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BM4 Part 1 > Immunology > Flashcards

Immunology Flashcards

1
Q

What are the 2 routes of adaptive immunity?

A

Humoral response and cell-mediated response.

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2
Q

What is the humoral response?

A

Production of a class of soluble proteins called antibodies from B cells.

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3
Q

What is the cell-mediated response?

A

A process where T cells directly kill pathogen-infected cells, or stimulates other immune cells to consume extracellular microbes (e.g. phagocytosis).

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4
Q

What are T and B cells?

A

Class of leukocytes and contribute 20-40% of WBCs in a healthy individual.

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5
Q

Clonal Expansion

A

Cells rapidly proliferate upon encountering an antigen that they leading to the formation of a large population of identical cells capable of recognising the same antigen.

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6
Q

What are the cells of the innate immune system?

A

Neutrophil, monocyte/macrophage, eosinophil, NK cell, tissue mast cells, basophil.

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7
Q

What percentage of leukocytes are neutrophils?

A

50-70%

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8
Q

What percentage of leukocytes are monocytes/macrophages?

A

1-6%

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9
Q

What percentage of leukocytes are eosinophils?

A

1-3%

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10
Q

What is the function of eosinophils?

A

Deals with infections that are greater than a single cell (e.g. parasites).

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11
Q

What is a Natural Killer cell?

A

A type of lymphocyte that can recognise and kill virus infected cells.

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12
Q

What is a mast cell?

A

Found in the tissue rather than circulation and activates due to antigen recognition or an innate response. Releases granular contents causing inflammation/swelling.

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13
Q

What percentage of leukocytes are basophils?

A

<1%

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14
Q

How does a newborn baby lose its mother’s passive immunity?

A
  1. Antibodies used up defending against pathogens.
  2. Antibodies effectively dilute as blood volume increases whilst child grows.
  3. Child does not inherit B cells/memory cells (this is the major reason as the other two are negligible).
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15
Q

How is acquired immunity passed from mother to baby?

A

Passage of antibodies across the placenta.
Secretion of antibodies in breast milk.

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16
Q

What are the 3 levels of innate immunity?

A
  1. Physical/chemical barriers.
  2. Recognition of conserved molecules expressed by microbes.
  3. Pathways and cells primed to activate in the absence of inhibitory signals (missing-self).
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17
Q

Examples of physical barriers

A

Epithelia of the skin, respiratory tract, GI tract, urogenital tract and conjunctivae.

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18
Q

Examples of chemical barriers

A

Sweat, mucus, tears, saliva, breastmilk, gastric acid.

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19
Q

PAMP

A

Pathogen Associated Molecular Patterns. Certain molecules that are common to certain classes of microorganisms.

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20
Q

Examples of PAMPs

A

Bacteria - peptidoglycan, LPS, flagellin, CpG DNA.
Fungi - zymosan
Virus - ssRNA

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21
Q

What are the 3 pathways following PAMP recognition?

A

Direct cytotoxicity.
Opsonisation and phagocytosis.
Intracellular signalling and inflammation.

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22
Q

Direct Cytotoxicity

A

Holes introduced into cell walls/membranes e.g. by complement, lysozyme or defensins.

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23
Q

Opsonisation

A

Coating of a foreign body with host molecules that signal for phagocytosis (e.g. CRP and C3b).

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24
Q

Phagocytosis

A

Uptake or ingestion of particulate material by cells, the purpose of which is to destroy the material through the exposure to a harsh chemical environment.

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25
Q

What are the 6 components of the phagocytosis environment?

A

Low pH.
Nutrient restriction (sequestration of iron).
H2O2 production (NADP oxidase).
NO production.
Anti-microbial peptides.
Proteases and lysozyme.

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26
Q

What cells carry out opsonisation and phagocytosis?

A

Neutrophils and macrophages.

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27
Q

What can trigger the complement cascade?

A

PAMPs, DAMPs and antigen-antibody complexes.

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28
Q

What are 4 symptoms/signs of immune response?

A

Increase in neutrophils
Increase in procalcitonin
Hypotension
Increase in lactate

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29
Q

Why can hypotension occur during an innate immune response?

A

Vasodilation to allow blood to flow to site of infection (promoting extravasation) and hypovalaemia due to movement of fluid into the tissue.

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30
Q

Complement

A

A series of plasma proteins which co-operate to facilitate direct killing, opsonisation and inflammation.

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31
Q

What is the function of C5?

A

C5 convertase cleaves C5 into C5a and C5b.
C5b recruits C6, C7 and C8 which inserts into the lipid membrane (MAC).
Once C8 has bound, it recruits C9 which polymerises and inserts itself through the plasma membrane forming a cylindrical pore with a hydrophilic core through which water and ions can enter.

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32
Q

Anaphylatoxins

A

C4a, C3a and C5a (released during complement cascade).
Cause smooth muscle contraction, vasodilation, histamine release from mast cells and enhance vascular permeability.

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33
Q

Opsonin

A

C3b

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34
Q

What is the starting component of the classical complement cascade?

A

C1q - acts as an initiating protein.

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35
Q

What is another name for CD8+ T cells?

A

Cytotoxic T cells.

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36
Q

What is another name for CD4+ T cells?

A

T helper cells.

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37
Q

What is Omenn’s disease?

A

An autosomal recessive form of SCID.
Usually have dermatological features, diarrhoea, faltering growth and hepatosplenomegaly.

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38
Q

Which immune cell releases histamine in response to an allergen?

A

Basophils.

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39
Q

Where are IgA antibodies produced?

A

By B cells in the mucosa.

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40
Q

Where are IgM antibodies produced?

A

B2 cells in the spleen and lymph nodes.

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41
Q

What are the first antibodies produced in response to an invading pathogen?

A

IgM.

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42
Q

Atopic Triad

A

Asthma, allergic rhinitis and atopic eczema.

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43
Q

What cytokines are produced by Type 2 helper T cells?

A

IL-4, IL-5 and IL-13.

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44
Q

What is the mechanism of Type I hypersensitivities?

A

Anaphylactic - antigen reacts with IgE bound to mast cells.

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45
Q

What are examples of Type I hypersensitivities?

A

Anaphylaxis, asthma, eczema, hayfever

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46
Q

What is the mechanism of Type II hypersensitivities?

A

Cell bound - IgG or IgM binds to antigen on cell surface.

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47
Q

What are examples of Type II hypersensitivities?

A

Autoimmune haemolytic anaemia
Immune thrombocytopenic purpura (ITP)
Good pasture’s syndrome
Acute haemolytic transfusion reactions
Pernicious anaemia
Rheumatic fever
Pemphigus vulgaris
Bullous pemphigoid

48
Q

What is the mechanism of Type III hypersensitivities?

A

Immune complex - free antigen and antibody (IgA, IgG) combine

49
Q

What are examples of Type III hypersensitivities?

A

Serum sickness
SLE
Post-streptococcal glomerulonephritis
Extrinsic allergic alveolitis

50
Q

What is the mechanism of Type IV hypersensitivities?

A

Delayed hypersensitivity - T-cell mediated

51
Q

What are examples of Type IV hypersensitivities?

A

TB/tuberculin skin reaction
Graft vs host disease
Allergic contact dermatitis
Scabies
Extrinsic allergic alveolitis
MS
GBS

52
Q

What is the mechanism of Type V hypersensitivities?

A

Antibodies that recognise and bind to the cell surface receptors, thus either stimulating them or blocking ligand binding.

53
Q

What are examples of Type V hypersensitivities?

A

Graves’ disease
Myasthenia gravis

54
Q

Hypersensitivity mechanisms

A

ACID
Anaphylaxis
Cell bound
Immune complex
Delayed

55
Q

IgA

A

Primary Ig found in secretions
Exists as a dimer
Mainly acts by neutralising pathogens and activating the alternative complement pathway

56
Q

IgD

A

Mainly located on B cells
Exists as a monomer

57
Q

IgE

A

Mainly located on mast cells and basophils
Exists as a monomer
Known for initiating Type I hypersensitivity reactions

58
Q

IgG

A

Most abundant Ig (80% of serum Ig)
Exists as monomer
Primarily found in serum and tissue fluids
Main functions include opsonisation, neutralisation and activation of complement cascade
Longest half-life of all Ig
Only Ig that can cross the placenta

59
Q

IgM

A

Expressed on surface of all naive B cells
Exists as pentamer
First Ig produced in infection
Therefore antigen-specific IgM in serum indicates recent infection
Main functions are agglutination, opsonisation and activation of classical complement cascade

60
Q

What are the functions of antibodies?

A

Neutralisation
Opsonisation
Complement fixation
Antibody-dependent cell-mediated cytotoxicity (ADCC)

61
Q

What is ADCC?

A

Antibody-dependent cell-mediated cytotoxicity
IgG recruits effector cells (e.g. NK cells) to infected cells, which are then targeted for apoptosis.

62
Q

Where do B cells develop?

A

Develop and mature in the bone marrow, arising from common lymphoid progenitor cells.

63
Q

What antibodies are on the surface of all naive B cells?

A

IgM and IgD

64
Q

What is the germinal centre response?

A

Activation and proliferation of B cells in the secondary lymphoid organs.
B cells undergo class switching and somatic hypermutation.

65
Q

What is antibody class switching?

A

Process by which activated B cells switch from producing IgM and IgD to expressing IgA, IgE or IgG in order to produce a more effective antibody reponse.

66
Q

What are memory B cells?

A

Long-lived resting B cells, capable of generating a faster and stronger adaptive immune response

67
Q

What are plasma cells?

A

Differentiated B cells capable of secreting high amounts of high-affinity antibodies.

68
Q

What is somatic hypermutation?

A

Diversification of antibodies produced by B cells allowing the production of the highest affinity antibodies for a specific infection

69
Q

Where do T cells develop and mature?

A

Develop in bone marrow before migrating to the thymus to mature

70
Q

What is an antibody?

A

Soluble protein produced from activated B-cells (plasma cells) that binds to a B-cell epitope of an antigen

71
Q

What 2 signals are required for antibody production?

A

Binding of antigen to surface-bound antibody on the B-cell (signal 1)
Presence of activated T-helper cell which recognises the same antigen (signal 2)

72
Q

What type of epitope can T-cells recognise?

A

Peptides

73
Q

When may only 1 signal be needed for antibody activation?

A

Presence of an array of multiple single B-cell epitopes (e.g. bacterial polysaccharides) so that there is sufficient signal 1

74
Q

What are the regions that make up an antibody?

A

Two light chains
Two heavy chains
Fab (antigen binding) region
Fc (constant) region

75
Q

Which antibodies directly promote phagocytosis?

A

IgG
IgA

76
Q

Which antibodies indirectly promote phagocytosis?

A

IgG (classical complement pathway - antibody + antigen + C1q)
IgM

77
Q

Which antibodies transfer across the placenta?

A

IgG

78
Q

Which antibodies are secreted?

A

IgA (main)
[IgM]

79
Q

Which antibodies bind to mast cells?

A

IgE - leading to hypersensitivity reactions

80
Q

Which antibody is the first to be produced?

A

IgM

81
Q

Which antibodies are monomers?

A

IgG
IgE
IgD
IgA = dimer
IgM = pentamer

82
Q

How is the variation in antigen binding sites generated?

A

‘Natural’ genetic recombination of heavy and light chains (light chain = V,J regions with constant C, heavy = V,J,FD,C)

83
Q

When does recombination of heavy and light chains occur?

A

During B-cell development

84
Q

What is negative B-cell selection?

A

Removing any B-cells that bind to self-antigen.

85
Q

What is the lifespan of B-cells?

A

3-6 months

86
Q

What is herd immunity?

A

The phenomenon that unvaccinated individuals are protected from disease due to proportion of population that is vaccinated

87
Q

What is the R0?

A

Basic reproduction number
The average number of individuals each infected individual will infect within a population that has no immunity to the disease

88
Q

What can cause severe complications from vaccination?

A

Pre-existing immune suppression
Reversion of live-attenuated vaccine
Allergic reaction to vaccine components
Other vaccine-related pathologies (e.g. intussusception with rotavirus vaccine)

89
Q

Why do purified carbohydrates from the surface of bacteria often represent poor vaccine candidates?

A

Don’t contain proteins, therefore cannot activate T-cells. T helper response is required for development of immunological memory.

90
Q

What is released by Th cells to activate antibody secretion by B cells?

A

IL-2

91
Q

What is released by Th cells to activate CTLs?

A

IL-2

92
Q

What is released by Th cells to activate NK cells?

A

IFN-gamma

93
Q

What is released by Th cells to activate phagocytosis by macrophages?

A

IFN-gamma

94
Q

Where does activation and proliferation of T and B cells occur?

A

Secondary lymphoid tissue (aka lymph glands)

95
Q

What are the 3 classes of T cells?

A

CTLs, T helper and T regulatory cells.

96
Q

How do B cells recognise antigens?

A

Through B Cell Receptor (BCR)

97
Q

Which cells are professional APCs?

A

Macrophages, B cells, dendritic cells

98
Q

Which cells recognise peptide bound to MHC Class I?

A

Cytotoxic T Lymphocytes (CD8)

99
Q

Which Class of MHC presents exogenous peptides?

A

Class II

100
Q

What is cross-presentation?

A

Carried out in DCs only.
Process of presenting exogenous peptides on MHC Class I molecule for recognition by CTLs.

101
Q

What chains make up the TCR?

A

Alpha and beta chains

102
Q

What is the major difference between acceptable B and T cell epitopes?

A

BCR can accept linear or conformational epitopes. TCR can only accept linear.

103
Q

When does T and B cell recombination occur?

A

B cell - continuous (bone marrow continuously generating naive B cells)
T cell - predominantly at the start of life

104
Q

What receptor is used by HIV to gain entry into cells?

A

CD4 receptor of T helper cells.

105
Q

What marker is found generally on all T cells?

A

CD3

106
Q

What stem cell line do lymphocytes originate from?

A

Lymphoid progenitors

107
Q

What is thymocyte positive selection?

A

Thymocytes expressing a TCR that weakly recognises self-MHC molecules on cortical epithelial cells survive

108
Q

What is thymocyte negative selection?

A

Thymocytes expressing a TCR that strongly recognises self-MHC molecules molecules in combination with self-peptide on DCs undergo apoptosis

109
Q

What is the key role of T reg cells?

A

Dampening/resolving an adaptive immune response

110
Q

What are the key cytokines secreted by T reg cells?

A

TGF-beta and IL-10

111
Q

What types of bacterial molecule will the T-cell be able to see as foreign?

A

Peptides

112
Q

What type of bacterial molecules will signal danger to the dendritic cell?

A

PAMPs

113
Q

What class of drug is prednisolone?

A

Synthetic glucocorticoid

114
Q

What type of receptor does prednisolone act upon?

A

Nuclear receptor (lipid soluble)

115
Q

Define the distinction between innate and adaptive immunity.

A

Innate immunity is the body’s first line of defense and provides immediate, nonspecific protection against pathogens, while adaptive immunity is a more specific and targeted response that develops over time.

116
Q
A

BM4 Part 1 (11 decks)

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