Microbiology Test 3

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Bibis

Prions

- Proteinaceous Infectious particle
- Inherited and transmissible by ingestion, transplant, and surgical instruments

- Spongiform encephalopathies: Sheep scrapie, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, mad cow disease

Prions cont...

- Prions cause a conformational change of native proteins into an abnormally structured form
- Meaning they cause normally proteins to change shape
- And now these abnormal proteins also act as prions

More Prions

-This change in the conformation of the proteins can have two effects
- Loss of function of the native protein
- Gain in toxicity of the abnormal conformation

- In addition, misfolded forms of proteins have a higher likelihood to aggregate

Terminology of microbial control

- Sepsis refers to microbial contamination
- Asepsis is the absence of significant contamination
- Aseptic surgery techniques prevent microbial contamination of wounds

More Terminology of microbial control

- Sterilization: Removing all microbial life
- Commercial sterilization: Killing C. botulinum endospores
- Disinfection: Removing pathogens
- Antisepsis: Removing pathogens from living tissue

Even more Terminology of microbial control

- Degerming: Removing microbes from a limited area
- Sanitization: Lowering microbial counts on eating utensils
- Biocide/germicide: Kills microbes
- Bacteriostasis: Inhibiting, not killing, microbes

Heat on microbes

- Heat appears to kill microorganisms by denaturing their enzymes
- As a result, altering their structure

Moist heat sterilization

- Moist heat denatures proteins
- Autoclave: Steam under pressure
- 121 °C and 15 psi

Pasteurization

- Reduces spoilage organisms and pathogens
- Thermoduric organisms survive

Filtration

Membrane filtration removes microbes >0.22 µm

Radiation

- Ionizing radiation (X rays, gamma rays, electron beams)
- Ionizes water to release OH•
- Damages DNA
- Nonionizing radiation (UV, 260 nm)
- Damages DNA
- Microwaves kill by heat; not especially antimicrobial

Types of Disinfectants

Phenols & Phenolics (carbolic acid)
Disrupt plasma membranes

Halogens

Iodine
Tinctures: In aqueous alcohol
Iodophors: In organic molecules
Alter protein synthesis and membranes

Alcohol

Ethanol, isopropanol
Denature proteins, dissolve lipids
Require water

Heavy Metals

Denature Proteins

History of chemotherapy

Alexander Fleming: Penicillum notatum

Antimicrobial Drugs

- 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

Broad spectrum
Narrow spectrum
Superinfection

The action of antimicrobial

Bactericidal
Kill microbes directly
Bacteriostatic
Prevent microbes from growing

Inhibitors of Cell Wall Synthesis

- Penicillin
- Prevents cross-linking of peptidoglycan

The Structure of Penicillins

Have Beta-Lactam Ring

Inhibitors of cell wall synthesis

- Antimycobacterial antibiotics
Isoniazid (INH)
- Inhibits mycolic acid synthesis
Ethambutol
- Inhibits incorporation of mycolic acid

competitive inhibitors

Sulfonamides (sulfa drugs)
Inhibit folic acid synthesis
Broad spectrum

Antiviral drugs

- Protease inhibitors
Indinavir: HIV
- Integrase inhibitors
HIV
- Inhibit attachment
Zanamivir: Influenza
Block CCR5: HIV
- Inhibit uncoating
Amantadine: Influenza

Concept of Immunity

Susceptibility: Lack of resistance to a disease
Immunity: Ability to ward off disease
Innate immunity: Defenses against any pathogen
Adaptive immunity: Immunity, resistance to a specific pathogen

Innate Immune system

How does the innate immune system recognize foreign materials such as bacteria?
Host Toll-like receptors (TLRs) attach to
Pathogen-associated molecular patterns (PAMPs)

The normal microbiota

- Normal Flora
- These microbes are typically take permanent residence of our body
Colonize
- Typically do not cause disease
Opportunistic pathogens

Formed elements in the blood

Blood consists of two parts
Plasma - Fluid component
Formed Elements - Cellular component
Leukocytes WBC

Leukocytes

- Granulocytes-
Contain large granules
- Agranulocytes

Granulocytes

Neutrophils - commonly known as polymorphonuclear leukocytes (PMNs)
- Highly phagocytic and motile

Agranuloctyes

Monocytes
Mature monocytes turn into macrophages

Action of Phagocytic cell

- Fixed macrophages Do not leave the tissue once they enter it
- Free (wandering) macrophages - Roam tissues and gather at sits of infection or inflammation

Action of phagocytic cells

When an infection occurs, the innate immune system is activated
Phagocytic cells such as neutrophils and monocytes migrate to the infected area
Migration into the infected tissue stimulates the maturation of monocytes into macrophages

Mechanism of Phagocytosis

Chemotaxis
Adherence
Ingestion
Digestion

More mechanism of phagocytosis

The phagosome detaches from the plasma membrane and enters the cytoplasm
Combines with a lysosome which contains digestive enzymes, forming the phagolysosome

Inflammation

Characteristics of inflammation
Redness
Swelling (edema)
Pain
Heat
Loss of Function (in extreme cases)

The complement system

Proteins of the complement system destroy microbes by:
Cytolysis
Inflammation
Phagocytosis
- Inactive until they are split into fragments (products)

Dual nature of adaptive

Humoral immunity
- B cells mature in the bone marrow
Due to antibodies

Dual nature of adaptive cont...

Cellular immunity
Due to T cells
T cells mature in the thymus

The nature of antigens

Antigens are compounds that provoke a highly specific immune response
Most antigens are either proteins or large polysaccharides
Often components of invading microbes
Capsules, Cell wall
Flagella, Fimbriae
Toxins
Viral coat
- All antigens are not components of microbes

The nature of antigens cont...

- Antibodies recognize and interact with specific regions on antigens called epitopes
- The size, shape, and chemical structure of the antibodies binding site dictates the epitope an antibody recognizes
- Hapten: Antigen is combined with carrier molecules

The nature of antibodies

Antibodies
Globular protein
Soluble proteins having a nearly spherical structures to varying degree of elliptical structure
Referred to as immunoglobulin (Ig)
Made as a response to an antigen, which can then bind to that same antigen

The nature of antibodies cont...

Antibody monomers are composed of 4 proteins
2 heavy chains
2 light chains
Each antibody has at least two identical sites that bind to epitopes
Antigen Binding Site

The nature of antibodies cont....still

There are 2 regions of an antibody
The variable(V) region
The constant(C) region
The stem of the antibody is known as the Fc region

The nature of antibodies cont....even still

There are 5 classes of Igs
IgG, IgM, IgA, IgD, and IgE

B cells and humoral immunity

B Cells
Produce antibodies when activated
When exposed to free or extracellular antigens
Each B cell carries immunoglobulins on its cell surface
Upon being triggered by an antigen
The B cell divides (clonal expansion), and the daughter cells synthesize and secrete antibodies
Two types of daughter cells
Plasma cells - produce antibodies
Memory cells - Long lived cells, responsible for an enhanced secondary response

B cells and humoral immunity cont...

- B cells activation typically require assistance of a T helper cell (TH) - T-dependent antigen
- The antigen is enzymatically processed by the B cell into fragments which are combined with the major histocompatibility complex (MHC)
- Antigens that stimulate B cells without T cells are called T-independent antigens

Results of Ag-Ab binding

Agglutination
Ab's cause antigens to clump together or aggregate
- Opsonization (Greek, to cater or prepare food)
Antigen is coated with Ab's which enhances its ingestion and lysis by phagocytic cells

Results of Ag-Ab binding cont...

Neutralization
IgG Ab's inactive a microbe by blocking their attachment sites to host cells
Neutralize toxins in a similar way
- Activation of Complement System
IgG or IgM triggers complement activation by the classical pathway

Results of Ag-Ab binding cont...

Antibody-dependent cell-mediated cytotoxicity
Resembles opsonization
Except the target cell remains outside of the immune cell

T cells and cellular immunity

Clusters of Differentiation (CD)
CD4+ and CD8+
TH cells are classified as CD4+
Because they bind to MHC class II molecules on B cells and Antigen Presenting Cells
TC cells are classified as CD8+ cells
Which bind to MHC class I molecules

types of adaptive immunity

Naturally acquired active immunity
Resulting from infection
Naturally acquired passive immunity
Transplacental or via colostrum
Artificially acquired active immunity
Injection of Ag (vaccination)
Artificially acquired passive immunity
Injection of Ab

Types of vaccination

Attenuated whole-agent vaccines
Uses live weakened microbes
Most closely mimic's an actual infection
Provides lifelong immunity without booster
95% effectiveness due to viral replication
Examples
MMR - Measles, Mumps, and Rubella
Polio vaccine

Types of vax

Inactivated whole-agent vaccines
Uses microbes that have been killed
By chemicals such as formalin or phenol
Examples
Pneumococcal pneumonia
Cholera

Types of vax

Toxoids
Inactivated toxins
Example
Tetanus toxoid
Diphtheria toxoid

Types of vax

Subunit vaccines
Fragment of a microbe that can best stimulate an immune response
Includes recombinant vaccines
Inherently safer because they cannot reproduce in the recipient
And also cause fewer adverse effects

Types of vax

Conjugated Vaccines
Based on capsular polysaccharides
Often are combined with proteins such as diptheria toxoid to improve response
Examples
Haemophilus influenzae type B

Types of vax

Nucleic Acid (DNA) Vaccines
DNA is injected into muscle, resulting in the production of the encoded protein antigen
Stimulates both the humoral and cellular immunity
Can be delivered by a needles injection device called the "gene gun"

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