Blood and Immune Flashcards
1
Q
What are the three functions of blood?
A
Transportation, Regulation and Protection
2
Q
What are the two aspects of protection?
A
– Leakage control system: blood clotting -
– Immune system: surveillance circuit, white blood cells and antibody molecules.
3
Q
What does blood regulate?
A
temperature, pH, salinity.
4
Q
What does the blood transport?
A
oxygen, carbon dioxide, nutrients, heat, wastes, hormones.
5
Q
What are the main percentages of the blood?
A
55% plasma, 45% formed elements
6
Q
What makes up majority of formed elements?
A
RBCs
7
Q
What are the proportions of white blood cells?
A
70% neutrophils,
22% lymphocytes
8
Q
What are the proportions of plasma?
A
91.5% water
7% proteins
9
Q
What are the proportions of plasma proteins?
A
- albumins 54%
* globulins 38% (immunoglobulin = antibody molecule)
10
Q
Name the layers of a test tube of blood from most dense to least dense and floating on the top:
A
RBCs at bottom
thin buffy coat composed of WBCs and platelets
Plasma floating on top
11
Q
red blood cells are filled with the red protein
A
hemoglobin
12
Q
Describe structure of RBCs
A
RBCs are biconcave disk shaped cells, without nuclei or internal organelles
filled with the red protein hemoglobin, which binds oxygen
They have blood group antigens on their surface
They have an Fe2+ ion and a heme
13
Q
What is a RBCs average lifetime?
A
120 days
14
Q
Where do RBCs originate from?
A
Originate from myeloid stem cells in bone marrow - reticulocytes -
15
Q
Explain the protein structure of haemoglobin
A
Hemoglobin has 4 chains
2 identical alpha 141aa
and 2 identical beta 146aa
16
Q
Explain the protein structure of serum albumin
A
Serum Albumin has 585 amino acids in
a single chain
17
Q
Explain the protein structure of Immunoglobulin
A
Immunoglobulin has
4 chains HHLL
2 identical heavy ~434aa
2 identical light ~213aa
18
Q
How does O2 bind to haemoglobin?
A
4 amino acid chains each binds one O2 molecule, bound via an iron containing heme group.
19
Q
What is serum albumin?
A
Main protein component of plasma
20
Q
What is the role of serum albumin?
A
Serves as carrier for smaller molecules - eg. steroids, lipids, hormones, man-made drugs like aspirin etc.
21
Q
What is the role of Immunoglobulins?
A
Key molecules for the immune system.
Can bind to all kinds of bacterium
22
Q
What shape are antibody molecules?
A
Yshaped
23
Q
Where does antigen binding occur?
A
at the tips of the arms of the Y
24
Q
What is the diameter of RBCs?
A
8 micrometers
25
Why are RBCs red?
Because of the reddish Fe2+ ion
26
What is the accuracy of a micrometer?
accuracy about 10 microns
27
1 micron = x nanometers
1000 nano metre
28
1000 microns = x millimetre
1000 microns = 1 millimetre
29
```
Order from largest to smallest:
WBC
Virus
Pollen
Bacteria
RBC
```
Pollen, White Blood Cell, Red Blood cell, Bacteria, Virus
30
What is lysozyme's role?
Found in tears and kills bacteria
31
How many amino acids are found in lysozyme?
129 amin acids
32
O2 Blood concentration is
150mg/ml
33
O2 concentration within RBC is
340mg/ml
34
What is the concentration of serum albumin in the blood?
Concentration about 35mg/ml
35
What foreign molecules are bound to serum albumin and how many of them are present per protein molecule?
5 lipid molecules
36
What holds the heavy and light chains of the antibody molecule together?
COVALENT disulfide bonds
37
Are neutrophils granular or not granular?
granular (they have VISIBLE cytoplasmic granules)
38
Where are monocytes produced?
In the bone marrow
39
How long do monocytes circulate in the blood before migrating to capillary walls and into tissues to become macrophages?
5-8 days
40
Monocytes comprise about x% of total circulating blood leukocytes. What is x?
8%
41
What is the role of macrophages?
They can recognise more obvious features of commonly occurring infections, and can ingest and destroy infecting material
Macrophages can also can report infection to the centralised ‘immune memory’ system for future reference. by presenting or displaying the pathogen's antigen on its cell surface.
42
What does HIV infect?
HIV infects a major class of T lymphocytes called T helper cells
43
What does HIV reduce the T helper cell concentrations to?
down from normal levels of about 1000/microlitre to 200/ μL
44
Lymphocytes comprise about x% of total circulating blood leukocytes. What is x?
25%
45
What is the role of T helper cells?
processing and storing information from possible infections, and responding rapidly in the event an infection is detected that has occurred before i.e. has been previously stored ‘in memory’.
46
What are the two types of cells that T helper cells can instruct other cells to take action?
B lymphocytes, which make antibody molecules, and
cytotoxic T lymphocytes, which can kill target cells.
47
How many chains does serum albumin have?
1 chain
48
What is the secondary structure of serum albumin?
alpha helical
49
What is the secondary structure of immunoglobin?
beta pleated sheets
50
Label the antibody diagram in your lecture guide
do it
51
What is an epitope?
the part of an antigen molecule to which an antibody attaches itself.
52
How much blood is in the human body? give a percentage
8% (roughly 5L for average 70kg male)
53
How much blood is in the human foetus?
300mL
54
What does the rhino virus cause?
the flu
55
1 Å =
1 bond length
| 1 × 10-10 meters (m) or 0.1 nanometer (nm).
56
As an Å (angstrom) is less than the wavelength of light and we can't use a light microscope to look at the structure of DNA and haemoglobin what is used to do so?
Xray crystallography
57
How does the lysozyme work?
targets carbohydrates on the surface of bacteria and viruses and is a non specific immune defines
58
What is the secondary structure of lysozyme?
alpha helical
59
Is the adult and metal Hb the same?
no
60
What is the secondary structure of Hb?
mostly alpha helical
61
How many folds in the immunoglobulin molecule?
12 folds
62
Where do all leukocytes and erythrocytes originate from?
Hematopoietic cells
63
What is the immune system repertoire?
The immune system memory bank of all possible foreign molecules of different molecules like antibodies.
64
Are neutrophils specific or non-specific defines?
They are non specific since they simply recognise all bacteria and engulf them by phagocytosis, then DIE
65
Which lymphocytes make antibodies?
B lymphocytes
66
Where are majority of the lymphocytes found?
in the lymph nodes
67
Lymphatic systems have lymph valves why?
Because the lymphatic system (unlike the cardiovascular system) does not have a pump, and needs a way to prevent back flow.
68
What are the phagocytes?
neutrophils, macrophages and B-cells ingest foreign cells and destroy them
69
What is the role of cytotoxic T-cells?
They destroy other cells e.g. cells infected by viruses.
70
What is the complement attack?
Antibodies bind, then complement proteins will also bind and cause pores in the cell membrane to undergo lysis and release its contents.
71
Explain neutralisation in terms of antibodies
Antibodies surround and attach to bacteria and viruses making sure it cannot attack a cell, then phagocytes can recognise these antibodies and surround the pathogen and kill it
72
How does antibodies cause cell lysis?
They bind to cell membrane of host cell and cause channels to open which kill the cell by letting out the contents of the cell.
73
Where is antibody memory stored in the body?
In lymph nodes.
74
Role of B cells
make antibodies
75
What are the two types of T-cells
T-helper cells and T-cytotoxic cells
76
How many litres of blood (called lymph) leave capillaries and enter tissues per day?
3L/day for average 70kg male containing 5L of blood
77
Where are most T lymphocytes located?
spleen and lymph nodes
78
What triggers swelling to occur at the site of infection?
triggered by tissue damage and caused by local opening of capillary walls.
79
Explain the immediate inflammatory response.
Some of the antibody molecules in the lymph fluid accumulating at the infection site may bind to pathogen.
Increased numbers of macrophages arrive at the infection site engulf and destroy bacteria, possibly recognising them because they are tagged with bound antibody molecules.
In addition B cells carrying bound antibody molecules flow by the infection site. If a B cell with the right specific bound antibody arrives (i.e. an antibody that binds bacterial protein), it can also recognise, engulf and destroy bacteria.
80
WHAT HAPENS AFTER Macrophages and B cells that have engulfed and digested bacteria?
They carry pieces of bacterial proteins attached to special molecules on the cell surface, in effect advertising a successful kill!
81
Explain Specific Helper T Cell Activation
Macrophages in lymph flowing back from the infection site will pass through lymph nodes on the circuit back to the blood stream.
Some lymph nodes on the return route will have small numbers of T cells specific for bacterial antigens, mixed together with vast numbers of T cells which are specific for other unrelated antigens.
When a macrophage carrying a piece of bacterial protein (‘presenting a peptide antigen’) finally finds the right specific T cell, that T cell is stimulated to divide, forming a clone of similar T cells all with the same specificity (called clonal expansion).
These cells, called helper T cells, can assist other cells to produce more antibody molecules
They can also stimulate the formation of cells which can specifically destroy other cells, which are either foreign, or which contain viruses.
82
Explain Specific B Cell Activation
B cells circulate in lymph and amongst these will be a few bacteria specific B cells from the infection site that have engulfed bacteria and are now presenting bacterial peptide antigens.
If one of these ‘successful killers’ finds the right specific helper T cell in a lymph node, the T cell triggers (i.e. ‘helps’) the B cell to differentiate and divide forming an activated B cell clone which produces large amounts of anti-bacterial antibodies
83
Explain B Cell Clonal Expansion
This is a delayed, and much more effective and specific response.
At this point, 7 to 14 days after the initial infection, there is now a much more effective amplified immune response.
Lymph nodes may be swollen and contain B cell clones producing huge amounts of specific antibacterial antibodies.
T cell clones have also grown in lymph nodes, and these can stimulate the development of still more antibacterial B cells.
All bacteria are eventually tagged with antibody molecules and destroyed by macrophages or B cells and the infection is cleared.
84
Explain the Memory Update step
The infection leaves its mark in the lymph nodes, where specific anti-bacterial T cell and B cell clones remain, ready to respond to future infections.
Increased levels of specific bacterial antibodies may also remain in the blood stream.
85
Explain why the second response to a previously encountered infection is much more faster and efficient:
There may be still increased levels of antibody in blood, so that initial recognition of a new infection is more likely, and happens sooner before the infection spreads.
In addition, there are now large clones of specific anti- bacterial B cell and T cell clones in lymph nodes, so that ‘memory alerts’ occur more rapidly and amplification happens more quickly.
86
Lymphocytes make up x% of the human body mass. What is x?
2% approximately 1.2L
87
What liquid flows through the lymphatic capillaries?
interstitial fluid.
88
Is the lymphatic system symmetrical?
No
89
What are the immune response steps?
```
Immediate inflammatory response
specific helper T-cell activation
B-cell activation
B-cell clonal expansion
Memory update
```
90
Are neutrophils antigen presenting cells?
no
91
What cells are antigen presenting cells?
macrophages and B-lymphocytes
92
What are MHC-II self antigens?
They are antigens of macrophages and B-lymphocytes that display proteins of the pathogen
93
Why is HIV a retrovirus?
Because it contains reverse transcriptase, in which the RNA is converted to DNA and incorporated into the genome of the infected cell during the viral replication cycle.
94
What is the diameter of the HIV virus?
100nm
95
Describe the outer coating of the HIV virus
HIV is surrounded by a lipid bilayer containing the surface proteins.
96
In the virus there are two copies of the _____ nucleotide RNA genome which includes __ genes that encode __ proteins.
In the particle there are two copies of the 9749 nucleotide RNA genome which includes 9 genes that encode 19 proteins.
97
The surface of the virus consists of closely packed ___________ molecules, each made of three copies of each of _____ and _____.
The surface of the virus consists of closely packed glycoprotein molecules, each made of three copies of each of gp120 and gp41.
98
How are gp120 and gp41 made?
These two proteins are made by proteolysis of the env gene product (proteolysis is why 9 genes can encode 15 proteins).
99
Explain HIV viral entry into the cell:
gp120 binds to a lymphocyte surface protein CD4. The CD4-gp120 complex then binds other cell surface molecules and somehow gp41 then allows the virus to enter the cell.
100
What type of cells does HIV destroy?
HIV destroys CD4+ immune system cells including helper T cells and macrophages, and eventually stops the development of immune responses by eliminating helper T cells (these are required for the ‘memory alert 1’ step).
101
Explain how reverse transcriptase works in HIV
After entry into the cell, reverse transcriptase molecules from the virus particle convert the single stranded RNA genome into double stranded DNA, which is then incorporated into the host cell genome by another viral protein, the integrase.
102
What are useful AIDS drugs?
Proteinase inhibitors taken together with reverse transcriptase inhibitors are the basis of current AIDS therapy.
103
What is proteinase and how does it work?
Many viral proteins are made from larger gene products (e.g. gp120 and gp41 are made from the env ‘polyprotein’ product) by proteolysis. The virus carries a specific small 99 amino acid proteinase to cleave polyproteins.
104
Explain how HIV causes AIDs
After infection a normal antiviral immune response occurs.
Antibodies against the viral surface proteins are produced in large numbers and tag virus particles for destruction by macrophages etc.
Another type of immune response – the cell-mediated response – also occurs, removing virus hidden in cells by eliminating cells infected with virus. These cells are tagged for destruction because they advertise pieces of virus proteins on surface MHC molecules, just like antigen presenting cells (APCs).
The result of this normal immune response is that nearly all HIV is removed from the system.
However, some HIV DNA can remain incorporated into host cell DNA, without producing proteins that would alert the immune system.
105
Hows does HIV spread throughout T cells?
When infected T helper cells are activated, incorporated HIV DNA is transcribed, producing new infectious HIV particles whenever an immune response occurs.
Even though new virus-free T cells and macrophages are continually produced from bone marrow, the chronic infection eventually predominates and the number of CD4 T cells drops to a dangerous level.
106
When does AIDS occur?
AIDS occurs when the level of helper T cells concentration falls to less than 20% of normal.
107
How is HIV transmitted?
via body fluids - milk, semen, and blood
108
When do HIV symptoms become obvious?
5-10 years after infection
109
When was HIV first identified?
1979
110
Where did HIV originate from?
Africa
111
What proportion of babies have been infected with HIV via breast milk?
10%
112
How have governments attempted to reduce the spread of HIV?
o education to overcome political discrimination and social prejudice about sexual and drug issues,
o promotion of safe-sex
o condom usage,
o HIV testing
o the distribution of drugs that slow the progression of the disease.
113
Label a diagram of the HIV virus
do it
114
What are the three polyproteins in HIV genome?
gag
pol
env
115
How are polyproteins made into proteins?
They are cleaved by proteinase into their constituent proteins.
116
Explain the interaction of gp41 and gp120
gp41 and p120 are joined
| gp41 is the stalk of the mushroom and the donut is gp120
117
Why do viruses mutate very fast? and why do people that are HIV + have many strains of HIV?
Reverse transcriptase makes a lot of error as it does not check for mistakes meaning there are many strains of HIV in one single person.
118
What happens to the relative antibody concentration of HIV antibody once infected by HIV?
Antibody concentrations remain constant and high in blood and once enough T helper cells decrease so does the antibody cocentartion in blood. This is a sign of the onset of AIDS.
119
What happens to the relative HIV concentration of HIV antibody once infected by HIV?
Upon infection HIV rapidly increases, then dramatically decreases, since they are killed off by the immune system. However some incorporate themselves into the host genome and hide for a few years. Therefore the HIV concentration slowly increases over the years and eventually reaches a similar concentration to the original value upon initial infection.
120
How do some people who are HIV + don't get AIDS?
Their B-cells make antibodies that neutralise almost all known HIV strains.
121
What is the difference between
| Innate Immune and Adaptive Immune?
Innate we already know how to kill it vs adaptive includes memory cells
122
What is the difference between Humoral and cellular?
Humoral is just blood components - e.g. antibodies, complement system cellular is anything including a cell killing another cell.
123
Why is HIV called a lentivirus?
Because it acts ten years later of onset
124
draw the HIV graph!!
do it
125
What does HAART stand for?
Highly active antiretroviral therapy
126
What are the Enzymes to target for HIV treatment?
* Reverse transcriptase (ssRNA —> dsDNA) AZT inhibits this
* Integrase (incorporates viral DNA into cellular DNA)
* Proteinase (99 amino acid, 9 genes —> 15 gene products
127
Explain the Myeloid lineage
```
Myeloid cell forms into
• Mast cell
• Monocyte (this is considered a white blood cell) (which become macrophages and osteoclasts (breaks down bone))
Macrophage is NOT a white blood cell
• Neutrophil
• Basophil
• Eosinophil
```
128
Explain the Lymphoid lineage
T-cells and B-cells (these contain the immune repertoire)
| these only include the cells that are part of the adaptive immunity
129
What are the granulocytes?
* Basophils
* Eosinophils
* Neutrophils
130
What are the Agranulocytes?
* Mast Cells
* Monocytes
* Lymphocytes
131
What do B cells produce?
Plasma cells and Memory cells
132
What do T cells produce?
Helper T cells (often referred to as CD4) and Cytotoxic T cells (often referred to as CD8)
133
What are the 3 Antibody Mechanisms?
✦ Neutralisation - antibodies stick all around the pathogen’s antigens, blocking cell surface receptors and prevent the pathogen to binding to host cell’s surfaces.
✦ Agglutination - Circular mass of antibodies forms
✦ Precipitation - occurs with soluble (polar molecules as we are made up of water) molecules (e.g. toxins). Chains of antibodies prevents toxins from being soluble and causes it to precipitate and ‘fall out of the solution’.
