BIOM 3200 - Immune System

What are the four fluids (humors) in the "humoral theory"?

• Blood

• Phlegm

• Black bile

• Yellow bile

What are the behaviours, symptoms, element, and season associated with blood?

• Sanguine (cheerful, energetic)

• Hot and wet

• Air

• Spring

What are the behaviours, symptoms, element, and season associated with phlegm?

• Phlegmatic (calm, slow to react)

• Wet and cold

• Water

• Winter

What are the behaviours, symptoms, element, and season associated with black bile?

• Melancholic (sad, depressed)

• Dry and cold

• Earth

• Autumn

What are the behaviours, symptoms, element, and season associated with yellow bile?

• Choleric (quick tempered, argumentative)

• Hot and dry

• Fire

• Summer

How would you treat someone in the basis of modern medicine until the 17th century?

- By treating them with the opposite humor

Why did the humoral theory last so long before being thought of as quackery and replaced by the 'new science' of Galileo, Descartes, Newton, and Boyle?

• Books that were distributed

• Respect of traditional ideas

• Support of church

• The ideas brought together many people's understandings of the world

Quackery science: Radium is treated like calcium in the body, so radioactive radium is taken up by the bones and degrades marrow. What does this cause?

• Anemia

• Bone cancer

Who is known for the "Anatomical Essay on the Motion of the Heart and Blood in Animals", one-way valves in veins, and the fact that blood circulates from left side of heart through arteries and returns to the right side through veins in 1628?

- William Harvey

What is the 21 year old Jam Swammerdam known for in 1658?

- First description of RBCs

What is Marcello Malpighi known for in 1661?

- The discovery of the capillary system

What animal was the first recorded blood transfusion in 1665?

- Dog to dog

What animal was the first human blood transfusion with in 1667 (that did not work)?

- A lamb

What did Anton Leeuwenhoek provide a microscope description of saying they were around 25,000 times smaller than a grain of sand in 1674?

- RBC

On September 17, 1683, what did Leeuwenhoek describe when talking about the plaque on teeth?

- Bacteria

What are single celled foraminafora (amoeboid protists) found?

- In marine environments and fossils

What are rotifera?

- Microscopic freshwater animals

What are nematodes?

- Roundworms found in many environments

James Blundell performed the first successful transfusion of human blood to a patient for the treatment of postpartum what in 1818?

Hemorrhage

Karl Landsteiner discovered that there were how many human blood types in 1901? What did this lead to?

• Three

• Viable treatments of blood transfusions

In 1914, there was a discovery of sodium citrate solutions. What did they prevent that allowed for viable storage for transfusion?

- Prevent coagulation (changing to solid)

Who organized a civilian blood donor service during the WWs leading to new developments in storing and using blood and saving countless lives?

- Red Cross

In 1959, Max Perutz, Nobel Prize winner, used X-ray crystallography to reveal what structure?

- Hemogloin

Lack of normal Factor VIII leads hemophilia, an X-chromosome inherited clotting disorder. What type of thawing frozen plasma precipitates Factor VII (antihemophilic factor)? Quickly or slowly?

- Slowly thaw frozen plasma

The discovery of Hepatitis B antigen (HBsAg) in 1971 led to laws requiring what?

- Testing of donor blood

In 1981, what retrovirus has its first cases (also showing that hemophiliacs develop it as well as it is a blood-borne pathogen? (Hint: it was identified in 1983/4)

- AIDS (HIV)

What are the three main functions of the circulatory system?

• Transportation o Respiratory (RBCs) o Nutritive (digestive) o Excretory (wastes)

• Regulation of homeostasis o Hormonal o Temperature

• Protection o From injury (clotting) o From pathogens (immune)

What are the three formed elements that blood consists of?

• RBCs

• WBCs

• Platelets

What are RBCs, WBCs, and platelets carried in?

- Fluid called plasma

When a blood sample is centrifuged, which elements are at the bottom, which are at the top?

• Bottom: heavier, formed elements

• Top: plasma

Neutrophils, eosinophils, basophils, lymphocytes, ad monocytes are all examples of what?

- White blood cells

Erythrocytes are an example of what?

- Red blood cells

What is hematopoiesis?

- The formation of blood cells

What can hematopoietic stem cells (HSCs) that originate in the embryo turn into?

- Any cell they want (migrating to different tissues)

What is a major hematopoietic organ of the fetus?

- Liver

What is a major hematopoietic organ after birth?

- Bone marrow

RBCs are produced in the red bone marrow of mammals through a process called what?

- Erythropoiesis

Label the following diagram: (Word bank - proerythroblast, erythrocytes, hemocytoblast, normoblast, reticulocyte, erythroblast)

1. Hemocytoblast

2. Proerythroblast

3. Erythroblast

4. Normoblast

5. Reticulocyte

6. Erythrocytes

Which hormone stimulates erythropoiesis?

- Erythropoietin (EPO)

RBCs are anucleated and do not have mitochondria. They have a lifespan of how many days? What do they rely on for ATP production?

• 120 days

• Anaerobic glycolysis

What is the processed being described? "The Fe atom in heme gets recycled from senescent RBCs by phagocytes in the spleen and liver"

- Hemolysis

What is the Fe attached to in order to travel in the blood to the bone marrow?

- Transferrin (protein carrier)

What type of endocytosis allows Fe to enter RBCs?

- Receptor-mediated endocytosis

What type of shape do RBCs have? Straight and concave, or disc shape and biconcave?

- Biconcave and disc shape

The movement of leukocytes through capillary walls is referred to as what?

- Diapedesis or extravasation

Uncommitted stem cells in the bone marrow also give rise to the progenitor cells for what? What is this called?

• Remaining blood cells and platelets

• Leukopoiesis

What are "uniformly shaped cell fragments of large cells called megakaryocytes found in the bone marrow"

- Platelets (thrombocytes)

What are "common myeloid progenitor cells give rise to these cells which are found in circulation"

• Neutrophils

• Monocytes

• Basophils

What are "derived from their own lineage of lymphocyte progenitor cells in the bone marrow, which give rise to lymphocytes in the circulation"

- Lymphocytes

What is the most abundant blood cell?

- Red Blood Cell

What are the thin, light interface called the "buffy coat"

- White Blood Cell and platelets

What can blood smears with biological dyes help distinguish?

- Between subtypes of blood cells and platelets

What makes up blood plasma?

• Water: ~92%

• Dissolved solutes (Na+), trace elements (vitamins), gases (CO2, O2): ~1%

• Organic molecules (plasma proteins): ~7%

Plasma proteins (fibrinogen, globulins, and albumins), amino acids, glucose, lipids, nitrogenous wastes, hormones, enzymes, and metabolites are all what?

- Organic molecules

What makes up plasma proteins?

• Albumins: 55-60%

• Globulins: the rest?

• Fibrinogen: 6%

Most plasma proteins are produced where? Why are gamma globulins not produced here?

• The liver

• Because antibodies need to be produced places other than just the liver

Albumins are important as they provide the [1] needed to draw water from [2] into [3]?

1. Osmotic pressure

2. Interstitial fluid

3. Capillaries

Alpha and beta globulins transport what?

• Lipids

• Fat-soluble vitamins

Gamma globulins are what?

- Antibodies

Why are fibrinogen important?

- For clot formation

True or false: plasma transfusions may rejuvenate an old rodent's brain?

- True

Elizabeth Báthory (1560-1614) killed hundreds of women. Why?

- Hypothesis: to take their blood to try and stay young

Antibodies target what, but do not destroy them? What do they do instead?

• Pathogenic bacteria

• Marks them as targets for immunological attack

What can these pathogenic bacteria get attacked by once they have been marked by antibodies?

• Innate immune cells o Macrophages o Neutrophils

• Opsonization

• Complement (defense system of serum proteins)

How many complement proteins are inactive in the plasma?

- 9

How do complement proteins become activated?

- By attachment of antibodies to antigens (bacteria)

What are the three components that complement proteins can be subdivided into?

• Recognition (C1)

• Activation (C2 - C4)

• Attack (C5 - C9) (through complement fixation)

What are the three complement pathways that all share a common terminal reaction that generates macromolecular membrane attack complex (MAC)

• Classical pathway

• Lectin pathway

• Alternative pathway

What activates the classical pathway? Which complex is activated?

• Antibody-antigen binding on the invading cell's plasma membrane

• C1 complex

When is Lectin initiated? What complex is activated?

• When mannose binding lectin (MBL) binds mannose residues on pathogen surface

• C1-like complex

True or false: It is uncommon for pathogens to have mannose.

- False. Most pathogens have mannose

What are "carbohydrate-binding proteins that are highly specific for sugar moieties"?

- Lectins

The C1 complex or the C1-like complex cleaves / activates what?

- C4 and C2

Active C4 and C2 bind to form what?

- C3 convertase

What does C3 convertase cleave / activate?

- C3

Active C3 binds to C3 convertase to form what?

- C5 convertase

C5 convertase cleaves / activates what?

- C5

Active C5 complexes with C6 to C9 to form what?

- MAC (membrane attack complex)

Label the following diagram:

1. Antibody

2. Complement protein C4

3. Soluble complement

4. Complement fixation

Label the following diagram: (Word bank - eosinophils, neutrophils, monocytes, erythrocytes, basophils, platelets, lymphocytes)

1. Neutrophils

2. Eosinophils

3. Basophils

4. Lymphocytes

5. Monocytes

6. Platelets

7. Erythrocytes

Red bone marrow of the long bones, ribs, sternum, pelvis, bodies of the vertebrae, and portions of the skull are what kind of tissue?

- Myeloid tissue

Lymph nodes, tonsils, spleen, and thymus are what kind of tissue?

- Lymphoid tissue

In the alternative pathway, what type of reaction of C3 will allow C3b to bind to microbial surfaces?

- Spontaneous hydrolysis (cleavage)

What factor will bind to the membrane bound C3b in the alternative pathway?

- Factor B

What factor will cleave (activate) Factor B, leading to the formation of C3 convertase in the alternative pathway?

- Factor D

At which convertase will the alternative pathway converge with the classical and lectin pathways?

- C3 convertase

What complex will form a pore in the membrane of the pathogen to allow water to enter, leading to cell lysis?

- Membrane attack complex (MAC)

Which pathway has a high level of activity and is the only pathway triggered by antigen-antibody binding?

- Classical pathway

Which pathway is continuously active at low levels like an engine idling?

- Alternative pathway

Which type of immunity is "ready to go" and in the blood?

- Innate (non-specific)

Which type of immunity is it when specialized to a pathogen (for antigen-antibody binding)?

- Adaptive (specific)

What are the three fates of complement fragments that do not become fixed into the membrane?

1. Chemotaxis

2. Opsonization

3. Stimulation of histamine release

What things attract phagocytic cells (such as neutrophils and macrophages) to the site of complement activation?

- Chemotaxis

What is the process that forms bridges between a phagocyte and victim cell to facilitate phagocytosis?

- Opsonization

What two C's can stimulate the release of histamine from mast cells and basophils leading to vasodilation and more phagocytic cells to the site of action?

• C3a

• C5a

Are all microbes bad?

- No, they are normal parts of our body

Do we have more microbes or human cells in our body?

- Microbes (by a factor of 10 to 1)

What is being described: "the overall collection of microbiotas that resides inside humans or on their skin surface"?

- Microbiome

About how much does gut microbiome weigh?

- About 2kg

True or false: our microbiome and immune system contain thousands of different species of microorganisms with a mixture of commensal and symbiotic bacteria?

- True