's cell membranes by;
Making protein channels in the plasma membrane
Membrane-Disrupting Toxins LeukocidinsHemolysins
Streptolysins
Disrupting phospholipid bilayer; damages host cell membrane.
Superantigens Cause an intense immune response due to release of cytokines from host cells
Corynebacterium diphtheriae A-B* toxin
Streptococcus pyogenes Membrane-disrupting erythrogenic
Clostridium botulinum neurotoxin
Vibrio cholerae enterotoxin
Vibrio cholerae Superantigen
LAL Assay, horseshoe crab blood Limulus amoebocyte lysate assay for endotoxins
Pathogenic Properties of Fungi waste products : Chronic infections provoke an allergic response -
Tichothecene toxins inhibit protein synthesis, weaponized : Fusarium
Proteases Candida, Trichophyton
Capsule prevents phagocytosis
Cryptococcus
Mycotoxins* Neurotoxins: Phalloidin, amanitin
Amanita mushroom, common lawn mushroom
protozoa Use host nutrients. Waste products may cause symptoms. Avoid host defenses by
Growing in phagocytes
Cell membrane alterations among generations, prevent immune recognition.
Pathogenic Properties of Algae Paralytic shellfish poisoning, red tide aerosol
Dinoflagellates
Saxitoxin
Portals of Exit, to infect new hosts Respiratory tract
Coughing and sneezing
Gastrointestinal tract
Feces and saliva
Genitourinary tract
Urine, urinary tract and vaginal secretions via intimate contact
Skin, eg. many viruses, bacterial infections.
Blood
Biting arthropods and syringes
Susceptibility Lack of resistance to a disease
Immunity: Ability to ward off disease
Innate immunity Defenses against any pathogen, nonspecific, short lived, eg. skin, mucous
Adaptive immunity Immunity, resistance to a specific pathogen, precise, long lasting, eg. T and B cells, takes time to develop.
Physical, Innate Factors Epidermis - consists of tightly packed cells.(skin)
Keratin - a protective protein, main component in hair and fingernails.
Physical, Innate Factors Mucous membranes
Mucus: Traps microbes
Ciliary escalator: Microbes trapped in mucus are transported away from the lungs  phlegm
Physical Factors Lacrimal apparatus: Washes eye, tears
Saliva: Washes microbes off
Urine: Flows out
Vaginal secretions: Flow out
Chemical Factors Fungistatic fatty acid in sebum, oily skin
Low pH (3-5) of skin
Lysozyme in perspiration, tears, saliva, and urine
Low pH (1.2-3.0) of gastric juice
Low pH (3-5) of vaginal secretions
Normal microbiota compete with pathogens or alter the environment
Commensal microbiota One organism (microbe) benefits and the other (host) is unharmed
Neutrophils
Macrophages
Phagocytosis
Basophiles Histamine; triggers inflammation
Eosinophils Kill parasites
Formed Elements in Blood Monocytes, Dendritic, Natural killer cells -Destroy targeted cells, including cancerous tissue
Inflammation Acute-phase proteins : Vasodilation :(edema)
Fever Abnormally high body temperature
Hypothalamus normally set at 37°C
fever - Advantages Increases transferrins to keep iron from pathogen
Increases IL-1 activity
Produces Interferons
fever - Disadvantages Tachycardia
Acidosis
Dehydration
44-46°C fatal
The Complement System Serum proteins , Activated by
Antigen-antibody reaction
C3b causes opsonization
Effects of Complement Activation Opsonization or immune adherence: Enhanced phagocytosis
Membrane attack complex: Cytolysis
Attract phagocytes
Evade Complement Capsules prevent C activation
Surface lipid-carbohydrates prevent membrane attack complex (MAC) formation
Enzymatic digestion of C5a
Interferons (IFNs) IFN- and IFN-: Cause cells to produce antiviral proteins that inhibit viral replication
Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria
Innate immunity Defenses against any pathogen
Adaptive immunity Induced resistance to a specific pathogen
T and B cells develop from stem cells
Humoral immunity, Antibodies B cells mature in the bone marrow
Cellular immunity Due to T cells
T cells mature in the thymus
Antigen (Ag): A substance that causes the body to produce specific antibodies or sensitized T cells
Hapten: Antigen is combined with carrier molecules for transport to Immune cells
Proteins, synonym immunoglobulins
antigen-binding sites determines valence;
IgG Antibodies Monomer
Cross placenta
Enhance phagocytosis; neutralize toxins and viruses; protects fetus and newborn
IgM Antibodies Pentamer, 5 linked antbodies
Agglutinates microbes; first Ab produced in response to infection
IgA Antibodies Dimer
Mucosal protection
Focus for "allergy shots
IgD Antibodies Monomer
On B cells, initiate immune response
IgE Antibodies Monomer
On mast cells*
Allergic reactions; lysis of parasitic worms *Histamine production, helps to induce inflammatory response
Agglutination clumping
Opsonization inducing phagocytosis with antibody "markers"
T helper cells boost immune response
T Cytotoxic Cells, CTL's Induce apoptosis (cell death) in target cell
CTL releases perforin(induces lysis) and granzymes, a protease
Apoptosis Cell membrane collapses
T Regulatory Cells, aka Supressor T's Suppress T cells from reacting against "self" cells.
Failure leads to autoimmune illnesses
Antigen-Presenting Cells, APC's Digest antigen or AG
Ag fragments on APC's surface with MHC*
*Major histocompatibility complex, markers
that identify your cells.
Activated Macrophages hunt AG bearing pathogens
Natural Killer (NK) Cells Granular leukocytes destroy cells that don't express MHC
Kill virus-infected and tumor cells
Attack parasites
Cytokines Chemical messengers used to induce localized immune responses, inflammation.
Overproduction leads to cytokine storm, a dangerous "feedback loop" causes excessive immune reaction, dangerous and can be lethal
Antibody titer is the amount of Ab in serum
Primary response occurs after initial contact with Ag(antigen)
Secondary (memory or anamnestic) response occurs after second exposure, raising Ab titer.
anaphylaxis an excessive systemic inflammatory reaction
Serology The study of reactions between antibodies and antigens
Antiserum The generic term for blood serum which contains Ab
Globulins Serum proteins, general term
Immunoglobulins Antibodies
Gamma globulin Mixed serum fraction containing various Ab's
Inactivated "no reproductive ability, dead",whole-agent vaccines
Salk polio
Toxoids "damaged", is antigenic but ineffective.
Tetanus
Subunit vaccines "parts" of the virus
Acellular pertussis
Recombinant hepatitis B
Nucleic acid (DNA) vaccines West Nile (for horses)
rDNA techniques In plants
Adjuvants non specific but enhance secondary immune response. Use is fading.
Deliver in combination
Sensitivity Probability (%) that the test is reactive if the specimen is a true positive
Specificity Probability that a positive test will not be reactive if a specimen is a true negative
Hybridoma : "Immortal" cancerous B cell fused with an antibody-producing normal B cell, produces
Monoclonal antibodies Very pure and specific, can be harvested in quantity.
Hemagglutination involves agglutination of RBCs
Some viruses agglutinate RBCs in vitro (outside of living organism)
Enzyme-Linked Immunosorbent Assay Also called ELISA
Enzyme linked to Ab is the indicator, enzyme activity results in detectable change in vitro
Precipitation Soluble antigens
Agglutination Particulate antigens
Hemagglutination Agglutination of RBCs
Neutralization Ab Inactivates toxin or virus
Fluorescent-antibody technique : Antibodies linked to fluorescent dye
ELISA
Type I (Anaphylactic) Reactions IgE attached to mast cells and basophils
Antigen binds to two adjacent IgE
Mast cells and basophils undergo degranulation, which release excessive immune mediators:
Histamine
Leukotrienes
Prostaglandin
Systemic anaphylaxis May result in circulatory collapse, suffocation and death
Localized anaphylaxis Hives, hay fever, and asthma
Preventing Anaphylaxis Desensitizating injections of Ag "allergy shots"
Cause IgG blocking Ab
Type II (Cytotoxic) Reactions Complement activation causes cell lysis or damage by macrophages
Type III (Immune Complex) Reactions IgG antibodies and antigens form immune complexes that lodge in basement membranes(zones where tissues are joined
Type IV (Cell-Mediated) Reactions Delayed-type hypersensitivities due to T cells and MHC, Ig not involved, eg. Crohns, multiple sclerosis, rheumatoid arthritis.

Cytokines attract macrophages and TC cells:
Initiate tissue damage
Takes a few days to manifest
Autoimmune Diseases (body attacks "self") Clonal deletion (deactivated "self" T and B cells)during fetal development usually ensures self-tolerance.
Autoimmunity is loss of self-tolerance
Cytotoxic Antibodies react with cell-surface antigens
Graves' disease (thyroid), diabetes (pancreas)
Immune complex IgM, IgG, complement immune complexes deposit in tissues
Systemic lupus erythematosus, SLE, connective tissues
Cell-mediated Mediated by T cell cytokines
Psoriasis(skin accumuation, various types) poorly understood
Histocompatibility antigens Self antigens on cell surfaces.
Major histocompatibility complex (MHC): Genes encoding histocompatibility antigens
Human leukocyte antigen (HLA) complex MHC genes used in human immune system cells.
Reactions to Transplantation may be attacked by T cells, macrophages, and complement-fixing antibodies. privileged sites do not cause immune response.
Stem cells may allow therapeutic cloning to avoid rejection, bone marrow transpant
Embryonic stem cells are pluripotent(can differentiate into other cell types.
Adult stem cells have been differentiated to form specific cells
Autograft: Use of one's own tissue
Isograft: Use of identical twin's tissue
Allograft Use of tissue from another person
Xenotransplantation product Use of nonhuman tissue, eg heart valves(pigs)
Hyperacute rejection Response to nonhuman Ag, C' and cytokine storm can lead to system failure. Transplanted organ must be removed immediately.
Graft-versus-host disease (GVH) can result from transplanted bone marrow (sometimes used to treat leukemias) that contains immunocompetent cells from donor, donor cells attack recipient.
Immunosuppression Prevents an immune response , suppress IL-2, inhibits T cell and B cell reproduction
TNF or tumor necrosis factor a cytokine inducing apoptosis
Immunotherapy Treatment of cancer using immunologic methods
Immunotoxins link poisons with a monoclonal antibody directed at a tumor antigen
Congenital Immunodeficiencie Due to defective or missing genes
Acquired Immunodeficiencie Develop during an individual's life
Due to drugs, cancers, and infections
Combination of both; increased probability
Origin of AIDS Crossed the species barrier into humans in Africa in the 1930s : 1959 in Congo
HIV Transmission Infected body fluids transmit HIV, including breast milk
Highly active antiretroviral therapy (AIDS"cocktail") Combinations of nucleoside reverse transcriptase inhibitors and other drugs, Highly effective, expensive
Chemotherapy The use of drugs to treat a disease
Antimicrobial drugs Interfere with the growth of microbes within a host
Antibiotic A substance produced by a microbe that, in small amounts, inhibits another microbe
Selective toxicity A drug that kills harmful microbes without damaging the host
Spectrum of Antimicrobial Activity Broad spectrum, kills many types, eg. gram neg.
Narrow spectrum, kills a few precise pathogens
Superinfection (an illness promptly follows another illness or invades while original pathogen is still present), eg. Quinolones
Bactericidal Kill microbes directly
Bacteriostatic Prevent microbes from growing
Inhibitors of Cell Wall Synthesis Penicillin group
Natural penicillins
Semisynthetic penicillins
Extended-spectrum penicillins
b-Lactam Antibiotics , disrupt critical cell wall component. Penicillin
Inhibitors of Cell Wall Synthesis Vancomycin
Glycopeptide
Important "last line" against antibiotic-resistant S. aureus, now overused, less useful
Antimycobacterial (eg. tuberculosis)antibiotics Isoniazid (INH)
Inhibits mycolic acid synthesis
Ethambutol
Inhibits incorporation of mycolic acid
Sulfonamides (sulfa drugs Inhibit folic acid synthesis
Broad spectrum
Antifungal Drugs Inhibition of ergosterol (part of cell membrane) synthesis
Inhibition of outer cell wall synthesis
Antiviral Drugs Nucleoside and nucleotides
Protease inhibitors Indinavir: HIV
Integrase inhibitors HIV
Inhibit viral attachment
Zanamivir: Influenza
Block CCR5: HIV
Inhibit viral uncoating
Amantadine: Influenza
Interferons Prevent spread of viruses to new cells
Alpha interferon: Viral hepatitis
Antiprotozoan Drugs Chloroquine
Inhibits DNA synthesis
Malaria, resistance is getting common
Diiodohydroxyquin
Unknown mode of action
Amoebic diseases
Antihelminthic (some parasites)Drugs Niclosamide - tape worms Praziquantel - flat worms
MIC Minimal inhibitory concentration
MBC Minimal bactericidal concentration
Antibiogram for direct sample testing ( smear of dog with tonsilitis)
Antibiotic Resistance Enzymatic destruction of drug
Prevention of penetration of drug
Alteration of drug's target site
Rapid ejection of the drug
Resistance genes are often on plasmids or transposons that can be transferred between bacteria
Antibiotic Resistance due to Misuse outdated or weakened - inappropriate conditions - Failing complete the prescribed regimen
Using someone else's leftover prescription
Synergism occurs when the effect of two drugs together is greater than the effect of either alone
Antagonism occurs when the effect of two drugs together is less than the effect of either alone
Therapeutic index risk vs. benefit

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