The Literal Actual Worst (Blood and Immune)

Question 1

Volume of Blood in a Human Body/ Safe volume to lose

Answer 1

5L. 10000L passes through heart per day. Can lose 20% without dying.

Question 2

Structure: Artery

Answer 2

Small volume, but high rate of flow due to high pressure and small lumen. Pressure needed to move blood efficiently through capillary bed.
Has thick walls to prevent rupture due to pressure.

Question 3

Structure: Vein

Answer 3

Large volume but low rate of flow due to low pressure and large lumen. Valves present to prevent backflow of blood.

Question 4

Systolic/ diastolic Pressure

Answer 4

Blood pressure when ventricles are most contracted/ least contracted.

Question 5

Hypertension

Answer 5

When systolic pressure exceeds 140 mmHg- vessels are narrowed/ remain constricted.

Question 6

Erythroid

Answer 6

Carries oxygen using haemoglobin. Non-nucleated and without mitochondria. 5-6 million/mL.

Question 7

Lymphoid

Answer 7

Not to be confused the lymphoid subcategory which makes up the adaptive immune response. Secrete antibodies to bind to pathogens. Includes B/T lymphocytes
Other subcategory is myeloid, which makes up the innate immune response. Phagocytic and binds to antigens.

Question 8

Platelets

Answer 8

Non-nucleated cell fragments. Promote blood clotting when the vessel/ nearby tissue is damaged and mediates tissue repair.

Question 9

Albumins

Answer 9

Acts as a protein sponge to absorb excess fluid to maintain osmotic potential of blood. Binds to small molecules to transport them.
Smallest and most numerous blood protein.

Question 10

Fibrinogen

Answer 10

Protein that gets cleaved by thrombin to fibrin during blood clotting.

Question 11

Immunoglobins

Answer 11

Antibodies which bind to and disable pathogens.

Question 12

Complement protein

Answer 12

9 proteins that aid the innate immune system by coating/opsonising pathogens.

Question 13

Electrolytes

Answer 13

“What plants crave”
Soluble ions and minerals.
Ca2+/K+ regulate cellular activity/ potential.
Maintains isotonicity.

Question 14

Other things dissolved in blood

Answer 14

Lipids- In lipoproteins (cholesterol)
Soluble gases such as CO2 and O2.
Soluble waste such as urea
Vitamin, glucose, hormones.

Question 15

Blood separation

Answer 15

Packed red cells- 40%
Buffy coat- 10% (WBCs)
Plasma- Soluble components and platelets.

Question 16

Haematopoesis- Myeloid Lineage

Answer 16

Pluripotent stem cell with CD34+ antigen forms myeloid progenitor. Can specialise into erythrocytes, mast cells, megakaryocytes (forms platelets) and myeloblasts.
Myeloblasts can specialise into cells of the innate immune system.

Question 17

Haemtaopoesis- Lymphoid Lineage

Answer 17

CD34+ Stem cell forms lymphoid progenitor, which can specialise into a large granular lymphocyte (Natural Killer Cells) or small lymphocyte, which specialises into cells of the adaptive immune system (T lymphocyte and B lymphocyte/ plasma cell)

Question 18

Haematopoetic factors

Answer 18

Erythropoetin- Secreted by kidneys in adult and liver in newborns-stimulates red bone marrow to produce more RBCs.
GMC-SF/G-CSF: Binds to myeloid progenitors to stimulate the production of more NK cells and cells of the innate immune system.

Question 19

The Classical Complement Cascade

Answer 19

All of this occurs on the surface of the pathogen
C1 binds to antigens to form C1 complex and stimulates the release of a protease which splits C4 and C2 to form C4a/b and C2a/b.
C4b and C2a form C3 convertase, which converts C3 to C3a and C3b.
C3b combines with C2a or C4a to form C5 convertase to split C5 to C5a and C5b.
C3a, C4a and C5a are called anaphylatoxins, which bind to receptors on a macrophage and lead them to the pathogen by chemotaxis.
C3/C5 convertases permanently bind to the pathogen and they’re called opsonins, because they mark/opsonise pathogens for phagocytosis.
C5b combines with C6-10 to form a cylindrical membrane attack complex, which can lyse pathogens.

Question 20

The Coagulation Cascade

Answer 20

Can follow an intrinsic (contact with external environment) or extrinsic (tissue damage) pathways, both leading to the common pathway.
Intrinsic- factors XII, XI, IX and VIII activated.
Extrinsic- Tissue factor, factors V and VII activated.
Common- Factor X is activated, turning into Xa. Xa and V converts prothrombin to thrombin, which can start cleaving fibrinogen.
Thrombin is inhibited by heparin/warfarin etc (anticoagulating agents).

Question 21

Haemoglobin

Answer 21

Quaternary structure of two alpha and beta globins, each with a haem group-Fe atom that forms complexes to oxygen.
Haem group has higher affinity for CO and CN-causes blood to turn cherry red/pink.
Oxygen binds to Fe when pO2 is high (high affinity for oxygen), and then detaches when pO2 is low (lower affinity for oxygen). Similarly with CO2.

Question 22

Virus

Answer 22

Relies on host cells to replicate. Immune system must be able to recognise infected cells.

Question 23

Bacteria

Answer 23

Mostly extracellular except for Myobacterium tuberculosis in macrophages.
Gram positive: Thick peptidoglycan cell wall- cannot be lysed by MACs and must be phagocytosed.
Gram negative: Thin peptidoglycan cell wall- can be lysed by MACs.

Question 24

Protozoa

Answer 24

Multicellular pathogens too large to be phagocytosed. Killed by mediators secreted by myeloid cells.

Question 25

Extravasation of Neutrophils

Answer 25

• Activation: Chemokines such as C5a cause neutrophils in the blood to slow down near the site of infection. They are released by damaged tissue or endothelium undergoing an inflammatory response.
• Tethering: Carbohydrate antigens called Siayl Lewis X on the neutrophil form weak interactions with selectin proteins on the endothelial cells. Expression of proteins involved in this interaction is upregulated by chemokines.
• Adhesion: Once neutrophils reach the site of infection, integrins on the neutrophil undergo conformational change and bind to ICAM-1 on the endothelial cell. Neutrophil flattens in preparation for diapedesis.
• Diapedesis Neutrophils squeeze between endothelial cells to reach interstitial space.
• Chemotaxis: Neutrophils reach site of infection by moving down a chemical gradient.

Question 26

FcR-mediated Phagocytosis

Answer 26

Antibodies bind to the pathogen and activate the classical complement cascade to opsonise the pathogen and attract neutrophils by chemotaxis.
Antibodies have Fc regions which bind to receptors on neutrophils. Neutrophils extend pseudopods with these receptors on the end to bind to Fc regions and pull pathogens towards them.
Neutrophil surface membrane forms an invagination, where the pathogen will ‘fit’, and a phagosome will pinch off around it.
Phagosome fuses with lysosome for form phagolysosome. Pathogen is hydrolysed by acid and proteases
Remains of cell excreted by exocytosis.

Question 27

Molecular Pattern Recognition/ Example

Answer 27

Pathogens present Pathogen Associated Molecular Patterns (PAMPs). Toll-Like Receptors on Neutrophils can bind to these molecules and trigger an immune response.
Liposaccharide (on gram negative bacteria) is a pyrogen that binds to the TLR-4 and stimulates a strong immune response. Can lead to septic shock where blood pressure drops too low, so excess vasodilation starts to damage tissue.

Question 28

Immunoglobin Domain Structure

Answer 28

Beta-barrel.
Two antiparallel beta-pleated sheets joined at the centre by disulfide bridges and at the ends by polypeptide loops, which make up the antigen binding sites.
12.5 kD

Question 29

Antibody Structure

Answer 29

Made of two heavy chains (4 domains), each bonded to a light chain (2 domains).
Divided into Fab which is the antibody binding region, and the constant region Fc where complement binds to initiate innate immune response.
Fab includes the complementarity determining region, which are loops joining the light and heavy chains to form two identical antigen binding sites.

Question 30

Affinity and Avidity

Answer 30

Affinity: How strongly an antibody binding site binds to an antigen and its readiness to remain bound. Defined as when attractive forces overcome repulsion.
Can be quantified by the concentration at which 50% of antibodies form antigen-antibody complexes, or the time required to dissociate after moving away from equilibrium (dissociation constant).
Avidity: Many weaker affinity contacts combining to give a strong strong attraction (includes other factors though which we don’t need to know). High affinity as it is hard to break many bonds. Avidity increases exponentially with affinities.

Question 31

Function of Different Ig’s

Answer 31

IgM: Produced by all naive B-cells. Has 10 binding sites to increase avidity and 5 Fc sites for complement. Found also as B-cell receptors.
IgG: Produced by B-cells selected for by clonal selection. Activates complement and is highly soluble. Can pass through placenta.
IgA: Secreted at mucoous membranes. Passed on in colostrum.
IgD: Found as receptors on B-cells and in serum.
IgE: Binds to mast cells and involved in hypersensivity response.

Question 32

Recombination at the Ig Locus

Answer 32

Transposases (RAGs 1 and 2) responsible for moving fragments of DNA enclosed by restriction sequences around the gene. Genes for those only found in B and T cells.
Random edition of the base pairs before recombination is the greatest source of diversity in the recombination process.
Occurs at the locus coding for the joining loops with the Variable, Diversity and Joining regions.
A random D segment is moved next to a J segment by recombinase, deleting all DNA between the two segments. A random V segment is moved next to the DJ segment, and all DNA between them is deleted.
Recombination is highly imprecise and base pairs are easily gained/lost- increases variability.
The Ig locus for the light chain does not have the D segment.

Question 33

Affinity Maturation and Clonal Selection

Answer 33

STOCHASTIC GENE REARRANGEMENT forms many variations of B-cell receptors.
Initially, low affinity cognates bind to antigens and stimulate clonal selection (in lymph nodes) of the B-cell with that cognate.
Somatic hypermutations occur during B-cell division leading to increased affinity of antibodies- such as activation at lower antigen concentrations.
Mature B-cells produce high affinity IgGs.

Question 34

T-cell maturation

Answer 34

Occurs in Thymus. Originate from CD4+CD8+ thymocytes, which split into CD4 helper T cells and CD8 cytotoxic T cells. TcRs are formed similarly to B-cell receptors- gene rearrangement. During maturation, they are exposed to self MHC/HLA. Those with too little affinity will be neglected (positive selection), while those with too much affinity will be actively killed (negative selection).

Question 35

Types of CD4+ Helper T-cells

Answer 35

Treg: Suppressives immune response.
Th1: Controls cell mediated immunity. Stimulates macrophage proliferation with GMSCF and cytotoxic T-cells.
Th2: Regulates humoral immunity and affects B-cells.
Th17: Regulates inflammation and attracts neutrophils and macrophages.

Question 36

HLA Classification

Answer 36

Divided into Type Is on normal somatic cells, and type II on antigen presenting leukocytes.
Many haplotypes of HLAs exist-each able to bind to a range of pathogenic polypeptides.
Type I: A, B, C
Type II: DR, DP, DQ
Codominant- every cell has 12 kinds of HLAs on surface.

Question 37

Roles of HLAs

Answer 37

Class I: Bind to and present viral polypeptides being produced in the cell. Cytotoxic T-cells can bind and trigger apoptosis if it recognises the HLA-antigen complex.
Class II: Binds to and presents parts of a phagocytosed pathogen. Helper T-cells will bind and, if it recognises the HLA-antigen complex, will release cytokines to stimulate proliferation of B-cells, macrophages and cytotoxic T-cells.

Question 38

Why is HLA polymorphism important?

Answer 38

Allows at least one individual in a population to be able to bind to viral poypeptides and generate an immune response.

Question 39

MHC restriction

Answer 39

TcRs only recognise an antigen when it is presented by a self HLA.
T-cells are selected by their ability to recognise and bind to self HLA.

Question 40

How was MHC restriction proven?

Answer 40

Cells were taken from mice which were congenic at every locus except the MHC locus. They were subject to the same virus and T-cells were extracted.
When T-cells from one mouse is exposed to infected cells from the other, there was no immune response.

Question 41

Type I Hypersensitivity

Answer 41

Involves overproduction of IgEs. Provide immunity against larger, more complex pathogens. by releasing IgEs to bind to Fc-E receptors on mast cells. When allergens bind to the IgE, histamine etc will be released.

Question 42

Type II Hypersensitivity

Answer 42

Uses the complement system. Binds to self antigens and causes phagocytosis of self cells/

Question 43

Type III Hypersensitivity

Answer 43

Accumulation of antigen-antibody complexes leading to inflammation and response by the adaptive immune system.

Question 44

Type IV Hypersensitivity

Answer 44

Adaptive immunity is exposed to antigen and undergoes clonal selection and B-cell maturation. Further exposure to antigen leads to secondary immune response

Question 45

Mechanism of Type I

Answer 45

Antigen presenting cell phagocytoses allergen and presents it to B-cell. B-cell secretes IgE, which binds to the Fc-E on Mast cells with very high affinity.
First exposure to allergen will lead to pre-coating of mast cells with IgEs against that allergen.
Allergen binds to IgE and leads to degranulation, where the mast cells splits and releases toxic contents such as histamine.

Question 46

Mechanism of Type II

Rhesus Example

Answer 46

Mother and foetus has different RhD.
Foetal red blood cells enter maternal blood stream. Adaptive immune system recognises foetal RhD as nonself and undergoes clonal selection to produce B-cells with antibodies complementary to the RhD-.
Antibodies cross placenta and opsonise RBCs in the foetus, causing haemolytic anaemia as they are lysed by macrophages.
Occurs from second pregnancy onward as there is a secondary response.

Question 47

Desensitisation treatment

Answer 47

Slow introduction of small but increasing amounts of antigen.
Stimulates clonal selection of B-cells for that antigen and production of IgG as a competitive inhibitor of IgE.

Question 48

Adv and Disadv of Monoclonal Antibodies

Answer 48

Advantages
Both the target antigen and the binding affinity can be controlled and specified. No off-target effects.
Can be humanised so they stay in the body for prolonged periods of time. Since they are normally found in the body there are no adverse reactions.
Can be modified to be bi-specific ie: able to bind to different antigens with each ‘arm’
Disadvantages
Difficult and expensive to produce commercially.
Side effects present and can be serious.

Question 49

HLA Structure

Answer 49

Class I: Two alpha chains forming a protein binding cleft using the variable region.
Class II: An alpha and beta polypeptide combining to form the protein binding cleft using the variable region.