Immunology and Healthcare theme 1 Flashcards
1
Q
What are the pathways to inflammation ?
A
chronic infection with plaque autoimmune hypersensitivity- allergic rhinitis etc metabolic disorder immunodeficiency
2
Q
Why is there redness in inflammation ?
A
increased blood flow
increased heat- against microorganisms
3
Q
What contributes to the inflammatory state in periodontitis ?
A
imparied host defence
4
Q
What is necrotising ulcerative gingivitis ?
A
ulceration
loss of epithelium due to acute infection
severe stimuli- stress, smoking and HIV, nutritional deficiency
5
Q
What is sjogren disease ?
A
autoimmune disorder
swelling of salivary gland
xerostomia
WBC accumulation in H and E slides - immune system destroys salivary glands
6
Q
What do gingival fibroblasts make in collagen turnover ?
A
MMP
7
Q
How is MMP stimulated ?
A
Macrophages make IL-1
stimulates MMP Production by fibroblasts
8
Q
What is IL-1 ?
A
pro inflammatory cytokine
9
Q
What happens in the disease state with MMP ?
A
bacteira in excess over stimulate macrophages to make IL-1 - fibroblasts respond with increased MMP
collagen turnover
increased tissue production
10
Q
Which over molecules can stimulate gingival fibroblasts to make MMP ?
A
leptin - type 2 diabetes and obesity
11
Q
How can we target MMP in periodontitis treatment ?
A
inhibit MMP with doxycycline
use as an adjucnt treatmnet with RSI
12
Q
How can we measure periodontitis improvement ?
A
probing depth
clinical attachment loss
13
Q
What are the main functions of the immune system ?
A
recognition of non self molecules
effector function- eradicate infection
Regulation to ensure correct response
Memory - allows stronger and quicker response on reinfection
14
Q
What are the characteristics of the innate immunity ?
A
rapid
fixed- cant adapt
limited number of specificities
constant during response
15
Q
What are the characteristics of adaptive immunity ?
A
slow response - cell interactions
variable- large or small
numerous selective specifiities- provide targeted response
improves during the response
16
Q
What does malfunction of the immune system lead to ?
A
chronic inflammation
17
Q
What are the ways in which skin acts as a barrier ?
A
thickened keratinised epidermis
sebaceous glands- fatty acids that lower pH
sweat glands- lactic acid
antimicrobial peptides
acts as a barrier to opportunistic infection
18
Q
What is the risk with burns ?
A
moist surface
vascular damage- promotes bacterial growth
19
Q
What do cuts and surgery promote ?
A
staph aureus infection
20
Q
What are examples of mucosal surfaces ?
A
urogenital tract
GI tract
respiratory tract
21
Q
What do mucosal surfaces act as ?
A
entry infection points
22
Q
What does ciliated epithelium allow ?
A
coagualtion of particles and ejection
23
Q
How does mucous work ?
A
mucin is a highly glycosylated protein
attracts water
coagulates particles and allows them to be swallowed
24
Q
Which cells secrete mucus ?
A
goblet cells
25
What does the saliva do ?
lysozyme and lactoferrrin
26
What does smoking do to epithelium ?
removes ciliated epithelium
27
When is sepsis likely and what can it cause ?
after colon surgery
| leads to septic shock
28
How do commensal bacteria have a protective function ?
stimulate colonic epithelial cells- in a balanced state of psychologic inflammation
commensal bacteria compete with pathogens for nutrients, attachmnet sites and space
bacteria produce antimicorbila lactic acid and fatty acids
29
How does a C.dificile infection occur ?
colon is colonised by commensal bacteria
antibiotics kill commensal bacteria - leads to dysbiosis
C. dificile produces toxins that cause mucosal imjury
neutrophils and RBCs that leak between epithelial cells
diarrhoea and anemaia
30
What are soluble mediators of innate immunity ?
enzymes- lysozyme and phospholipase- cell membrane and wall
complement system
antimicorbial peptides
31
What are the fucntions of the complement system ?
opsinisation
chemotaxis
lysis
32
What is the structure of antimicrobial peptides ?
amphipathic
33
What do antimicrobial peptides do ?
kill bacteria, fungi and enveloped viruses - disrupt membranes
34
Which cells make alpha defensins ?
neutrophils and paneth cells
35
Which cells make beta defensins ?
epithelial cells
36
What are paneth cells ?
specialised cells of small intestine
37
What do paneth cells make ?
alpha defensins
lysozyme
phospholipase
38
What is the complement system ?
innate effector function
family of 30 blood proteins
potent so a re highly regulated and kept inactive
39
How are complement proteins activated ?
blood clotting
| apoptosis
40
Which pathways activate complement system ?
lectin
alternative
classical
41
What happens in activation complementation ?
activation of c3 and c5
42
What ar the actions of the activated complement ?
perforation of cell membranes
opsinisation
chemotaxis
43
How do complement proteins attack membranes ?
make a membrane attack complex which disrupts bacterial outer membranes
leads to bacterial cell death
44
How does opsinisation for phagocytosis work ?
bacteria in a capsule cant be engulfed by a neutrophil
antobody bound to bacteria activates complement and allows C3 binding to bactiera
engulfment can now be activated by Fc receptors and complement receptors
granules fuse with phagosommes- release toxic oxygen metbaolites that kill bacteria
45
What is lymphatic tissue ?
rich in lymphocytes
| immune response mediation
46
What is primary lymphoid tissue ?
bone marrow and thymus gland
lymphocyte formation and maturation
b cells mature in bone marrow
t cells mature in the thymus gland
47
What is secondary lymphoid tissue ?
filters monitoring the blood and lymph for antigens and APCs
lymphocytes are acitvatedh ere
48
What are examples of secondary lymphoid tissue ?
```
lymph nodes
tonsils
spleen
peyers patches
MALT
```
49
What is the structure of they thymus gland ?
bilobed organ above the heart
lobular
outer fibrous cortex and inner medulla
50
What is the function of the thymus gland ?
T cell maturation
51
What is the purpose of the spleen ?
protects against blood bourne infections especially against encapsualted bacteria
52
What is the structure of the lymph nodes ?
```
no lobules
kidney shaped
no cortex/medulla
ring structure- follicle
afferent lymphatic vessel
lymphatic vessel spreads to the thoracic duct - spread lymphocytes
germinal center
```
53
What is the purpose of the germinal center ?
centre and location of the immune response
54
What is the function of lymph nodes ?
activation
expansion
presentation of cells
55
What is a peyers patch ?
mass of lymphatic tissue in the ileum of small intestine
56
What is the structure of a peyers patch ?
follicle structure
no afferent lymphatics
surrounded by villi
57
What is within the peyers patch ?
T cells
germinal centrrs
B lymphocytes
macrophages
58
What is the unique cell in the peyers patch ?
M cell
| provides antigen for the dendritic cell in the patch
59
What is waldayers tonsilar ring ?
patches of lymphoid tissue around the pharync and mouth
lingual tonsil
palatine tonsil - between muscles
pharyngeal tonsil
60
What are the sites of MALT ?
```
GI tract
nasopharynx
thyroid
breast
lung
salivary glands
antibodies and stimulated lymphocytes move between these regions
```
61
Which cells encounter antigens in the mucosa ?
macrophages
T cells
B cells
plasma cells
62
What are the innate immune effector cells ?
```
phagocytes
macrophages
granulocytes- neutrophils
mast cells
dendritic cells
```
63
What are monocytes ?
circulate in the blood
| enter tissues to become macrophages
64
What is the function of macrophages ?
phagocytosis
antigen presentation
scavengers
activation of T cells
65
What happens in the process of phagocytosis ?
bacteria binds to receptors on the neutrophil - its been covered in complement or antibodies
into phagosome
phagosome acidified- kills most
fuses with lysosome
degradation via lysosome by lysozyme and AMPs
NO and ROS also assist
66
What are neutrophils ?
granular
lobed nucleus
large reserves in bone marrow
67
What is the function of neutrophils ?
engulf microorganisms
rapidly mobilised on early staged of infections like gingivities
contribute to inflammation
68
What happens between macrophages and phagocytes in the inflammatory response ?
macrophaes engulf bacteria
induce cytokines and trigger neutrophil release from bone marrow
endothelial cells expand - tissue is red and swells and neutrophils enter
neutrophils phagocytose bacteria
neutrophils themselves are phagocytosied by macrophages
69
What are mast cells ?
release granules that contains histamine
part of defence against parasites
mediates hypersensitivity
70
What are dendritic cells ?
professional APCs
phagocytose
present antigen to initiate the immuen response in secodnary lymphoid tissues
71
Which cells are APCs ?
dendritic cells
macrophages
B cells
72
Phagocytes activate effector functions like ?
chemotaxis of new phagocytes like neutrophils
interferon response
systemic effects
activation of adaptive immunity
73
What is the interferon response ?
the anti viral response
74
Which type of immunity is inherited specifically in a genome ?
innate
75
Which type of immunity has receptors expressed by all cells of a specific type ?
innate
76
Which type of immunity triggers an imemdiate response ?
innate
77
Which type of immunity interacts with a range of molecules of a specific type ?
innate
78
Which type of immunity is coded for in multiple gene segments ?
adaptive
79
Which type of immunity requires gene arrangement ?
adaptive
80
Which type of immunity has clonal distribution ?
adaptive
81
Which type of immunity is able to discriminate between closely related structures ?
adaptive
82
What do PRRs do ?
recognise a wide range of molecular structures- PAMPs
83
Where are PAMPs found ?
on pathogens
84
What must precede adaptive recognition ?
innate recognition
85
What are adjuvants ?
used in vaccines
| allow the innate response to occur first and then adaptive response
86
What is the structure of PRRs ?
can be free receptors in the serum - mannose binding lectin
| can be membrane bound - on Dendritic cells
87
What is the mannose receptor and what does it do ?
a PRR
| recognises carbohydrate structure on pathogens
88
What are the classes of PRRs ?
Toll like receptors
| NOD like receptors
89
How many different types of Toll like receptors in humans and where are they ?
10 types in humans
| theyre in macrophaes, dendritic cells, B cells and epithelial cells
90
What do cell surface toll like receptors detect ?
extracellular pathogens and their products
91
What do intracellular TLRs detect ?
phagocytosed pathogens
| or viruses- theyre intracellular
92
What does TL4 recognise ?
LPS in gram negative
| lipoteichoic acid in gram positive
93
Are Toll like receptors specific ?
no they have a broad range
94
What does double stranded RNA act as ?
a non self indicator as humans only have single stranded RNA
95
What is the conformation of the TLR ?
heterodimer
most of it is intracellular
activate an intracellular pathway when ligand binds
96
What happens when a PAMP binds to TL4 ?
IRF and NKB transcription factors are made
IRF induces type 1 interferon leading to the antiviral response
NKB induces cytokines, chemokines and AMP leading to chemotacis, bacterial lysis and inflammation
97
What do mutations in TLRs lead to ?
immunodeficinecies
| recurrent bacterial infections
98
How do immunosupressant drugs work ?
interfere with TFs produced from the binding of the PAMP to the TLR
99
What do NOD like receptors respond to ?
intracellular infections
100
What do NOD like receptors identify ?
cell wall peptidoglycan
101
How do NOD like receptors link to crohns disease ?
NOD like receptors are mutated
inappropriate AMP response
commensal bacteria invade colonic epithelium leading to inflammation
102
What happens when macrophages sense microbial products ?
secrete pro-inflammatory cytokines
103
What are some of the effects of the cytokines produced by macrophages that have sensed PAMPs ?
activates vascular endothelium
activate lymphocytes
increases vascular permeabilty
recruits neutrophils
104
What attracts neutrophils to the site of infection ?
chemokines allow chemotaxis
| extravasation from blood to tissues
105
What do dead neutrophils form at wound margins ?
pus
106
What are the type 1 interferons and how are they secreted ?
IFN alpha
IFN gamma
secreted by virally infected cells and cells where TL3 and RIG have been activated by nucleic acids
plasmacyoid dendritic cells makes more IFN than any other cell
107
Describe the IFN response ?
```
virally infected cells
IFN alpha and gamma
induce resistance to viral replication
Increase MHC class I expression
increases antigen presentation in cells
activate dendritic cells and macrophages
activate NK cells to kill viruses
induce chemokines to recruiit lymphocytes
```
108
What are NK cells ?
kill virally infected cells early in the infection
type of innate lymphoid cell
activated by IL12 and type 1 IFN
have activating and inhibitory receptors
109
How do NK cells recognise infected and non infected cells ?
via TLR and Fc receptors and disregulated MHC expression - infected cells
non infected cells- characterisitc MHC expression
110
How do NK cells activate T cells and macrophages ?
secretion of IFN gamma- type II IFN
111
What is the mechanism of action of NK cells ?
contain the infection
activate T cells to provide targeted response and long term response - prevents infection spreading
hence why herpes doesnt spreasd
112
What type of cell are NK cells ?
lymphoid
| innate
113
How are ILCs distinguised from T and B lymphocytes ?
lack of antigen receptors
114
What are the fucntions of NK cells ?
amplify signals via cytokine secretion
fucntion as effector cells in response to inante recognition
ampligy interferon response to a viral infection
115
What is the early induced innate resposne ?
PAMPs recognised
| effector cells made
116
What is the adaptive response ?
transport antigen to lymphoid organs and recognition by B and T cells - clonal expansion of effector cells
117
Why do we need the adaptive response ?
the innate response is insufficient in removing pathogen
118
How do B lymphocytes develop ?
develop in the bone marrow from common progenitor
| mature in bone marrow
119
How do T lymphocytes develop ?
Develop from bone marrow progenitor but mature in the thymus gland
120
What are the 2 classes of T cells ?
CD4+
| CD8+
121
What are CD4+ cells ?
helper T cells- helps CD8+ cells and B cells
122
What are CD8+ Cells ?
cytotoxic T cells
| kill infected cells
123
What are the characteristics of adaptive immunity ?
delayed response
| more specific response
124
What is key to the adaptive response ?
activation of CD4+ T cells - go on to activate CD8 cells and B cells
125
What is the evidence that CD4 + cells are key for immunity ?
HIV- severely reduced CD4+ T cells
SCID- RAG deficiency
susceptible to infection
126
Which cells link the innate and adaptive immune responses ?
APCs- dendritic cells
| T cells are activated by processed antigen presented on APC
127
What does the interaction between dendritic cells (APCs) and T cells lead to ?
immunity to pathogens
| tolerance to self antigens
128
Why do we need to develop tolerance to self antigens ?
to prevent auto immunity
129
Where do dendritic cells interact with T cells ?
in lymph nodes
130
How is migration of the dendritic cells mediated ?
Dendritic cells remain in tissues and survey for pathogen
express a chemokine that allows them to remain in tissues- CCR7
pathogen detected and phagocytosed
danger signals like PAMPs activate the dendritic cell
change chemokine receptor- recruit migration to lymph node
T cell and dendritic cell interact
131
What is the signal mechanism of antigen recognition ?
signal 1- recognition of antigen, presentation by APC to T cell via MHC
signal 2- co-stimualtion
signal 3- cytokines
132
Which receptors detect PAMPs in the innate system ?
PRRs- NOD and TOL
133
Which receptors detect antigens in the adaptive response ?
TCRs and BCRs
134
How is the antigen presented by APCs ?
the antigen is processed by the APC and presented by MHC molecules
135
What are MHC molecules ?
transmembrane glycoproteins expressed on surface of cells
136
What are the classes of the MHC molecules ?
Class I- Activates CD8 cells
| Class II- activates CD4 Cells
137
Why is MHC difficult for pathogens to evade from ?
Polygenic- encoded for by several genes
Polymorphic- SNPs produce differnet alleles in the population- produces different MHC proteins capable of binding a variety of antigens
population is mostly heterozygous
138
How are MHC genes inhertied ?
MHC Molecules are inhertied alongside the polymorphisms that increase the variety of the antigen binding site
139
What is significant about MHC alleles ?
inherited in haplotypes
| selected for by populations in evolutionary terms
140
How can automimmune diseases be linked to MHC ?
autoimmune disease might come about from mutations that induce MHC molecules that bind self antigens
141
What does MHC class I present to ?
CD8 + T cells
142
Which cells express MHC class I ?
most nucleated cells
| allows most cells to be killed by CD8
143
What size peptides does MHC class I bind to ?
8-10 amino acids long
144
What is the structure of MHC class I ?
3 alpha domains- alpha 1,2 and 3
B2 microglobulin unit
peptide binding groove in the alpha subunits
145
How is the single heavy chain class I encoded for ?
```
6 class I genes
have a lot of allotypes
increasing number of MHC possibilities
```
146
What does MHC class II present to ?
CD4 t Cells
147
Which cells express MHC class II ?
APCs and thymus cells
| hence only a small number of cells can activate CD4 cells
148
What size peptides does CD4 cells bind ?
13-18 amino acids long
149
What is the structure of MHC class II ?
2 alpha domains- alpha 1 and 2
2 beta chains- beta 1 and 2
peptide binding groove in alpha 1 and beta 1
150
How is MHC class II encoded for ?
3 alpha and 6 beta genes
151
How are class I antigen complexes assembled ?
via intracellular cytosolic pathway
| for endogensou or intracellular antigens and viruses
152
Describe the intracellular cytosolic pathway ?
antigen in cytosol degraded by proteosome into short peptides
peptides transported to ER via TAP protein
peptide binds to class I in the ER- in the peptide binding groove
MHC antigen complex expressed on cell
CD8 recognises antigen- kill infected cells with help of CD4
153
Multiple MHC class I moleule on a single cell does what ?
increases chances of presenting different peptides
154
Which cells express MHC class II ?
Macrophages - semi professional APC
B cells - semi professional APC
Dendritic- professional APC
Fibroblasts, epithelilial and endothelial cells- Non professional APC- induced to express class II via IFN gamma
155
How are MHC class II antigen complexes made ?
via the extracellular exogenous pathway
156
Describe the exogenous extracellular pathway ?
Bacteria phagocyosed by APC
proteolysis to break antigen down
Antigen in a phagosome binds to lysosome
MHC class II in golgi and ER binds to antigen via peptide binding groove
expressed on surface
CD4 T cell recognises MHC class II and activates
157
What type of receptors do T cells ahve ?
each t cell is covered in TCR of one type - single antigen specificity
creates a large repertire of T cells that have a high diversity of binding sites for antigen.
158
What is the structure of a TCR ?
Dimeric- 1 alpha and 1 beta chain
span whole membrane
each TCR has constnat and variable region
159
How many genes encode for individual domains of the TCR ?
several
160
Where are TCRs generated ?
thymus
161
How do TCR genes recombine ?
via random somatic DNA recombination by RAG
162
What does RAG deficiency result in ?
no functionally active T cells
163
What is the nature of the TCR ?
randomly assembled and different but unique to one antiggen
164
What is MHC restriction ?
each TCR recognises parts of the antigen and the MHC
| each TCR is specific to a specifc antigen MHC complex
165
What does positive selection ensure ?
TCRs recognise specific MHC
166
How does positve selection work ?
in the thymus gland
different TCRs interact with specific MHC
if no recognition- die by apoptosis
if there is recognition of MHC by the TCR- t cell survives and moves into the blood- t cells are now MHC restricted
167
What is a co receptor ?
```
CD8 cells have CD8 protein on surface acts as a co receptor and recognises the specifc MHC class I too
same for CD4 protein and class II
```
168
How can CD4 cells be subdivided ?
Th1 cells- help CD8 cells via IFN gamma
| Th2 cells- help B cells make antibodies via IL4
169
What happens in signal III ?
cytokines produces that polarise the effector cells to become a specifc effector T cell
170
What is the vigorous training process that T cells undergo ?
positive and negative selection
171
What is the purpose of T cell training ?
to ensure that T cells only respond to foreign antgen only and dont recgonise self antigen
172
What happens during positive selection ?
make sure TCRs bind to MHC and recognise it
in the thymus cortex
Interaction between the TCR and the MHC antigen complex
if there is no recognition the T cell dies by apoptosis
recognition- T cell survives and is MHC restricted
173
What happens during negative selection ?
Ensures the TCR does not have a strong affinity for self antigen - known as central tolerance
takes place in the medulla
T cell interact with MHC antigen complex
binds strongly- dies by apoptosis
recognition at the right level- survives and enter blood and is known as naive T cell
174
What are naive T cells ?
antigen inexperienced and first bind to the APC
175
What leads to expression of costimulatory molecules on cell surface ?
activation of PRRs by PAMPs
| leads to expression of CD80 and CD86 on the cell surface
176
What are the co stimualtory molecules ?
CD80 AND CD86
177
What is the purpose of the costimualtory moelcules ?
increases the ability of the CD4 T cell to interact with APC
178
What is the interaction between the APC and the CD4 t Cell ?
CD4 T cell expressed CD28
| interacts with CD80 and CD86 on the APC
179
What does co stimulation lead to ?
support ability of CD4 T Cell to proliferate and differentiate into effector form
180
What does accumulation signal 1 and 2 lead to ?
IL2 is made and IL2 receptor
| IL2 is a survival factor- allows T cell to survive and proliferate into effector cells
181
What is the purpose of signal 3 ?
polarises the T cells to become specific effector cells
182
How is signal 3 initiated ?
PAMPs bind to PRRs which trigger cytokine production by the APC
different PAMPs produce different cytokines that polarise the T cells
virus - IL-12
Parasite- IL-4
183
What do the cytokines produces in signal III do ?
act on receptors on the naive T cell
determines the type of T cell via TFs
allows appropriate cells fro the pathogen to be produced,
184
Describe the process of T cell polarisation ?
Cytokines produced by the APC (triggered by PRR)
STAT pathway
TF
cell profile made
cytokines also produced by the newly polarised T cell
185
What are the different T cell profiles ?
```
Th1
Th2
Th17
Tfh
iTreg
```
186
What are the cytokines like that are produced by the newly polarised T cell ?
most cytokines and pro-inflammatory mediators
| except for TGB IL10 and IL35- made by iTreg which turns of inflamamtion and regualtes the immune response
187
How do newly polarised CD4 T cells contribute to positive feedback loops ?
the polarised cells produce cytokines that induce their own polarisation allowing more polarisation from the naive T cell to the effector cell
188
How can CD4 t Cells also contribute to negative feedback loops ?
Th1 cells produce IFN gamma that acts on Th2 cells inhibiting their proliferation
Th2 cells produce IL-4 which inhibits differentiation of Th1 cells
negative feedback loops can suppress other T cell responses
189
When an effector T cells detects an antigen which 3 braod classes of activity can they take ?
cytotoxic- CD8
Helper- CD4- Th1 and Th2
regulatory- Treg
190
What are cytotoxic T cells ?
```
CD8 cells
kill infected cells with intracellular antigens that are expressed by MHC class I
```
191
What are the killing mechanisms of cytotoxic T cells ?
cytotoxins -perforin and granzymes - induce apoptosis
Fas L - Fas L expressed on T cell interacts with Fas on target cell- signal for apoptosis
get help from Th1 CD4 T cells
192
What is the function of regulatory T cells ?
some cells escape central toelrance and can respond to self peptides
peripheral tolerance in the periphery is set up to counteract this
maintain immune homeostasis by supressing proliferation of self reactive t CELLS -
193
What are the mechanisms of action of T reg cells ?
Produce tolerogenic molecules like adenosine
consuption of IL-2 survuval factor
inhibtion of costimualtion- using ctal4 to block action of CD28 on T cell
granzymes and apoptosis
194
What are memory T cells ?
T cells that persist after most have died (most go to site of infection and some stay to activate B cells)
responsible for long lasting protective immunity following reexposure to pathogen
195
Why are memory cells faster ?
reactivated in an antigen specific manner
more quickly
lower threshold for activation
196
What happens to B cells ?
they take up antigen and present To Tfh cells that are involved in B cell maturation
b cell activates and turns into plasma cell - secrete antibody
197
What do B cells have on their surface ?
antibodies
198
What are the cellular features of plasma cells ?
eccentric nucleus
| excessive ER
199
Which cells stimulate B cell maturation ?
Tfh cells
200
What happens to antibodies during the immune response ?
undergo affinity maturation
| isotype switching from igG to igM
201
What are the fucntions of antibodies ?
activate complement
target bound antigen to other immune cells
neutralise toxins
prevent pathogens gaining entry to cells
202
What is the N terminii on an antibody ?
amine group that forms antigen binding site
203
What is the c terminii on the antibody ?
carboxylic acid group
204
What does the hinge region on the antibody allow ?
flexibility
205
What is the variable region of the antibody ?
unique to an antigen type
206
What is the most abundant antibody in body fluids ?
igG
207
Where is igG made ?
lymph nodes
bone marrow
spleen
208
Where can igG get to ?
extracellular spaces and across placenta to protect developing embryo
209
Which immunoglobulin has the most effector functions ?
igG
210
What does the antibody class determine ?
the response
211
How are antibodies divided into class ?
on the basis of heavy chain structure
212
What is the first antibody produced in the immune response ?
igM
213
Where is igM prodcued ?
lymph nodes
spleen
bone marrow
214
What does igM do ?
circulates in blood and lymph
| stimulates complement activation and phagocytosis
215
What is the structure of igM ?
pentametric
| multivalent - multiple binding sites
216
What are the forms of igA ?
monomeric in the blood
| dimeric in the tissues
217
Where is igA found ?
gut
saliva
sweat
tears
mucosal immunity - protect agaisnt streptococci
can be made by GALT- tonsils and peyers patches
218
What is the function of igE ?
binds to Fc receptors on mast cells
already bound
little circulating amounts- bound to Fc receptors
219
What triggers mast cells ?
cross linking of antigen (pollen) on IgE on mast cells leads to degranulation and activation of innate immunity
increased blood flow
neutrophil migration
histamine released
220
What does excessive activation of mast cells lead to ?
hypersensitivity
| originally developed for parasitic protection
221
What is clonal selection ?
lymphocytes present antigen to Tfh cell
maturation from B cell to plasma cell
clonal selection- plasma cells produced that make an antibody specific to that antigen
222
How Ig diversity generated ?
many immunoglobulin genes in every B cell
3 loci for the heavy chain and 2 loci for the light chain
genes are randomly selected from loci
make different combinations
D and J genes also inserted
223
What happens in the rearrangement of DNA in B cells ?
Each B cell has different rearrangement of D and j genes
combined with C genes
continuous sequences in the variable region
happens in heavy and light chains
224
What is somatic recombination of DNA in B cells ?
random rearrangments of somatic DNA via VDJ recombinase
225
What is VDJ recombinase ?
multi enzme complex evovled from DNA repair enzymes
226
Which cells is RAG gene expressed in ?
lymphocytes
227
What are the mechanisms of diverisity in VDJ genes ?
combinatroial and jucntional
228
What is combinatorial diversity I ?
multiple genes which can be selected and combines together
229
What is junctional diversity I ?
Imprecise cutting and pasting of nucletodies by VDJ recombinase
230
What is junctional diversity II ?
addition of non germline nucleotides between D and J genes and V segments
231
What is combinatorial diversity II ?
Assembly of the Ig molecule by heavy and light chains
232
What is the order of change in immunoglobulin genes ?
```
recombination of DNA somatically
generation of junctional diversity
somatic hypermutation
microevolution of affinity
isotype switch
```
233
What does somatic hypermutation allow ?
during successive immune responses introduces mutations that alter iG protein structure
allows higher affinity igG to be secreted
234
What is the microevolution of affinity ?
increasing affinity for antigen provides better immune response
B cells that express high affinity igG survive
those that express low affinity igG die due to natural selection
235
What is the isotype switch ?
from igM to igG
236
What are the changes that occur to antibodies after repeated immunisations ?
increased quantity of antibody
increased affinity of antibody due to somatic hypermutation
isotype switch
produces better quality response
237
What are memory cells ?
B cell sin lymph nodes develop into plasma cells and memory cells under the influence of cytokines from Tfh cells
memory cells remain in blood- provide more vigorous response next time
238
Why are there variations in the immune system ?
```
vaccination history
malnourishment- affects immune system
lifestlye factors- exercise and smoking
hormonal status
gut flora
early life events
stress
```
239
What is normal ageing assocaited with ?
reduction in functional reserve capacity
240
What is the biological basis of ageing ?
random cellular damage
accumualtion of cellualr defects
age related frailty, disability and disease
241
How can ageing be accelerated ?
accelerated by stress, poor diet and behaviour
242
How can ageing be delayed ?
good diet
lifestyle
good environment
243
Why are there decreased immune responses in the elderly ?
poor nutrition
244
What happens in protein energy malnutrition ?
lack of dietary protein and macronutrients
| seen in 10% of over 65
245
What are some immune measures ?
```
IL-1
IL-2
IL-6
Antibody production
gut barrier fucntion
all decreased in elderly with PEM
```
246
What is the link between malnutrition and infection ?
undernutrition
diminished host defence
infection
bidirectional as infection amkes more malnourished
247
How are nutrients lost in infection ?
anorexia
diarrhoea
impaired absorption
diarrhoea
248
What do diarrhoea and intestinal damage cause ?
exaggerated inflammatory response
249
What do EPA and DHA improve ?
rheumatoid arthrits
decrease prostaglandins
leads to less NSAID usage and improved clincal scrores
250
What is reduced with B6 deficiency ?
IL-2 and lymphocytes
251
What does zinc deficiency result in ?
reduced innate and acquired responses
| increased susceptibility to viral and bacterial infections
252
What does zinc deficiency result in ?
reduced T cell
reduced NK cells
reduced antibodies
253
What can large amounts of zinc result in ?
copper deficiency
interference between copper and zinc uptake
can impair immune function
254
What can zinc be beneficial in ?
periodontal health
pocketing
lower plaque and lower pocket depth
255
What can micronutrient deficiencies do ?
make individual more susceptible to infection
256
Does ageing have an effect on the immune system ?
ageing has less influence on the immune system
| environmental factors have more of an effect on the immune system
257
Nam 2 vascular changes responsible for inflammation ?
vascular dilation
| increased blood flow
258
What histological signs can you see in a tissue with lymphovytic infiltrate ?
densely stained cells with no shape or bounday
259
What practical evidence is there that MMP mediated tissue distruction in periodontitis ?
Doxycycline and MMP inhibitor is used as an adjucnt treatment in RSI
260
Give 2 examples of emerging human pathogens ?
ebola and HIV
261
Give 2 examples of re emerginig human pathogens ?
TB and measles
262
Give 2 examples of pathogens that have been eradicated ?
polio and small pox
263
Why are there small numbers of effective viral vaccines ?
no economic imperative
| antigenic variation due to mutation
264
Which pathogen affects lesions due to burns and CF ?
pseudomonas aureginosa
265
Which location has the majority of disease due to mucosal infection ?
lungs
266
Which molecules stimulate neutrophil chemotaxis ?
complement
| chemokines
267
How is haematopoieses regulated ?
cytokines
| bone marrow stromal cells
268
Where does haemoatopoiesis take place ?
in bone marrow
269
What are the 3 haemoatopoietic lineages ?
myeloid
lymphoid
erythroid
270
Where do lymphatics drian into the blood circulation ?
thoracic duct into subclavian veins
271
Which mucosal tissue protects mouth ?
salivary glands
272
How do macrophages signalt to T cells ?
via cytokines like IFN gamma
273
What is the shape of monocyte ?
kidney shaped nucleus
274
What is the shape of lymphocyte ?
small and round nucleus
275
Which part of the Ig molecule do phagocytes interact with ?
Fc region
276
Which molecules mediate pathgoen destruction through neutrophils ?
ROS- NO
AMPs
lysozyme
protease
277
Why dont we know much about basophils and eosinophils ?
few in circulation
278
What are the 4 consequences of innate signalling- local and systemic ?
neutrophil chemotaxis
activation of adaptive immunity
vascular changes
systemic- acute phase response
279
Which 3 compartments might you fins different PRRs ?
membrane bound- TL4
serum- mannose binding lectin
Endosome- TL3
280
Which PRR recognises double stranded RNA and where can you find it ?
TLR3
| virus
281
Name an important TF activated in response to immune signalling ?
NF-kB
282
Give examples of interferons ?
type I- IFN alpha and beta- released by virally infected cells
type II- IFN gamma released by NK cells
283
Which cytokines allow Th1 cell development ?
IFN gamma and IL12
284
Which cytokines allow Th2 cells to develop ?
IL4
285
Which cytokines allow Th17 cells to develop ?
TGFB
286
Which cytokines allow Tfh cell to develop ?
IL21
287
Which cytokines allow iTreg development ?
TGFB
| IL10
288
Which transcription factor is needed for Th1 development ?
T-bet
289
Which transcription factor is needed for Th2 development ?
GATA3
290
Which transcription factor is needed for Th17 development ?
RORyt
291
Which transcription factor is needed for Tfh development ?
Bcl 6
292
Which transcription factor is needed for Treg cells ?
Foxp3
293
What is the job of Th1 cells ?
activate macrophages via IFN gamma
| target intracellular bacteria like
294
What is the job of Th2 cells ?
activate mast cells, eosinophils and basophils
B cell actication
allergy
295
What is the job of Th17 cells ?
reinforce innnate immunity with neutrophils
| target extracellular bacteria
296
What is the job of Tfh cells ?
B cell activation and maturation
help with isotype switching and affinity maturation
IgM to IgG
297
What do Treg cells do ?
regulate immune response
| lack of T cell activation
