MCB2000 Exam 4

Chemotherapeutic agents

Any chemical used in the treatment, relief, or prophylaxis of a disease

The characteristics of an ideal antimicrobial drug

* Selectively toxic (non-toxic to host)
* Microbicidal rather than microbistatic (killing rather than stopping growth)
* Relatively soluble
* Remains potent long enough to act and is not broken down by the body prematurely
* Doesn’t lead to antimicrobial resistance
* Remains active in tissues
* Doesn’t cause allergies

Natural antibiotics

Penicillins extracted from cultures of *Penicillium* fungi are called natural penicillin

Semi-synthetic antibiotics

Developed in attempts to overcome the disadvantages of natural penicillins. Part of the penicillin is produced by the mold, and part is added synthetically.

Sites on infectious agents that antimicrobial agents target

* Cell wall (human cells don’t have it, best for peptidoglycan in bacteria)
* Cytoplasmic membrane (best for fungi because of ergosterol)
* Cellular synthesis and metabolism
* Protein synthesis
* DNA and RNA synthesis

Beta-Lactam Ring and examples of antibiotics

All penicillins contain a beta-lactam ring within their nucleus that allow it to function as an antibiotic. Cephalosporins also have this. These drugs target the cell wall. Some bacteria like staphylococcus have beta-lactamase. MRSA is resistant to it.

Why are Ribosomes excellent targets against many infectious diseases?

they are excellent targets against many infections because prokaryotic ribosomes are different in size and composition from eukaryotic ribosomes. Antimicrobial drugs can selectively target prokaryotic ribosomes, which gives them selective toxicity against prokaryotes but not their eukaryotic hosts.

Which groups of microorganisms produce antibiotics and why?

More than half of the antibiotics used today are produced by a bacteria called streptomyces. Some fungi also produce antibiotics. This gives the microbe an advantage when competing for food and water and other limited resources in a particular habitat, as the antibiotic kills off their competition.

Drugs that target the cell wall

* Penicillin (Beta-Lactam Ring)
* Cephalosporins (Beta-Lactam Ring)
* Carbapenems
* Misc. (Vancomycin for MRSA, Bacitracin)

Drugs that target protein synthesis

* Aminoglycosides (Streptomycin)
* Tetracycline
* Glycylcyclines
* Macrolides

Drugs that target Folic Acid synthesis

Sulfonamides (Trimethoprim)

Drugs that target DNA/RNA synthesis

* Fluoroquinolones (Ciprofloxacin for DNA replication)
* Rifamycin for RNA transcription

Agents used to treat fungal infections (targets ergosterol membrane)

* Macrolide **polyenes** (**Amphotericin** B)
* **Azoles** (Ketoconazole, fluconazole, miconazole, clotrimazole)

Drugs for inhibition of virus entry

* Fuzeon (HIV), Relenza, Tamiflu, and Amantadine (Flu)
* Prevents cell binding to membrane or protein receptors

Drugs for inhibition of nucleic acid synthesis

* Acyclovir (Zovirax) (Herpes) - terminate DNA replication
* Zidovudine (AZT) (HIV) - stops reverse transcriptase
* Ribavirin (RSV)

Drugs for inhibition of viral assembly/release

* Indinavir
* fights protease enzyme
* Protease inhibitors inhibit protease activity
* Best for HIV

Explain the rational behind the use of antimetabolites such as sulfa drugs and trimethoprim in treating \n bacterial infections

* antimetabolites block function of metabolic pathways, often structural analogs for true metabolites, folic acid pathway is unique to bacteria so it is a good target with selective toxicity
* sulfonamides (sulfa drugs)- act as a structural analog of a precursor involved in pathway in the synthesis of folic acid
* trimethoprim- interferes with folic acid synthesis

How does UV light radiation damage bacteria?

It damages the cell by forming thymine dimers, a mutation, superficial.

How does X-Rays and Gamma Rays damage DNA?

The shorter the wave, the higher the energy and the more damaging. X-Rays and Gamma Rays are the shortest. They break chromosomes and cause irreversible damage. Deep, penetrating, and cancer-causing.

Selective toxicity

The property of some antimicrobial agents to be toxic for a microorganism and nontoxic for the host.

Why is selective toxicity a difficulty for anti-viral drugs?

Viral infections are particularly difficult to treat because the pathogen is within the human host’s cells and because the genetic information of the virus is directing the human cell to make viruses rather than to synthesize normal cellular materials.

Why is selective toxicity difficult for anti-fungal drugs?

At the cellular level, these organisms resemble the human cell much more closely than a bacterial cell does. So, a drug that targets these pathogens usually damages the host, too.

List the Mechanisms by which bacteria develop resistance and spread the resistant genes to other \n bacteria

* Inactivate the drug
* MRSA with beta-lactamases
* Prevent drug entry
* Change target receptors
* Drug is immediately eliminated
* Multidrug resistant pumps transport drugs out
* Binding sites for drugs are decreased in number/affinity
* Modify target sites
* Affected metabolic pathway is shut down and alternative is used

Sterilization

Process that destroys or removes all viable microorganisms (including viruses) kills all life forms, even endospores. Example: autoclave

Decontamination

A process or treatment that renders a medical device, instrument, or environmental surface safe to handle. Sterilization, disinfection, and antisepsis are all forms of decontamination.

Sanitation

Cleaning technique that mechanically removes microorganisms as well as other debris to reduce contamination to safe levels.

Example: soaps, detergents, commercial dishwashers

List the microbes according to their resistance to physical and chemical agents.

Most resistant to least resistant:


1. Prions (Infectious proteins, CJD, Mad Cow, requires burning)
2. Bacterial endospores (Dormant life forms)
3. Mycobacterium
4. Staphylococcus or pseudomonas (Opportunistic infections, porins)
5. Protozoan cysts
6. Protozoan trophozoites (Overall protozoans are harder to kill than bacteria, fungi or viruses)
7. Most G- bacteria
8. Fungi and fungal spores
9. Nonenveloped viruses
10. Most G+ bacteria
11. Enveloped viruses

Why is G- bacteria more resistant to chemicals?

* Outer membrane with porins, which don’t allow chemicals to get in
* Layer of peptidoglycan
* Hard for antibiotics as well

Name a specific gram-negative bacteria that is very resistant to killing by chemicals, and it is a major cause of \n opportunistic infections in hospitals.

Pseudomonas aeruginosa 

What is the difference between disinfectants and antiseptics?

Disinfectants are harsh chemicals which can’t be used on animate things. Antiseptics are milder and can be used on living tissues.

Physical methods of fighting microbial growth

* Heat, Moist Heat Sterilization (Boiling, Pasteurization, Autoclaving)


* Filtration
* Radiation
* High Pressure, Osmotic Pressure


* Low Temperatures
* Desiccation

Chemical methods of fighting microbial growth

* Chemical agents on living tissue as antiseptics
* Chemical agents on inanimate objects as disinfectants
* Few achieve sterility

Mechanical methods of fighting microbial growth

* Sanitization mechanically removes microorganisms
* Soaps, detergents, commercial dishwashers
* Degerming before receiving an injection
* Filtration

Chemotherapeutic Drug

Any chemical used in the treatment, relief, or prophylaxis of a disease

Prophylaxis

Use of a drug to prevent imminent infection of a person at risk

Antimicrobial Chemotherapy

The use of chemotherapeutic drug to control infection

Antimicrobials

All-inclusive term for any antimicrobial drug, regardless of its origin

Antibiotics

Substances produced by the natural metabolic processes of some microorganisms that can inhibit or destroy bacteria

Semisynthetic Drugs

Drugs that are chemically modified in the laboratory after being isolated from natural sources

Synthetic Drugs

Drugs produced entirely by chemical reactions

Narrow-Spectrum (Limited)

Antimicrobials effective against a limited array of microbial types- for example, a drug effective mainly against gram-positive bacteria

Broad-Spectrum (Extended)

Antimicrobials effective against a wide variety of microbial types- for example, a drug effective against gram-positive and gram-negative bacteria

Antibacterial actions of skin

* Low pH
* Salt
* Sweat
* Lysozyme (kills cell wall of bacteria (tears, saliva)
* Normal flora compete with bacteria

Antibacterial actions of mucous membrane

* Cilia in respiratory and trachea push microbes back up
* Digestive has bile, bile salts, stomach acid, intestinal enzymes, and elimination

Where do all blood components come from?

WBC, RBC, and platelets come from bone marrow

What are MHC Proteins?

* Major Histocompatability Complex
* A group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances


* T cells mature in the thymus gland. Thymic selection removes T cells that don’t recognize MHC molecules of the host and T cells that will attach host cells presenting self proteins in MHC.


* Helper T cells recognize antigens processed by antigen-presenting cells and presented with MHC II.


* Cytotoxic T cells recognize antigens processed by all host cells and presented with MHC class I.

Which cells interact with MHC I?

* CTL cells react with MHC I
* They destroy target cells on contact

Which cells interact with MHC II?

* Th cells react with MHC II
* Th cells interact with an antigen to “present” it to a B cell for antibody formation

Differences between B cells and T cells

* B cells mature in Bone marrow and T cells mature in Thymus
* B cells produce antibodies (immunoglobulins)
* B cells can directly see Antigens, while T cells require antigen processing cells
* B cells are plasma and memory cells, while T cells have several types of memory cells
* B cells inactivate toxins, neutralize toxins, and complement fixation
* B cells are antibody mediated immune response, while T cells are antigen-specific cell-mediated immunity.

Antibodies

Proteins made and secreted by activated B cells called plasma cells. Each B cell produces one type of antibody

Cytokines

* Proteins produced by immune cells, used for attacking bacteria, communication, and activating each other
* APCs presents to T-helper cells and releases cytokines
* Cytokine release stimulates other cells
* Ex: Tumor Necrosis Factor (TNF) important for fighting cancer cells, Inflammatory Mediators

Interferons

* Important against viruses
* Type of cytokine that attacks viruses
* Kills the RNA and blocks replication

Complement Proteins

* Group of proteins floating in the blood on a regular basis
* If infection enters the body, they become activated
* Leads to Complement Fixation once activated

Complement Fixation

* Process by which Complement Proteins are activated
* As activated the fragments of c.p. accumulate on the surface of the cell of bacteria
* Accumulation results in the formation of membrane attack complex (MAC), which pokes a hole on the bacteria.
* Leaks, lysis, killed
* Coat bacteria with c.p. after (opsonization)
* Attracts phagocytic cells

Lymphocyte

A leukocyte involved in specific immune responses (T and B cells, for ex)

Leukocyte

A white blood cell, involved in the immune system

Erythrocyte

A red blood cell, carries oxygen

Active immunization

* Making your own B/T cells and antibody
* Naturally: Getting sick
* Artificially: Vaccine

Passive immunization

* Receive antibody from someone else (NO B/T cells)
* Naturally: mother to baby, through placenta or breast milk
* Artificially: Immunotherapy, antivenom

Practical uses for ELISA test

* Enzyme-Linked Immunosorbent Assay
* Direct test for antigens
* Indirect test for antibodies
* Common day pregnancy test based on it
* Direct ex is drug test in urine, hantavirus, measles virus
* Indirect ex is HIV antibodies in blood

Natural acquired immunity

* Naturally obtaining antibody
* Active: getting sick
* Passive: mother to baby

Artificial acquired immunity

* Artificially obtaining antibody
* Active: getting a vaccine
* Passive: receiving immunotherapy or antivenom

Cell-mediated Immunity

immunity against intracellular pathogens, where it identifies cells that are cancerous or infected with bacteria, viruses, fungi, and other parasites and kills them. This kind of immunity involves T cells and the natural killer cells

Humoral Immunity

* Mediated by antibody molecules that are secreted by plasma cells
* The immunity against extracellular pathogens
* This kind of immunity involves the activation of B cells, which produce antibodies, and memory cells

The difference between Cellular Immunity and Humoral Immunity

Cellular immunity responds to intracellular antigens; humoral immunity responds to antigens in body fluids.

Antibody Structure

* The Y-shaped molecule is composed of two light chains and two heavy chains linked by disulfide bridges (S—S).
* Most of the molecule is made up of constant regions (C), which are the same for all antibodies of the same class.
* The amino acid sequences of the variable regions (V), which form the two antigen-binding sites, differ for each B cell.
* The Fc region attaches to host cell

Opsonization

* The coating of antigens with antibodies or complement proteins
* Promotes attachment of a phagocyte to a microbe
* IgG or Cb3 molecule of complementary system

Hypersensitivity

Exaggerated immune response, organized in four different types

Type 1 Hypersensitivity

* Immediate
* IgE-mediated; involves mast cells, basophils, and allergic mediators
* Examples: anaphylaxis, allergies, hay fever, asthma

Type 2 Hypersensitivity

* Antibody-Mediated
* IgG, IgM antibodies act upon cells with complement and cause cell lysis
* Includes some autoimmune diseases
* Examples: blood group incompatibility, myasthenia gravis

Type 3 Hypersensitivity

* Immune-Complex Mediated
* Antibody-mediated inflammation
* Circulating IgG complexes deposited in basement membranes of target organs
* Includes some autoimmune diseases
* Examples: serum sickness, inflammation, rheumatoid arthritis, and lupus

Type 4 Hypersensitivity

* T-Cell Mediated
* Delayed hypersensitivity and cytotoxic reactions in tissues
* Includes some autoimmune diseases
* Examples: contact dermatitis, cosmetics, CMI

Primary Immunodeficiency

* Genetic
* B Cell Defects: Agammaglubulinemia (low levels of B Cells)
* T Cell Defects: DiGeorge Syndrome: Missing T-Cells
* Combined B Cell and T Cell defects: SCID, ADA Deficiency
* Complement Defects: lacking one of the C components. Hereditary angiodema associated with rheumatoid diseases, for example.

Secondary (Acquired) Immunodeficiency

* Natural Causes:
* Infections (AIDS) or Cancers
* Nutrient deficiencies
* Stress, pregnancy, aging
* Immunosuppressive Agents:
* Irradiation
* Severe Burns
* Steroids
* Immunosuppressive drugs (Cyclosporine)
* Spleen removal

Difference between autoimmune diseases and immunodeficiency

Immunodeficiency is when the immune system doesn't respond adequately to infection. Autoimmunity is when the immune system is overactive and responds to healthy cells as though they were foreign.

Killed vaccine

Stimulates B/T Cells and develops immunity. Bacteria or viruses.

Live attenuated vaccine

* Weakened version to produce mild symptoms.
* More effective than dead cells because it grows and provides long-lasting immunity.
* Requires less dosage.
* Particularly effective at inducing cell-mediated immunity.

Subunit vaccine

Take a piece of microbe for vaccine

Toxoids

Inactivated toxins, DTP vaccine

Adjuvant vaccines

a molecule that is added to a vaccine to make it more effective by enhancing the body's immune response to an antigen

Conjugate vaccines

involves the combination of a weak antigen with a strong antigen as a carrier so that the immune system mounts a stronger-than-usual response to the weak antigen

Primary lymphoid organs

Bone marrow and thymus

Secondary lymphoid organs

Lymph nodes, spleen, tonsils, and various mucous membranes

MALT, BALT, GALT, SALT

* Lymphoid tissues found in the intestinal mucosa (mucosa-associated lymphoid tissue = MALT)
* In the wall of the main bronchi (bronchus-associated lymphoid tissue = BALT)
* In the gut (gut-associated lymphoid tissue = GALT)
* In the skin (skin-associated lymphoid tissue = SALT)

Primary Immune Response

* First exposure ever of a specific infection
* IgM shows up, the predominant antibody
* Slow to develop and doesn’t last very long, low level response

Secondary Immune Response

* Higher titer: greater response
* More antibodies (mainly IgG)
* Lasts longer
* Exactly why we have vaccines, which mimic primary response

First line of defense

* Innate, nonspecific
* A surface protection composed of anatomical and physical barriers that keep microbes from penetrating sterile body compartments
* Physical barriers like skin and mucous membranes
* Chemical barriers

Second line of defense

* Innate, nonspecific
* A cellular and chemical system that comes immediately into play if infectious agents make it past the surface defenses
* Consists of gamma-delta T cells and natural killer T cells
* Phagocytosis, inflammation, fever, antimicrobial proteins

Third line of defense

* Acquired, specific
* Includes specific host defenses that must be developed uniquely for each microbe through the action of specialized white blood cells
* Consists of gamma-delta T cells, natural killer T cells, and B cells (lymphocytes)
* NK cells are lymphocytes that vary from innate to acquired

Name phagocytic cells

* Dendritic cells (APC)
* Macrophages (APC)
* Monocytes
* Neutrophils

Characteristics of antigens

* A molecule that triggers and activates the immune system
* Immune system recognizes molecules on cell surface
* Proteins are most antigenic
* Antigens must be recognized by B-cells and T-cells

Lysosome

An organelle containing digestive enzymes

Phagosome

A food vacuole of a phagocyte; also called a phagocytic vesicle

What happens when lysosomes and phagosomes make contact?

* Fuse to form a single, larger structure called a phagolysosome.


* The contents of the phagolysosome brought in by ingestion are digested in the phagolysosome.
* After enzymes have digested the contents of the phagolysosome brought into the cell by ingestion, the phagolysosome contains indigestible material and is called a *residual body.*
* This residual body then moves toward the cell boundary and discharges its wastes outside the cell.
* Provides innate immunity, totally annhilates and dissolves bacteria

Degranulation

* A cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells


* It is used by several different cells involved in the immune system, including granulocytes (neutrophils, basophils, and eosinophils) and mast cells
* It is also used by certain lymphocytes such as natural killer (NK) cells and cytotoxic T cells, whose main purpose is to destroy invading microorganisms
* An example of the granules released is histamine along with other mediators, which create the allergic reactions, swelling, redness, and difficulty breathing

Which cells are transplanted during a bone marrow transplant?

Stem cells

IgA

* Secretions like saliva and bodily fluids
* Mucosal immunity, protects from incoming infection