Immunology Flashcards
1
Q
What are the key features of innate immunity?
A
instinctive
non-specific
doesn’t depend on lymphocytes
present from birth
response not improved by repeat infection
rapid response
involves phagocytes, NKC, lysosomes, complement, interferon
2
Q
What are the key features of adaptive immunity?
A
specific acquired/learning immunity requires lymphocytes antibodies resistance improved by repeat infection slower response (days/weeks) involves B and T lymphocytes
3
Q
What are the 3 layers of a blood sample?
A
top (yellow): plasma (90% water, electrolytes, proteins, lipids, sugar)
middle (white): buffy coat of wbc
bottom (red): 45%, rbc and platelets
4
Q
Neutrophils: % of blood lifespan role extra details
A
65% 6hrs - 12 days innate immunity: phagocytosis 2 intracellular granules kill microbes by secreting toxic superoxides
5
Q
Monocytes: % of blood lifespan role extra details
A
5% months innate immunity: phagocytosis adaptive immunity: antigen presentation = remove foreign stuff lysosomes contain peroxidase
6
Q
Macrophages: examples lifespan role extra details
A
Kupffer cells, microglia (brain) months/years innate immunity: phagocytosis adaptive immunity: antigen presentation to T cells remove foreign and self debris 1st line of non-self recognition
7
Q
Eosinophils: % of blood lifespan role extra details
A
5%
8-12 days
granules contain Major Basic Protein: activates neutrophils, induces histamine release + bronchospasm: allergy
associated with allergic and parasitic infections
8
Q
What do eosinophil granules stain for?
A
acidic dyes
eosin = red
9
Q
Basophils:
% of blood
lifespan
role
A
2%
2 days
immunity to allergic reactions and parasitic infections
10
Q
Basophils and mast cells are ver similar apart from what?
A
mast cells: fixed in tissue
basophils: circulate
11
Q
What do basophil granules stain for?
A
basic dyes
haemotoxylin: blue
12
Q
Monocytes differentiate into what when they reach tissues?
A
macrophages
13
Q
What kind of high affinity receptors do basophils have? What happens when they are activated?
A
IgE receptors
when IgE binds: de-granulation = histamine release = allergic reaction
14
Q
What is the role of a mast cell?
A
immunity to allergic reactions and parasitic infections
have high affinity IgE receptors like basophils
15
Q
T lymphocytes: % of blood lifespan role extra details
A
10%
hours to years
adaptive immunity: recognise APCs and bind antigens via specific TCRs
produce cytokines and oil infected host cells
16
Q
B lymphocytes: % of blood lifespan role extra details
A
15%
hours to years
adaptive immunity: recognise ACPs
differentiates into plasma cells which produce antibodies
17
Q
Where are B lymphocytes found in the body?
A
blood, lymph nodes, spleen
18
Q
What is the role of dendritic cells?
A
adaptive immunity: act as APCs and induce primary immune response in inactive T lymphocytes = ONLY CELLS THAT CAN DO THIS
produce cytokines = B cell activation and differentiation
19
Q
Where are dendritic cells found?
A
in tissue that has contact to outside environment e.g. skin, lining of lung and nasal cavity
20
Q
What is the role of natural killer cells?
A
recognise and kill virus infected cells and tumour cells by apoptosis
expressed CD56
21
Q
Where are natural killer cells found?
A
spleen and tissues
22
Q
What are the 4 types of T cell?
A
- T-regs
- T helper (CD4, Th1 and Th2)
- Cyotoxic (CD8)
- TH17
23
Q
What do neutrophils look like?
A
3 lobes
lots of granules
neutral stains
24
Q
What do eosinophils look like?
A
lots of granules
2 lobes
acidic stains
25
What do basophils look like?
basic stains
| 2 lobes
26
What do monocytes and macrophages look like?
monocytes: few granules
| gain more granules and cytoplasm when they mature to macrophages
27
What do T and B cells look like?
little cytoplasm
| T-cell: no indentation
28
What is complement secreted by?
liver
29
What needs to happen for complement to be functional?
must be activated
30
What are the 3 main things complement does? Which molecules carry out each property?
direct lysis (MAC)
attract more leukocytes to infection site (chemotaxis) and enhance inflammation (C3a and C5a)
opsonisation (C3b)
31
What 3 main properties do immunoglobulins have?
soluble
secreted
bound to B cells
32
What type of protein are Igs?
glycoproteins
33
What is an epitope?
part of the antigen that binds to the antibody
34
What are the 5 immunoglobulins?
IgG, IgA, IgM, IgD, IgE
35
What are the key properties of IgG?
most predominant
goes everywhere in body due to small size
only one too ross placenta to give neonates immunity
36
What are the key properties of IgM?
mainly found in blood: too big to cross endothelium
have multiple complement binding sites
primary immune response: initial contact with antigen
main role = intravascular neutralisation
37
What are the key properties of IgA?
predominant Ig in mucous secretions: milk, saliva, bronchiolar, genitourinary
SECRETORY
38
What are the key properties of IgE?
basophils and mast cells express IgE specific receptors
binding = histamine release
associated with hypersensitivity allergic reactions and parasitic infections
39
What are the key properties of IgD?
on naive B cells
| acts as B-cell antigen receptor
40
What are the 5 main functions of immunoglobulins? Which Ig is associated with each function?
neutralise toxins by binding to it (IgA, IgG)
immobilise motile microbes (IgM)
increase opsonisation: aids phagocytosis
activates complement using Fc receptors (IgG, IgM)
bind Fc receptors: phagocytes (IgG, IgA), mast cells (IgE), natural killer cells (IgG)
41
What is a cytokine?
soluble proteins secreted by lymphocytes, monocytes or macrophages that act as stimulation or inhibitory signals to cells
42
What are the 4 types of cytokine?
interferons (IFN)
interleukins (IL)
colony stimulating factors
tumour necrosis factors (TNF alpha and beta)
43
What do interferons do?
induce state of antiviral resistance in uninfected cells
| = limits spread of viral infection
44
What are the 3 types of interferon? What are they produced by?
IFN alpha and beta produced by virus infected cells
| IFN gamma released by activated Th1 cells
45
What do interleukins do?
act between cells of the immune system
| cause cells to divide, differentiate and secrete factors
46
What are they 2 types of interleukin?
pro-inflammatory (IL1)
| or anti-inflammatory (IL10)
47
What do colony stimulating factors?
direct division and differentiation of bone marrow stem cells
= precursors of leukocytes
48
What do tumour necrosis factors do?
mediate inflammation and cytotoxic reactions
49
What are chemokines?
chemotactic cyotkines
| direct movement of leukocytes from blood to tissues by binding to specific receptors on cells
50
What are the 4 key chemokines?
CXCL: mainly neutrophils
CX3CL: T lymphocytes and NKC
CCL: monocytes, lymphocytes, eosinophils, basophils
XCL: mainly T lymphocytes
51
What are the 3 key parts of innate immunity?
```
physical and chemical barriers
phagocytic cells (neutrophils and macrophages)
blood proteins (complement, acute phase)
```
52
What are the physical and chemical barriers of the body used in innate immunity?
anatomical barriers: skin
mucous membranes: saliva and tears: lysozyme (cilia)
commensal colonies: mouth, vagina, skin, gut
pH: gastric acid, decreased in vagina
53
What are the hallmarks of inflammation?
increased blood supply
increased vascular permeability
increased leukocyte transendothelial migration extravasation
54
Which immune cells are found in the blood and which are in the tissues?
blood: monocytes, neutrophils
tissues: macrophages, dendritic cells
55
What is a Pathogen Associated Molecular Pattern (PAMP)?
on microbes
innate immunity depends on an immune cell recognising some general molecular features common to lots of pathogens = PAMP
e.g. a lipopolysaccharide
56
What is a Pattern Recognition Receptor (PRR)?
recognise and bind to variety of pathgogen ligands
| activation drives cytokine production by APCs that increases T cell activation
57
What are Toll-like Receptors?
type of PRR
proteins that recognise and bind to PAMPs
2nd messenger is generated = inflammatory mediators released
58
Where are toll-like receptors found?
on macrophages, dendritic cells and neutrophils
59
What are the 3 activation pathways for complement?
1. classical (Ab bound to microbe)
2. alternative (C' binds to microbe)
3. lectin (mannose-binding lectin binds to microbe)
60
How does the classical activation pathway of complement work?
IgM or IgG binds to an antigen and reveals a binding site for C1 = antibody dependent
Attachment to Fc region on 2 Ig molecules is required
C4bC2a is formed when C1r and C1s bind together
C4bC2a complex has enzymatic action on C4 and C2 = splits these into a and b
C4b and C2 combine to form C4bC2a aka C3 convertase
Cleaves C3 into C3a and C3b
C3 convertase remains on surface of pathogen to cleave C3
regulated by C1 esterase inhibitor
61
How does the lectin pathway of complement activation work?
independent of antibodies: activated when mannose-binding lectin binds to mannose on bacterial cell walls, yeast walls or viruses
joins classical pathway: forms C3 convertase to cleave C3
62
How does the alternative pathway of complement activation work?
activated by microbial cell surfaces
generates C3 convertase without the need for C1, C4 or C2
spontaneous cleavage of C3 occurs: C3b and B combine to form C3bB
converted to C3bBb = C3 convertase
cleaves C3 into C3a and C3b
regulated by factors H and I which cleave and inactivate displaced C3b
63
What do all forms of A complement do?
enhance inflammation
64
Explain the membrane attack complex pathway
1. C3b can bind to C3 convertase (C4bC2a) to form C3/C5 convertase (C4bC2aC3b)
2. this cleaves C3 into C3a and C3b or C5 into C5a and C5b
3. C5b initiates formation of MAC
4. with other complement proteins, MAC is formed and destroys pathogens
65
Explain how extravasation is used to attract wbc from the blood to the tissue?
1. macrophage secretes pro-inflammatory molecule once it binds to a pathogen = attracts more immune cells
2. TNF Alpha activates endothelium so it becomes sticky
3. neutrophils bind to the endothelium = tethered: they roll along it to slow down initially
4. TNF alpha causes chemokines to be released = stick to molecules on endothelial surfaces
5. neutrophils interact with the chemokines, they tell neutrophils to stop
6. neutrophil binds to integrin: holds it in place and signals it to move to the tissue
7. squeezes between gaps in the endothelium, up a chemokine gradient
8. most chemokines are by the site of infection where they are released = neutrophils move here
66
What are the 2 methods of microbial killing b neutrophils and macrophages?
1. oxygen dependent: reactive oxygen intermediates (ROI)
superoxides > H202 > OH radical
nitric oxide: vasodilation increases extravasation and is anti-microbial
2. oxygen independent
enzymes: lysozyme
proteins: defensives, TNF
pH
67
What are the hallmarks of adaptive immunity?
specific
quicker response
response and memory specific to antigen
requires lymphocytes
68
What is the difference between cell-mediated and humour adaptive immunity?
cell mediated: involves T cells for intracellular microbes
| humour: involves B cells for extracellular microbes
69
Why do we need adaptive immunity?
microbes evade innate immunity (proteases etc)
intracellular viruses and bacteria hide from innate immunity
need memory to specific antigens
70
What are the 3 key players in adaptive immunity?
T cells
B cells
APCs: dendritic cells, macrophages and B cells
71
Where are T cells produced? Where do they mature and travel to?
produced in bone marrow > primary lymphoid: mature in thymus > secondary lymphoid
72
Where are B cells produced? Where do they mature and travel to?
primary lymphoid: produced and mature in bone marrow > secondary lymphoid
73
Where are APCs produced? Where do they mature and travel to?
primary lymphoid: produced in bone marrow > tissue > recirculates to secondary lymphoid
74
What do adaptive immunity cells accumulate in the body?
secondary lymphoid tissue e.g. spleen, lymph nodes, MALT
75
What is MALT?
mucosal associated lymphoid tissue: patches of specialised tissue e.g. in mouth, tonsils, gut
76
Which cells are involved in cell-mediated immunity?
APCs: dendritic cells, macrophages, B cells
| T cells
77
What are the 5 key requirements for cell-mediated immunity?
1. intimate cell to cell contact: to control Ab response via contact with B cells + recognise and kill viral infected cells
2. a Major Histocompatibility Complex
3. intrinsic/endogenous (intracellular) antigens
4. extrinsic/exogenous (extracellular) antigens
5. recognise self and non-self proteins
78
What is a Major Histocompatibility complex?
- present antigenic peptides from self or non-self proteins to T cells
- antigenic specific receptor of the T cell only recognises antigens if they are part of a complex with an antigenic peptide and it's specific MHC
- safety: stops immune system getting activated too easily
79
What kind of antigens do T cells and B cells respond to?
T cells DO NOT respond to soluble antigens, B cells do
| T cells ONLY respond to intracellular presented antigens
80
The structure of a T cell receptor is similar to what?
Fab region of Igs
81
What do T cell receptors recognise and bind to?
```
T cells are committed to an antigen
TCR recognises small antigen peptides in association with EITHER a major histocompatibility complex class I (cytotoxic T cell CD8) or class II (T helper CD4)
```
82
What are Major Histocompatibility complexes coded by?
Human Leukocyte Antigen genes
83
Major Histocompatibility complex class I is associated with what kind of antigens and T cells? Where is it found? What is its function?
intracellular antigens e.g. virus
Tc (CD8)
found on the surface ALL nucleated cells e.g. all cells but erythrocytes
kill infected cell with intracellular pathogen
84
Major Histocompatibility complex class II is associated with what kind of antigens and T cells? Where is it found? What is its function?
extrinsic antigens e.g. phagocytosis
Th (CD4)
found only on APCs: macrophages, B cells, dendritic cells
HELP B cells make Ab kill extracellular pathogens and HELP directly kill
85
Explain how T cells recognise an antigen and are then activated?
1. APC presents antigen with a Major Histocompatibility complex to the T cell receptor
2. CD4 or CD8 binds to this complex: required for full T cell activation
3. once bound: send intracellular signals inside T cell
4. intracellular signals tell T cell to release IL-2
5. IL-2 acts on IL-2 receptor on same T cell: receptor activated and can send signals to T cell
6. tells T cell to divide: more T cells to kill cells expressing this antigen = CLONAL EXPANSION
also tells them to differentiate: more mature + active, gives effector functions, some become memory cells
86
How do naive T cells become functional T cells? Explain the 2 pathways.
becomes activated and follows 1 of 2 pathways
1. naive T cell becomes CD8 (cytotoxic T cells): kill intracellular pathogens directly
2. naive T cell becomes CD4
in high levels of IL-12, CD4 then becomes Th1: helps kill intracellular pathogens by secreting IFN-gamma and IL-2 = helps viral response
in low levels of IL-12, CD4 becomes Th2: produces antibodies, secretes IL-4, 5 and 10
87
What are CD8 T cells also called?
cytotoxic T lymphocytes (CTL)
88
How are CD8 cells activated?
1. virus-infected cell contains viral proteins: broken down in cytosol
2. peptides transported to endoplasmic reticulum and binds to Major Histocompatibility complex class I on cell surface
3. naive CD8 cells activated by antigens presented on the MHC class I molecules
89
How do CD8 cells kill infected host cells once activated?
- mature cytotoxic T cells (Tc) provide protection: release pro-inflammatory and macrophage activating cytokines
- kill infected host cells by forming proteolytic granules and releasing perforin and granulysin: form holes in cell membrane of pathogens and kill them
- CD8 also induce apoptosis
90
How are CD4 cells activated?
1. APC presents an antigen with MHC II to a naive CD4 cell
| 2. High levels of IL-12 activate naive cells to CD4 Th1 cells
91
After activation, what happens to CD4 Th1 cells to allow them to carry out their function?
1. Th1 cells travel to secondary lymphoid tissues - spleen, lymph nodes
2. Proliferate: CLONAL EXPANSION (more Th1 cells available to recognise this specific antigen)
3. Th1 cell recognises antigen on infected cells with MHC II via TCR
4. Can then carry out various functions
92
What is the function of Th1 CD4 cells?
Mediates functions associated with cytotoxicity and local inflammatory reactions
Produces IL-2, IFN-gamma, TNF beta
- IFN-gamma stops virus spreading and causes apoptosis = kills IC pathogens
Activates macrophages by producing cytokines = triggers inflammation
Helps CD8 develop into effector cells: kill virally-infected target cells and activate macrophages infected with intracellular pathogens
Induce B cells to make IgG
93
What is the function of Th2 CD4 cells?
Produce IL-4, 5, 6, 10 and 13
Activate eosinophils and mast cells
Important in helminth infections and allergies
Induce B cells to make IgE: promotes release of inflammatory mediators
Stimulate B cells (by IL-4, 5, 10) to proliferate and produce antibodies, especially IgE
94
B cells express membrane bound Ig. Which types of Ig?
IgM or IgD
95
What happens to B cells that recognise self?
Killed in bone marrow
96
In the first state of their activation, B cells present an antigen to what? Explain the process.
T cells.
1. IgM (or IgD) binds to the antigen
2. Phagocytosis occurs
3. Peptide is displayed on the surface of the naive B cell with MHC II
4. TCR of naive Th CD4 binds to MHC II
Lots of other co-stimulators molecules are needed
97
Once the naive Th CD4 cell is bound to the B cell, what happens for B cells to become activated?
1. Th cells become primed Th2 cells on binding to the APC
2. Th2 now secretes cytokines (IL-4, 5, 10 and 13)
3. Cytokines cause B cells to divide: clonal expansion
4. B cells differentiate in plasma cells (AFC): make antibodies and memory B cells (Bm)
98
What is the exact stage at which B cells are said to be activated?
On binding with the complementary antigen
99
Where do activated B cells go for clonal expansion?
Lymph nodes
100
What type of antibodies do plasma cells usually produce?
IgM initially
| Later turn into IgG
101
What are the primary lymphoid organs?
Thymus
| Bone marrow
102
Name the secondary lymphoid organs and tissues?
```
Waldeyer’s ring: tonsils and adenoids
Bronchus associated lymphoid tissue
Lymph nodes
Bone marrow
Spleen
Lymphoid nodules
Mesentery lymph nodes
Peyer’s patch
Urogenital lymphoid tissue
```
103
How do we handle bacteria and fungi?
Phagocytosis and killing
104
How do we handles viruses?
Cellular shut down
Self sacrifice
Cellular resistance
Apoptosis
105
What are the main problems with immunity?
Immunological memory is very protective but takes weeks whereas infections arrive quickly and unpredictably
Adaptive memory is highly specific: cross reacting or self targeting is a risk
106
What is pattern recognition? What properties do these patterns have so that so many can be recognised?
Recognise patterns associated with particular organisms
| Patterns have limited characteristics and are shared across organisms
107
Give 3 examples of where similar patterns are distinguished in the body.
Gram positive and negative bacteria show different patterns
Double stranded RNA is used for detecting viruses
CpG motifs: part of DNA where cytosine and guanine are separated and have a phosphate group
108
What are the main 2 types of pattern recognition receptor?
1. Secrets and circulating PRRs
| 2. Cell associated PRRs
109
What are secreted and circulating PRRs? Where are they found? What are they secreted by?
Antimicrobial peptides
Found in lining fluids of epithelial and mucosal surfaces and phagocytes
Cells there and immune system components secrete them
110
Give 3 examples of groups of secreted and circulating PRRs?
Human defence proteins eg defending, cathelicidin
Lectins and collectins
Pentraxins
111
What 2 ways do human defence protein PRRs cause pathogen clearance?
1. Direct killing: interrupt metabolic activity by bilateral disruption, binding to specific lipid receptors, disruption of membrane bound channels
2. Immune modulation: recruitment and activation of immune cells leads to inflammation, enhanced pathogen killing and assists phagocytosis
112
What are lectins and collectins? Give an example of each.
```
Carbohydrate containing proteins
Type of PRR
Bind carbohydrates or lipids in microbe walls
Eg mannose binding lectin
Eg surfactant proteins A and D
```
113
What are the 2 main roles of lectins and collectins?
Activate complement
| Improve phagocytosis
114
What are the 4 main roles of pentraxins? Give an example of a pentraxin.
Have some antimicrobial actions
Can react with C protein of pneumococci
Activate complement
Promote phagocytosis
Eg proteins like c-reactive protein
115
Where are cell-associated PRRs found?
Cell membranes or in the cytosol
116
What is the main family of cell-associated PRRs?
Toll-like receptors
117
Which 3 TLRs respond to viral components? What do they do? Where are they found?
TLR 3, 7 and 9
Trigger anti-viral immune response
Not on cell surface but in endoscopes where viral components can be endocytosed
118
What exogenous and endogenous ligand activate TLR-3?
Exogenous: double stranded RNA
Endogenous: mRNA
119
Why is TLR-4 important?
As little as 10 cells of lipopolysaccharides (LPS) or other activators can lead to the induction of TLR-4
Components of LPS sensed by CD14 (adaptor molecule) > TLR-4 is oligomerized > signal induced
120
What endogenous and exogenous ligand activate TLR-4?
Exogenous: lipopolysaccharides, pneumolysim, viral proteins
Endogenous: heat shock proteins, HMGB1, hyaluronan, fibrinogen
121
Give 3 examples of other membrane bound PRRs?
Receptors that sense fungi: eg mannose receptor on macrophages
Dectin -1: on phagocytes, helps recognise beta glucans in fungal walls
Scavenger receptors: non-specific, on macrophages cell surface
122
How do PRRs target intracellular pathogens? Give 2 examples of pathogens which multiply inside cells.
Have receptors in cytoplasm not just on the cell surface or in endoscopes
Eg viruses multiply in the cytoplasm
Bacteria such as salmonella burst of out phagolysomes and multiply in the cytoplasm
123
What are nod-like receptors? Give 3 examples of the most common.
PRRs found in the cytoplasm - target intracellular pathogens
Can detect components of bacterial cell walls
Eg NOD1 and 2, NLRP3
124
What is significant about the NOD-2 intracellular PRR? What is its main function?
Widely expressed
Recognises breakdown projects of peptidoglycan such as MDP (pep is found in gram pos and neg bacteria)
Activates inflammatory signalling pathways
125
What diseases are associated with NOD-2 when it is non-functioning and when it is hyper functioning?
Non functioning: associated with Crohn’s
| Hyper functioning: Blau syndrome
126
What are rig-like helicases? What do they do? Where are they found? Give 2 examples.
Intracellular PRRs in the cytoplasm
Especially for viruses
Activate interferon production = antiviral response
Eg RIG-1, MDA5: detect intracellular double stranded viral RNA and DNA
127
In what 4 ways do TLRs play a role in homeostasis?
1. Independent of lipopolysaccharides, TLR-4 plays a role in the number of neutrophils circulating
2. Endotoxin tolerance in the gut: gut has a lot fo bacteria, don’t want the body to react to them all
3. Maturation of the immune system: mediate macrophage activation
4. Maintain balance with commensalism organisms: don’t overreact to pathogens that routinely colonise the skin, gut etc
128
How are PRRs involved in damage recognition?
When cells are damaged, they release products that can be sensed by PRRs
In unfamiliar contexts, these molecules can activate TLRs
= activates immunity to initiate tissue repair and increase local antimicrobial signalling
129
What extracellular and intracellular products to cells release when they are damaged?
EC: fibrinogen, hyaluronic acid, tenascin C - from EC matrix, coagulation system
IC: HMGB1, mRNA, heat shock proteins, uric acid, strathmin
130
In what 2 ways are PRRs involved in adaptive immunity?
1. activation of PRRs drives cytokine productions by APCs = increases successful T cell activation
2. TLR-4 agonists can be used alongside vaccines to enhance immune responses
131
How are PRRs linked to disease?
recognition of host molecules: hyper functioning PRRs in autoimmune disease
failure to recognise pathogens
increased inflammatory response = increased likelihood of sepsis
abnormal immune responses can perpetuate damage: atherosclerosis, arthritis, COPD, IBD
132
How can PRRs be used in therapy to treat disease?
increase TLR signalling: improve immunity and adjuvants in vaccines
inhibit TLR signalling in sepsis, inflammation or arthritis
modify adaptive immune responses e.g. in cancer
133
According to immunological theory, what are the 4 key ways that a vaccine effects the immune system?
manipulating an immune item to generate a persistent protective response
immunisation that can trigger an immune response and safely mimic an infection
mobilise appropriate arms of the immune system to form immunological memory
can be transferred to others: passive immunity
134
What is passive immunisation?
the transfer of preformed antibodies
135
What is natural passive immunisation?
transfer of maternal antibodies across the placenta to the developing foetus/breast milk
136
Which diseases does natural passive immunisation protect against?
```
diphtheria
tetanus
rubella
mumps
poliovirus
```
137
What is artificial passive immunisation?
treatment with pooled normal human IgG or immunoserum against pathogens or toxins
138
When is artificial passive immunisation used?
- individuals with agammaglobulinaemias (especially B cell defects)
- exposure to a disease that could cause complications e.g. immunocomprised patients to measles
- when there is no time for active immunisation to give protection (e.g. a pathogen with a short incubation time like rabies)
- acute danger of infection
- anti-toxins and anti-venins
139
What is the biggest downside to passive immunisation?
doesn't activate immunological memory so doesn't provide long term protection
140
With some pathogens, the main hazard is not the primary infection. What is it? Give 2 examples of diseases like this.
the effect of toxins released by bacteria
the primary infection can be eliminated by the immune system
e.g. tetanus, botulism
141
What are deactivated toxins called?
toxoids
142
Why is natural immunity to toxins very difficult to achieve?
toxins are very lethal at very low doses
143
What treatment used to be used to neutralise toxins? Why was this a problem?
antisera
possibility of a reaction to anti-sera: it is non-self so the 2nd time it is used it will be immune to itself which can lead to anaphylaxis
144
What effect do botulum and tetanus toxins have?
prevents fusion of vesicles at NMJs so NTs can't cross the synapse
botulum: Ash
tetanus: glycine and GABA
145
Passive immunisation is used when the body is exposed to which diseases? Name the type of passive immunisation used for each one.
botulism, tetanus, diphtheria = anti-toxins
hepatitis, measles, rabies = used prophylactically to reduce chance of establishing infection after exposure
snake bite, insects, jellyfish = anti-venin
146
What is the 5 step process in forming active immunity?
1. engage innate immune system
2. elicit danger signals that activate system e.g. PAMPs
3. engage TLR receptors via the PAMPs
4. activate specialist APCs e.g. Langerhans cells
5. engage adaptive immune system: generate memory T and B cells, activate T helper cells
147
What is active immunity? (5 characteristics)
challenging immune system to induce state of immunity
production of high affinity protective antibodies against the immunogen
produced by own immune system
usually long lasting
achieve initial exposure without risks of actual infection
148
What happens in the primary response to an antigen? Which Ig predominates?
```
relies on innate immune system
no of antibodies is low
low affinity IgM predominate
essentially germline repertoire
memory T and B cells generated
```
149
What happens in the secondary response to an antigen? Which Ig predominates?
```
rapid and large reaction
high levels of high affinity IgG predominate
somatic hypermutation
T cell help
does not rely on innate immune system
```
150
What are the 5 things that make a perfect vaccine?
achieve long term protection
stimulate B AND T cells
induce memory B and T cells
stimulate protective high affinity IgG production
importance of memory B cell response depends on nature of pathogen
151
What is the time of onset for the influenza virus? What does this mean for influenza vaccines?
rapid onset - can be established before immunological memory can be activated
important to maintain high levels of antibody = annual boosts needed
mutates often so requires generation of new vaccines constantly
152
What is the time of onset for polio? What does this mean for polio vaccines?
can take 3 days to establish infection in NS
lag gives time for memory to be activated and to generate antibodies
boosts not needed
153
What are the 5 types of vaccine?
```
whole organism
subunit
peptides
dna vaccines
engineered virus/recombinant vector
```
154
What are the 2 types of whole organism vaccines?
live attenuated pathogen
| killed inactive pathogen
155
Give 2 examples of live attenuated vaccines. Explain how they are produced.
TB: grown for 13 years on medium containing bile > adapts with reduced virulence
Polio sabin: grown on monkey kidney epithelial cells > prolonged culture > adapts with lower virulence
156
What is the TB vaccine called?
BCG vaccine: Bacillus Calmetie-Guerin
157
What are the advantages and disadvantages of live attenuated pathogen vaccines?
+ set up transient vaccine
+ activates full natural immune response
+ prolonged contact with immune system
+ stimulation of memory response in T and B cells
+ often only a single immunisation is required
- immunocompromised patients may become infected
- in some vaccine it can revert to its virulent form e.g. measles
- complications e.g. encephalomyelitis in measles vaccine
- needs to be refrigerated for storage
158
Give 3 examples of killed inactivated pathogen vaccines.
anthrax, cholera, hep A
159
What are the advantages and disadvantages of inactivated pathogen vaccines?
+ no risk of infection
+ storage less critical
+ good immune response possible
- tends to just activate humoral response
- lack of T cell involvement
- without transient infection, immune response can be weak
- repeated boosters needed - problems with patient compliance
160
What are the 3 types of subunit vaccines? Give examples for each and briefly how they work.
a. toxoids (inactivated exotoxins): pathogens often produce symptoms as a result of exotoxins e.g diphtheria, tetanus
b. antigenic extracts/capsular polysaccharides (block opsonisation) e.g. Men C
c. recombinant proteins: cloning and expression of a single gene in a recombinant host e.g. Bexsero
161
What are the advantages and disadvantages of subunit vaccines?
+ theoretically safer than active/inactive pathogens
+ no risk of infection
+ easier to store
- immune response less powerful than live
- repeat vaccinations and adjuvants needed
162
What is an adjuvant in a vaccine?
substance added to a vaccine that stimulates the immune system
163
Give 6 examples of adjuvants in vaccines.
whole killed organisms: not used in humans
toxoids: trigger immune system and send out danger signals
proteins
chemicals e.g. aluminium salts (potentiate opsonised phagocytosis), paraffin oil
TLR agonists
saponins
164
What are peptide vaccines?
field advancing slowly
needs to include immunodominant B cell epitopes
stimulate T memory cell development
165
What are the difficulties with peptide vaccines?
can be stimulatory or suppressive
most B cell epitopes are conformational
knowledge of HLA presentation of peptides essential
166
What are DNA vaccines? How do they work?
transiently express genes from pathogen to host cells
generates immune response similar to natural infection = produces T and B cell memory
expression vector > transfected into muscle cells
167
What are the advantages and disadvantages of DNA vaccines?
+ don't require complex storage
+ safe
+ delivery can be simple: no refrigeration needed
- no transient infection
- limited to proteins: can build up tolerance or anti-DNA antibodies
- mild immune response = needs boosters
168
Which cell types can take up DNA from a DNA vaccine?
usually muscle cells
| other types can e.g. APCs
169
What is a engineered virus vaccine? How does it work?
initiate effect of transient infection with pathogen but using a non-pathogenic organism
genes for pathogenic antigens introduced into a non-pathogenic/attentuated microorganisms > then introduced to a host
170
Give a viral and bacterial example of an engineered virus vaccine?
viral: attenuated poliovirus
bacteria: attentuated strains of salmonella
171
What are the advantages and disadvantages of engineered virus vaccines?
+ produce immunological memory
+ flexible: components can be engineered in
+ safe relative to live vaccines
- requires refrigeration
- immune response to virus can negate effectiveness
- illness in immunocompromised
