Immunology Flashcards
1
Q
What are the 3 polymorphonuclear leukocytes?
A
- Neutrophils
- Eosinophils
- Basophils
2
Q
What are the 3 mononuclear leukocytes?
A
- Monocytes
- T-cell
- B-cell
3
Q
What do monocytes differentiate into?
A
Macrophages.
4
Q
What do T-cells differentiate into?
A
- T-regs
- T-helper cells (CD4) (Th1 and Th2)
- Cytoxic T cells (CD8)
5
Q
What do B-cells differentiate into?
A
Plasma cells.
6
Q
What other immune cells should we be aware of?
A
- Mast cells (migrant granulated cell)
- Natural killer cell (lymphocyte family)
- Dendritic cell (antigen-presenting cells in tissues)
7
Q
Where is complement secreted?
A
The liver.
8
Q
What are the 3 modes of action for complement?
A
- Direct lysis
- Attract more leukocytes to site of infection
- Coat invading organisms
9
Q
How do antibodies circulate in the blood?
A
- Bound to B-cells
- Free in plasma
10
Q
Which part of the antibody is responsible for antigen binding?
A
- Fab regions
- Variable in sequence
- Bind to specific antigens
11
Q
Which part of the antibody is responsible for antigen elimination?
A
- Fc region
- Constant sequence
- Binds to complement, Fc receptors on phagocytes and natural killer cells
12
Q
What are the 5 classes of antibodies?
A
- IgG (most abundant in serum and tissues)
- IgA
- IgM
- IgD
- IgE
13
Q
Describe the structure of IgG antibodies.
A
- Monomer
- 2 heavy chains (bind to B cell)
- 2 light chains (bind to antigen)
14
Q
Describe the structure of IgA antibodies.
A
- Mostly a monomer
- Can be a dimer (20% in humans)
- Held together by a J chain and a secretory unit
15
Q
Describe the structure of IgM antibodies.
A
- Pentamer (formation dependant on J chains)
- Monomeric form bound to B cells
16
Q
Where are IgG antibodies mainly found?
A
Most abundant serum antibody.
17
Q
Where are IgA antibodies mainly found?
A
Mucous secretions - known as secretory IgA (sIgA).
Also found in serum.
18
Q
Where are IgM antibodies mainly found?
A
Largely in blood as they are too large to cross vascular endothelium.
19
Q
Where are IgD antibodies mainly found?
A
The mature form are mostly found bound to mature B cells.
20
Q
Where are IgE antibodies mainly found?
A
50% in blood, the rest are bound to mast cells and basophils.
21
Q
What are IgG antibodies responsible for?
A
- Main antibody in the adaptive immune response
- Secondary/memory responses
- Crosses placenta
22
Q
What are IgA antibodies responsible for?
A
- First line of defence
23
Q
What are IgM antibodies responsible for?
A
- Initial contact with antigen (principal immune response)
- 10 sites for antigen binding (mopping up antigens in blood supply)
24
Q
What are IgD antibodies responsible for?
A
- No effector functions have been identified (it does bind to antigens)
25
what are IgE antibodies responsible for?
- Binds to basophils and mast cells which express a high affinity IgE-specific receptor
- Stimulates histamine release from basophils and mast cells
- Hypersensitivity reactions and defence against parasitic infections
26
Describe the mechanism of action of antibodies.
- Direct attack on the invader
- Activation of complement system
27
Describe the mechanism of action of direct attack (antibodies).
1. Agglutination (antigen-presenting particles are bound together)
2. Precipitation (molecular complex is so large it comes out of solution)
3. Neutralisation (antibodies cover the toxic sites)
4. Lysis
28
What are cytokines?
Proteins secreted by immune and non-immune cells.
29
What is the action of interferons?
Induce a state of viral resistance in uninfected cells and limit the spread of viral infection.
30
Give the 3 types of interferons.
1. IFN⍺
2. IFNβ
3. IFN𝛾
31
Which cells secrete interferons?
Virus-infected cells secrete IFN⍺ and β.
Activated Th1 cells secrete IFN𝛾.
32
What do interleukins do?
- Can be pro-inflammatory (IL1) or anti-inflammatory (IL10)
- Can cause cells to divide, differentiate and secrete factors
33
What do colony-stimulating factors do?
Direct the division and differentiation of bone marrow stem cells (leukocyte precursor).
34
What do tumour necrosis factors do?
Mediate inflammation and cytotoxic reactions (TNF⍺ and β).
34
What are chemokines?
~40 proteins that direct the movement of cells from the blood stream to the tissues
35
Define innate immunity.
- Primitive
- Instinctive response
- Does not require immune recognition by lymphocytes
- No long-lasting memory
- Integrated with adaptive immunity
36
What are Pattern Recognition Receptors (PRRs)?
Receptors on immune cells that detect the presence of PAMPs.
37
What are Pathogens Associated Molecular Patterns (PAMPs)?
Pathogen-specific molecules that can be detected by PRRs.
38
What are toll-like receptors (TLRs)?
A type of PRR, that recognise structurally conserved molecules derived from microbes.
39
What are the components of innate immunity?
1. Physical and chemical barriers (eg. skin)
2. Phagocytic cells (neutrophils and macrophages)
3. Blood proteins (complement and acute phase proteins)
40
What are the 3 features of inflammation?
1. Increased blood supply
2. Increased vascular permeability
3. Increased leukocyte extravasation
41
Which cells detect the presence of antigens in the blood?
Monocytes and neutrophils.
42
Which cells detect the presence of antigens in tissues?
Macrophages and dendritic cells.
43
What are the 3 activation pathways for complement?
1. Classical (antibody binds to microbe)
2. Alternative (complement binds to microbe)
3. Lectin (activated by mannose-binding lectin bound to microbe)
44
What are the three ways complement can act on microbes?
1. Lyse microbes directly through the action of MAC (membrane attack complex)
2. Chemotaxis
3. Opsonisation (make them easier to phagocytose)
45
Describe the 3 ways phagocytosis can be initiated.
1. Antibodies bound to antigens on microbe can bind to antibody receptors
2. C3b opsonised on microbe binds to complement receptor
3. Mannose receptors bind to carbohydrates on bacteria wall
46
What are the 3 steps to phagocytosis?
1. Binding
2. Engulfment
3. Phagosome formation
47
What are the 2 pathways in neutrophils and macrophages?
1. Oxygen-dependent
2. Oxygen-independent
48
Describe the oxygen-dependent pathway in neutrophils and macrophages.
- Uses reactive oxygen intermediates (ROI)
- Superoxide ions are converted to H2O2 then to a hydroxide free radical
49
Describe the oxygen-independent pathway in neutrophils and macrophages.
- Enzymes (eg. lysosome)
- Proteins (eg. defensins inserted into the membrane of the microbe)
- pH
50
What are the 3 possible outcomes after phagocytosis?
- Debris gets secreted by the phagocytic cell
- Cell components converted to energy
- Antigens get presented on cell surface via MHC class II receptor
(MHC = major histocompatibility complex)
51
Why is adaptive immunity required?
- Microbes can evade innate immune responses
- Intracellular viruses and bacteria evade innate immunity
- Memory of specific antigens allows a faster response
52
What is the function of T cells and B cells?
T cells - intracellular microbes (cell-mediated)
B cells - extracellular microbes (humoral)
53
What's the link between innate and adaptive immunity?
Antigen-presenting cells of the innate immunity activate T cells of the adaptive immunity.
54
What do T lymphocytes respond to?
Intracellular presented antigens.
55
What does the T cell receptor do?
- Recognises foreign antigens in association with MHC
- Activates the T cell
56
Which MHC class presents intrinsic agents and where is it expressed?
MHC class I (expressed by all cells except RBCs).
57
Which MHC class presents extrinsic pathogens and where is it expressed?
MHC class II (expressed by antigen-presenting cells).
58
How can you remember which CD cells bind to which MHC class?
They multiply to equal 8.
CD8 binds to class I and CD4 binds to class II.
59
How can you remember the action of T cells?
CD8 is full of hate (Tc killer cells).
60
What must happen for full T-cell activation?
Co-stimulatory molecules CD28 on T cells bind to CD80/CD86 on antigen-presenting cell.
61
What happens when a T cell is activated?
IL-2 is secreted and binds to IL-2 receptor on the T cells (autocrine).
62
What does T cell activation lead to?
- Division
- Differentiation (CD4 and CD8)
- Effector functions
- Memory
63
What does Tc (CD8) activation lead to?
- Apoptosis
- Secretion of IFN𝛾 (inhibiting viral invasion)
- Secretion of chemokines
- Kills cells directly
64
What does Th1 (CD4) activation lead to?
- Travel to secondary lymphoid tissue (eg. lymph nodes)
- Th1 cells recognise antigen on infected cells via T cell receptor
65
What does Th2 (CD4) activation lead to?
- Bind to B cells which are presenting antigens
- T cell secretes cytokines
- These cause the B cell to divide and differentiate
66
Which membrane bound antibodies do B cells express?
IgM or IgD monomers.
67
How many types of antibodies can an individual B cell make?
- 1 antibody specific to 1 antigen
- We are born with all the B cells required to identify any pathogen
68
What happens when a B cells recognises self?
Its killed in the bone marrow.
69
How do B cells present antigens to T cells?
- Phagocytose pathogen
- Present antigen on MHC II
- T cell receptor binds to MHC II
- Lots of co-stimulatory molecules required
70
What happens when B cells become activated?
B cell becomes a plasma cell and produces immunoglobulins.
71
What do B cells differentiate into?
- Plasma cells (antibody forming cell)
- Memory cells
72
What is the function of memory cells?
- Long lasting immunity
- Responds quickly next time it detects the same antigen
- Vaccination
73
What is the immunological theory?
Infection leads to the production of 'protective substances' in serum which can neutralise and kill pathogens.
- Protection persists (memory)
- Protection transfers to other individuals
74
Define passive immunisation.
The transfer of pre-formed antibodies.
75
What are the 2 types of passive immunisation?
- Natural immunisation
- Artificial immunisation
76
Describe natural passive immunity.
Transfer of preformed maternal antibodies across placenta or through breast milk.
Provides protection against:
- Diptheria
- Tetanus
- Rubella
- Mumps
- Poliovirus
77
Describe artificial passive immunity.
Treatment with pooled human IgG (immunoserum).
Effective for:
- Immunocompromisation
- Pathogens with a short incubation time
- Acute danger of infection (eg. rabies)
- Anti-toxins or anti-venoms
78
What are the disadvantages of passive immunisation?
- Does not provide immunological memory
- No long term protection
- IgG is cleared from circulation
79
How do toxins act on a nerve cell to produce toxic effects?
Toxin prevents fusion of vesicles at the synapse so the neurotransmitters cannot get into the synapse.
80
How does a tetanus toxin act on the synapse?
Tetanus toxin vesicles contain lysine and GABA which prevents muscle relaxation, causing muscle contraction (spasticity).
81
How does a botulinum toxin act on the synapse?
Botulinum vesicles contain ACh which prevents muscle contraction, causing muscle relaxation.
82
Define active immunisation.
Manipulation of the immune system to generate a persistent protective response against pathogens by mimicking natural infection.
83
How does inoculation differ from active immunisation?
Inoculation refers to the introduction of viable microorganisms into an individual to evoke an immune response.
84
What are the advantages of active immunisation?
- Antigen specificity and diversity
- Mobilises immune system to generate memory
- Learned immunological behaviour (fast response)
- Specific self/non-self recognition
85
What are the 4 stages of active immunisation?
1. Engage innate immune system
2. Mimicking agent elicits danger signals, triggering PAMPs and TLRs
3. Activation of specialist antigen-presenting cells
4. Engage adaptive immune system to generate memory T and B cells
86
Describe the polysaccharide antigen response. (Pnemovax vaccine)
- Produces T-cell independent B-cell response
- Produces the required antibody
- Cannot be used in children under 2 as they do not have T-cell-independent B-cell response
87
Describe the protein antigen response.
(Men-C vaccine)
- Requires both T-cell and B-cell to process and produce immune response
- Combines polysaccharide and protein structure
- Effective in children
88
How does the onset of influenza affect the activation of immunological memory?
- Rapid onset so the infection can become established before immunological memory can be activated
- Requires repeated, annual immunisation
89
How does the onset of polio affect the activation of immunological memory?
- Takes up to three days to establish infection of the nervous system
- Provides opportunity for immunological memory activation
90
What are the different antigen options used in vaccines?
- Whole organism (live attenuated or killed/inactivated)
- Subunit
- Peptides
- DNA/RNA
- Engineered virus
91
Give an example of whole organism vaccinations.
- Live attenuated pathogen (eg. TB, typhoid, MMR)
- Killed, inactivated organism (eg. influenza, Hep A, anthrax)
92
What are the advantages of live-attenuated vaccination?
- Causes transient infection
- Activates full, natural immune response
- Prolonged contact with the immune system
- Produces memory response
- Long and comprehensive protection
93
What are the disadvantages of live-attenuated vaccination?
- Immunocompromised individuals at risk of infection
- Complications
- Risk of reverting to virulent form
- Can lead to outbreaks in areas with poor sanitation
94
What are the advantages of dead/inactive pathogen vaccination?
- No risk of infection
- Storage is less critical
- Strong immune response possible due to different antigenic components
95
What are the disadvantages of dead/inactive pathogen vaccination?
- Tend to just activate humoral response (lack of T cell involvement)
- Immune repsonse is weaker
- Booster vaccination required
96
Give examples of subunit vaccinations.
- Inactivated exotoxins (eg. diptheria and tetanus)
- Antigenic extracts (eg. Men C)
- Recombinant microbial antigens
97
What are the advantages of subunit vaccinations?
- No risk of infection
- Easier to store and preserve
98
What are the disadvantages of subunit vaccinations?
- Produce weaker immune response
- Repeated vaccinations and adjuvants required
- Must consider genetic heterogeneity of the population by choice of antigen
99
Give an example of synthetic peptide vaccinations.
- Therapeutic cancer vaccines (peptides from tumour associated antigens)
- No current vaccines
100
What is a major disadvantage of peptide vaccinations?
Not efficient due to the heterogeneity of the HLA molecules in the population.
101
How does DNA vaccination work?
- Transient expression of pathogenic genes into host cells in order to generate immune responses
- Involves injecting a genetically engineered plasmid containing the DNA sequence encoding the antigen
- No current vaccines
102
What are the advantages of DNA vaccination?
- No risk of infection
- Cost effective
- Stability in shipping and storage
- In vivo expression
103
What are the disadvantages of DNA vaccination?
- No transient infection (mild response)
- Require booster vaccinations
- Limited to protein imunogens
- Small risk of affecting genes controlling cell growth
104
How does recombinant vector vaccination work?
- Combining the physiology of a pathogenic organism with the DNA of a non-pathogenic
- Imitates the effect of transient infection
- Used to make Ebola vaccine for 2018 outbreak
105
What are the advantages of recombinant vector vaccinations?
- Ideal stimulus to immune system
- Produces immunological memory
- Flexible (different components can be engineered)
- Safe (relative to live attenuated vaccination)
106
What are the disadvantages of recombinant vector vaccinations?
- Require refrigeration for transport
- Can cause illness in immunocompromised individuals
- Immune response to virus in subjects can negate effectiveness.
107
What is an adjuvant?
Any substance added to a vaccine to stimulate an enhanced immune response.
108
Give an example of an adjuvant and how it enhances immune response.
Aluminium salts:
- Activates macrophages and lymphocytes
- Help the antigen-presenting cells absorb antigen
- Extend presence of antigen in the blood
- Potentiate opsonised phagocytosis
109
What cells are involved in cell-mediated immune response?
- Neutrophils and monocytes (phagocytes)
- Lymphocytes (antibody production)
110
What is involved in non-cellular (humoral) immune response?
- Immunoglobulins (antibodies)
- Complement
- Surfactant proteins
111
When are humoral response antibodies made during the immune response?
- IgM - made at the beginning of infection
- IgG - targets single epitomes
- IgE - specific to allergens
112
What are the common features of anaphylaxis?
- Rapid onset
- Blothcy rash
- Swelling of face and lips
- Wheeze
- Hypotension
- Cardiac arrest (if severe)
113
What drugs most commonly cause hypersensitivity reactions?
- Amiodarone
- Bleomycin
- Methotrexate
- NSAIDs
- Nitrofurantoin
- Novel Ig-based treatments
114
Describe Type 1 Hypersensitivity.
1. B cells are stimulated to produce IgE antibodies
2. IgE binds to mast cells and basophils (sensitisation)
3. Second exposure causes IgE cross-linking, anaphylactic degranulation of mast cells and release of inflammatory mediators
4. Leads to acute anaphylaxis
115
Give examples of Type 1 Hypersensitivity reactions.
- Allergic rhinitis (hayfever)
- Asthma
- Nut, food and drug allergies
116
What is atopy?
An inherited tendency to produce an exaggerated IgE response to an antigen.
117
How is Type 1 Hypersensitivity diagnosed?
Skin Prick Tests (SPTs)
(Or Radioallergosorbent Tests (RASTs), serum is exposed to bed of suspected allergen)
118
What is the treatment for hayfever?
- Prevent exposure
- Anti-histamines
- Steroids (reduce local inflammation)
- Desensitisation therapy
119
What is the treatment for acute anaphylaxis?
- Avoid exposure
- Anti-histamines (prevent/ease acute symptoms)
- Acute resuscitation (adrenaline, fluids etc)
- Decrease ongoing inflammation
120
Give examples of extrinsic asthma.
- Atopy-related asthma (IgE driven)
- Occupation asthma induced by acute irritants (or long term exposure to allergens or endotoxins)
121
Give examples of intrinsic asthma.
Late-onset asthma caused by conditions, eg. nasal polyposis and aspirin sensitivity.
122
Describe Type 2 Hypersensitivity.
Antibody mediated process by which IgM and IgG are directed against allergen cell surface antigens.
Leads to cell lysis, tissue damage or loss of function (through classical complement pathway and antibody-dependent cell-mediated cytotoxicity).
123
Give examples of Type 2 Hypersensitivity reactions.
- Transplant rejection
- Autoimmune diseases
124
Describe Type 3 Hypersensitivity.
Immune complex accumulation.
Occurs when immune complexes have not been cleared by innate immune cells, increasing activation and leukocyte recruitment.
125
Give examples of Type 3 Hypersensitivity reactions.
- Systemic Lupus Erythematosus
- Post-streptococcal glomerulonephritis
- Rheumatoid arthritis
126
Describe Type 4 Hypersensitivity.
Delayed T-cell mediated hypersensitivity.
1. CD4 and T-helper cells recognise antigens in complex with MHC class II
2. The APC secretes IL-12 (stimulates proliferation of CD4 and TH1 cells)
3. IL2 and INF induce further TH-1 cytokine release
4. Immune response leads to the activation of CD8 T cells and macrophages
127
What is a key presentation of Type 4 Hypersensitivity reactions?
Granulomas - collection of T-cells and macrophages formed during inflammation to wall-off foreign substances that the body is unable to eliminate.
128
Give examples of Type 4 Hypersensitivity reaction.
- TB
- Contact dermatitis
- Sarcoidosis
129
What drugs most commonly cause hypersensitivity reactions?
- Amiodarone
- Bleomycin
- Methotrexate
- NSAIDs
- Nitrofurantoin
- Novel Ig-based treatments
130
What is involved in the diagnosis and treatment of drug hypersensitivity?
Diagnosis:
- Lung function tests
- CT scans
- Chest X-rays
Treatment:
- Withdraw offending drug
- Steroids for severe respiratory failure
