Block 4 - The Immune System Flashcards
1
Q
How many litres of blood are there in the body?
How many litres can you lose and still recover?
A
4-6 litres
1-1.5 litres
2
Q
What percentage of the blood is liquid and cells?
A
55% plasma liquid
45% cells (99% RBC, 1% WBC and platelets)
3
Q
What is serum?
A
Plasma with clotting factors
4
Q
Is straw coloured plasma clotted or not clotted?
A
NOT clotted
5
Q
How does the bone marrow control production of blood cells?
A
Stromal cells and 3D mesh
6
Q
What is the beginning of the haematopoesis lineage?
A
Haematopoetic stem cell –> Multipotent progenitor –> Common myeloid progenitor OR common lymphoid progenitor
7
Q
What does the myeloid lineage give rise to?
A
Erythrocytes, Megakaryocyte, Thrombocytes
Mast cells, Basophils, Neutrophils, Eosinophils, Monocytes, Macrophages, Dendritic cells
PHAGOCYTES
8
Q
What does the lymphoid lineage give rise to?
A
Dendritic, Natural killer, B lymphocyte, T lymphocyte
LYMPHOCYTES
9
Q
What controls the production of: Erythrocytes Platelets Immune cells of the myeloid lineage Immune cells of the lymphoid lineage
A
Erythrocytes: EPO
Platelets: TPO
Immune cells of the myeloid lineage: Granulocyte Colony Stimulating Factor
Immune cells of the lymphoid lineage: Interleukins
10
Q
How is the porphyrin ring of Hb excreted?
A
Bilirubin
11
Q
What does hypoxia lead to?
A
Kidneys increase EPO
12
Q
How does EPO increase the production of erythrocytes?
A
It binds to erythropoetin kinase linked receptors on progenitor cells
13
Q
Erythrocyte production flow chart (8)
What is special about the nucleus in RBC?
A
Haemocytoblast (stem cell) –> Proerythroblast (committed cell) –> Erythroblast –> Nomoblast –> Reticulocyte –> Erythrocyte
When the cell is a nomoblast the NUCLEUS IS EJECTED
14
Q
What do platelets secrete?
A
Platelet derived growth factor
15
Q
Where is TPO produced?
A
Kidney and liver
16
Q
How are plaelets produced (lineage - 4)
What type of mechanism is used to produce platelets - what does this allow to occur?
A
Myeloid stem cell –> Megakaryoblast –> Megakaryocyte –> Platelet
‘Budding off mechanism’ - proliferation
17
Q
What are neutrophils involved in? What is their lifespan?
A
Phagocytosis and inflammation
1-2 days
18
Q
What are eosinophils involved in? What is their lifespan?
A
Phagocytose and helminths
2-5 days
19
Q
What are basophils involved in? What is their lifespan?
A
Allergies
1-2 days
20
Q
What are monocytes involved in? What is their lifespan?
A
Phagocytes and turn into macrophages
1-7 days
21
Q
What are natural killer cells involved in? What is their lifespan?
A
Kills viruses
14 days
22
Q
Define leukocyte
A
White blood cell
23
Q
2 types of lymphocytes
Characteristics (4)
Lifespan?
A
B and T cells
Small, large nucleus, different markers, many subdivisions
Weeks - years
24
Q
What does the haematocrit test do?
A
Measures the proportions of centrifuged blood to see if anything is wrong
25
How are WBC levels measured?
Flow cytometry
26
What type of disorder is myelofibrosis?
What happens during it?
What is it caused by?
Myeloproliferate disorder
Increased WBC and platelets, decreased RBC
JAK2 mutation
27
What type of disorder is polycythaemia vera?
What is another name for it?
What happens during it?
What is it caused by?
Myeloproliferate disorder
Primary polycythaemia
Increased levels of all blood cells
JAK2 mutation
28
What type of disorder is essential thrombocythaemia?
What is another name for it?
What happens during it?
What is it caused by?
Myeloproliferate disorder
Secondary polycythaemia
Increased platelets, other cells normal
JAK2 mutation
29
Three treatments for polycythaemia
Aspirin
Venesection (removal of blood)
Chemotherapy (to decrease the speed of proliferation)
30
Explain what JAK2 does normally and what changes when it gets mutated?
What can it be used to diagnose and treat?
A signalling receptor that acts downstream of EPO receptors
Activates receptors without EPO by phosphorylation causing excessive proliferation of erthyroid, myeloid and megakaryocyte cells
Polycythaemia vera
31
What are the ABO antigens?
| What
Carbohydrate structures on glycoproteins/lipids of RBC
32
What are the main carriers of the ABO antigens?
N-glycosylated glycoproteins, anion exchanger (band 3) and glucose transporter (GLUT1)
33
What do the ABO genes code for and what does this gene do?
| What is the difference between the enzyme for A, B and O
The enzyme glucosyl-transferase which adds the carbohydrate chain to the cells
A: N-acetylgalactosaminyltransferase
B: Galactosyltransferase
C: No transferase
34
What are the 5 rhesus antigens and the 2 genes that encode them
Antigens: D,C,E,c,e
Genes: RHD, RHCE
35
What is kernicterus?
A complication of severe jaundice which can cause brain damage/deafness
36
What happens during Anti-D therapy
The mother is given a drug which binds to the rhesus antigens on the baby's cells, preventing the formation of antibodies
37
What is pallor?
What is tachycardia?
What is glossitis?
What is koliohychia?
What are these all signs of?
Pallor: Lack of red in the eye
Tachycardia: Increased pulse
Glossitis: Swollen and painful tongue
Koliohychia: Spoon nail due to iron deficiency
Anaemia
38
10 symptoms of anaemia
| Which ones are severe?
Weakness, tiredness, shortness of breath, confusion, thirst
| Severe: Jaundice, enlarged liver and spleen, angina, fever, cardiac faliure
39
What are the types of anaemia
Microcytic: Iron-deficiency, Sideroblastic, Thalassemias
Normocytic: Haemolytic, Bone marrow disorders, Trauma, Changes in RBC number
Macrocytic: Vitamin deficiency, Reticulocytosis
40
What is the difference between the multipotential and erythroid stage of RBC development?
Multipotential: Forms the progenitors and regulated by stem cell cytokines in the bone marrow
Erythroid: Forms the red blood cells and regulated by EPO in the bone marrow and blood
41
What is pure red cell aplasia?
Conditions that affect erythropoesis in the bone marrow
42
What is pancytopenia?
| Example
Conditions that affect other cells (e.g. WBC and platelets)
| Virus attacks stem cells, stopping their ability to self-renew
43
What is haemolytic anaemia?
When RBC are destroyed prematurely
44
What is allo-immune haemolysis?
Example
What type of anaemia is it?
When the immune system attacks foreign erythrocytes (e.g. rhesus disease)
Haemolytic
45
What is auto-immune haemolysis?
What is it usually a result of? (2)
What type of anaemia is it?
When the immune system attacks your own erythrocytes
Usually as the result of an illness/ idipoathic
Haemolytic
46
What are microspherocytes?
Smaller erythrocytes
47
What type of condition is sickle cell?
| What is is caused by?
Autosomal co-dominant
| Mutation in the beta globulin gene
48
What four molecules regulate RBC production and haem metabolism?
Fe, B12, B6, folate
49
What 4 things make it hard to absorb iron?
Tea, coffee, calcium and PPI's
50
What happens during sideroblastic anaemia?
| What are the resulting cells called?
Haem is not incorporated into erythrocyte precursor cells due to mutations in genes which regulate haem synthesising
Sideroblasts
51
Full blood count:
| Hb, RBC, MCV, RDW, MCH, MCHC, HCT
```
Hb: Haemoglobin
RBC,: Red blood cell
MCV: Mean cell volume
RDW: RBC distribution width
MCH: mean cell Hb
MCHC: MCH concentration
HCT: Haematocrit
```
52
What bones does the majority of blood cell production occur in an adult?
Pelvis, sternum, vertebrae, cranial bones
53
What type of organisation does bone marrow have?
Local-organisation
54
What does the secondary lymphoid tissue do?
| 3 examples
Turn on the acquired response
| Spleen, lymph nodes, mucosal associated lymphoid tissue
55
What are the two parts of the thymus?
Medulla: dark and dense
Cortex: light and less dense
56
Where are lymph capillaries not found?
CNS. epidermis and cartilage
57
What route do superficial lymphatics follow? Where does the fluid drain?
Route of superficial veins
| Fluid drains into lymph nodes in the auxillary, inguinal or cervical areas before draining into the deep lymphatics
58
What route do deep lymphatics follow? Where does the fluid drain?
Route of main vessels from organs
| Drain into para/pre-aortic lymph nodes
59
What do lymphs in the URQ drain into
What do lymphs in the other 3 quadrants drain into?
How?
URQ: R brachiocephalic vein
| Other quadrants: L brachiocephalic vein (via thoracic duct)
60
The lymph node fluid supply
Arterial and venous supply
Afferent and efferent lymphatic supply
Blood enters via artery and leaves via vein
Lymphocytes enter via artery and leave via efferent lymphatic
61
main parts of the lymph node
Medullary sinus (middle)
Marginal sinus (outside)
Germinal centre and lymphoid follicle (B cells)
T cell area
62
How is the efficiency of a lymph node increased?
Compartamentalism
63
What type of lymphoid organ is the spleen?
Secondary
64
What type of infections does the spleen alert of?
Blood infections
65
What are the two types of pulp in the spleen?
Red and white
66
What is hypersplenism
Presence of erythrocytes with nuclear fragments in the spleen
67
What directs the structure and behaviour of gut-associated lymphoid tissue?
Non-haematopoetic 'stromal' cells
68
Give 5 examples of physical defence barriers to pathogens
Epithelial cells joined by tight junctions
Cilia and longitudinal flow of air
Decreased pH
Enzymes (pepsin, lysozome in saliva degrades cell walls)
69
3 routes that start the complement cascade
Alternative and Lectin pathway: Direct interaction between the complement and pathogen
Classical pathway: Needs antibodies
70
What do the complement molecules do?
C3a and C5a: Inflammation via chemotactic signals and recruitment of mast cells
C3b: Helps phagocytes interact with pathogens
C5a: Starts the cascade forming C6-C9 --> membrane attack complex
71
What do mast cells release?
| What does this molecule do?
Histamine
| Allergies and increases blood vessel permeability
72
What is opinisation?
A ligand on C3b that binds to the pathogen and receptor on the phagocytes --> recognition
73
What do phagocytes have on their surface?
Receptors that detect pathogens or C3b
| These are linked to intracellular pathways that produce cytokines and chemokines
74
Name 6 microbial mechanisms of phagocytes
Acidification, antimicrobial peptides, competitors, enzymes, toxic oxygen derived products, toxic NOx
75
How do phagocytes activate the acquired response
They activate other cells (e.g. dendritic cells, monocytes, macrophages and neutrophils)
These can enter the lymph nodes
76
What cells can commit suicide after trapping bacteria in their DNA?
Neutrophils
77
What are cytokines and chemokines?
| What are they also known as?
Hormones of the immune system
| Interleukins
78
How do you prevent septic shock?
Release cytokines and chemokines in low concentrations for localised contact
These chemicals are also short-acting
79
How are antibodies found in relation to the B cell?
Released from the B cell
| Bound to the B cell through the transmembrane region
80
How many domains do the light and heavy chains of an antibody have?
Heavy chain: 3 domains
| Light chain: 2 domains
81
Define affinity
Goodness of fit and interaction strength
82
Define avidity
| What increases it?
Increased interaction stability
| Increased if there are more antibodies
83
What can antibodies do aside from bind to pathogens?
Bind to toxins produced by pathogens
Regulate the immune response indirectly
Terminate the immune response
Cell recruitment
84
What is Fab?
Fragment antigen binding
| Made from the variable region
85
What is Fc?
Fragment crystallisation
Made from the constant region
Many phagocytes have receptors for this region
86
3 ways to increase the genetic diversity of antibodies during production
Germ line diversity: Different genes code for different parts
Combitoral diversity: Difference in how the segments are joined
Junctional diversity: A change in the 'glue' --> different structure
87
What is somatic hypermutation and where does it occur?
When B cells select for increased affinity
| In the germinal centre
88
What happens during somatic recombination?
| What happens if the enzymes that carry out this cannot mature?
Sections of DNA are looped and cut out to make different antibodies
Immunodeficiency diseases
89
Where are the genes for light and heavy chains found?
On separate chromosomes
90
How do the different classes of antibodies arise?
| What are they?
Different CONSTANT region
| IgA, IgD, IgE, IgG, IgM
91
What are the two structures of antibodies?
| What does a secretory piece allow?
Pentameric structure: 5 antibodies held together in a pentagon by a J chain
Dimeric structure: 2 antibodies held by a J chain with a secretory piece that allows transport into the mucosa without breakdown by digestive enzymes
92
```
What is class switching?
What 2 things does it involve the recognition of?
```
B cells change their antibody isotope but keep the antigen binding site the same
It involves recognition of cytokines and T cells
93
Four things that can control B cell production
Cytokines, chemokines, dendritic cells and microenvironment
94
How do T cells control B cell production?
Helper T cells stick to B cells at an immunological synapase before they produce antibodies
95
What process do T cells go through before they are released?
Thymic selection
96
What molecule turns tertiary molecules to linear ones?
Phagocytes
97
What are the 2 chains of a T cell receptor?
How many polypeptide chains?
How many domains?
Alpha chain and Beta chain
2 polypeptide chains
2 domains
98
What defines why everyone's immune system is different?
Major incompatibility molecules
99
What is the role of MHC's and what are the 2 types and the differences between them?
Transport linear peptides to T cells
Class 1: Capture from the CYTOPLASM, expressed on nucleated cells and present to CD8+ cells
Class 2: Capture from PHAGOSOMES, expressed on antigen presenting cells and present to CD4+ cells
100
2 ways in which T cells can be signalled - differences in what they singal them to do
'Go no go' signal from a T cell receptor (how and when to respond)
Cytokines released from phagocytes --> costimulatory signals (what response)
101
What is cancer immunotherapy based on?
Costimulatory signals
102
Where do phagocytes reside?
Bone marrow
103
What 4 things do dendritic cells do?
Capture and process antigens
Co-stimulation signal
Cytokines to turn on T cells
Pattern recognition receptors
104
What immune cell contains MHC-2 molecules?
Dendritic cells
105
What causes secondary polycythaemia vera?
| 3 examples
A consequence of something else
e. g. hypoxia (need more cells to increase oxygen levels to cells)
e. g. EPO secreting tumours
e. g. newborn babies due to maternal blood cell transfusion
106
What is relative polycythaemia vera?
When there is a decrease in plasma volume relative to RBC proportion
107
Type 1 hypersensitivity:
What type of antibody response is it?
What antibodies are involved?
Why does it happen immediately? (2)
Misdirected
IgE
Mast cells have receptors for the fc part of IgE antibodies --> fast degranulation of histamine
IgE is a preformed antibody
108
Type 2 hypersensitivity:
What antibodies are involved and what do they do?
Two types of tissue cytotoxicity caused?
IgG or IgM
ADDC: Antibody dependent cellular toxicity
CDC: Complement dependent cytotoxicity (causing cell death)
109
```
Type 3 hypersensitivity:
What antibodies are involved?
What other molecules are involved?
What is created?
Where?
How does damage occur and what does this cause?
3 reasons why the complexes are formed
```
IgG and soluble molecules
Protein complex that precipitates forming tissue deposits
In the kidneys, blood vessels and synovial joints due to increased pressure
Damage through complement/phagocytosis --> Systemic diseases
Complexes formed due to infection, environment or autoantigens
110
Type 4 hypersensitivity:
Explain the primary and secondary response
What is a Hapten?
What class of diseases also come under this?
Primary: Sensitisation and memory cell production when APC presents Haptens (sensitising agents that bind to self-proteins in the epidermis --> neoantigens)
Secondary: APC with hapten presents to CD4+ cells --> T cell and macrophage activation
Autoimmune diseases
111
Example of a primary immunodeficiency disorder
| What causes it and what happens during it?
Chronic Granulomatomus disease
Genetic disorder in PHOX genes
Stops phagocytes killing
Granuloma's form as the body works harder to kill the pathogen
112
Example of a secondary immunodeficiency disorder
| How does it show the difference in T cell activation between diseases?
HIV/AIDS
| Some diseases do not form until the T cell count is really low meaning they are not usually fought off by T cells
113
Example of a cancer where there are too many B/T cells
Acute lymphoblastic leukaemia
114
How can B and T cells help with cancer?
They can kill the tumour cells
115
What is auto-inflammation?
Prolonged and unwanted activation of the innate response leads to uncontrollable phagocytosis
116
What can bacterial cells do that can trigger autoimmune disease?
Turn on cells that shouldn't be turned on
117
What can form if a blood clot dislodges?
Embolism
118
What are the three stages of haemostasis?
1. Vascular Spasm: Decreased blood flow to the area
2. Platelet Plug Formation: Platelets bind and form a plug (Primary haemostasis)
3. Coagulation: Stable clot forms (Secondary haemostasis)
119
How is a clot made?
| What is the structure of the fibres in a clot?
By converting fibrinogen to fibrin
| Cross-linked
120
What are the macrophages called which destroy platelets?
Kupfer cells
121
What do alpha secretory granules contain?
Adhesive proteins: Fibrinogen, fibronectin, vWf
Specific proteins
Membrane proteins: Receptors for the molecules released from platelets
122
What do dense secretory granules contain?
Vasoconstrictive agents: Serotonin
Platelet agonists: Increase platelet activation (e.g. ADP)
Ca and Mg for cell surface proteins
123
Are there more alpha or dense secretory granules in a platelet?
Alpha
124
How do platelets bind to the sub-endothelium?
What increases adhesion?
How are platelets activated and what do they do?
Bind to vWf on the collagen sub-endothelium
Blood flow rolls the pltelet --> increased adhesion and associations with vWf
Firmer adhesion activates platelets --> granule release and strong adhesion
125
Explain how a platelet plug forms
| 2 examples of platelet agonists
A platelet monolayer causes the release of platelet agonists (e.g. thromboxane and fibrinogen) which increases the number of platelets attracted to the plug
These platelets create spindles which form fibrinogen cross-bridges
126
Define 'coagulation factors'
A group of inactive precursors of enzymes called 'zymogens' which are found in the plasma and work in the coagulation cascade
127
What factor does the extrinsic pathway activate?
Factor 3 (tissue factor)
128
What factor does the intrinsic pathway activate?
Factor 12
129
Name the coagulation cascade
What happens to the factor when it is activated?
Intrinsic: 12 --> 11 --> 9 --> 8a+9a --> 10
Extrinsic: 3 --> 7 --> 3a+7a --> 10
Final common pathway: 10 --> 5 --> (Prothrombin to thrombin) --> (Fibrinogen to fibrin) --> 13
It has an 'a' on the end
130
What do tissue factor inhibitors and anti-thrombin's do?
| What disorders to tissue factor inhibitors target?
Tissue factor inhibitors: Inhibits interaction between factor 7 and factor 3
(Target for haemophiliac disorders)
Anti-thrombin: Inhibits factor 5,9 and 11
131
Explain how a coagulation test works
Plasma with no platelets in a machine with a metal ball that spins to a magnetic stirrer
Add a reagent to activate coagulation, the plasma turns to jelly and the metal ball stops moving
Measure the time taken for the ball to stop moving
132
Which pathway does prothrombin time and partial prothrombin time measure?
Prothrombin time: Extrinsic pathway
| Partial prothrombin time : Intrinsic pathway
133
What are the two types of Haemophilia?
What are their causes?
Which one is more common?
Type A: Decrease in factor 8 (more common)
| Type B: Decrease in factor 9 (less common)
134
How does immune thrombocytopenia occur?
Antibodies bind to platelet proteins forming a complex which is then cleared in the liver
135
What is Glanzmann's Thrombasthenia?
What do the mutations do and what does this lead to?
What are the two types of mutations and how do these cause different severities of the disorder
An autosomal recessive bleeding disorder which decreases the number of megakaryocytes
Mutations change the fibrinogen receptors leading to decreased aggregation
Stop/missense --> no protein and haemorrhage
Point --> different protein and mild bleeding`
136
What is the difference between acute and chronic inflammation
Examples
Acute: Sudden event e.g. cut or allergic reaction
Chronic:Long term e.g. persisting infections, transplants, autoimmune diseases
137
5 examples of inflammation driven by the immune system
```
Infection
Allergies
Graft vs Host disease
Transplant rejection
Autoimmune disease
```
138
Mediators of the inflammatory response (11)
Histamine, serotonin, complement
Basophils, neutrophils, macrophages, cytokines,
Platelets, prostaglandins, factor 12, leukotrines
139
What happens at the end of the inflammatory response?
| 3 molecules which also help?
Fibroblasts --> collagen
| Lipoxins, resolvins and protectins
140
How is Arachidonate Acid produced?
Metabolised from phospholipids by phospholipase 2
141
What does Arachidonate Acid produce? (5)
Prostaglandins, thromboxanes and prostacyclins
| Lipoxins and leukotrines
142
What does COX 1 produce?
Prostacyclin for the stomach
| Prostaglandin and thromboxanes for platelets
143
What does COX 2 produce?
| How is it activated?
Prostaglandins, proteases (free radicals) and hydrogen peroxide for inflammation
Prostacyclin to switch platelets off and vasodilate
Activated by inflammation
144
How does high levels of Aspirin increase the risk of a myocardial infarction?
COX 2 produces prostacyclin which switches platelets off and vasodilates; when this is blocked platelets are switched on and the vessels are vasoconstricted --> clots
145
How does Aspirin actually work?
Stops platelets from metabolising arachidonate acid to thromboxanes
Arachidonate acid is therefore metabolised to lipoxins which solve the response
146
What are steroids produced from?
| What enzyme controls their production?
Cholesterol
| ACTH
147
What is the role of the complement system?
Coordinate the response and return it to normal after
148
What three symptoms does histamine cause and how?
Reddening: Vasodilation of arterioles
Wheal: Increased permeability of venules
Flare: Stimulation of nerves and vasodilation
149
What receptors does Histamine act on in the stomach?
| 5 things it does
H1, H2, H3, H4
| Cardiac stimulation, gastric secretion, smooth muscle contraction, vascular permeability and vasodilation
150
What 3 things cause hypersensitivity reactions?
Infection, self-antigens and the environment
151
What do hypersensitivity reactions cause?
Tissue damage
152
Define allergen
What do they contain?
3 ways they can enter the body
What immune cell do they stimulate?
Antigens that cause allergy
Proteases
Inhaled, injected, drugs
Helper T cells
153
Define Allergy
An immune response that occurs due to repeated exposure to an allergen
Sensitisation and activation of IgE antibodies
154
Define Atopy
When there is a predisposition to develop an IgE immune response
155
What are the 6 mediators which are released immediately during a Type 1 hypersensitivity reaction?
Explain briefly what they do
Cytokines: Change in vasculature and inflammation
Enzymes: e.g Tryptase activates complement
Histamine: GI, vasculature, airways, red and itchy skin
Interleukins: Activate helper T cells
Leukotrines: Contraction of gut and airways; chemotaxis
Prostaglandins: Vasculature change, smooth muscle contraction
156
Which mediator is released hours after the initial response during a Type 1 hypersensitivity reaction?
Explain briefly what it does
Migration of eosinophils
| Peroxide and mediator release
157
What is the spectrum for autoimmune diseases?
Organ specific to systemic
158
What are many autoimmune diseases caused by?
MHC 2 gene expression
159
An alternatives to organ transplant
Mechanical maintenance
160
How is transplant an investment?
It costs a lot to instate but you save money in the long term due to a decrease in mechanical maintenance
