IMMUNOLOGY Flashcards

1
Q

What must the immune system do in order to be effective?

A

Must discriminate self from non-self

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2
Q

Describe innate immunity

A
Non-specific
Instinctive 
Present from birth 
First line of defence 
Based on physical and chemical barrier and phagocytosis (No lymphocyte involvement)
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3
Q

Give examples of physical and chemical barriers used in innate immunity

A

Skin, mucociliary escalator, gastric acid, hairs, lysozymes

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4
Q

What is the function of a lysozyme?

A

To destroy bacterial cell walls

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5
Q

Describe adaptive immunity

A
Specific
Acquired/learned immunity
Requires lymphocytes 
Antibodies 
Memory and quicker response
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6
Q

Name 3 polymorphonuclear leukocytes

A
  1. Neutrophil
  2. Eosinophil
  3. Basophil
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7
Q

Name 3 mononuclear leukocytes

A
  1. Monocytes
  2. T lymphocytes
  3. B lymphocytes
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8
Q

In which primary lymphoid tissue do T cells mature?

A

Thymus

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9
Q

In which primary lymphoid tissue do B cells mature?

A

Bone marrow

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10
Q

How do T cells recognise antigens?

A

Antigens must be displayed by an antigen presenting cell and bound to MHC1/2
(T cells can’t recognise soluble antigens)

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11
Q

What is the function of a T helper 1 (CD4)?

A

Helps immune response against intracellular pathogens

Secretes cytokines

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12
Q

What is the function of a T helper 2 (CD4)?

A

Helps produce antibodies against extracellular pathogens

Secretes cytokines

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13
Q

What is the function of cytotoxic T cell (CD8)?

A

Kills cells directly by binding to antigens - they induce apoptosis

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14
Q

What is the function of T reg?

A

They regulate the immune response

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15
Q

Which cells express MHC 1?

A

All nucleated cells

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16
Q

Which cells express MHC 2?

A

Antigen presenting cells - macrophages, B cells and dendritic cells

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17
Q

Which MHC would an intracellular antigen (endogenous) lead to the expression of?

A

MHC 1

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18
Q

Which MHC would an extracellular antigen (exogenous) lead to the expression of?

A

MHC 2

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19
Q

What type of T cell binds to MCH 1?

A

Cytotoxic T cells (CD8)

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20
Q

What type of T cell binds to MCH 2?

A

Helper T cells (CD4)

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21
Q

What do B cells differentiate into?

A

Plasma cells

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22
Q

What do plasma cells produce?

A

Antibodies

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23
Q

What does a helper T cell bind to?

A

A T cell receptor which is bound to an antigen epitope which Is bound to MHC 2 on an APC

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24
Q

Which interleukin is secreted when a helper T cell is bound to a T cell receptor?

A

IL-2
IL-2 binds to an IL-2 receptor on the T cell and produces positive feedback mechanism leading to division and differentiation

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25
Q

How many antibodies can each B cell make?

A

Only 1 antibody which can only bind to 1 epitope

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26
Q

What happens to B cells that recognise ‘self’?

A

They are killed in bone marrow

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27
Q

Describe the process of a T helper cell binding to a B cell

A

A B cell antibody binds to an antigen
Phagocytosis
Epitope is displayed on the surface of the B cell bound to an MHC 2
TH2 binds to B cells
Cytokine secretion induces B-cell clonal expansion
Differentiation into plasma cells and memory B cells

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28
Q

Give 3 functions of antibodies

A
  1. Neutralise toxins
  2. Opsonisation
  3. Activate classical complement system
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29
Q

Name 5 immunoglobulins

A
IgG
IgA
IgM
IgD
IgE
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30
Q

What are the 2 most common immunoglobulins?

A

IgG (70-75%) and IgA (15%)

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31
Q

What is an IgE response associated with?

A

Hypersensitivity allergic response and defence against parasitic infections

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32
Q

What is the predominant Ig in mucous secretions?

A

IgA

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33
Q

Which region of an antibody binds to antigens?

A

The Fab region

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34
Q

Which region of an antibody binds to B cells?

A

The Fc region

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35
Q

Name 4 types of cytokines

A
  1. Interferons (IFN)
  2. Interleukins (IL)
  3. Colony Stimulating factors
  4. Tumour necrosis factors (TNFa &b)
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36
Q

What is the function of interferons?

A

Produce antiviral proteins

IFNy - released by activated Th1 cells

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37
Q

What is the function of interleukins?

A

Interleukins causes cell division and differentiation

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38
Q

What is the function of colony stimulating factors?

A

CSF causes division and differentiation of bone marrow stem cells

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39
Q

What is the function of tumour necrosis factors?

A

TNF mediates inflammation and cytotoxic reactions

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40
Q

What is the function of chemokines?

A

Chemokines attract leukocytes to the site of infection

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41
Q

Give examples of secondary lymphoid tissue

A

Spleen, lymph nodes, mucosa associated lymphoid tissue (MALT)

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42
Q

Describe the process of phagocytosis

A
  1. Pathogen binds to neutrophil/macrophage
  2. Engulfment of pathogen
  3. Phagosome formation
  4. Lysosome fusion - phagolysosome
  5. Pathogen is destroyed
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43
Q

Give 3 examples of O2 dependent mechanism of killing

A
  1. Killing using reactive oxygen intermediates
  2. Superoxides can be converted to H2O2 and then to hydroxyl free radicals
  3. NO leads to vasodilation and increased extravasation and so more neutrophils etc are in the tissues to destroy pathogens
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44
Q

What is the role of NO in killing pathogens?

A

NO leads to vasodilation and increased extravasation

This means that more neutrophils etc are in the tissues to destroy pathogens

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45
Q

Why can superoxides be used to destroy pathogens?

A

Superoxides can be converted to H2O2 and then to hydroxyl free radicals
Hydroxyl free radical are highly reactive and can destroy pathogens

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46
Q

What mechanisms or cells are involved in O2 independent killing of microbes?

A

Lysozyme, defensives, TNF, pH

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47
Q

What are the complement system plasma proteins derived from?

A

Liver

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48
Q

What are the 3 main outcomes of complement system activation?

A
  1. Pathogen lysis
  2. Activation of leukocytes
  3. Increased phagocytosis
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49
Q

Name the 3 complement activation pathways

A
  1. Classical
  2. Lectin
  3. Alternative
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50
Q

What activates the classical complement pathway?

A

Antibodies

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51
Q

What activates the Lectin complement pathway?

A

Mannose binding protein

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52
Q

What activates the alternative pathway?

A

Bacterial cell walls and endotoxin

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53
Q

Describe Th1 (CD4) activation

A

Antigen presenting cell presents antigen with MHC II to a naïve CD4 T-cell
Stimulation with high levels of IL-12 activate naïve cells to CD4 T helper 1 cells
Th1 cells travel to secondary lymphoid tissue
Proliferate (clonal expansion)
Recognise antigen on infected cells with MHC II via T cell receptor (CD4)
Th1 secretes INFy causing apoptosis

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54
Q

Describe cytotoxic (CD8) T cell activation

A

Antigen presenting cell presents antigen with MHC 1 to a naive CD8 T cell
Activation to a cytotoxic T cell
Chemokines released –> inflammatory cell recruitment
Proteolytic granules release perforins and granulysin –> apoptosis and killing of pathogen
IFN release –> macrophage activation –> intracellular killing

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55
Q

Which complement plasma proteins have opsonic properties when bound to a pathogen?

A

C3b and C4b

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56
Q

What is the function of MAC in a pathogens’ membrane?

A

MAC is a leaky pore like channel

Ions and water pass through the channel and disrupt the intracellular microbe environment –> microbe lysis

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57
Q

Which complement plasma proteins are pro-inflammatory and cause chemotaxis and activation of neutrophils and monocytes etc?

A

C3a and C5a

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58
Q

Name things Th 1 cells do

A

Produce IL-2, IFNy and TNFb
Activate macrophages –> inflammation
Promotes production of cytotoxic T cells
Induce B cells to make IgG antibodies

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59
Q

Name things Th 2 cells do

A

Produce IL-4,5,6,10
Activate eosinophils and mast cells
Important in secondary infections and allergy
Induce B cells to make IgE - promotes release of inflammatory mediators

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60
Q

Why is innate immunity needed?

A

To handle pathogens we need a rapid response to

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61
Q

What are pattern recognition receptors (PRRs) a receptor for?

A

Pathogen-associated molecular pattern molecules (PAMPs)

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62
Q

Name 3 receptors that make up the PRR family

A
  1. Toll-like receptors (TLR)
  2. Nod-like receptors (NLR)
  3. Rig-like receptors (RLR)
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63
Q

What is the main function of TLR’s?

A

Send signals to the nucleus to secrete cytokines and interferons –> initiate tissue repair
Enhanced TLR signalling = improved immune response

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64
Q

What is the main function of NLR’s?

A

Detect intracellular microbial pathogens

Release cytokines and can cause apoptosis if the cell is infected

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65
Q

What disease could be caused by a non-functioning mutation of NOD2?

A

Crohn’s disease

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66
Q

What is the main function of RLR’s?

A

Detect intracellular double stranded RNA

Triggers interferon production –> antiviral response

67
Q

TLR’s are adapted to recognise damage molecules. What characteristic do the damaged molecules often have in common?

A

Often hydrophobic

68
Q

What kind of TLR’s can be used in vaccine adjuvants?

A

TLR4 agonists

69
Q

Give examples of diseases that can be caused by PRR’s failings to recognise pathogens

A

Atherosclerosis
COPD
Arthritis

70
Q

Give 3 examples of extracellular PRRs

A
  1. Mannose receptors
  2. Scavenger receptors
  3. TLR’s
71
Q

What is the function of mannose and scavenger extracellular receptors?

A

Induce pathogen engulfment

72
Q

Give an example of an intracellular PRR

A

NLR

73
Q

What are circulating PRRs secreted from?

A

Epithelia, phagocytes and the liver

74
Q

What happens when PAMP binds to a PRR?

A

The innate immune response and inflammatory response is triggered

75
Q

What is extravasation?

A

Leukocyte migration across the endothelium

76
Q

What do macrophages at the tissues secrete to initiate extravasation?

A

TNF alpha (pro inflammatory molecule)

77
Q

Describe the process of extravasation

A
  1. Macrophages at tissues release TNF alpha
  2. The endothelium is stimulated to express adhesion molecules and to stimulate chemokines
  3. Neutrophils bind to adhesion molecules; they roll, slow down and become stuck to the endothelium
  4. Neutrophils are activated by chemokines
  5. Neutrophils pass through the endothelium to the tissue to help fight infection
78
Q

Give 3 advantages of active immunity

A
  1. Induces immunological memory
  2. Produces high affinity antibodies
  3. Produces a persistent protective response against pathogens
79
Q

Give 2 advantages of passive immunity

A
  1. Immediate effect

2. Useful treatment for acute dangers (e.g. snake venom)

80
Q

Give 3 disadvantages of passive immunity

A
  1. Short term
  2. No immunological memory produced
  3. Reaction is possible
81
Q

Describe the first immune response to initial exposure

A
  1. Innate immune response
  2. IgM predominated
  3. Low affinity
82
Q

Describe the second immune response following exposure to a pathogen encountered before

A
  1. Rapid and larger than the first
  2. High affinity IgG
  3. Adaptive immunity, T cell help
83
Q

Give 3 advantages of live vaccines

A
  1. Very effective, prolonged and comprehensive
  2. Immunological memory produced
  3. Often only 1 vaccine is needed
84
Q

Give 2 disadvantages of live vaccines

A
  1. Immunocompromised patients may become ill

2. Vaccines often need to be refrigerated which can be a problem in remote areas

85
Q

Give 2 advantages of inactivated vaccines

A
  1. There is no risk of infection

2. Storage is less critical

86
Q

Give 3 disadvantages of inactivated vaccines

A
  1. Inactivated vaccines tend to only activate the humoral response; there is a lack of T cell involvement
  2. The response is often weak
  3. Boosters are needed and so patient compliance may be poor
87
Q

What is the role of an adjuvant?

A

It is a substance added to a vaccination to stimulate an immune response - convince immune system you are infected

88
Q

What can be used as an adjuvant?

A

Toxoids, proteins, chemicals

89
Q

What are 5 features of an ideal vaccine

A
  1. Safe
  2. Induces a suitable immune response
  3. Shouldn’t require repeated boosters
  4. Generates immunological memory
  5. Stable and easy to transport
90
Q

Which cells express high affinity IgE receptors?

A

Mast cells, basophils and eosinophils

91
Q

Give 5 examples PAMPs

A
  1. Lipopolysaccharides
  2. Endotoxins
  3. Bacterial flagellin
  4. Peptidoglycans
  5. Double stranded RNA
92
Q

Give examples of inactivated vaccines

A

Polio (viral)
Hep A (viral)
Rabies (viral)
Pertussis (bacterial)

93
Q

Give example of live attenuated vaccines

A

MMR (viral)
Rotavirus (viral)
BCG (bacterial)

94
Q

Name other forms of vaccine

A
  1. Recombinant proteins
  2. Synthetic proteins
  3. DNA vaccines
  4. Polysaccharide-protein conjugates
95
Q

Activation of naïve T cells is better achieved by which antigen presenting cells?

a) Neutrophil
b) Mast cells
c) Macrophages
d) Dendritic cells

A

d) Dendritic Cells

96
Q
What cell type is described below? 
Located exclusively in tissues, has an important role in both the innate and adaptive immune system, are antigen presenting cells and have phagocytic properties
a)	Macrophage
b)	Neutrophil
c)	Eosinophil
d)	Mast cell
e)	Fibroblast
A

a) Macrophage

97
Q

Which of the following is not involved in innate immune mechanisms?

a) Anatomic barriers
b) Phagocytic
c) Inflammatory mechanisms
d) Antibody production
e) Skin

A

d) Antibody production

98
Q

T cells recognise antigen…

a) In solution in plasma
b) When presented on red blood cells
c) Following presentation on antigen presenting cells
d) In a 3-dimensional form
e) Following presentation on pattern recognition receptors

A

c) Following presentation on antigen presenting cells

99
Q

Influenza vaccine is targeted towards ‘at risk’ groups in the UK. Which of the following are classified as ‘at risk’?

a) Over 65 years
b) 16 years old
c) The obese of any age
d) Teenagers
e) Under 2 years old

A

a) Over 65 years
AND
e) Under 2 years old

100
Q

Which of the following is administered as a live attenuated vaccine in the UK

a) Hepatitis A
b) Measles, Mumps, Rubella
c) Tetanus
d) Flu
e) Polio

A

b) Measles, Mumps and Rubella

101
Q

Complements are the proteins that are involved in the clearance of antigen/bacteria. Which of the following is not part of the Elimination phase of complement activation?

a) Opsonisation
b) Target cell lysis
c) Chemoattraction of leukocytes
d) Production of interferons
e) Phagocytosis

A

d) Production of interferons

102
Q

Which of the following is a polysaccharide vaccine?

a) Anthrax vaccine
b) Hib vaccine (Haemophilus influenza type b)
c) Rabies vaccine
d) Hepatitis A

A

b) Hib vaccine

103
Q

Which of the following are features of the adaptive immune response?

a) Does not require prior contact with the pathogen
b) It works with B and T lymphocytes
c) Lacks specificity
d) Distinguishes “self” from “non-self”
e) Enhanced by complement

A

b) It works with B and T lymphocytes

104
Q

What are the two types of immune response in humans?

a) Immunological tolerance
b) Immune surveillance
c) Innate and acquired
d) Intrinsic and extrinsic
e) Overt and covert

A

c) Innate and acquired

105
Q

Which of the following is not an organ-specific auto-immune disease?

a) Ulcerative colitis
b) Type 1 diabetes mellitus
c) Graves disease
d) Hashimoto’s thyroiditis
e) Sjogren’s syndrome

A

a) Ulcerative colitis

106
Q

Which of the following is not a classical PAMP?

a) Peptidoglycan, found in bacterial cell walls
b) Flagellin, a protein found in bacterial flagella
c) Lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria
d) Interleukin 12
e) Nucleic acids such as viral DNA or RNA

A

d) Interleukin 12

107
Q

what are the main compounds involved in reperfusion injury?

A

Free radicals e.g. H2O2, O2-, OH-. They damage cell walls.

108
Q

Define allorecognition.

A

The ability of an organism to distinguish its own tissues from those of another. Recognition of non-self antigens.

109
Q

What are the consequences of transplant rejection?

A

Fibrosis and scarring.

110
Q

Describe the immune responses to detection of graft antigens.

A
  1. Innate immune response is activated.
  2. T cell mediated cytotoxicity.
  3. Ab mediated cytotoxicity.
  4. Hypersensitivity.
  5. Tolerance.
111
Q

Give 6 ways of preventing transplant rejection?

A
  1. Manage risk factors.
  2. Tissue typing.
  3. Cross match.
  4. Immunosuppressive agents.
  5. Sensitisation and desensitisation.
  6. Tolerance.
112
Q

Give 3 advantages of transplantation.

A
  1. Improved quality of life.
  2. Improves survival rates.
  3. Cost effective.
113
Q

Why are immunosuppressive agents needed to prevent rejection?

A

Transplanted organs are recognised as non self and therefore are seen as a threat. Graft v host disease; T-cells destroy graft cells.

114
Q

Which PRR responds to lipopolysaccharides?

A

TLRs.

115
Q

True or False. The heavy and light chains of an antibody are coded for by the same gene.

A

False. Distinct sets of genes code for the heavy and light chains.

116
Q

What region determines Ig class?

A

The constant region!

117
Q

Describe complement fixation.

A

An antibody binds multiple antigens so as to bring the Fc regions together. The complement pathway is initiated in this process and you get MAC formation.

118
Q

Which compound is responsible for signalling when an antigen binds to an antibody?

A

Tyrosine kinase.

119
Q

Describe the process of class switching.

A

Antigen engagement and T cell help will result in class switching. A different FC region is used and there is affinity maturation.

120
Q

Describe somatic hypermutation.

A
  1. Random mutations in CDR.
  2. Amino acid sequences are effected meaning Ab-Ag affinity is altered.
  3. High affinity B cell clones are selected via natural selection.
121
Q

Briefly describe the steps involved between T cell stimulation and plasma cell differentiation.

A
  1. T cells are stimulated.
  2. Cytokine release.
  3. B cell proliferation.
  4. Somatic hypermutation.
  5. High affinity B cell clones differentiate into plasma cells and memory cells.
122
Q

Describe type 1 hypersensitivity.

A

IgE mediated hypersensitivity. Acute anaphylaxis. IgE becomes attached to mast cells, IgE cross linking leads to mast cell degranulation -> histamine.

123
Q

Describe type 2 hypersensitivity.

A

IgG mediated cytotoxicity.

124
Q

Describe type 3 hypersensitivity.

A

Immune complex deposition; immune complexes have not been adequately cleared by innate immune cells, giving rise to an inflammatory response.

125
Q

Describe type 4 hypersensitivity.

A

T cell mediated.

126
Q

Give 6 features of anaphylaxis.

A
  1. Rapid onset.
  2. Blotchy rash.
  3. Swelling of face and lips.
  4. Wheeze.
  5. Hypotension.
  6. Cardiac arrest if severe.
127
Q

What can cause a type 1 hypersensitivity reaction?

A

Pollen, cat hairs, peanuts etc. (allergies).

128
Q

What can cause a type 2 hypersensitivity reaction?

A

Transplant rejection.

129
Q

What can cause a type 3 hypersensitivity reaction?

A

Fungal.

130
Q

What can cause a type 4 hypersensitivity reaction?

A

TB.

131
Q

What is the treatment for anaphylaxis?

A
  1. Commence basic life support (ABC).
  2. Stop infusion of drug.
  3. Give adrenaline and anti-histamines.
132
Q

Give 4 risk factors for hypersensitivity.

A
  1. Protein based macromolecules.
  2. Female > male.
  3. Immunosuppression.
  4. Genetic factors.
133
Q

Where are mast cells found?

A

They are only found in tissues, not in the blood!

134
Q

What is the name of the variable region on an antibody?

A

Fab region.

135
Q

Name 3 cytokines secreted by TH1.

A
  1. IL-2.
  2. Gamma-interferon.
  3. TNF-beta.
136
Q

Name 2 cytokines secreted by TREG.

A
  1. IL-10.

2. TGF-beta.

137
Q

Give 3 cytokines secreted by TH2.

A
  1. IL-4.
  2. IL-6.
  3. IL-13.
  4. IL-5.
  5. IL-10.
138
Q

Give 4 uses of antibodies in medicine.

A
  1. Diagnostic tools.
  2. Immunoassays, Ab’s are used to measure the presence of a molecule.
  3. Flow cytometry, Ab’s label cells in suspension.
  4. Therapeutic uses, monoclonal Ab’s can act as specific antagonists for biological targets e.g. HERCEPTIN.
139
Q

In what region of the antibody is there reversible bonding between antibodies and antigens?

A

Complementarity determining region (CDR).

- Hydrogen bonds and VDW’s etc form cumulative weak interactions that together form a strong force.

140
Q

What is allergy?

A

An abnormal response to harmless foreign material.

141
Q

What is atopy?

A

The tendency to develop allergies.

142
Q

Which immunoglobulin is most commonly involved in allergic responses?

A

IgE.

143
Q

Which cells are most commonly involved in allergic responses?

A

Mast cells! Also eosinophils and basophils.

144
Q

What happens to IgE receptors when a ‘threat’ is identified?

A

The receptors cross-link.

145
Q

Which cells express high affinity IgE receptors?

A

Mast cells, basophils and eosinophils.

146
Q

What are the steps in an allergic response?

A

Allergen/threat is identified -> high affinity IgE receptors cross link -> IgE binds -> Mast cells are activated -> granules released -> histamine and cytokines. Cytokines induce a TH2 response.

147
Q

What is the main IgE receptor cell?

A

MAST CELLS!

148
Q

Which compound causes blood vessel dilation and vascular leakage in an allergic response?

A

Histamine.

149
Q

What is the role of cytokine release in an allergic response?

A

They induce a TH2 response.

150
Q

Which cells and which immunoglobulin is commonly involved in anaphylaxis?

A
  • Mast cells and basophils.

- IgE.

151
Q

Give examples of anaphylactic systemic effects.

A
  • CV: vasodilation, lowered BP.
  • Resp: bronchial SM contraction, mucus.
  • Skin: rash, swelling.
  • GI: pain, vomiting.
152
Q

Give 5 possible treatments for allergy and hypersensitivity.

A
  1. Avoid allergens.
  2. Desensitisation (immunotherapy, some risks).
  3. Prevent IgE production (interfere with TH2 pathway).
  4. Prevent mast cell activation.
  5. Inhibit mast cell products (e.g. histamine receptor antagonists).
153
Q

What compound prevents excessive activation of the classical complement pathway?

A

C1 inhibitor.

- C1 inhibitor leads to a negative feedback loop.

154
Q

Which immunoglobulin is found in breast milk and other secretions?

A

IgA.

155
Q

What kind of immunity are PRR’s and PAMP’s associated with?

A

Innate immunity.

156
Q

Why is it important to get the balance right when using immunosuppressive agents?

A

Too much = infection.

Too little = rejection.

157
Q

What is involved in tissue typing?

A
  1. Blood group matching.

2. HLA typing.

158
Q

What is involved in cross matching?

A

Detecting anti HLA antibodies.

Cell based assays and solid phase assays can be used.

159
Q

Which PRR responds to lipopolysaccharides?

A

TLRs.

160
Q

Give 4 causes of acquired immunodeficiency.

A
  1. Cancer.
  2. HIV.
  3. Having chemotherapy.
  4. Taking immunosuppressants.
161
Q

What is the name of the disease that is characterised by B cell deficiency?

A

Hypogammaglobulinaemia.

162
Q

What are the consequences of complement deficiency?

A

Impaired opsonisation of encapsulated bacteria.

163
Q

How can immune function be assessed?

A
  1. Looking at neutrophil numbers, morphology and flow cytometry.
  2. Looking at B and T cell subsets, numbers and response to vaccines.
  3. Genetic studies.