Immunology Flashcards
1
Q
What is SCID
A
Severe combined immunodeficiency
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
3
Q
Describe recognition strategy 1
A
Recognising molecular patterns
Hundreds of receptors
Germ-line encoded
Uses PRRs
4
Q
What are PRRS
A
Pattern recognition receptors Includes PAMP (Pathogen associated molecular patterns) and DAMP (Damage associated molecular patterns)
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
6
Q
Describe recognition strategy 2
A
Recognising precise structures
Millions of receptors
Generated by random recombination of gene segments (must be activated first)
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
8
Q
What is the epitome
A
The site on the antigen where antibodies bind to
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
10
Q
Give some features of innate immunity
A
Destroys nucleic acids in the cytoplasm
Activates inflammatory pathways
Type 1 interferon
11
Q
Give some features of adaptive immunity
A
Memory cell formation
Priming required
Cellular or humoral (lymphocytes)
12
Q
How does innate immunity relate to adaptive immunity
A
Buys time for adaptive immunity and promotes and directs the correct reponse
13
Q
What percentage of WBCs do lymphocytes make up in blood and lymph
A
20-60%
99%
14
Q
Which cells and substances are involved with innate response
A
Neutrophils Macrophages Eosinophils Complement Acute phase - P
15
Q
Which cells and substances are involved with adaptive immunity
A
T cells
B cells
Antibodies
16
Q
Which cells and substances are involved with adaptive AND innate immunity
A
Basophils
Dendritic
Natural Killer
Cytokines
17
Q
Describe clonal selection
A
Polyclonal naive lymphocyte, activation, proliferation, effector lymphocyte
Genetic recombination generates diversity of immunoglobulin and TCR
18
Q
What are primary lymphoid organs and give examples
A
Organs where lymphocytes are produced (lymphopoiesis) e.g. bone marrow and thymus
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
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
21
Q
Give some features of the thymus
A
Bi-lobed
Proliferating lymphocytes
Cortex and medulla
22
Q
How does the thymus change during infection
A
No obvious change
23
Q
Where are Hassal’s corpuscle and what do they do
A
Fibroblast cells for T-reg development in the thymus
24
Q
How does age effect the thymus
A
As one ages, there is a decreased output of NEW T cells
25
Give some features of bone marrow
B cell and RBC production
Foetus = lots of marrow
Adult = lot so fat with large and flat bones
26
How does the bone marrow change during infection
Increased WBC production
27
Describe the lymphatic system
Drainage system that collects antigens and filters them through nodes. Antigens are likely to enter the lymph.
28
What structures can be found in the lymph nodes
High endothelial venues (HEV) = cells move from the blood to the lymph node
Germinal centres = where B cells proliferate
29
How does the lymph node change during infection
Lymph nodes enlargen
30
Where are B and T cells found in the lymph nodes
B cells = outside
T cells = inside
Due to chemokines
31
What does the spleen do
Filters for antigens in the blood
32
What is red and white pulp and where is it found
Found in the spleen
red= RBCs
White = WBCs
33
How does the spleen change during infection
larger follicles
34
Give 2 features of the spleen
Not many HEV
| Contains germinal centres
35
How does epithelium act as a defence
physical barrier with a very large SA
Mucosae-associated lymphoid tissue (MALT)
Villi have lymph drains
36
What are Peyer's patches and where are they found
Found in the gut with large aggregates of B cells and germinal centres
37
What are microfold cells and where are they found
M cells that sample antigens in the gut in the peyer's patches
38
How does the cutaneous tissue contribute to immune response
Epidermal langerhans cells captures pathogens from the skin. Also intraepidermal lymphocytes, T cells, dermal dendritic cells and macrophages
39
What is the purpose of recirculation
Ensures that the antigen meets the lymphocyte with the specific receptor
40
Where does recirculation occur
Between the blood and peripheral lymphoid tissue
41
What does extravasation mean
Movement from blood to lymph node
42
Describe the process of extravasation
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
43
What are CD markers
CD = cluster differentiation
| Systemic nomenclature for cell surface membranes
44
What CD markers to all T cells show
CD3
45
How to T cells differ from B cells in recognising antigens
T cells recognise PROCESSED antigens using the TCR while B cells can recognised unprocessed antigens
46
Which CD markers do B cells show
CD19 and CD20
47
Which MHC class do B cells show
MHC II
48
Describe APCs
Antigen presenting cells that present processed antigen to T cells in adaptive response. Includes dendritic cells, macrophages and B lymphocytes
49
How does skin act as a barrier
Acidic environment
50
Give physiological features on innate immunity
body temperature
Acidic pH
Chemical mediators e.g. complement, lysozyme, interferons
51
Give features of neutrophils
phagocytose
40-75% of lymphocytes
Short lived
First cells recruited
52
How do neutrophils move into the lymph
```
rolling
Infection releases chemokine
Signal from endothelium
Forms a high affinity neutrophil
Diapedesis through
```
53
Define opsonisation
Micro-organism is coated with proteins for phagocytsosis
54
What are NETs
Neutrophil extracellular traps where granules and chromatin are released to form extracellular fibres
55
Give the features of eosinophils
Phagocytosis and granule release
Defence against parasites
Help in GALT (IgA)
56
Give the features of basophils
release of granules
| May act as APCs
57
Give the features of monocytes
Phagocytosis, cytokine release, APC
| When they leave the blood they become macrophages
58
Give the features of mast cells
Granule release, histamine and leukotrienes, phagocytosis
Mucosal or connective tissue
Complement production (anaphylatoxins)
vasodilation and increased vascular permeability
59
Give the features of dendritic cells
APCs and cytokine secretion
60
Give the features pf natural killer cells
Infected cell lysis
Large granulated lymphocytes (cytotoxic)
Secretes interferon gamma
Binds to opsonised cells
61
What are soluble mediators
small secreted proteins important in cell-cell communication that are generally local acting and short-lived
62
What are the types of soluble mediators
```
Interleukins (between leukocytes)
Interferons (anti-viral)
Chemokines (chemotaxis)
Growth factors
Cytotoxic
```
63
What is complement
A complex series of proteins and glycoproteins that triggers enzyme cascade systems . Role in complementing activity of specific antibodies.
64
Where is complement produced
Liver produces inactivated precursors
65
How is complement activated
Cleaving the end
66
What are the three complement activation pathways
Classical - antibodies
Lectin - lectin proteins that bind to carbs
Alternative - bacterial surfaces directly activates
67
What is a common stage of the three complement pathways
Activation of Cab and the Membrane attack complex (MAC)
68
What can immunoglobulins do water binding
Complement activation
Opsonisation
Cell activation via Fc
69
Draw/describe the structure of an immunoglobulin
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
What are hyper variable regions
there are 3 on immunoglobulins 1,2,3 and 3 complement determining regions (CDR)
71
What is the immunoglobulin superfamily
They have a similar domain to the antibody
72
What forces are involved in binding
Hydrogen bonds
Ionic bonds
Hydrophobic interactions
Van der Waals
73
Define antibody affinity
strength of the total non covalent interactions between single antigen binding site and single epitope
74
Define antibody avidity
The overall strength of multiple interactions between antibody with multiple binding sites and complex antigen with multiple epitopes
75
Define antibody-cross reactivity
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
What separates the different immunoglobulin classes
Different heavy chains, same light chains
77
Give the features of IgG
Most abundant
Actively transported across the placenta
Classical complement
Gamma heavy
78
Give the features of IgA
second most abundant
Dimer
Mucosal surface protection
Alpha heavy
79
Give the features of IgM
```
First Ig at the site
Pentamer
Multiple binding sites
agglutination and complement
Micro heavy
```
80
Give the features of IgE
```
Allergic reactions
parasitic infecitons
Binds to mast cells for histamine release
Very low levels
E heavy
```
81
Give the features of IgD
Very low levels
Expressed in B cell development and activation
Delta heavy
82
Which immunoglobulins are found in the blood
IgG and IgM
83
What is the purpose of Ig gene rearrangement in the bone marrow
undergo selection to destroy self targets
84
What enzyme is used in Ig gene rearrangement
VDJ recombinase
85
Where is MHC I found and what can it indicate
Found on all nucleated cells, indicating health via protein presentation
86
Where is MHC II found
APC cells - dendritic, macrophage, B lymphocytes
87
Describe the process of B cell activation
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
What does class switching involve
```
IgM and IgD are "weak"
When signals (lymphokines) are given from T helper there is a class switch
```
89
Where does affinity maturation occur
Germinal centres
90
Describe the process of affinity maturation
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
Explain clonal selection
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
What are the advantages and disadvantages of B cells
Major vaccine targets
Monoclonal antibody use
Negative role in autoimmune conditions, involved in allergies and cancers
93
Describe the T cell independent activation pathway
A repetitive bacterial polysaccharide acts as the first signal
Microbial constituent or accessory cell provides second signal e.g. LPS
94
What causes differences in Ig for T cell independent and dependent
No lymphokines released in T cell independent
95
Describe the TCR
The Fab region of an antibody, top is variable, bottom is constant. One alpha and one beta and a cytoplasmic tail.
96
What is the difference between the alpha and beta TCR
```
alpha = V and D and 1 recombination
Beta = V, D and J and 2 recombinations
```
97
What are CD4 and CD8 and where are they found
Co-receptors that bind to MHC. CD4 is found one T helper cells while CD8 is found on T cytotoxic cells
98
Give the structural differences between MHC I and MHC II
MHC I - 1 cytoplasmic tail, asymmetrical, (gap at the corner)
MHC II - 2 cytoplasmic tails, symmetrical (gap at top)
99
What is HLA
Human leukocyte antigen - genes found in all vertebrates that code for MHC. polygenic
100
Where is HLA found
Chromosome 6
101
What type of expression is HLA
Co-dominant
102
Relationship between HLA and MHC
```
MHC class I = A,B,C
MHC class II = DP, DQ, DR
```
103
What is haplotype
Group og MHC alleles on 1 chromosome
104
Describe the endogenous MHC pathway
MHC I. Synthesised in the cytoplasm
1. TAP transports protein to RER
2. calnexin and calreticulin and tapasin fold and stabilise the MHC
4. molecules transport to the golgi
105
Describe the exogenous MHC pathway
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
Why may antibodies be inefficient
```
Pathogens:
Can hide within cells
Can change antigen shape
Can coat the antigen with antibodies
Can produce fake antigens
```
107
What are T cells defined by
inputs (STAT) and outputs (cytokines)
108
How do Tc cells induce apoptosis
Granule release - Perforin, granzyme, granulising
| Fas ligand - binds to Fas
109
What is Th1 involved in
Macrophage activation
Delayed type hypersensitivity
B cell activation
110
Describe delayed type hypersensitivity
Recruits monocytes
| Activates monocytes and macrophages and keeps them at infection site
111
What occurs when the macrophage cannot kill the pathogen e.g. tuberculosis
Cytokine release, endothelial cells express proteins monocyte and Th1 migration Th1 activates monocyte and macrophage
112
What is the process of Th1 amplification
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
Give features of Tfh
Activation by dendritic cells
| Stimulates B cells
114
What is the role of Th2
Targets eosinophils
Trigger in tracheal epithelia
Travels from dendritic to naive
115
What Cluster differentiation is expressed by naive memory T cells
CXC45RA
116
What CD is expressed on central memory cells
CCR7
117
What are immune checkpoints
Expressed on T cells after a large number of exposures (co-stimulatory receptors) causes a longer time for response
118
What is the function of Treg
Regulation of T cells and tolerant of self-antigens
119
What is the function of Th17
Interleukin 17, bacterial control and neutrophil recruitment
120
Describe the process of T cell development
Produced in the bone marrow (CD4-CD8-TCR-)
IN the cortex = CD4+CD8+TCR+
In the medulla = CD4+CD8-TCR+ vice versa
121
Describe selection in the thymus of T cells
Thymocyte can't bind = apoptosis
Weak binding = survival (+ve selection)
Strong binding = apoptosis (-ve election)
122
what is the largest burden of disease
Acute lung disease
123
What is the purpose of Interferon type 1
Activation of NK
124
What is the purpose of interferon type 2
Produced by T cells pre-inflamamtion
125
Define cytokine storm
Over production of cytokines and accumulation of cells
126
Compare bacterial and viral defence
Complement and antibody opsonisation vs Interferons and inflammatory mediators + acute phase proteins
Phagocytes vs NK cells
127
What are the features of an eradicable disease
```
Simple and cheap to diagnose
Genetically stable pathogen
Accessible host species
Eliminated persistent infection
Safe and effective vaccine
```
128
What are the features of the ideal vaccine
```
Completely safe
easy to administer
cheap
stable]active against all variants
life-long protection
```
129
Define tolerance
Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen
130
Give examples of autoimmune disease
Hashimoto's, myasthenia gravis
131
Define pathogenesis
Susceptibility genes and environmental triggers
132
Describe hypercytokinaemia
Too much immune response
positive feedback loop
pathogens enter the wrong compartment (Sepsis)
133
What is the 3 signal model
Licensing response
Antigen recognition
Co-stimulation
Cytokine release
134
What is AIRE
AutoImmune Regulator
| A specialised transcription factor that allows expression of genes
135
What is the function of IL-10
Pleitropic
Blocks pro-inflammatory cytokine synthesis
Downregulates macrophages
