2a Flashcards
what are the bodies defences?
skin, mucous membrane, iron-binding proteins, phagocytosis
what defense is skin? how does the skin act as a defense?
mechanical barrier
-acid pH: sebaceous secretion and sweat contain unsaturated fatty acids
-lower temp that is suboptimal for some bacteria
what defense is mucous membrane? function?
mechanical barrier
- cilia of respiratory tract eliminate particles larger than 5 microns (e.g., large bacteria carrying dust particles).
- lysozymes (antibacterial substance e.g., in tears)
- pH - e.g., gastric juice pH, acid pH in vagina, urine.
iron-binding proteins
that bind the iron necessary for growth
e.g transferrin, lactoferrin
phagocytosis
polymorphonuclear white blood cells and monocytes as well as fixed macrophages
in the tissues engulf and eventually destroy bacteria
what is specific immunity? what types are there?
mechanism aimed at particular infecting organisms
- humoral immunity (specific circulating antibodies)
- cell mediated immunity (cells to attack invading specific organism)
humoral immunity
antibodies which are modified serum
globulins, physico-chemically tailored to react with particular chemical components of previously
encountered invading organisms and produced only in response to these encounters
what are antiboies produced by?
B-lymphocyte’s; also known as B-cells
-In order to produce antibodies, B lymphocytes need antigen-presenting cells
how is antibody production regulated
T-helper and Tsuppressor cells
when is humoral immunity an important role in preventing infections?
-involves production of toxins
- presence of a capsule
-some viral infections
what are antigens
stimulate the production of antibodies; foreign invaders
important aspects of antigen
- must be recognized by body as foreign
- stimulates the production of antibodies
- usually a protein, but can be glycoprotein, lipoprotein, polysaccharide
- molecular weight at least 10,000 to trigger an immune respons
-can be particulate or soluble
-bacterial cells contain antigenic materials (capsular substance, flagell, cell wall)
– viruses often have polypeptide antigens
general properties of antibody
- referred to as immunoglobulin (Ig);
- produced by the body in response to stimulation by antigen;
- synthesized by specific B lymphocytes (plasma cells);
- ability to distinguish foreign macromolecules (NON-SELF) from ‘normal’ body constituents
(SELF); - high specificity in combination with antigens;
what are the 5 classes of immunoglobins (antibody)?
IgG, IgA, IgM, IgE and IgD
which Ig are involved in defense mechanisms
IgG, IgA, IgM,
where is igE involved
hypersensitivity states
basic shape found in igG
Y-shaped molecule
IgG
-two combining sites
-combine specifically with antigens (lock and key)
-bind phagocytes and macrophages
-cross placenta and protect newborn
-y shaped
IgM
-5 units joined together
-MAIN immunoglobin
-produced early in immune response
-doesn cross placenta
IgA
-2 units
-found in secretion
-mucosae (reformatory)
-tears
-milk
the serological reaction
-presence of antibodies in a serum sample (blood screening)
-observable antigen-antibody reaction
-titration of antibody
- unknown microorganisms can be identified with known diagnostic antisera
Cell-Mediated Immunity (CMI)
exposure to an antigen induces
production of “trained” cells active against that antigen or any organism that carries it
main difference between cmi and humoral
- soluble antibodies are not involved
- based on a large number of T-cell subpopulations and a complex system of interactions
- active in most microbial infections and is essential in the defense against intracellular organisms, parasites, and tumor cells and foreign cells (transplants)
what is the importance of APC’s?
- mediate the response upon exposure to an antigen
- display the antigen on its surface and, along with major histocompatibility complexes
-drive cellular or humoural immune
responses by interacting with Th1 or Th2 cells
what affects the quality and intensity of the immune system?
age, race, stress, nutritional status
4 ways immune response can be harmful to the system
- Allergy and hypersensitivity states (overreaction to antigens; anaphylaxis)
- Auto-immune diseases (immune system believing itself to be foreign)
- Immunodeficiency states (lack antibody, CMI, or both.)
- Graft rejection (kidney, bone-marrow, heart, etc; foreign supress rejection by drugs)
passive immunization? IgG in animals? Humans?
- preformed antibody injection
-IgG of animals cleared from recipient in 10 days
-risk of IgE antibodies (serum sickness and anaphylaxis)
- IgG of human disappears after several weeks
no risk of hypersensitivity
-short lived
immune serum globulin or gamma globulin
- IgG fraction pooled from a large group of blood-donors
-antibody for naturallly occuring disease
Hyperimmune globulins
IgG fractions from human subjects with high titers of antibody to a specific disease that have resulted from natural exposure or hyperimmunization.
Active immunization
-Antigen injection stimulate antibody
-long lasting
Major active immunization strategies (Live attenuated vaccines, Killed vaccines, subunits vaccines and toxoids,
1) Live attenuated vaccines
mild illness, limited extent, disease prevention
provide IgA and IgG (develop faster in live than killed)
2) Killed vaccines, subunits vaccines and toxoids
no infectivity, administered multiple times for satisfactory secondary response
3) Recombinant vaccines
produced by DNA recombinant technology
avoids chance if live virus surviving inactivation process
e.g. hepatitis B vaccine
4) Adsorbed vaccines
mixed with inorganic salts absorbed by tissue ensures prolonged effect
5) Conjugate vaccines
capsular material is attached (conjugated) to an altered, non-toxic protein. In this form, the polysaccharide becomes immunogenic.
6) Combined vaccines several vaccines administered together
7) Schedule of immunizations orderly time-table under which several routine immunization procedures are carried out in infancy and childhood.
Combined active-passive immunization? examples? site of injection?
-used in a few situations potential exposure to a given microbial agent, it is desirable to provide the patient with immediate protection
e.g. tetanus, hepatitis B, rabies exposure
- injected at two diff sites and syringes
what antibiotic was hailed as a miracle drug in 1940s to 1950s?
penicillin
what has been dramatically reducing the efficacy of antibiotics
antibiotic resistance
Reasons underlying the marked increase in antibiotic resistant bacteria
(a)Use and misuse of antibiotics in agriculture and aquaculture.
(b) Use and misuse of antibiotics in the human population (mainly in developing countries).
(c) With advances in medical therapies, many more immunocompromised patients are remaining alive
longer and are serving to harbour and transmit antibiotic resistant bacteria.
what is Antibiotic Resistance? most common in who?
-develop resistance to virtually any antibiotic given sufficient time
- Resistance common & more quickly in immunocompromised patients resulting in increased morbidity, increased length of hospital stay and higher mortality
Antibiotic resistance is generally classified into two major types
1) Intrinsic resistance- predictable form of resistance based on the mechanism(s) of action of the antibiotic and the characteristics of the microorganisms
2)Acquired resistance - described as a previously susceptible organism becoming resistant to an
antibiotic’s action. This type of resistance is clinically more important and involves three main mechanisms
of resistance:
(i) Alteration in drug target
(ii) Production of inactivating enzymes
(iii) Decreased antibiotic uptake
Genetics of Antibiotic Resistance
Antibiotic resistance genes can be encoded by the bacterial chromosome or by extrachromosomal entities
such as plasmids
Ways bacterias exchange info
Conjugation (plasmid)
Transformation
Transduction
Transposition
Conjugation (plasmid)
This mode of exchange requires cell-to-cell contact as well as specialized bacterial structures known as conjugative pili for the transfer of DNA molecules usually in the form of plasmids, which are extrachromosomal DNA elements that replicate in bacteria
transformation
uptake of free or naked DNA from the environment, its
incorporation into the bacterial genome and subsequent gene expression
transduction
This involves the transfer of genetic material among bacterial cells using a bacteriophage as vector or carrier
-random; accidental incorporation of bacterial DNA within a phage particle
- high host specificity and host restriction/modification systems
Transposition
Conjugative transposons can jump from the chromosome of one organism to the chromosome of another thus
circumventing plasmid-host range restrictions
intregrons, is a mobile DNA element with a specific structure consisting of two
conserved segments flanking a central region in which “cassettes” that encode functions such as
antibiotic resistance may be inserted.
how do chromosomes effect antibiotic resistance
(i)encoding the target site of the antibiotic, rendering the site functional but nonsusceptible.
(ii) being a regulatory element which controls alternative pathways or efflux mechanisms.
(iii) controlling cell permeability and regulating the uptake of the antibiotic and, consequently, the
intracellular concentration of the drug.
What is the primary response
-Exposed to antigen for first time
-Triggers productions of antibody by B cell
-5-10 days circulation
-max 3 weeks then drops
2nd response
Basis of immunization
-occurs when Ab is introduced
-less lag rapid Ab increase 2-3 days, slow decrease
-booster to maximize Ab levels
-3-5 injections for full immunity
role of APC cell on humoral or cmi if activated?
APC cells
-take in antigen presents it on surface
-bunds special receptor on t helper cells
-receptors are mhci or mhcii
-T helper we th1(CMI) or th2 (humoral)
What do mutation lead to
Change in site of antibiotic target
Regulator gene (turn on alternative path or turn in efflux mechanism)
How to decrease microbial resistance
-Withhold antibiotic (not use for viral infection they don’t work)
-right concentrations by classifying organism first
-prevent infection (hygiene)
-educate ( when,how, proper duration)
-early detection of therapeutic failure
