Immune system Flashcards
what are the main functions of the circulatory system
- transportation
- all substances essential for cellular metabolism including RBCs, digestive and waste products - regulation
- hormonal and thermo - protection
- from injury (clotting) and pathogens (immune)
What are the constituents of blood
- plasma
- formed elements (includes RBCs and Buffy coat)
- RBCs are the most abundant blood cells
- buffy coat consists of WBCs and platelets
what are the types of WBCs
- neutrophils
- eosinophils
- basophils
- lymphocytes
- monocytes
what is hematopoiesis
the formation of blood cells from HSCs
- liver = major hematopoietic organ of the fetus
- bone marrow = major hematopoietic organ after birth
differentiation of progenitor HSC
- progenitor HSC either becomes a common myeloid progenitor or common lymphoid progenitor
- common lymphoid progenitor will further divide into lymphocytes
- common myeloid progenitor will further divide into all other blood cells
what is Erythropoiesis
- the production of RBCs in red bone marrow
- consists of stepwise differentiation of a progenitor cell - the erythroblast
- stimulated by the hormone erythropoietin
- during early stages the nucleus is expelled
pathway of erythropoiesis
erythroblast - normoblast - reticulocyte - erythrocyte
what is the significance of the nucleus being removed from erythrocytes
- RBCs rely on anaerobic glycolysis for ATP production
- they carry oxygen but we don’t want them to use it for energy since O2 has to reach other places
structure of hemeglobin
- 4 globulin proteins each with a heme group containing a Fe atom
- 2 alpha and 2 beta chains
- the Fe atom combines with oxygen in the lungs and releases oxygen in the tissues
Iron in hemegloblin
- each hemoglobin contains 4 iron atoms therefore can carry 4 O2
- the Fe atom in heme gets recycled from senescent RBCs by phagocytosis in the spleen and liver (hemolysis)
- this Fe travels in the blood to bone marrow attached to transferrin
- Fe can enter RBCs via receptor-mediated endocytosis
what is transferrin
- a protein carrier that transports molecules such as iron through the blood
what is leukopoiesis
- the formation of blood cells other than RBCs (so WBCs and platelets - leukocytes)
- uncommitted stem cells in the bone marrow give rise to these cells
how lymphocytes generated
- lymphoid progenitor cells (different that progenitor cells of other blood cells)
what do CDCs measure
- hematocrit: % total vol packed RBCs
- hemoglobin: O2 capacity of RBCs
- RBC count
- WBC count
what does blood plasma contain
- water ( ~92%)
- dissolved solutes
- trace elements
- gasses
- organic molecules (~7%)
what are the organic molecules found in blood plasma
Majority: plasma proteins (fibrinogen, globulins and albumins)
Minority: AAs, glucose, lipids, hormones, enzymes, etc.
what are albumins
- plasma protein (55-60%)
- provide the osmotic pressure needed to draw water from the interstitial fluid into capillaries
- help to transport hormones
What are globulins
- plasma protein
- alpha and beta transport lipids and fat-soluble vitamins
- gamma globulins are antibodies
what is fibrinogin
- plasma protein (least abundant)
- important for clot formation
which is the only plasma protein not produced in the liver and why
Gamma globulins
- since they are antibodies, they would respond to antigens in the liver (bad)
What is the compliment pathway
- a defence system of serum proteins to kill a pathogenic cell
what are the ways which pathogens can be attacked
- could be attacked by by innate immune cells (macrophages, neutrophils - OPSONIZATION)
- can be attacked by complement - a defence system of serum proteins
Basis of the complement pathway
- there are 9 complement proteins (C1-9) that are inactive in plasma
- they become activated by the attachment of antibodies to antigens (bacteria)
- specific to the invader
complement proteins can be subdivided into 3 categories…
- Recognition (C1)
- Activation (C4, 2 and 3)
- Attack (C5-9: complement fixation)
what is the common terminal reaction of all complement pathways
- generates the macromolecular membrane attack complex (MAC)
steps in the classical/lectin complement pathways
1.a) CLASSICAL is initiated by an antibody-antigen binding in the invading cells PM - activates C1
1.b) LECTIN is initiated when MBL binds mannose residues on the pathogen surface - activates C1-like
2. The C1(like) complex cleaves (activates) C4 and C2
3. active C4 and C2 bind to form C3 convertase
4. C3 convertase cleaves (activates) C3
5. active C3 binds to C3 convertase to form C5 convertase
6. C5 convertase cleaves (activates) C5
7. active C5 complexes with C6-9 to form the MAC
steps in the alternative compliment pathway
- spontaneous hydrolysis (cleavage) of C3 will allow C3b to bind to microbial surfaces
- Factor B will bind to the membrane-bound C3b
- Factor D will cleave (activate) Factor B, which leads to the formation of C3 convertase
- C3 convertase binds to active C3 to form C5 convertase
- the rest of the steps are the same as the classical path
what is the membrane attack complex (MAC)
- forms a pore inside the membrane of the pathogenic cell which allows fluid (water and Na+) to flow into it
- the cell will swell and lyse
how is the complement pathway innate (non-specific)
- it is ready to go and in the blood
how is the complement pathway adaptive (specific)
- specialized to pathogen (in the classical pathway antigen-antibody binding)
what happens to the complement fragments that don’t become fixed into the membrane?
- Chemotaxis: attract phagocytic cells (neutrophils, macrophages) to the site of complement activation
- Opsonization: form bridges between the phagocyte and victim cell to facilitate phagocytosis
- Stimulation of histamine release: C3a and C5a (cleaved off parts) can stimulate the release of histamine from mast cells and basophils, leading to vasodilation and more phagocytes to site of action
what is the function of the immune system
protects against pathogens, bacteria, etc.
- recognizes self from non-self
what is the microbiome
- the overall collection of microbes that resides inside humans or on our skin surface
- plays critical roles in the training and development of the immune system
commensal vs symbiotic bacteria
commensal: we provide them nutrients but they don’t help us
symbiotic: we provide them nutrients and they help us with something in return
why are babies considered “microbe magnets”
for 2-3 years their microbiomes grow while their immune system develops
- have to learn how not to attack friendly bacteria
how can bacterial residents of the intestines influence influence neurons in the brain
- may infiltrate blood vessels for direct ride to the brain
- promote neuropod cells in the gut lining, stimulate the vagus nerve which connects to the brain
- indirectly activate enteroendocrine cells which send hormones throughout the body
- influence immune cells and inflammation which can affect the brain
shape of RBCs
- concave due to cytoskeleton
- flexible: swell in hypotonic medium and shrink in hypertonic medium
what is the total arterial O2 carrying capacity in the blood?
O2 bound to Hb + unbound O2
total = ~200mL O2/L blood
O2 saturation depends on location…
blood entering tissues: 200mL O2/L
blood leaving tissues: 155mL O2/L
- therefore, 45mL of O2 out of the 200mL is unloaded to the tissues
O2 saturation expressed in %…
- in systemic arteries 97% of Hb is in oxyhemoglobin form
- blood leaving the systemic veins has an oxyhemoglobin saturation of ~75%
- ~ 22% of the oxygen is unloaded to the tissues
the extent to which deoxyhemoglobin and hemoglobin exchange will happen depends on…
- the partial pressure of O2 of the environment
- the affinity (bond strength) between Hb and O2
- partially temperature as well
the oxyhemoglobin dissociation curve
- top of the curve shows arterial blood saturation
- Plato point shows how the % oxyhemoglobin decreases by ~22% as blood passes through the tissues from arteries to the veins
- the steepest point (from 0 and up) shows oxyhemoglobin that remains in venous blood (oxygen reserve) - doesn’t get exchanged unless emergency
how does pH affect the oxyhemoglobin dissociation curve
- changing Hb conformation may affect O2 binding affinity
- when pH decreases, decreased Hb affinity for O2
- dissociation curve shifts right
- allows skeletal muscles receive more O2 when active than at rest
how does temperature affect the oxyhemoglobin dissociation curve
- changing Hb conformation may affect O2 binding affinity
- when temperature increases, decreased Hb affinity for O2
- dissociation curve shifts right
- allows skeletal muscles receive more O2 when active than at rest
how does a decreased pH affect O2 unloading to tissues
- body pH changes with activity - muscle fibres produce lactic acid which releases H+
- [H+] increase causes blood acidity to rise and the affinity of Hb for O2 decreases and more O2 is unloaded to tissues
what is the Bohr effect
- a shift in the Hb saturation curve due to a pH change
- shoot right = greater unloading of oxygen in tissues
oxyhemoglobin dissociation curve axis labels
y axis = % oxyhemoglobin saturation
x axis = PO2 (mmHg)
how does increased temperature affect unloading onto tissues
- Hb’s affinity for O2 is decreased
- increasing the temperature weakens the bond between O2 and Hb allowing more to be unloaded to tissues
- curve shifts right
- similar effects to a decrease in pH
how do RBCs obtain energy through anaerobic metabolism of glucose
- during the glycolytic pathway, a side reaction occurs in the RBCs that result in the production of 2,3-DPG
how does low PO2 in RBCs (at high altitude) result in increased O2 unloading to tissues
- low PO2 = less oxyhemoglobin
- less inhibition of 2,3-DPG production
- increased 2,3-DPG
- lower affinity of hemoglobin for oxygen
- increased O2 unloading
DISSOCIATION CURVE SHIFTS RIGHT