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first line defense
- 1. mechanical factors
- 2. chemical factors
- 3. normal flora
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mechanical factors
- - skin- keratin
- - mucuous membrane- ciliary escalator
- - glands
- - hair
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chemical factors
- - skin secrete sebum- pH 3-5
- - gastric juice- pH 1-3
- - lysozomes and peroxidase
- - transfeerins in blood compete for iron binding
- - nitric oxide- inhibits ATP production
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normal flora
relationship bewteen microbes and host
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synergism
give them something to survive off of and they give us something in return
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commensalism
we dont benefit but bacteria isnt harmful either
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antagonism
one benefits at the other expense
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second line defenses
- 1. WBC
- 2. phagocytosis
- 3. lymphatic system
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basophils
produce histamine
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eosinophils
toxic to parasites, allergic reactions, some phagocytosis
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monocytes
phagocytosis as mature macrophages
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fixed macrophages
spleen, liver, lungs
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wondering macrophages
roam tissues
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chemotaxis
cells recruited to infection
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process of phagocytosis
- 1. chemotaxis
- 2. attachment
- 3. engulfment
- 4. phagosome lysosome fusion
- 5. destruction
- 6. exocytosis
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cardinal signs
heat, pain, swelling, redness
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chemicals released by damaged cells
histamine, kinins, prostaglandins, leukotrienes
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apoptosis
programmed cell death
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what causes fever?
pyrogens
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endogenous
fever inducing cytokines
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exogenous
bacterial endotoxins
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what is the complement system?
- - inactive proteins
- - strengthens adaptive immunity
- - casade of enzymatic reactions
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name the pathways of the complement system
- 1. classical
- 2. alternative
- 3. lectin
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classical pathway
- - quickest and most efficient
- - activation requires antibodies
- - membrane attack complex
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alternative pathway
- - easily initated
- - activation by C3b to cell surface
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lectin pathway
- activation requires mannon-binding lectins
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alpha and beta interferons
cause cells to produce antiviral proteins that inhibit viral replication
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gamma interferon
causes neutrophils and macrophages to phagocytize bacteria
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2 kinds of adaptive immunity
- 1. cell-mediated
- 2. humoral
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primary lymphoid organs
- - bone marrow- B cells maturation
- - thymus- T cells maturation
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secondary lymphoid organs
- - encounter antigens
- - nodes, spleen, tonsils
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epitopes
stimulates immune system
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3 antigen characteristics
- 1. protein structure
- 2. can be carbohydrates
- 3. molecular wieght > 10 kilo Daltons
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2 parts of anitbody
- 1. Fc region (constant)- determines class
- 2. Fab region (variable)- binding site
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IgM
- - first to respond to infection
- - pentamer but found on B lymphocytes as a monomer
- - only one formed by the fetus
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IgG
- - dominant in circulation
- - monomer
- - can cross placenta
- - memory
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IgA
- - found in secretions, not circulating
- - monomer in serum but dimer in secretions
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IgD
- - maturation of antibody response
- - monomer
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IgE
- - barely detectable in circulation
- - monomer
- - allergic rxns
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clonal selection
specific response of mature B cells to an antigens epitopes
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clonal expansion
repeated cycles of cell division generates population of copied antibodies
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neutralization
prevents toxin from interactin with cell
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opsonization
coating of bacteria with antibody to enhance phagocytosis
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affinity maturation
- - form of natural selection
- - occurs among proliferating B cells
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cell-mediated immunity
- - T cells never prducec antibodies
- - antigens must be present by antigen presenting cell to T cell receptor
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2 components of MHC
- 1. class 1- expressed on every nucleated cell
- - binds to CD8 cells
- - endogenous
- 2. class 2- expressed only on APC like macrophages
- - binds to CD4
- - exogenous
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2 parts of helper T cells
- - Th1- related to cell mediated immunity, sends out cytokines
- - Th2- activate B cells to produce eosinophils, IgM, IgE
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what does CD8 kill the cell with?
perforin
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delayed hypersensitivity T cells
allergic rxns, TB test
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suppressor T cells
turns off immune system when no antigen in present to avoid autoimmune effect
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what do natural killer cells lack?
antigen specidicity
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how do natural killer cells recognize antigens?
the Fc portion of the IgG antibodies
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natural killer cells recognize destroyed host cells with...
- no MHC class 1 surface molecule
- - important for viral infections
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interleukin 1
stimulates CD4
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interleukin 2
activates CD4, B, CD8, and NK cells
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interleukin 12
differentiation of CD4 cells
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clonal deletion
process of destroying B and T cells that react to self antigens
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B cells undergo positive or negative selection?
negative
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T cells undergo positive or negative selection?
both
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positive selection
differentiation of T cells will only occur if the cell recognizes MHC molecule
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naturally acquried active immunity
antibodies resulting from infection
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naturally acquired passive immunity
Ab through placenta
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artifically acquired active immunity
injection of antigens (vaccines)
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artifically acquired passive immunity
injection of Ab
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attenuated vaccines
live, weakened form of the pathogen
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inactivated vaccines
contains killed organisms or inactivated virus
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what are the advantages of attenuated vaccines?
- - usually a single dose
- - has added potential for being spread to un-immunized individuals
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what are the disadvantages of attenuated vaccines?
- could cause disease in immunocompromised individuals
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what is the advantage of inactivated vaccines?
- - can not cause disease
- - immunogenic- process of gaining immunity
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what are the disadvantages of inactivated vaccines?
- - magnitude of response is limited
- - no amplification of the dose in vivo (booster shots)
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examples of whole agents that are inactivated vaccines
cholera, plague, flu, salk polio
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examples of fragment agents that are inactivated vaccines
DTP and hep B
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what is type 1 hypersensitivitiy called?
immediate IgE mediated
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immediate IgE mediated
- - inherited
- - charaterized by immediate reaction of the sensitized individual
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sensitization
occurs when antigen induces plasma cells to secrete IgE antibodies
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Fc region of IgE binds to receptors on what cells?
mast and basophils
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what is type 2 hypersensitivity called?
cytotoxic
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type 2 hypersensitivity involves what antibodies?
IgG or IgM or ADCC that all cause cell death
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examples of type 2 hypersensitivity
tranfusion rxns and hemolytic disease of the newborn
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what is type 3 called?
immune complex mediated
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immune complex mediated
IgG and antigens form complexes (usually adhere to the Fc receptors are destroyed and removed)
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immune complex mediated initates what?
blood clotting mechanism and inflammation
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immune complex mediated complexes are deposited where?
skin, kidneys, joints
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type 4 hypersensitivity is called?
delayed cell mediated
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what is delayed hypersensitivites due to?
cytotoxic T cells that release cytokines that initiate inflammation that attracts marcophages (nothing to due with Ab binding to Ag)
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septicemia
acute life threatening illness causes by infectious agent or its products circulating in blood
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what are the steps for a pathogen to take in order to establish a diesase?
- 1. adherence
- 2. colonization- multiplying on a body surface
- 3. delivery of effector molecules that induce changes in the recipient cell
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communicable disease
disease transmitted from one host to another
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what are the 2 things for a pathogen in a communicable disease?
- - must have a suitable environment (reservoir)
- - must leave the reservoir to be transmitted
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morbidity rate
number of cases of illness divided by population at risk
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mortality rate
population that dies from disease
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incidence
number of new cases per specific time period
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prevalence
total number of existing cases
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reservoirs affect....
the extent and distribution of disease
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name 3 reservoirs
humans, animals, environmental (nearly impossible to elimate)
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horizontal transmission
pathogen passed to next reservoir via contact with food, water or living agent
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epidemiologists investigate disease outbreak to determine...
- - causative agent
- - reservoir
- - route of transmission
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cross- sectional study
survey of range of people to determine prevalence of number of characteristics
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retrospective study
comparing to healthy individuals that already had the disease
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prospective study
looking ahead to see if risk factor from retrospective study predict tendency to develop disease
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nosocomial infections are known as
hospital acquired infections
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what factors determines which organisms and agents are responsible for nosocomial infections?
- - length of time of exposure
- - manner of exposure
- - virulence and number of organisms
- - state of host defenses
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antibiotics
antimicrobial substance is synthesized and secreted by some true microorganism
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semisynthetics
antibiotic that is chemically altered after purification to impart new characteristics
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synthetics
antimicrobial substance synthesized in a lab
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a high therapeutic index is more or less toxic to a patient?
less
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bacteriostatic drugs
- - inhibit bacterial growth
- - relies on host immunity to eliminate pathogen
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bacteriocidal drugs
- - kills bateria
- - useful when host defenses can not be relied upon to control pathogen
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if gram (+) then antimicrobial drugs cause...
inhibition of cell wall synthesis
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antimicrobial drugs can cause inhibition to...
- 1. cell wall synthesis- high therapeutic index
- 2. protein synthesis- targets ribosomes
- 3. nucleic acid synthesis- targets enzymes necessary for DNA replication
- 4. metabolic pathways- folic acid
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this drug binds to gram (-) that alters the permeability which leads to leakage of cell components and cell death
polymyxin B
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synergistic drugs
2 drugs working together
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