MCB55 Mid Term 1

Passive Immunizations

Collect antibodies from animal/human and transfer to give protection. No long term, lasts as long as antibodies survive

Active Immunizations

Vaccines making memory T and B cells

Preventive Vaccines

Given before you've been infected. Provides protection against primary infection

Therapeutic Vaccines

Given to currently infected to reduce disease. (Given to cancer patients to stimulate anti-tumor response)

Attenuated Vaccine

- Requires only one dose

- Less Stable

- Grown in culture with adverse conditions

- May revert to virulent form

Inactivated Vaccine

- Requires multiple does

- More stable (more advantageous in Third World countries refrig is limited)

- Made inactive through chemicals or radiation

- Cannot revert to virulent form

Adjuvants

Provide inflammatory response to activate adaptive immune response. Used for non replicating cells in vaccines

Virus

- Most people are asymptomatic

- 24% of people develop fever, headache, and/or sore throat

- Only 1 in 150 have neurological infection

- Paralysis in <1%

- Infect neurons that control breathing (needed to be in Iron Lung)

Polio

Why Was Polio so Successful?

Highly contagious and able to infect up to 100% of humans

- High number of asymptomatic

- No treatment

Virus

- Only found in humans

- No Latent or persistent infections

- Good in dense areas (spread through coughing)

-Can spread when <10% of pop are susceptible

- Highly contagious almost impossible to contain outbreak

- No drug treatment

- Most death from immune suppression

Measles

Encephalitis

Rare type of Measles infection that goes into the CNS infecting the tissue surrounding the brain (deafness blindness)

Antony van Leeuwenhoek

- Spoke dutch (not well educated)

- Ground lens to magnify (50-275x)

- Made basic diagrams of most kinds of microbes

- Discovered microbes (1-2 microns) (1/1000th of a louses eye)

Spallanzani

Tried to disprove Spontaneous Generation with boiling broth experiment

Came after leeuwenhoek and before Pasteur

Pasteur

- Discovered role of fermentation in beer and wine

- Invented pasteurization

- Furthered Spallanzani's experiment added swan neck flask

- Found disease from microbes in silk worms support for Germ Theory of Disease

Microbe

Any microscopic living organism

Negative Controls

Experimental conditions where the phenomenon of interest is NOT expected to occur

Positive Controls

Experimental conditions where the phenomenon of interest is STILL expected to occur

Robert Koch

- Prove anthrax is caused by Bacillius anthracis

- Grew bacteria in culture at first eye of an ox (assistant invented petri dish)

- Identified the bacilli that causes Tuberculosis (TB) passage on blood-serum jelly

- Proved microbes make people sick and specific microbes cause specific diseases

- Observed anthrax can form spores (very resistant)

Gram Staining

Gram positive have different cell wall structures that allows them to retain the crystal violet better than gram negative

Koch's Postualtes

1. The microorganism must be found in all organisms suffering from the disease (but not in healthy organisms.)

2. The microorganism must be isolated from a diseased organism and grown in pure culture.

3. The cultured microorganism should cause disease when introduced into a healthy organism.

4. The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

Koch's TB "vaccine"

Didn't prevent TB but gave current patients an immune boost (delayed hypersensitivity response)

Electric Theory

Theory Cholera was caused by atmospheric electricity

Ozonic Theory

Theory Cholera was caused by shortage of ozone

Telluric Theory

Theory Cholera was caused by emanation from the Earth

Max Von Pettenkofer

Drank culture of Cholera and didn't get infected to disprove Koch's postulates

Typhoid Mary

Asymptomatic carrier of Typhoid bacteria

DNA

A string of nucleotides (A, G, T, C). The order determines biological properties of the organism

- Double helix that mirrors each other (different sequences still has full genetic information)

RNA

- Similar to DNA but an extra oxygen atom in each nucleotide

- RNA uses uridine (U) instead of thymidine (T)

- RNA is more chemically unstable

- Used as a temporary messenger

Protein

- Linear sequence of Amino acids

- 20 different amino acids

DNA -> RNA -> Protein

Ribosomes

The machine that reads the RNA and makes proteins

- They are made of RNA and protein

Retroviruses

(e.g. HIV) Can make DNA from an RNA template. This is called reverse transcription

Reverse Transcription

Making DNA from RNA template (HIV)

RNA Replication

RNA viruses makes RNA copies directly from RNA

Gene

A segment of DNA that gives rise to a protein

Genome

All the nucleic acids that are passed from parent to progeny

Eukaryotes

-Genetic material (DNA) in nucleus

- Organelles

Gram Positive

Bacteria with One membrane

Thick cell wall (peptidoglycan)

No lipopolysaccharide

Gram Negative

Bacteria with Two membranes

Thin layer of peptidoglycan

Outer membrane contains lipopolysaccharide

Gram Variable organisms

Are like gram positive, except they are surrounded by thick layer of mycolic acid "waxy coat"

Eukaryotic pathogens

- Fungal

- Protozoan parasites

- Helminths (parasitic worms)

Prokaryotic pathogens

- Gram positive or negative bacteria

- Intracellular or Extracellular

- Obligate or Facultative

Extracellular Bacteria

More exposed to immune system but replicate faster and produce toxins to kill host

Intracellular Bacteria

Hide from some parts of the immune system

Obligate

Obligated to live in cells

Facultative

Capable of living and producing inside or outside cells, and dont need oxygen

Barriers for Immune system

Skin

Mucocillary clearence

Lysozyme

Innate Immune System Phagocytes

Macrophage

Dendritic Cell

Neutrophils

Innate Immune System Non-Phagocytes

Mast Cells

Natural killer cells

PAMPs

Pathogen Associated Molecule Patterns

- Recognized by receptors

- Receptor binds to PAMP then a biochemical sginal is transmitted into cell

- Cell initiates immune response (produces cytokines)

Acute Inflammation benefits

1. Brings innate immune cells to an infections site to phagocytize pathogens

2. Fluid can cleanse infection

3. Inflammation brings immune molecules (antibodies)

4. Provides "signals" to activate adaptive immune system

Chronic Inflammation

Same symptoms as acute but leads to tissues destruction

Cytokines

When immune system detects pathogen cytokines are produced as signals for immune response both adaptive and innate

Too much => shock

Too little => failure to contain infection

Adaptive Immunity

Responds to pathogens by recognizing specific antigens

- Able to see difference in antigens

- 3-7 days for response

- Has memory

Antigen

molecules from pathogens that can be recognized by the immune system

Epitopes

Smaller pieces of antigens also recognized

B cell meditated immunity

Antibodies produced by B-cell interact with pathogens

T-cell mediated immunity

T cells only recognize antigen as a small peptide fragment bound to an MHC molecule and displayed at the cell surface

B Cells

Main function to produce antibodies (only one capable of this)

One B cell produces a single kind of antibody

Antibody Isotypes

IgM, IgG, IgA, IgE

Neutralization

Antibodies bind to antigens or pathogen or toxin and blocks function

Opsonization

Antibody enhances phagocytosis

Complement activation

Binds to antibodies molecules bound to pathogen or infected cells and enables lysis or phagocytosis (pokes holes)

Can also lead up to opsonization

Two types of T cells

Cytotoxic T cells

T helper cells

Cytotoxic T cells

Kill virally-infected cells (CD8 T cells)

T helper cells

Produces cytokines (CD4 T cells)

Master regulators needed for

- Making B cells produce antibodies

- Cytotoxic T cells become best killer possible

- Macrophages to kill off pathogens inside

T Cell Receptor (TCR)

Receptor on surface of cell

Only recognize antigen when its presented by MHC

MHC

Major Histocompatibility Complex Displays fragments of pathogens on the host cell surface

Dendritic, B cells, and macrophages present it to T helper

Variola Major

Variola Minor

Virus

- Mortality Rate of ~30%

- Virus is shed before visible

- Cause of death most likely excessive immune response

- Effective at immune system evasion (inactivate cytokines and inhibit lysis)

- Eradicated by WHO in 1980

Small Pox-

Vaccinia

vaccine for smallpox

- Elicits both protective antibody, T helper cell and Cytotoxic T cell (CTL)

- very effeicacious: 100% protection 1-3 years and protection continues over 30 years after

Bacteria

Gram Negative

Virulence factors contained on plasmids

Yersinia Pestis (plague)

Virulence Factors

What cause symptoms and usually deadliness

Yops

Plague virulence factor that blocks phagocytosis from the macrophages, cytokine production, and also kills macrophages

Pla

(plasminogen activator) plague virulence factor; a protease secreted into the blood and blocks blood coagulation and complement

Capsule

Plague virulence factor: coat on surface that inhibits phagocytosis

Bubonic

Fever, bubo, replication of bacteria in lymph

Septicemic

Fever, inflammatory response syndrome, replication of bacteria in blood

Coagulation of blood in organs can cause death

Pneumonic

Fever, pneumonia, replication in lungss

Bubo

enlarged lymph gland, usually appearing in groin, armpit, or neck

Plague Treatment

Biggest problem is its hard to identify but antibiotics take care of it easily if noticed decently early

Mortality from plague

14% of people in US die

50-60% of bubonic cases who fail to receive antibiotics die

Untreated septicemic or pneumonic is almost always fatal

Category A Pathogens

Anthrax

Botulism

Plague

Smallpox

Tularemia

Ebola (Viral Hemorrhagic fevers)

Cholera who discovered

Filipo Pacini first discoverd then Koch rediscovered

Classic Biotype

Generally clumped together and has more symptomatic cases, now outcompeted by El Tor biotype

El Tor biotype

Gernally spread around when grown in culture (more asymptomatic cases), now competes the classic biotype

Cholera

- Bacteria

- Infectious dose is millions of bacterium

- Fecal/oral transmission

- Incubation period 2-7 days (in intestines)

- Dehydration is main issue

Why Does Cholera cause the poops

Tricks intestineal cells into producing lots of CAMPs which induce cell to pump out chloride, to keep the balance water and sodium pump out (poops)

Cholera Toxin (CT)

A phage that infects Cholera its the main thing that gives diarrhea

AB type toxin

- A subunit is the actual toxin

- B subunit binds to human cells

Oral Re-hydration

Treatment for Cholera revitalizes electrolytes comes in form of salts

IgG

Antibody subclass found in all bodily fluids (blood) protects against bacteria and virus

IgA

Antibody subclass found mostly in mucous membranes

IgM

Antibody subclass found mostly in blood and lymph fluid the first antibody to be made by the body to fight new infections

Thomas Kuhn

Coined term "paradigm shift" wrote largely about examples from physics

Hooke

First use of term Cell and also discovered split ends in hairs

Hookes "cell" was" about 20 microns

Fermentation

Process that produces energy without consuming oxygen

Codon

Sequence of three nucleotides that together form a unit of genetic code in DNA

FC Receptor

A protein that is found on the surface of certain cells that contribute to the protective functions of the immune system

Endemic

In a specific area for a long period of time and can rise at any time

Epidemic

Sudden outbreak of particular disease to several communities all at once