Micro Final

13-15

Innate Immune System

“born with it,” immediately available; nonspecific, can react against anything

Adaptive Immune System

“Learned/Acquired,” memory, allows immune system to remember “nonself” it’s seen before; specificity; fast response and powerful once memory is established

Antigen

a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies; can bind to an antibody or T-call receptor; can be proteins peptides, polysaccharides, etc.

Two molecules used by the innate immune system

1. TLRs: “toll-like receptors,” are a family of proteins that help in the innate immune system by recognizing pathogen-associated molecular patterns (PAMPs), which are structures found in pathogens

2. cytokines: IL-1, IL-6, IL-8…they have different signals they look for and they send messages to the immune system if something is found, and gives directions on what to do

Macrophages

Destroy bacterial, fungal, and protozoan pathogens by phagocytosis; remove virus-infected cells-and tumor cells; present antigen to adaptive immune system

Mast Cells

Produce chemical mediators, recruit effector cells; influence adaptive response

Dendritic Cells

Present antigen to adaptive immune system; perform phagocytosis

Natural Killer Cells

Kill tumor cells and pathogen infected host cells

Two Parts of the Innate Immune System

1. Physical and Chemical Barriers: Skin, membranes, hair; saliva, stomach acid, enzyme

2. Cellular Responses: Phagocytosis, inflammation, interferon, complement system, fever

Phagocytosis

ingesting foreign bodies and destroying; goal = remove antigen

Inflammation

Helps destroy infectious agents and signal that the area is damaged and need repair/replacement inflammation includes: swelling, heat, pain, redness chemokines help to mediate/signal inflammation

Fever

Why? availability of iron (important micronutrient for microbes/temperature sensitive microbes, helps lower growth inactivates toxins (proteins) by changing their shape

Complement system

• enhances (complements) the innate and adaptive immune system

• functions: membrane attack, phagocytosis, and inflammation

  • c proteins mediate the complement syste

  • 1. classical: antibodies specific to antigen

  • 2. alternative: LPS and other surface antigens

  • 3. lectin: mannose (carb not on human cells)

Interferon

A type of cytokine applies to viral infected cells; viral infected cells produce interferon to “warn” neighboring cells to make anti-viral proteins.

T-cells

2 main kinds:

1. T cytotoxic cells:

   Roles: learn antigen and kill pathogen or learn antigen and become memory T cell

2. T helper cells

   Roles: learn antigen and talk to a B cell or learn antigen and become memory T cell

Learn by being presented with an antigen

MHC: major histocompatibility complex, non-specific proteins, “present” the antigen

B-cells

• activate into plasma cells; plasma cells make antibodies

Antibodies

proteins produced by the body’s immune system to help fight off foreign substances, like bacteria and viruses that can cause disease.

Immunoglobulins (Ig)

IgM: 1st antibody to appear in primary response (against polysaccharide)

IgG: “golden one,” most specific; highest affinity for antigen (against peptides)

epitope

a part of the antigen to which antibodies bind

How do the innate and adaptive immune system work together?

The innate system acts first, recognizing broad patterns on pathogens and initiating a rapid inflammatory response. If the innate system fails to clear the infection, it signals to the adaptive system, which then develops a specific response tailored to the pathogen, often involving B cells and T cells. 

Sterilization

used on inanimate objects; destruction or removal of all viable organisms

• ex: cells, viruses, spores

Disinfection

killing, inhibition, or removal of pathogens-just ones that make people sick

Sanitization

microbial population is decreased to a safe level

• ex: laundry, washing dishes, scrubbing into surgery

Antisepsis

preventing infection of living tissue by microbes

Antiseptics

agents used for antiseptics

• ex: hand sanitizer

Chemotherapy

chemicals used internally to kill/inhibit of microbes within tissues

Bacterial Cidal

to kill

Bacterial static

inhibit growth

Bacterial lytic

agent that induces cell lysis

Pattern/measure of microbial death

Conditions that affect effectiveness of antimicrobial agent acitivty

• properties of microbe

• strength/concentration

• population size

• temperature

• pH

Relative resistance of different microbes

Control Methods

• physical agents: 1. heat 2. radiation

• chemical agents: 1. gas 2. liquid

• mechanical removal: filtration

• biological agents: 1. phage 2. Bdelloubrio

Chemotherapeutic agents

Chemicals used to treat disease; destroy microbes or inhibit growth within a host

Penicillin

Alexander Fleming stole the work of Ernest Duchesne; discovered the antibiotic properties of penicillin cause he had a nasty work space and it got discovered on accident

Characteristics of antimicrobials

• narrow spectrum: “attack” only a few types of bacteria

• broad spectrum: “attack” a large #/types of bacteria

• bacteriocidal: kill bacteria

• bacteriostatic: prevent growth

How is effectiveness of an antimicrobial measured?

• MIC: minimum inhibitory concentration; minimum concentration of antibodies required to inhibit growth

• MLC: minimum lethal concentration; minimum concentration of antibodies required to kill growth

How to we determine level of antimicrobial activity?

1. Kirby Bauer

2. Dilution

3. Level of turbidity

Categories of Antimicrobials

1. antibodies

2. antivirals

3. antifungals

4. antiparasitics

5. antiprotozoans

Antibiotic Mechanisms of Action

1. Cell Wall

2. Nucleic acid synthesis

3. protein synthesis

4. metabolism

Cell Wall Synthesis Inhibitors

Protein Synthesis Inhibitors

Nucleic Acid Synthesis Inhibitors

Metabolism

folate synthesis inhibition; ex: sulfonamides, quinolones- associated with ligament damages

Factors that affect effectiveness of drugs

1. ability of drug to reach the site of infection

2. susceptibility to drug

3. ability of drug to reach/exceed MIC/MLC in body

   • depends on: amount (dose), route of administration, rate of clearing, rate of uptake, pharmacology

Antibiotic resistance mechanisms comes from where?

1. Mutation

2. Horizontal Gene Transfer

Antibiotic resistance mechanisms

1. Modification of target

2. Enzymatic inactivation

3. Removal from cell

4. Metabolic bypass

Persister cells

• not resistant to antibiotics

• dormant cells so antibiotics don’t bother them as antibiotics only work on actively growing cells

• when antibiotic is removed, persister cell start growing again

Gut microbiome→brain interaction

The gut microbiome influences brain function and vice versa

• plays a role in cognition and neurological disorders

C. sphaerosperum

a type of fungus that helps prevent from radiation poisoning-uses melanin to absorb radiation; used for the site around Chernobyl

Using microbes for our benefit

• radiation shielding

• radioprotective drugs

• speed up rate of plant growth

• bioremediation- microbial cleanup of oil, toxic chemicals, etc.

• biodegradation- disintegration of materials by bacterial, fungi, or other microbes

Microbes in space

Microbes in space become more virulent and have higher antibiotic resistance; biofilms are able to form in space