1
Q
compare and contrast the strategies of of immune surveillance in bacteria, invertebrates and vertebrates
A
Bacteria:
- Restriction enzymes, CRISPR/Cas9
Invertebrates:
- Negative surveillance (ie cells marked with ‘self’ protein labels; unlabelled non-self cells destroyed by phagocytes)
Vertebrates:
- External barriers
- Negative surveillance by major histocompatibility proteins (MHC) - v polymorphic (it’s difficult for a pathogen to mimic these self-protein labels)
- Positive surveillance system – specific recognition of foreign cells
2
Q
describe the features (when you get it/specificity/response/cell types/soluble factors) of the innate immune system
A
- What you’re born with
- Broad specificity
- Resistance not improved by repeat infection
- Rapid response (hrs)
- Leucocytes: phagocytes, natural killer cells
- Soluble factors: lysozyme, complement, interferons
3
Q
describe the features (when you get it/specificity/response/cell types/soluble factors) of the adaptive immune system
A
- Born with elements of it but it mainly adapts during lifetime
- Highly specific
- Resistance improved by repeat infection
- Slower response (days/weeks)
- Leucocytes: B and T lymphocytes
- Soluble factors: antibody
4
Q
name 5 external barriers to infection
A
Keratinized skin: keratin
Secretions: sebum, sweat, fatty acids, lactic acid, lysozyme
Mucous: cilia (respiratory tract)
Low pH: stomach pH 2.5
Commensals: friendly bacteria/fungi that prevent colonisation
5
Q
what is a leucocyte?
A
white blood cell
6
Q
name the types of phagocyte
A
neutrophil mononuclear phagocytes (monocytes and macrophages, dendritic cells)
7
Q
name a type of lymphocyte
A
natural killer cell
8
Q
describe the features of a neutrophil
A
Multilobed nucleus and granules in cytoplasm (slightly green, why snoosh is green)
Main phagocyte in blood
Short-lived, fast-moving
Lysosomes release enzymes H2O2 etc
9
Q
describe the features of the mononuclear phagocytes
A
Monocytes (when in the blood) Macrophages (when in the tissues) Monocytes and macrophages are the same but macrophages have slightly more complex morphology Long-lived (months/years) Helps initiate adaptive responses
10
Q
describe the features of lymphocytes
A
Characteristic granules in cytoplasm
Kill virally infected cells non-specifically
Important in self/non-self recognition
May kill cancer cells (have altered properties that NKs can recognise)
11
Q
describe the difference in pathogen recognition by innate cells (phagocytes and NKs)
A
Phagocytes:
- Have general pathogen-recognition receptors (PRRs) that recognise pathogen-associated molecular patterns (PAMPs)
Natural killer cells:
- Kill targets unless they recognise a self-protein (MHC)
12
Q
describe the structure and function of defensins (type of soluble factor)
A
- Peptides that have +ve charges meaning they can enter bacterial membranes and disrupt them
- Made by neutrophils
13
Q
describe the function of interferons (type of soluble factor)
A
- Produced by virally infected cells and give to uninfected cells to protect them
- Activate macrophages and NK cells
14
Q
describe the function of cytokines (type of soluble factor)
A
‘hormones of the immune response’
- small secreted proteins involved in cellular communication
- eg interleukins – initiate and control immune responses
- Produced by cells of the innate and adaptive immune system (in particular T-lymphocytes)
15
Q
describe the function of inflammatory mediators (type of soluble factor)
A
cause inflammation eg histamine and prostaglandins
16
Q
describe how inflammation occurs
A
- Dilation of blood vessels (increases amount WBCs that can enter tissue)
- Increased capillary permeability
- Phagocytes migrate into tissues
17
Q
what is an acute phase response?
A
a group of physiologic processes occurring soon after the onset of infection
18
Q
state what happens during fever and how and why this occurs
A
On infection macrophages may release interleukin 1 (type of cytokine)
- Acts on hypothalamus
- Raises temperature
- Stimulates phagocytosis
- Reduces level of iron in blood (bacteria need high levels of iron to survive and replicate)
19
Q
where are leucocytes made?
A
bone marrow stem cells
20
Q
where are the 2 types of lymphocyte made? where do they mature?
A
B-Lymphocytes: - Mature in bone marrow - Receptor is antibody T-Lymphocytes - Mature in thymus - They then go to the peripheral lymphoid tissue and undergo antigen-dependent differentiation (lymph nodes/spleen)
21
Q
what type of immune response do the 2 types of lymphocytes have?
A
B-lymphocytes:
- humoral (antibody)
T-lymphocytes:
- cell-mediated (stimulate release phagocytes, other T-cells and cytokines)
22
Q
who came up with the clonal selection hypothesis? describe this theory
A
When we get an infection (with an antibody that recognises the antigen) there is clonal expansion
- This is the proliferation of correct antibody on B-cell
- The plasma B-cells produce soluble antibodies
- Some plasma cells differentiate into memory cells – used in 2ndry infection
- Lymphocytes that recognise self are deleted in early development
23
Q
name the 2 ways in which a vaccine is made
A
Types of vaccine:
- Subunit eg toxoid (derived from toxin)
- Attenuated strains
24
Q
briefly describe the primary and secondary responses to infection
A
Primary response: takes longer to respond and [Ab] is not as high (this is what vaccination stimulates as well)
Secondary response: takes less time to respond and [Ab] is much higher (infection)
25
describe the cell-mediated and humoral (antibody) responses
Cell-mediated (T-cell) immune responses:
When a T-cell meets an antigen, it undergoes clonal selection/expansion and then differentiation therefore giving the cell immunological memory.
T-cells can only recognise antigen bound to host cells
Humoral (antibody) immunity:
Antigen stimulates B-cells which differentiate into plasma cells which produce soluble antibodies
(B-cells packed full of ER --> make loads of soluble antibodies)
Widely used in research and medicine
26
what type of protein is an antibody?
glycoprotein
27
name the 5 types of antibody, their heavy chain and their structure (eg monomer, dimer etc)
IgG – γ (monomer):
IgM – μ (pentamer – linked by disulphide bonds):
IgA – α (monomer in serum or dimer in secretions):
IgD – δ (monomer):
IgE- ε (monomer):
28
what do the 5 classes of antibody do?
```
IgG:
- Main class in serum and tissues
- Important in secondary/memory responses
- Crosses placenta (only one that can do this)
IgM:
- Important in primary responses
IgA:
- In serum and secretions
- Protects mucosal surfaces
IgD: (don’t really know what it does)
IgE:
- Present at very low levels
- Protective against extracellular parasites
- Involved in allergy
```
29
what are the two types of light chain an antibody can possess?
2 light chain types: κ (kappa) and λ (lambda)
30
how are the variable and constant regions encoded?
they are encoded by different exons, and can therefore recombine in different combinations to match specific antigens
31
which antibodies are released in the priamry and secondary immune system response?
Primary response – IgM and then IgG a few days later
Secondary response – IgG (loads & lasts ages because of long half-life) and then some IgM
Secondary response can also include IgA or IgE depending on infection type
32
which antibodies can neutralise viral toxins
IgG and IgA
33
which antibodies can immobilise motile microbes?
IgM
34
which antibodies can prevent binding and infection of host cells?
IgM, IgA
35
which antibodies can activate complement?
IgG, IgM
36
which antibodies can bind phagocytes by their Fc region?
IgG, IgA
37
which antibodies can bind mast cells by their Fc region?
IgE
38
which antibodies can bind NK cells by their Fc region?
IgG
39
what are the 3 main biological activities of complement?
1) Activation of WBCs: induces neutrophils to move out of bloodstream into tissues, also induces inflammation – peptides C5a and C3a can act as chemoattractants to neutrophils. Mast cells (WBC) also have C5a/C3a receptors – induce anaphylatoxin (histamine) release
2) Opsonisation: C3b binds bacterial surface, phagocytes have C3b receptors and therefore can recognise them and take up bacteria more efficiently
3) Cell lysis: Membrane attack complex: C9 --> polymerize -->hollow cylinders which form pores in bacterial membranes. Bacteria is porous and molecules escape = osmotic shock and death
40
what is complement?
Immune defence against bacteria (and viruses slightly). 20 serum proteins activated via an enzyme cascade.
41
name the 3 ways in which complement can be activated
the classical pathway, the MB-lectin pathway or the alternative pathway
42
name the complement factors in compliment, which is the most abundant?
C1, 4, 2, 3, 5, 6, 7, 8, 9 (in order but you don't need to know the order)
C3 is the most abundant
43
describe the classical pathway
the globular heads of C1 can bind to the Fc region of 2 IgG molecules or 1 Fc region of IgM. C1, 2, 3, 4 activated to form the membrane attack complex
44
why is IgM a more potent activator of compliment?
IgM can form a pentamer therefore there are more Fc regions
45
how do IgG and IgA act as opsonins?
IgA/M bound to a bacterium bind to Fc receptors on phagocyte. This creates pseudopods which engulf and fuse around the antibody coated bacterium. This creates a phagosome (vesicle containing bacterium) which then fuses with the lysosomes forming a phagolysosome. The bacteria is then destroyed by acid/peptides/proteins/toxic oxygen derivatives/enzymes
46
what are mast cells? where are they usually found?
mononuclear phagocytes involved in the release of inflammatory mediators. usually found underlying mucosal tissue
47
which antibody(s) can bind to NK cells?
IgG
48
describe antibody dependent cell-mediated cytotoxicity
NKs are lymphocytes which recognise infected host cells (not phagocytic)
Fc receptor on NK binds antibody bound to antigen on an infected host-cell
NK starts to make perforin (protein) – perforates membrane of infected cell (structure like membrane attack complex)
This doesn’t kill the host cell, the NK uses it as a channel in which it pumps granules full of enzymes to make the infected cell undergo apoptosis
49
how are Fc receptors on mast cells used in an allergic response?
initial exposure to the allergen means it (the allergen) binds to IgE and causes a large amount of IgE to be produced. During a second exposure IgE binds to Fc receptors on mast cells. The IgE cross-link and trigger the response of the mast cell which undergoes degranulation. Inflammatory mediators are released and cause local inflammation. This is beneficial in response to parasites.
50
whats the difference between polyclonal and monoclonal antibodies?
monoclonal: A Monoclonal antibody, by contrast, represents antibody from a single antibody producing B cell and therefore only binds with one unique epitope
polyclonal: antibodies that are secreted by different B cell lineages within the body. They are a collection of immunoglobulin molecules that react against a specific antigen, each identifying a different epitope.
51
how are polyclonal antibodies produced?
- Immunise animal with pure preparation of molecule you’re interested in
- primary and secondary response occurs
- Take a sample of blood, allow to clot to remove clotting factors, take clear solution left (contains antibodies
52
how are monoclonal antibodies produced?
- Derived from single B-cell fused with a tumour cell line
- Tumour cell is a type of mutant plasma cell which can’t make its own antibodies
- Hybrid cells make antibody and divide indefinitely
53
name the 4 ways in which antibodies are used in research, diagnostics and therapy
1) Identifying and labelling molecules in complex mixtures
2) Serotyping pathogens – the differentiation between different bacterial strains
3) Characterising cell surface proteins, identifying cell types
4) Humanised antibodies are used in therapy - antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans.
54
name the 2 major subgroups of T cells and what they do
```
T-helper cells (CD4 +ve):
- Help B cells make antibodies
- Activate macrophages and NKs
- Help development of cytotoxic T cells
T-cytotoxic cells (CD8 +ve)
- Recognise and kill infected host cells
```
55
describe the structure of the T lymphocyte receptor
Receptor only ever on the membrane, never secreted
α-helix allows the receptor to cross the membrane
Two domain structure, linked by disulphide link (α and β units)
Similar to Fab arm of antibody
- Has variable and constant regions (constant closest to membrane)
56
how do T and B cells differ in antigen recognition?
B-cells recognise soluble, free, native (antigen that hasn’t been processed in anyway) antigens
T-cells recognise cell-associated (attached to body’s own cells), processed (broken into peptides) antigen
57
what are Major Histocompatibility Proteins (MHCs)?
small proteins that bind to processed antigen in order for infected host cells to be recognised by T-cells
58
how are Major Histocompatibility Proteins (MHCs) encoded?
Encoded by the Major Histocompatibility gene Complex (MHC) on chromosome 6
59
what is the significance of MHCs being highly polymorphic?
their polymorphism (variability of alleles at each gene) means they can bind a wide range of processed antigens (peptides) and therefore have a broad specificity.
60
which cells express MHC I and which cell do they present to?
Expressed by all nucleated cells
| Display antigen to CD8 +ve (cytotoxic) T-cells
61
which cells express MHC II and which cell do they present to?
Expressed by macrophages, dendritic cells, B-cells
| Display antigen to CD4 +ve (helper) T-cells
62
how do MHC I processed antigens reach the cell membrane? how does the specific T-cell deal with the infected host cell?
Virus-infected cell --> viral proteins, broken down in cytosol (proteosomes)
Peptides transported to ER, bind MHC I --> cell surface
Activated cytotoxic T-cells kill the infected cell (via perforins etc) by inducing apoptosis
63
how do MHC II processed antigens reach the cell membrane? how does the specific T-cell deal with the infected host cell?
Macrophage/dendritic cell/B-cell intenalises and breaks down foreign material
Peptides bind to MHC II in endosomes --> cell surface
Activated T helper cells help B cells make antibodies, produce cytokines that activate/regulate oter leucocytes
64
cytokines are produced and act locally, why is this?
Cytokines are toxic in high concentrations therefore need to act locally
65
what are the 4 main groups of cytokines
interleukins
chemokines
colony stimulating factors
interferons
66
which cells usually produce interleukins? roughly how many interleukins are there?
usually T cells
| approx 38 of them
67
when are interferons released? which ones are released when?
- Viral infections eg IFNα, IFNβ
| - Immune system cell activation eg IFNγ
68
what do chemokines do?
cell movement (chemotaxis)
69
what do colony stimulating factors do?
stimulate leukocyte production
70
what happens when a cytokine binds to its receptor?
Binding of a cytokine to its receptor can cause cell activation and changes in gene expression
- Many are dimeric enzyme-coupled receptors
- Chemokine receptors are G-protein coupled receptors
71
name the 2 subgroups of CD4+ve cells
TH1 and Th2 cells
72
what do TH1 and TH2 cells do?
```
TH1 cells:
- Produce IL-2, γ-interferon and TNFβ.
- Activate macrophages
- Induce B-cells to make opsonizing antibodies (IgG)
TH2 cells:
- Produce IL-4, 5, 6, 10, 13.
- Induce B-cells to make IgE
```
73
what do T regulatory cells (TREGs) do?
Produce IL10, IL35 – suppress other T-cells
74
what is the hygiene hypothesis and who came up with it?
the lack of exposure to 'dirt' (bacteria). Insufficient exposure to certain types of infection skew TH1/TH2 balance towards TH2 (which is parasite/allergy TH cell type)
BUT negative correlation between helminth (parasite) infections and allergic disease
Infection releases both TH1&2 as well as TREGs therefore insufficient exposure to infection prevents TREG development
75
how does lymph travel through the body?
Lymph is an extracellular fluid that accumulates in tissues and is carried by lymphatic vessels back to through the lymphatic system to the thoracic duct and into the blood
76
what happens when bacteria enter the skin and it becomes infected? (ie describe the activation of adaptive immunity in the draining lymph node)
1st: bacteria are phagocytosed by macrophages; and presented on dendritic cells
2nd: dendritic cells and macrophages enter the lymphatic system and travel to lymph node
3rd: if T-cell comes across dendritic cell with foreign antigen => T cell activation (production cytokines)
4th: Cytokines stimulate B cells to divide and differentiate into plasma cells => antibody production
5th: Antibodies and T cells exit lymph node to circulate
77
what type of virus is HIV?
retrovirus
78
what does the HIV nucleocapsid contain?
Nucleocapsid contains 2xssRNA, RT, protease, integrase
79
how does HIV replicate?
Virus binds cell receptor – virus recognises membrane proteins
Virus envelope fuses with plamsa membrane
Nucleocapsid enter cytoplasm
Viral RNA reverse transcribed into dsDNA
Viral DNA trasnported to nucleus and integrates into host cell genome – forms a provirus
- Provirus is not replicating or making proteins
80
HIV infections can be classed into 3 groups: latent, permissive, lytic. Describe each of these groups
Latent:
- Provirus
Permissive:
- Small amounts of transc/transl and the host cell is kept alive
Lytic:
- Lots of proteins being made, cell death by lysis
81
which immune cell is susceptible to HIV infection?
CD4+ve cells (T helper cells) susceptible to infection (GP120 protein binds to CD4+ve receptor)
82
how do latent HIV proviruses become activated?
T cell stimulation activates HIV provirus transcription
- Number of T cells infected increases with each round of viral replication
- Will eventually lyse cells
83
what is the significance of monocytes becoming infected with HIV?
Monocytes may traverse the blood/brain barrier --> CNS involvement
84
what happens if there are no chemokine receptors on CD4+ve cells when HIV has entered the body?
CD4+ve expression not sufficient for HIV infection – must be expression of coreceptor (chemokine receptors) on cell surface for HIV to use
- In an experiment a human CD4+ve receptor was expressed in a mouse without coreceptors, the mouse’s cells weren’t infected by HIV
85
why do young and healthy people take longer to develop AIDS?
they produce lots of chemokine which occupy chemokine receptors meaning HIV can’t bind
86
how are T helper cells depleted by HIV?
Direct lysis by virus
Killed by cytotoxic T cells or other immune mechanisms
Apoptosis
87
what happens if the T helper cell conc decreases below:
- 500 T cells per μl
- 200 T cells per μl
- 500 T cells per μl: symptoms develop
| - 200 T cells per μl: AIDS
88
what are some of the symptoms associated with AIDS?
Opportunistic infections
Reactivation of latent viruses
Rare cancers
CNS involvement, dementia
89
state the origin, lineages and severity of HIV-1
Origin = Central Africa
4 lineages (M, N, O, P) each transmitted independently from primates to humans
- M is the pandemic form
- Likely source is a subgroup of chimpanzees
- Cross-species transmission in ’10-‘30
- 9M subtypes that predominate in different locations
90
state the origin and severity of HIV-2
Origin = W Africa
Predates HIV-1
Likely source = sooty mangabees
Less virulent and less easily transmitted
91
how is HIV transmitted? when are you most infectious if you have HIV?
```
Most infectious immediately after infection
Unprotected sex
Blood/blood products
Breats-feeding
Mother to foetus
```
92
name the 5 methods of preventing and/or treating HIV
```
vaccines
drug therapy
immunisation (kick and kill)
passive immunisation
gene editing(? - this is one for the future)
```
93
name the problems associated with vaccination and HIV
High mutation rate of virus
Humoral immunity may not be protective you need to induce the cytotoxic T cells
Several vaccine trials (some failures but also some recent successes)
Success: RV144 pox virus (inactivated) + HIV proteins (30% success rate)
94
name the problems associated with drug therapy and HIV
High mutation rate
Toxicity (side effects)
Viral latency (person doesn’t express symptoms so early treatment isn't possible and late treatment is significantly less effective)
Cost
95
what is combination therapy?
3 different drugs used in tandem; HIV can’t mutate fast enough to overcome them
96
name 4 examples of drug therapy
AZT (prevents viral replication)
Inhibitors of reverse transcriptase
HIV protease inhibitors
Fusion inhibitors
97
describe the kick and kill method of treatment
Vaccine stimulates cytotoxic T cells – boosts own immune system so they start killing the virally infected T helper cells.
Then drugs are used to induce the infection (activate latent infection)
The vaccine-stimulated cytotoxic T cells then kill the infected T helper cells
MBB163
flashcards
Decks in class (12)
# Cards
-
Gilmour 116
-
Mesnage - Microbial Diversity11
-
Mesnage - Virus structure and function13
-
Mesnage - Cell structure and function in bacteria20
-
Mesnage - Archaeal Diversity8
-
Gilmour - Eukaryotic Microbial Diversity21
-
Gilmour - Metabolic Diversity of Microbes41
-
Gilmour - Food & Industrial Microbiology15
-
Gilmour - Microbial Ecology61
-
Mesnage - Bacterial Growth49
-
Partridge - Immune System97
-
Fenton - Pathology and Disease74
