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Immunology Flashcards

1
Q

What is SCID

A

Severe combined immunodeficiency

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2
Q

Describe pathogen vs host

A

Bacteria and viruses replicate very quickly so they evolve
Exertion of selection pressure resistant bacteria
Individuals who are resistant to bacteria will survive and reproduce
Polymorphic genes control immunoresponse

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3
Q

Describe recognition strategy 1

A

Recognising molecular patterns
Hundreds of receptors
Germ-line encoded
Uses PRRs

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4
Q

What are PRRS

A 
Pattern recognition receptors
Includes PAMP (Pathogen associated molecular patterns) and DAMP (Damage associated molecular patterns)
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5
Q

What are the advantages and disadvantages of recognition strategy 1

A

Many cells express the same receptor so it’s rapid and effective
Limited diversity and some pathogens will not be recognised

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6
Q

Describe recognition strategy 2

A

Recognising precise structures
Millions of receptors
Generated by random recombination of gene segments (must be activated first)

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7
Q

Give the advantages and disadvantages of recognition strategy 2

A

Massive diversity so all structures potentially recognised
Fewer cells have this so it takes a long time
Random nature can lead to autoimmunity

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8
Q

What is the epitome

A

The site on the antigen where antibodies bind to

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9
Q

Compare innate immunity to adaptive immunity

A

Independent of previous exposure vs adaptation to previous exposure
Depends on pre-formed and rapidly synthesised components vs depends on clonal selection
Fast vs slow
Limited specificity vs very specific

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10
Q

Give some features of innate immunity

A

Destroys nucleic acids in the cytoplasm
Activates inflammatory pathways
Type 1 interferon

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11
Q

Give some features of adaptive immunity

A

Memory cell formation
Priming required
Cellular or humoral (lymphocytes)

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12
Q

How does innate immunity relate to adaptive immunity

A

Buys time for adaptive immunity and promotes and directs the correct reponse

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13
Q

What percentage of WBCs do lymphocytes make up in blood and lymph

A

20-60%

99%

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14
Q

Which cells and substances are involved with innate response

A 
Neutrophils
Macrophages
Eosinophils 
Complement
Acute phase - P
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15
Q

Which cells and substances are involved with adaptive immunity

A

T cells
B cells
Antibodies

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16
Q

Which cells and substances are involved with adaptive AND innate immunity

A

Basophils
Dendritic
Natural Killer
Cytokines

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17
Q

Describe clonal selection

A

Polyclonal naive lymphocyte, activation, proliferation, effector lymphocyte
Genetic recombination generates diversity of immunoglobulin and TCR

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18
Q

What are primary lymphoid organs and give examples

A

Organs where lymphocytes are produced (lymphopoiesis) e.g. bone marrow and thymus

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19
Q

What are secondary lymphoid organs and give examples

A

Organs where lymphocytes interact with antigens and other lymphocytes e.g. spleen, lymph nodes, mucosal-associated lymphoid tissue

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20
Q

Describe/ draw the structure of the thymus

A

Between the right and left lung in front of the heart. Thyroid lies above the C cartilage. Bi-lobed

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21
Q

Give some features of the thymus

A

Bi-lobed
Proliferating lymphocytes
Cortex and medulla

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22
Q

How does the thymus change during infection

A

No obvious change

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23
Q

Where are Hassal’s corpuscle and what do they do

A

Fibroblast cells for T-reg development in the thymus

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24
Q

How does age effect the thymus

A

As one ages, there is a decreased output of NEW T cells

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25
Q

Give some features of bone marrow

A

B cell and RBC production
Foetus = lots of marrow
Adult = lot so fat with large and flat bones

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26
Q

How does the bone marrow change during infection

A

Increased WBC production

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27
Q

Describe the lymphatic system

A

Drainage system that collects antigens and filters them through nodes. Antigens are likely to enter the lymph.

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28
Q

What structures can be found in the lymph nodes

A

High endothelial venues (HEV) = cells move from the blood to the lymph node
Germinal centres = where B cells proliferate

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29
Q

How does the lymph node change during infection

A

Lymph nodes enlargen

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30
Q

Where are B and T cells found in the lymph nodes

A

B cells = outside
T cells = inside
Due to chemokines

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31
Q

What does the spleen do

A

Filters for antigens in the blood

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32
Q

What is red and white pulp and where is it found

A

Found in the spleen
red= RBCs
White = WBCs

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33
Q

How does the spleen change during infection

A

larger follicles

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34
Q

Give 2 features of the spleen

A

Not many HEV

Contains germinal centres

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35
Q

How does epithelium act as a defence

A

physical barrier with a very large SA
Mucosae-associated lymphoid tissue (MALT)
Villi have lymph drains

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36
Q

What are Peyer’s patches and where are they found

A

Found in the gut with large aggregates of B cells and germinal centres

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37
Q

What are microfold cells and where are they found

A

M cells that sample antigens in the gut in the peyer’s patches

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38
Q

How does the cutaneous tissue contribute to immune response

A

Epidermal langerhans cells captures pathogens from the skin. Also intraepidermal lymphocytes, T cells, dermal dendritic cells and macrophages

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39
Q

What is the purpose of recirculation

A

Ensures that the antigen meets the lymphocyte with the specific receptor

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40
Q

Where does recirculation occur

A

Between the blood and peripheral lymphoid tissue

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41
Q

What does extravasation mean

A

Movement from blood to lymph node

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42
Q

Describe the process of extravasation

A

Naive T cell rolls along the epithelium
proteins and carbs bound to epithelium
Receptors on the lymphocyte bind to chemokine on the epithelium
Lymphocytes signals the T cells
Change in structure of integrin
Integrin becomes high affinity binding and stops movement
Transport of the T cell through the epithelium

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43
Q

What are CD markers

A

CD = cluster differentiation

Systemic nomenclature for cell surface membranes

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44
Q

What CD markers to all T cells show

A

CD3

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45
Q

How to T cells differ from B cells in recognising antigens

A

T cells recognise PROCESSED antigens using the TCR while B cells can recognised unprocessed antigens

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46
Q

Which CD markers do B cells show

A

CD19 and CD20

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47
Q

Which MHC class do B cells show

A

MHC II

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48
Q

Describe APCs

A

Antigen presenting cells that present processed antigen to T cells in adaptive response. Includes dendritic cells, macrophages and B lymphocytes

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49
Q

How does skin act as a barrier

A

Acidic environment

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50
Q

Give physiological features on innate immunity

A

body temperature
Acidic pH
Chemical mediators e.g. complement, lysozyme, interferons

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51
Q

Give features of neutrophils

A

phagocytose
40-75% of lymphocytes
Short lived
First cells recruited

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52
Q

How do neutrophils move into the lymph

A 
rolling
Infection releases chemokine
Signal from endothelium
Forms a high affinity neutrophil
Diapedesis through
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53
Q

Define opsonisation

A

Micro-organism is coated with proteins for phagocytsosis

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54
Q

What are NETs

A

Neutrophil extracellular traps where granules and chromatin are released to form extracellular fibres

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55
Q

Give the features of eosinophils

A

Phagocytosis and granule release
Defence against parasites
Help in GALT (IgA)

56
Q

Give the features of basophils

A

release of granules

May act as APCs

57
Q

Give the features of monocytes

A

Phagocytosis, cytokine release, APC

When they leave the blood they become macrophages

58
Q

Give the features of mast cells

A

Granule release, histamine and leukotrienes, phagocytosis
Mucosal or connective tissue
Complement production (anaphylatoxins)
vasodilation and increased vascular permeability

59
Q

Give the features of dendritic cells

A

APCs and cytokine secretion

60
Q

Give the features pf natural killer cells

A

Infected cell lysis
Large granulated lymphocytes (cytotoxic)
Secretes interferon gamma
Binds to opsonised cells

61
Q

What are soluble mediators

A

small secreted proteins important in cell-cell communication that are generally local acting and short-lived

62
Q

What are the types of soluble mediators

A 
Interleukins (between leukocytes)
Interferons (anti-viral)
Chemokines (chemotaxis)
Growth factors 
Cytotoxic
63
Q

What is complement

A

A complex series of proteins and glycoproteins that triggers enzyme cascade systems . Role in complementing activity of specific antibodies.

64
Q

Where is complement produced

A

Liver produces inactivated precursors

65
Q

How is complement activated

A

Cleaving the end

66
Q

What are the three complement activation pathways

A

Classical - antibodies
Lectin - lectin proteins that bind to carbs
Alternative - bacterial surfaces directly activates

67
Q

What is a common stage of the three complement pathways

A

Activation of Cab and the Membrane attack complex (MAC)

68
Q

What can immunoglobulins do water binding

A

Complement activation
Opsonisation
Cell activation via Fc

69
Q

Draw/describe the structure of an immunoglobulin

A

Fab at the top and Fc at the bottom
2 heavy chains and 2 light chains linked by disulphide bonds
Hinge region at the middle corner

70
Q

What are hyper variable regions

A

there are 3 on immunoglobulins 1,2,3 and 3 complement determining regions (CDR)

71
Q

What is the immunoglobulin superfamily

A

They have a similar domain to the antibody

72
Q

What forces are involved in binding

A

Hydrogen bonds
Ionic bonds
Hydrophobic interactions
Van der Waals

73
Q

Define antibody affinity

A

strength of the total non covalent interactions between single antigen binding site and single epitope

74
Q

Define antibody avidity

A

The overall strength of multiple interactions between antibody with multiple binding sites and complex antigen with multiple epitopes

75
Q

Define antibody-cross reactivity

A

Antibody elicited in response to an antigen can recognise antigens of a different structure e.g. vaccination for cowpox effective for smallpox, common intestinal bacteria and carbs on RBC

76
Q

What separates the different immunoglobulin classes

A

Different heavy chains, same light chains

77
Q

Give the features of IgG

A

Most abundant
Actively transported across the placenta
Classical complement
Gamma heavy

78
Q

Give the features of IgA

A

second most abundant
Dimer
Mucosal surface protection
Alpha heavy

79
Q

Give the features of IgM

A 
First Ig at the site
Pentamer
Multiple binding sites
agglutination and complement
Micro heavy
80
Q

Give the features of IgE

A 
Allergic reactions
parasitic infecitons
Binds to mast cells for histamine release
Very low levels
E heavy
81
Q

Give the features of IgD

A

Very low levels
Expressed in B cell development and activation
Delta heavy

82
Q

Which immunoglobulins are found in the blood

A

IgG and IgM

83
Q

What is the purpose of Ig gene rearrangement in the bone marrow

A

undergo selection to destroy self targets

84
Q

What enzyme is used in Ig gene rearrangement

A

VDJ recombinase

85
Q

Where is MHC I found and what can it indicate

A

Found on all nucleated cells, indicating health via protein presentation

86
Q

Where is MHC II found

A

APC cells - dendritic, macrophage, B lymphocytes

87
Q

Describe the process of B cell activation

A

Dendritic cell and B lymphocytes endocytose the antigen (attaches to BCR) which is then processed and presented using MHC II
T cell recognises the antigen on the dendritic cell using TCR
T cell finds the B lymphocyte presenting the same antigen and activates it
CD28 production provides signalling and cytokines produced
Lymphokine is secreted

88
Q

What does class switching involve

A 
IgM and IgD are "weak"
When signals (lymphokines) are given from T helper there is a class switch
89
Q

Where does affinity maturation occur

A

Germinal centres

90
Q

Describe the process of affinity maturation

A

AID enzyme deliberately causes mutation in antibody coding genes of B cells (somatic hypermutation)
Cells can become worse -> apoptosis
Cells can become better -> stronger antibody -> plasma or memory cell

91
Q

Explain clonal selection

A

From a large population, 1 cell is activated via antigen binding to BCR which leads to proliferation (clonal selection). Division and differentiation is clonal expansion

92
Q

What are the advantages and disadvantages of B cells

A

Major vaccine targets
Monoclonal antibody use
Negative role in autoimmune conditions, involved in allergies and cancers

93
Q

Describe the T cell independent activation pathway

A

A repetitive bacterial polysaccharide acts as the first signal
Microbial constituent or accessory cell provides second signal e.g. LPS

94
Q

What causes differences in Ig for T cell independent and dependent

A

No lymphokines released in T cell independent

95
Q

Describe the TCR

A

The Fab region of an antibody, top is variable, bottom is constant. One alpha and one beta and a cytoplasmic tail.

96
Q

What is the difference between the alpha and beta TCR

A 
alpha = V and D and 1 recombination
Beta = V, D and J and 2 recombinations
97
Q

What are CD4 and CD8 and where are they found

A

Co-receptors that bind to MHC. CD4 is found one T helper cells while CD8 is found on T cytotoxic cells

98
Q

Give the structural differences between MHC I and MHC II

A

MHC I - 1 cytoplasmic tail, asymmetrical, (gap at the corner)
MHC II - 2 cytoplasmic tails, symmetrical (gap at top)

99
Q

What is HLA

A

Human leukocyte antigen - genes found in all vertebrates that code for MHC. polygenic

100
Q

Where is HLA found

A

Chromosome 6

101
Q

What type of expression is HLA

A

Co-dominant

102
Q

Relationship between HLA and MHC

A 
MHC class I = A,B,C
MHC class II = DP, DQ, DR
103
Q

What is haplotype

A

Group og MHC alleles on 1 chromosome

104
Q

Describe the endogenous MHC pathway

A

MHC I. Synthesised in the cytoplasm

  1. TAP transports protein to RER
  2. calnexin and calreticulin and tapasin fold and stabilise the MHC
  3. molecules transport to the golgi
105
Q

Describe the exogenous MHC pathway

A

MHC II. Antigens from external environment

  1. invariant chain stabilised the MHC complex
  2. transport to the golgi
  3. invariant chain is digested to leave a CLIP
  4. Antigen is endocytose and broken down
  5. Peptide presented on MHC
  6. MHC exocytosed
106
Q

Why may antibodies be inefficient

A 
Pathogens:
Can hide within cells
Can change antigen shape
Can coat the antigen with antibodies
Can produce fake antigens
107
Q

What are T cells defined by

A

inputs (STAT) and outputs (cytokines)

108
Q

How do Tc cells induce apoptosis

A

Granule release - Perforin, granzyme, granulising

Fas ligand - binds to Fas

109
Q

What is Th1 involved in

A

Macrophage activation
Delayed type hypersensitivity
B cell activation

110
Q

Describe delayed type hypersensitivity

A

Recruits monocytes

Activates monocytes and macrophages and keeps them at infection site

111
Q

What occurs when the macrophage cannot kill the pathogen e.g. tuberculosis

A

Cytokine release, endothelial cells express proteins monocyte and Th1 migration Th1 activates monocyte and macrophage

112
Q

What is the process of Th1 amplification

A

Activated Th1 binds to MHC II and CD40 on the B cell
Secretion of IFN gamma
Upregulation of MHC II, CD40 and tumour necrosis factor alpha
Increase in TNF alpha secretion (autocrine)

113
Q

Give features of Tfh

A

Activation by dendritic cells

Stimulates B cells

114
Q

What is the role of Th2

A

Targets eosinophils
Trigger in tracheal epithelia
Travels from dendritic to naive

115
Q

What Cluster differentiation is expressed by naive memory T cells

A

CXC45RA

116
Q

What CD is expressed on central memory cells

A

CCR7

117
Q

What are immune checkpoints

A

Expressed on T cells after a large number of exposures (co-stimulatory receptors) causes a longer time for response

118
Q

What is the function of Treg

A

Regulation of T cells and tolerant of self-antigens

119
Q

What is the function of Th17

A

Interleukin 17, bacterial control and neutrophil recruitment

120
Q

Describe the process of T cell development

A

Produced in the bone marrow (CD4-CD8-TCR-)
IN the cortex = CD4+CD8+TCR+
In the medulla = CD4+CD8-TCR+ vice versa

121
Q

Describe selection in the thymus of T cells

A

Thymocyte can’t bind = apoptosis
Weak binding = survival (+ve selection)
Strong binding = apoptosis (-ve election)

122
Q

what is the largest burden of disease

A

Acute lung disease

123
Q

What is the purpose of Interferon type 1

A

Activation of NK

124
Q

What is the purpose of interferon type 2

A

Produced by T cells pre-inflamamtion

125
Q

Define cytokine storm

A

Over production of cytokines and accumulation of cells

126
Q

Compare bacterial and viral defence

A

Complement and antibody opsonisation vs Interferons and inflammatory mediators + acute phase proteins
Phagocytes vs NK cells

127
Q

What are the features of an eradicable disease

A 
Simple and cheap to diagnose
Genetically stable pathogen
Accessible host species
Eliminated persistent infection
Safe and effective vaccine
128
Q

What are the features of the ideal vaccine

A 
Completely safe
easy to administer
cheap
stable]active against all variants
life-long protection
129
Q

Define tolerance

A

Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen

130
Q

Give examples of autoimmune disease

A

Hashimoto’s, myasthenia gravis

131
Q

Define pathogenesis

A

Susceptibility genes and environmental triggers

132
Q

Describe hypercytokinaemia

A

Too much immune response
positive feedback loop
pathogens enter the wrong compartment (Sepsis)

133
Q

What is the 3 signal model

A

Licensing response
Antigen recognition
Co-stimulation
Cytokine release

134
Q

What is AIRE

A

AutoImmune Regulator

A specialised transcription factor that allows expression of genes

135
Q

What is the function of IL-10

A

Pleitropic
Blocks pro-inflammatory cytokine synthesis
Downregulates macrophages

?? (14 decks)

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