blood and the immune system Flashcards
1
Q
What makes up the Innate Immune System?
A
- 1st line of defense (physical & chemical surface barriers)
- 2nd line of defense (internal cellular & chemical defense)
2
Q
What does the Humoral Theory state?
A
- the humors are blood, phlegm, black bile and yellow bile
- an imbalance in these humors causes disease
3
Q
What did Galen do?
A
- formalized the relationship between humoral medicine and Greek natural philosophy
- the four humors are made up of qualities (hot, cold, dry, wet
- body humors and physical world elements shared a common qualitative nature
4
Q
What is the 1st line of defense?
A
physical & chemical surface barriers
5
Q
What is microcosm?
A
little world of human body
6
Q
What is the 2nd line of defense?
A
internal cellular & chemical defense
7
Q
What is macrocosm?
A
greater world
8
Q
What was the solution to restore health balance before the 17th century?
A
- Lifestyle - diet and exercise
- medication - herbs
* opposites cure opposites - cold remedy cures hot illness
* illness was seen as internal disorder of the body, not as the result of a specific agent like bacteria
9
Q
What makes up the Adaptive Immune System?
A
- 3rd line of defense: (immune response – if pathogen survives nonspecific, internal defenses)
10
Q
What is the 3rd line of defense?
A
immune response (if pathogen survives
nonspecific, internal defenses))
11
Q
What was aristotelian, qualitative, natural philosophy replaced with after the late 17th century?
A
mechanical, chemical mathematical vision of the world and body (Galileo, Descartes, Newton, Boyle)
12
Q
What is Leukopoiesis?
A
Uncommitted stem cells in bone marrow also give rise to the
progenitor cells for the remaining blood cells & platelets…
-
Platelets: develop to the megakaryocyte stage in the bone
marrow, & are released as platelets in the circulation -
Neutrophils, monocytes, basophils: progenitor cells give rise
to these cells which are found in circulation -
Lymphocytes: derived from their own lineage of lymphocyte
stem cells in the bone marrow, which give rise to
lymphocytes in the circulation
13
Q
What species was the first recorded blood transfusion between?
A
dog -> dog
14
Q
Neutrophils, Eosinophils and Basophils are a type of (1), which are all types of (2).
A
- Granulocytes
- Leukocytes
15
Q
Which species was used for the first human blood transfusion
A
lamb
16
Q
What years were the first successful human blood transplants?
A
1800-1900s
17
Q
What are the three functions of the circulatory system?
A
- Transportation of substances essential for cellular metabolism (respiratory, nutritive, excretory)
- Regulation (hormonal and temp.)
- Protection (from injury and pathogens)
18
Q
Lymphocytes, Monocytes, and Macrophages are a type of (1), which are all types of (2).
A
- Agranulocytes
- Leukocytes
19
Q
What are the key characteristics of Neutrophils?
i.e. morphology, stain, and function
A
- Morphology: segmented nucleus with 2-5 lobes
- Stain: cytoplasmic granules stain slightly pink
- Function: immunity (early first responders to infections, and phagocytose ~5-20 bacteria during their short lifespan)
20
Q
What are the key characteristics of Basophils & Mast Cells?
i.e. morphology, stain, abundance and function
A
- Morphology: lobed nucleus
- Stain: cytoplasmic granules stain blue in hematoxylin dye
- Abundance: most abundant leukocyte (make up 54-62% of white blood cells)
- Function: inflammatory reactions & allergies (release anticoagulant heparin to slow blood clotting, and histamine to increasing blood flow to tissues)
21
Q
What are the key characteristics of Eosinophils?
i.e. morphology, stain, abundance and function
A
- Morphology: bilobed nucleus
- Stain: cytoplasmic granules stain bright red
- Abundance: make up ~1.3% of white blood cells
- Function: defence against parasites (in GI tract, lungs, urinary & genital epithelia – attach to large, antibody-coated parasites & release substances from granules to damage/kill)
22
Q
What are the key characteristics of Monocytes & Macrophages?
i.e. morphology, abundance and function
A
- Morphology: 2-3 times larger than RBCs
- Abundance: make up ~3-9% of white blood cells
- Function: phagocytic (primary tissue scavengers that are larger & more effective than neutrophils – ingest 100 bacteria per lifetime and remove debris such as old RBCs & dead neutrophils)
23
Q
What are the key characteristics of Lymphocytes?
i.e. morphology, abundance and function
A
- Morphology: only slightly larger than RBCs
-
Abundance: make up ~25-33% of white blood cells (~5% are circulating while the rest are in tissues encountering
pathogens) - Function: Immune response (Natural killer [NK] cells, T lymphocytes [T cells], B lymphocytes [B cells])
24
Q
What is hematopoiesis?
A
Formation of blood cells
25
Where do hematopoietic stem cells originate?
embryo
26
What is the major hematopoietic organ after birth
bone marrow
27
Which are the most abundant blood cells?
Red blood cells
28
What is found after centrifugation of the blood and where are they found in the tube?
* **RBCs** packed at the bottom
* **WBC, platelets** in the middle
* **Plasma fluid** at the very top
29
What is erythropoiesis?
* when uncommitted stem cells go through a series of stages in the bone marrow
* once the nucleus is expressed, the reticulocyte forms and the cell is released into the circulation where it becomes a mature RBC (erythrocyte)
* one the nucleus is expelled, the reticulocyte moves into circulation and becomes an RBC
30
Where are basophils found?
in circulation in low numbers (make up <1% of
WBC)
31
Where are mast cells found?
in tissues
32
33
What is the most abundant leukocyte?
neutrophils (make up 54-62% of
white blood cells)
34
What is the shape of erythrocytes?
* cytoskeleton creates a **concave shape**
* **flexible** - swell in hypotonic, shrink in hypertonic
* **illnesses can impact RBC shape** ie: sickle cell anemia
35
What are the steps of Neutrophil Extravasation?
1. Roll along endothelial wall
2. Are tethered, captured, & activated
3. Crawl to exit sites (endothelial cell junctions)
4. Exit sites open due to signals between leukocytes & endothelial cells
36
How is most O2 found in the blood?
bound to hemoglobin in RBCs
37
What gives blood its red colour?
hemoglobin
38
What is an RBC made up of?
* **4 globin proteins** (2 alpha, 2 beta)
* each globin protein has a **heme group binding an iron molecule**
39
What is the function of hemoglobin?
* aids in O2 delivery to tissues
* Heme iron combines with O2 in the lungs and releases oxygen into tissue
40
What is the equation for the arterial O2 carrying capacity in the blood?
O2 bound to Hb + unbound
41
How many molecules of oxygen can each RBC carry?
**over a billion** (280 million Hb molecules / RBC x 4 heme groups)
42
What does oxygen saturation depend on?
location
43
What percentage of hemoglobin is saturated with oxygen (oxyhemoglobin) in the systemic arteries? Leaving in systemic veins?
97% ; 75% (ie: 22% of oxygen is unloaded to tissues
44
From a volume perspective, how much O2 does blood entering and leaving tissues contain?
200mL O2/L blood ; 155mL O2/L blood (ie: 45mL O2 unloaded to the tissues)
45
What physiological factors can change Hb conformation and impact O binding?
* **Decrease in pH decreases affinity for O2** - more O2 offloaded into tissues
* **Increase in temp. decreases Hb affinity for O2** - more offloaded into tissues - bond between O2 and Hb is weakened
46
Where are monocytes found?
found in the bloodstream
47
Where are macrophages found?
in tissues
48
monocytes are precursors for...
**macrophages** (monocytes enlarge & differentiate into macrophages during their 8 hour commute from blood to tissue)
49
Tissue macrophages in the liver were originally called...
Kupfer cells
50
Tissue macrophages in the bone were originally called...
Osteoclasts
51
Tissue macrophages in the brain were originally called...
Microglia
52
Tissue macrophages in the spleen were originally called...
Reticuloendothelial cells
53
Tissue macrophages originally called...
the “reticuloendothelial
system”
54
Tissue macrophages in the skin were originally called...
Histiocytes
55
Tissue macrophages are currently reffered to as...
the “mononuclear phagocyte system”
56
What is the oxygen reserve?
* Oxyhemoglobin remaining in venous blood
* enough to sustain the brain and heart for 4-5mins without breathing or CPR
* can also be used when tissue requirements increase like in exercise
57
Natural killer (NK) cells are a part of which immune response?
2nd line of defense (Innate Immune System)
58
How do RBCs obtain energy?
anaerobic metabolism of glucose
59
T lymphocytes (T cells) are a part of which immune response?
3rd line of defense (Adaptive Immune System)
60
At a certain point in the glycolytic pathway for energy production for RBCs, a side reaction occurs that produces _______
2,3-Diphosphoglyceric acid (2,3-DPG)
61
B lymphocytes (B cells) are a part of which immune response?
3rd line of defense (Adaptive Immune System)
62
What is the function of Natural Killer (NK) Cells?
**Protect against viral infections & some cancers** *(can respond very quickly compared to other lymphocytes)*
- Destroy target cells (infected or cancerous but not
pathogens) by cell-cell contact
- Can release interferons (IFNs) & other cytokines to warn
uninfected cells
- Can release IFNs & other cytokines to enhance the immune response mediated by other cell types
63
What three organelles to mature RBCs lack?
nuclei, mitochondria, ER
64
What is 2,3-DPG inhibited by?
oxyhemoglobin ; when levels decrease, more 2,3-DPG is produced
65
What's an antigen?
a molecule, often on the surface of a pathogen, that the
immune system recognizes as a specific threat
66
What does increased 2,3-DPG concentration do?
increase O2 unloading
67
What's a MHC marker?
- **Used primarily in the recognition of pathogens in immune responses but also used in self recognition**
- Proteins expressed on the surface of a cell
- Display both self & non-self antigens
68
What are the types of MHC markers (2), and where are they found?
- **MHC-I:** found on the cell surface of all nucleated cells in the bodies of vertebrates
- **MHC-II:** found mostly on macrophages, B cells, & dendritic cells (APCs)
69
which way does a **decrease** in O2 unloading shift the Oxygen-hemoglobin dissociation curve?
Left
70
Which way does an **increase** in O2 unloading shift the Oxygen-hemoglobin dissociation curve?
right
71
Where does Initial “priming” of a lymphocytes to a antigen occur?
inside the lymph tissues (such as spleen, lymph nodes, tonsils, gut)
72
How long does it take RBCs to develop?
7 days
73
How long is the RBC lifespan?
120 days
74
What happens when old RBCs are destroyed in the spleen?
**Bilirubin produced when old RBCs are destroyed in the spleen**:
* breakdown product of heme from Hb
* liver enzymes bind bilirubin and it is excreted into bile
* phototherapy can also aid in breakdown
* circulates in bile, some lost in urine/feces
75
What are the steps of T Cell Activation?
**Step 1: Threat**
- An invader enters the body
**Step 2: Detection**
- A macrophage encounters, engulfs, & digests the invader (e.g. a bacterium)
- The macrophage places a piece of the invader (antigen) on its surface with the self (MHC) marker
**Step 3: Alert**
- The macrophage presents the antigen to a helper T cell & secretes a chemical that activates the helper T cell
- Complex set of signals to activate helper T cell (recognition + verification to ensure it’s responding to non-self)
- Helper T cell divides & transforms into effector helper T cell
**Step 4: Alarm**
- Effector helper T cell activates *Cell-mediated (T cell) response*, (Naïve cytotoxic T cell activated) and *Antibody mediated/humoral (B cell) response* (Naïve B cell activated)
## Footnote
*there more more steps dependent on which cells are activated..more cards in in the deck depicting those pathways*
76
What health consequence is associated with high blood concentrations of bilirubin from death of RBC (hyperbilirubinemia)
Jaundice
77
How is jaundice treated?
phototherapy with blue light
78
What population is susceptible to jaundice as discussed in the lecture slides?
* healthy newborns - rapid decrease in blood Hb at birth
* Preemies - inadequate amounts of liver enzymes needed to bind bilirubin so that it can be excreted in bile (toxic)
79
What is Thalassemia?
* inherited defect in Hb
* **Alpha thalassemia**: decreased synthesis of alpha Hb chains
* **Beta thalassemia**: impaired synthesis of beta Hb chains
* excessive destruction of RBCs
* leads to stillbirth, anemia, growth abnormalities, iron overload (heart failure in young adults)
80
What are the steps of a Cell-Mediated (T-cell) Response?
**Step 1: Building specific defenses**
- Naïve cytotoxic T cell divides into effector cytotoxic T cell (Step 2: Defense), & memory cytotoxic T cell (Step 3: Continued surveillance)
**Step 2: Defense**
- Effector cytotoxic T (CD8) cells targets cells displaying foreign antigen (tissue cells infected with intracellular pathogen, cancer cells, cells of organ transplants, etc.)
- Bind to MHC-I & kill infected cells by chemical means (perforin forms pores in target cell → granzymes enter pores → target cell apoptosis)
**Step 3: Continued Surveillance**
- Memory T cells stored for continued surveillance
81
What is sickle cell anemia?
* inherrited, recessive disease - 2 copies of a gene that produces **Hb-S** instead of **Hb-A**
* single amino acid substitute in beta globin chain
* when **deoxygenated**, Hb-S polymerizes into long fibres (RBC gets sickle-shaped) which promotes hemolysis
* lifelong, 45 year life expectancy
* high resistance to malaria because of plasmodium parasite - cannot live in heterozygous RBCs (therefore, there is a heterozygous environmental advantage)
82
What are the steps of a Antibody & cell-mediated response?
**Step 5: Building specific defenses**
- Naïve B cell divides into plasma cell (effector B cell; Step 2: Defense) & memory B cell (Step 3: Continued Surveillance)
**Step 6: Defense**
- Plasma cell (effector B cell) secretes antibodies which neutralize foreign proteins (toxins), trigger release of more complement, & attract more macrophages
- Antibodies attack the foreign antigens wherever they find them – circulation, tissues, etc. i.e. B cells themselves don’t engage
- Antibodies target pathogens or toxins outside of cells by binding to the specific antigen(s) that initiated prior events
**Step 7: Continued Surveillance**
- Memory B cells stored for continued surveillance
- When re-exposed to appropriate antigen, rapidly expand & produce more effector plasma cells & memory cells
83
What are the components of plasma?
* 92% water
* 1% dissolved solutes, trace elements (vitamins), gases (O2, CO2)
* 7% organic molecules (amino acids, glucose, lipids, nitrogenous waste, proteins)
84
What proteins are found in blood plasma?
* albumins
* globulins
* fibrinogen
85
What is albumin?
* produced in liver
* provide osmotic pressure needed to draw water from surrounding tissue fluid into capillaries (maintain blood vol + pressure)
* most of plasma proteins
86
What is the Clonal Selection Theory?
- Many B cells at birth but almost all of them are different
- B lymphocytes “inherit” ability to produce particular antibodies
- Any given B cell can produce only one type of antibody but they are “naïve”
- Exposure to their antigen stimulates B cell to divide many times until a large population of genetically identical B cell clones are produced
87
What happens during the secondary response?
- Lymphocyte clones & memory cells result in faster & stronger response
- Produces IgG antibodies
88
What happens during the primary response?
- First exposure to antigen
- Slower & weaker response
- Produces mostly IgM antibodies
89
What are globulins?
* alpha and beta
* produced in liver
* transport lipids and fat soluble vitamins
* gamma - antibodies produced by lymphocytes that function in immunity
90
What is fibrinogen?
* produced in the liver
* important for clot formation
91
What is agglutination?
clumping of RBCs
92
How does agglutination occur?
* A-type RBCs mixed with anti-A-type antibodies
* B-type RBCs mixed with anti-B-type antibodies
93
How do antibodies target pathogenic bacteria?
Does not destroy them, just **marks them as targets for
immunological attack** (pathogen may be attacked by innate immune cells, such as macrophages, neutrophils, or by complement (blood protein defense system)
94
What is the Rh factor?
another group of antigens on RBCs
95
is Rh+ or Rh- more common?
Rh+
96
What are the implications of the Rh factor during birth?
* Rh antibodies can cross the placenta (unlike A and B antibodies)
* Rh- mother and Rh+ baby might cause issues **during birth** (not during pregnancy because blood is seperated
* At birth, mother may start producing Rh antibodies
* during next pregnancy, antibodies can cross placenta and cause RBC hemolysis in fetus (hemolystic disease in newborns)
* **Treatment**: IV Rh imune globulin (RhIG) after brith of Rh+ baby to destroy fetal cells left in circulation before they elicit immune response
97
What is the The Complement Pathway?
- *9 complement proteins (C1-C9)* that are inactive in the plasma, and become activated when antibodies mark the antigens (bacteria)
- a type of both innate and adaptive humoral immunity
- when triggered, proteases cleave specific proteins & initiate an amplifying cascade followed by additional cleavages
**End result:**
**1. Massive amplification of response**
**2. Formation of cell-killing membrane attack complex (MAC)**
98
The Compliment Pathway has 3 possible routes that lead to the same outcome -- what are they?
**1. Classical pathway** (high level activity triggered by antibody)
**2. Alternative pathway** (low level, continuous activity)
**3. Lectin pathway** (high level activity triggered by antibody
99
What are the roles of the 9 protiens (C1-9) in the The Complement Pathway?
**1. Recognition:** C1
**2. Activation:** C4, C2, C3 *(in this order)*
**3. Attack:** C5, C6, C7, C8, C9
100
What are the three steps during blood clotting?
1. Vasoconstriction
2. Formation of platelet plug
3. Production of a web of fibrin proteins that penetrate and surround platelet plug
101
What proteins are involved in clot formation and what do they do?
fibrinogen is converted to fibrin by thrombin
102
How does the Classical Pathway begin (Complement Cascade)?
starts with antibodies & C1 proteins binding to the surface of the pathogen
103
How does the Lectin Pathway begin (Complement Cascade)?
starts with lectins binding to mannose residues on the surface of the pathogen
104
What are the two pathways for clot formation?
* **extrinsic** - in vivo
* **intrinsic** - in vitro
105
What is the extrinsic pathway for blood clotting initiated by?
**tissue factor**
* membrane glycoprotein
* in walls of blood vessels and cells of surrounding tissue
106
107
What happens during clot formation n the extrinsic pathway?
* initiation by tissue factor
* blood vessel injury exposes tissue factor to factor VII and others in the blood, creating a complex
* complex acts as an enzyme to activate factor X
* Pathway generates thrombin which can generate fibrin from fibrinogen
108
What are the steps of the The Complement Cascade?
**1.** Activation of C1 (classical pathway)
**2.** C1 catalyzes hydrolysis of C4 into C4a & C4b
**3.** C4b binds plasma membrane & is active
**4.** C3 cleaved into C3a & C3b due to intermediate step involving splitting of C2 -- alternative pathway also results in the cleavage of C3 through a different sequence of events (pathways converge at this point)
**5.** C3b converts C5 into C5a & C5b
**6.** C3a & C5a stimulate mast cells to release histamine, and serve as chemokines (attract macrophages, neutrophils, monocytes, & eosinophils)
**7.** C5, C6, C7, C8, & C9 inserted into bacterial cell membrane to form a membrane attack complex
109
What happens during blood clot dissolution?
plasminogen converted to plasmin which digests fibrin
110
How are myocardial infarctions, strokes and blood clots **initially** treated?
* chewable aspirin
* stops platelet clumping
* TPAs (tissue plasminogen activators)
111
What is the Membrane Attack Complex (MAC)?
Large pore that kills bacterial cell through
osmotic influx of water
112
What are the 4 key signs of inflammation? Describe the mechanisms behind them.
Injured tissue releases chemical signals causing...
**Blood vessels to widen:**
*1. Redness* – blood flow carries defensive cells & chemicals to damaged tissue, removing toxins
*2. Heat* – increases the metabolic rate of cells in the injured area to speed healing
**Capillaries to become more permeable:**
*3. Swelling* – fluid containing defensive chemicals, blood-clotting factors, oxygen, nutrients, & defensive cells seeps into injured area
*4. Pain* – hampers movement, allowing the injured area to heal
| 4 signs of inflammation: Redness, Heat, Swelling, Pain (treat w RICE)
113
What are ST elevated myocardial infarctions (STEMIs) and how are they treated?
* artery supplying blood to the heart becomes blocked - most severe type of heart attack
* fibrinolytic drugs can achieve reperfusion
* fibrinolytics convert plasminogen to plasmic which cleaves fibrin resulting in clot dissolution and restoration of blood flow to tissues
114
What is acute inflammation?
inflammation due to things such as bruises & torn tissue
115
What is chronic inflammation?
inflammation due to disease states such as
arthritis, obesity, etc.
116
What is the main cause of fevers?
infection
117
What are Autoimmune Diseases?
a failure of the immune system to
recognize & tolerate self-antigens
118
Explain 6 reasons why self-tolerance may fail
**1.** An antigen that does not normally circulate in the blood may become exposed to the immune system
**2.** A self-antigen that is otherwise tolerated may be altered by combining with a foreign hapten
**3.** Antibodies may be produced that are directed against other antibodies
**4.** Antibodies produced against foreign antigens may cross-react with self-antigens
**5.** Self-antigens may be presented to helper T cells together with MHCII
**6.** Autoimmune diseases may result when there is inadequate activity of regulatory (suppressor) T lymphocytes
119
What are the two things that can cause allergies? What are these two types of allergies called?
**1. Immediate hypersensitivity:** Abnormal responses by B cells
**2. Delayed hypersensitivity:** Abnormal responses by T cells
120
What happens during immediate hypersensitivity?
- Allergen stimulates Th2 cells to secrete IL4 & IL13 which stimulate plasma cells to secrete IgE antibodies instead of IgG
- Plasma cells bind to mast cells & basophils, stimulating them to release histamine & other cytokines (produces immune reaction i.e. trouble breathing, itching, sneezing, tearing up, runny nose, etc.)
| *Not allergic: allergen stimulates Th1 cells to secrete IFNg, IL2*
