TW: Exam 1 (Post Group): Lecture Slides
Lecture 1 Slides
The Immune System defends the host against harmful microbes.
But a defective immune system can place the host in danger. Ex.) allergies, autoimmunity, immune deficiency
Scientific Method: 1. observation. 2. hypothesis 3. experimentation 4. conclusion
immunis = exempt. An observation made in 430 BC during the Plague in which only those that recovered from disease could safely nurse the sick.
15th Century: Smallpox (variola): hypothesis- if naive individuals [person that never has been exposed] are given mild smallpox (variola minor) and recovers, then they should be protected from deadly smallpox (variola major).
Inoculation - induced vaccineby a needle into a person. Also, experimentation = variolation.
Variola (two types)
Major: 30% would die
Minor: 5% would die
Next topic is about Smallpox: Dr. Edward Jenner observed the beauty of milkmaids (smooth scarred skin. People that once had smallpox will have scars.) Cowpox- similar to smallpox but milder, and would only affect the area of contact.
So Dr. Jenner came up with a hypothesis - if naive individuals are given mild cowpox (variola minor) and recover, then they should be "immune" too deadly smallpox (variola major). (Dr. Jenner was immune to disease so he had to use a naive person)
Cowpox experimentation - Jenner introduced the pus from cowpox lesion (from milkmaid Sarah Nelms) into 8-year old James Phipps...and then he exposed the boy to smallpox.
Vaccine- The conclusion was that Jenner's cowpox (vaccinia) inoculation proved to be an effective means for smallpox prevention.
Vaccines in Western Europe and the world was being used by the 1800's. By the 1950's, smallpox was eradicated [no more cases] from the U.S. and childhood vaccinations were discontinued. The World Health Organization (WHO) distributed vaccine to developing countries dealing with epidemic smallpox ("ring" vaccinations - when immune people surround a population of naive or infected people). Last natural case of small was in Somalia 1977. Smallpox declared eradicated in 1980 in the WORLD!
Herd Immunity, if we have enough people immune, a disease can be eradicated. You limit the transport of the virus which will burn out the virus.
1963 Enders and Katz's measles vaccine is licensed.
1970's MMR [Measles, Mumps, Rebeles - combo vaccine] vaccine was put into use in US. In the year 2000, measles was basically/virtually eradicated from US.
How did they generate the vaccine? They create weaker forms of it. Like measles that get used towards chicken (embryos), then re-introduced into humans (which won't harm the humans.)
I don't feel like linking the chart or importing it, but talking about the Somali incident of people not vaccinating due to fears, and the disease became more popular. - Vaccine Fears!
in 1998, Andrew Wakefield (UK) suggests MMR vaccine linked to bowel disease and autism in children. In the 2000s, UK measles vaccine rates decline as lawsuits increase....and measles outbreaks pop up.
In 2008, measles outbreaks emerge in the US. In 2010 Wakefield was retracted by "The Lancet". In 2014, another outbreak in a unvaccinated Amish community in Ohio. In 2015, the origin of recent measles outbreaks traced to Disneyland.
Then we explained all the things wrong with the Wakefield paper.
Lecture 2 Slides
Hoes does the body defend against foreign invaders?
2nd Line of Defense: "Innate". You're born with innate immunity which included white blood cells, phagocytes (eat anything that doesn't belong.)
3rd line of defense: "Adaptive. Very specific Immunity.
1st line of defense: "Barrier Defense". Ex.) Skin- a nonspecific organ that will try to block everything. Bad or worse, will attempt to block everything
Pro: Because the adaptive immunity is so specific, it will only attack very specific microbes. Con: Antibodies will circulate the body as proteins and tag certain microbes. However, it takes a long time to adapt to create an antibody.
Co-evolution: Microbes and our immunity are constantly evolving to counter.
Goal: Stop the spreading. Con: often breached
How does the body recognize and remember?
Memory - "recognition program" - Antibodies are stored and used months, years incase of an infection, again. Slow the first time, but memory response is fast, but memory response is fast the second time. More protected each time.
Concepts
Host-Pathogen relationships [nothing personal, just trying to survive]
The goal of a pathogen is to reproduce.
It can't be: too successful because the pathogen will kill all the hosts that are needed to survive.
It can't be: not successful because the pathogen will have been defeated entirely.
Co-evolution - a balanced relationship that is not too strong or weak, but if deadly, probably have an efficient mechanism to reproduce to prevent burning out.
ex.) Seasonal Flu. The population develops adaptive immunity to a specific strain. The Virus mutation creates a new strain, which is how the virus gets over the adaptive defense (co-evolution). The Population may not only have partial protection.
Microbes evolve faster than humans. So microbes that are newly introduced into populations cause more severe disease since there is no partial protection. A good example would be "Bird or Swin Flu" since the virus jumps from one species to the next.
Host Recognition of Pathogens
Pathogen-associated molecular patterns (PAMPs)
Antigens
Conserved molecules of related microbes that are recognized by innate immune cells. Must be recognized as foreign & harmful. The innate immune cells will generally recognize the "PAMPs".
Specific molecules that differentiate microbes and are recognized by adaptive immune cells. Molecules (mainly proteins) that are specific to certain microbes. Similiar to a "key & a lock" mechanism. The measles' viruses have an antigen that could possibly bind to another.
There are 2 types of cells.
Extracellular - "Outside of the Cell." Which colonize the surfaces, circulate in fluids, and replicate outside of host.
- Bacteria
- Fungi
- Parasitic
Intracellular - "Inside of the cells". Which invade host cells, replicate within (harder to get out, because which cells are good or bad?) host cells.
- Viruses
- (some bacteria)
simple, unicellular, prokaryotic microbes. Most are extracellular.
Bacteria have specific molecules that no other species have, such as, peptidoglycan for their cell wall.
used given information to sift and determine if foreign & harmful.
Ex.) MRSA, Group A strep
Complex, unicellular, eukaryotic microbes, Most are extracellular.
lipopolysaccharide (LPS) <-- something only gram-negative bacteria have.
PAMPs (is it fungi, virus, bacteria?) Antigen (What kind of species is it?)
Unicellular eukaryotic microbes - Protozoa
Their nucleic acid genome is made up of DNA and RNA (high mutation rate). A protein coat that is called a capsid (Proteins are important antigens to tell the difference between two different kinds of species or viruses. Lipid envelope (coding of lipids) with glycoprotein spikes - which budding from host cell membrane occurs.
Considered to be obligate intracellular pathogens - host required for reproduction. Also when the virus is in the cell, phagocytes can't reach them.
Recognition & Tolerance
Same Lecture, Slide 14 and onward
PRRs
Antigens
PAMPs
Receptors
Molecules that are used to distinguish a vast group of pathogens. Is it viral, bacterial, fungus etc. Also sends an emergency signal to tell what kind of microbe is in the body.
"Structure of the pathogen"
"Receptors for white blood cells"
"Pathogen Recognition Receptor" [Book] White blood cells, proteins encoded in their genomic DNA and are always expressed by many different immune cells.
harmful vs. non-harmful
Markers that help tell the difference between two different species; virus vs. Virus. Is not a self body cell or not? Adaptive Immunity.
self vs. non-self
Why not attack every single non-self cell? Shouldn't attack every piece of pollen, dust, or food - might be neutral or beneficial to us! Only attack non-self & harmful. So both immunities need to communicate.
Let's talk about Innate Immunity. Harmful vs non-harmful
Again, this relates to PAMPs & PRRs; mainly about intracellular signalling.
Cytokines [The signal released by the T-cell receptor] causes inflammation . Inflammation is the increase of blood flow so that white cells into the blood can be activated by any kind of PAMPs. This will cause recognition of the antigen on the Pathogen, how to attack, and what group they belong too.
(IL -> inter-between Leukins - the communication between white blood cells.
Let's Talk about the Adaptive Immunity, self vs. nonself
Antigen Receptors
B-cell receptor (BCR)
T-Cell Receptor (TCR)
Cytokine stimulation
Released by T-helper cells 
Antibodies - lock with an antigen, flag it, and then prevents the antigen from binding to anything else. Then the phagocytes will attack.
Evolution of Defense
Circulation and movement of defense cells/molecules when/where they are needed, the W.B.C. and Luekocytes.
Innate immunity - general circulating
Adaptive immunity - highly specific, circulating, memory.
Natural barriers (our skin) - simple, highly nonspecific, static
Highest energy cost for the body. The speed of the first response is highly costly, but the second time will be much easier/less.
Anatomy of the Immune System
Development: the red area is where our immune cells will be produced; entire circulation once matured
Recruitment: Effector Cells - ask tony
Surveillance: PAtrol & calls for back-up. Cells can communicate. Cytokines are what is used by the cells to send a signals.
Elimination:
Hematopoiesis - is the process of creating new blood cells in the body. This occurs in the bone marrow and thymus. This makes multipotent stem cells that will give rise too...
- leukocytes - WBC, Neutrophiles (type of WBC), phagocytes
- megakaryocytes - platelets, used for blood clotting wounds.
- erythrocytes - red blood cells, transport O2.
Cells
Names and descriptions
- Eosinophils
- Basophils & mast Cells
- Monocytes, macrophages, and dendritic cells (DCs)
- Neutrophils
- Lymphocytes
- Cytokines and communication
Intracellular signaling
Chemokines and chemotaxis
immune cells are being attracted to chemokines which is produced at the site of infections.
Lecture 3 Slides
click to edit
ligand binding --> signal transducers --> kinases --> transcription factors --> gene expression
I DON't KNOW HOW TO ORGANIZE THE LAST 4 Slides
50-70% of circulating leukocytes; phagocyte granulate that is recruited to site of infection.
<1% of circulating leukocytes; produces cytokines such as histamine to trigger inflammation; similar to mast cells.
1-3% of circulating leukocytes; defense against parasitic worms; minor phagocyte.
5-10% of circulating leukocytes; differentiate into phagocyte macrophages and dendritic cells when entering tissues.