Immunology Flashcards
1
Q
Describe features of innate immunity
A
Non-specific
Instinctive
Does not depend on lymphocytes
2
Q
Describe features of adaptive immunity
A
Specific ‘acquired’ immunity
Requires lymphocytes
Antibodies
3
Q
What is the general purpose of immune system?
A
To distinguish from self and non-self
4
Q
What are the three types of leukocytes
A
Lymphocytes
Phagocytes
Auxillary cells
5
Q
What cell do all leukocytes originate from
A
Haematopoietic Pluripotent/Multipotent Stem Cell
6
Q
What progenitor cells are formed from haematopoietic pluripotent stem cells
A
Myeloid Progenitor
Lymphoid Progenitor
7
Q
Which two cells in blood (or tissue) derive from haematopoietic pluripotent stem cells but not a progenitor cell (from hp stem cells)
A
Eosinophil
Basophil
8
Q
What 4 cells/parts of the blood derive from Myeloid progenitors
A
Erythrocytes
Platelets
Monocytes
Neutrophils
9
Q
What cell forms platelets
A
Megakaryocyte
10
Q
What cell forms erythrocytes
A
Reticulocytes
11
Q
What do monocytes differentiate into?
A
Macrophages
12
Q
What are 2 types of cells macrophages can differentiate into
A
M1 and M2
13
Q
What chemicals allow differentiation of macrophages into M1 cells
A
LPS
INF(gamma)
14
Q
What chemicals allow differentiation of macrophages into M2 cells
A
IL-4
IL-13
TGF(beta)
15
Q
What cells are formed from lymphoid progenitor
A
B cell T cells (regular, helper, cytotoxic)
16
Q
How is B cell formed form Haematopoietic pluripotent stem cell
A
HP stem cell > Lymphoid progenitor >Pro-B cell > Pre-B cell > B-cell
17
Q
What cell can lymphoid progenitor differentiate into which can then differentiate into T-cells
A
Thymocyte
18
Q
Where are thymocytes found
A
Thymus
19
Q
What 2 types of cells can B cells differentiate into
A
Plasma cell Memory cell (only some)
20
Q
Where do plasma cells and T-cells drain into
A
Lymph nodes
21
Q
What cells are considered Polymorphonuclear leukocytes
A
Neutrophils
Eosinophils
Basophils
22
Q
How big are neutrophils
A
10-14 micro metres
23
Q
What is the normal lifespan of a neutrophil
A
6h to 12d
24
Q
What is the normal concentration of neutrophil in the blood and what % of cells does this make up
A
3000 to 11000 per mm^3 blood
65%
25
What is CD66b
activation marker for human granulocytes (but full understanding on eosinophils not known)
expressed by neutrophils
26
what is the role of Neutrophils in INNATE immunity
Phagocytosis
27
What are 2 main intracellular granules of neutrophils
Primary lysosomes
| Secondary granules
28
What chemicals are found in primary lysosomes in neutrophils
```
Enzymes:
Myeloperoxidase
Muramidase
Acid hydrolyses
Proteins (Defensins)
```
29
What is function of primary lysosomes in neutrophils
Combine with phagosomes containing microbes to digest them
30
What chemicals are found in secondary granules in neutrophils
Lactoferrin
| Lysozyme
31
How do neutrophils kill microbes
By secreting toxic substances like superoxides
32
Which of these is not a feature of neutrophils:
- Primary lysosomes combine with phagosomes containing microbes to digest them
- They have Fc and complement receptors
- They can kill microbes by secreting toxic substances
- Primary granules contain lactoferrin and lysozyme
- They are 10-14 micro m
Secondary granules contain lactoferrin and lysozyme (not primary)
33
Describe monocyte
Mononuclear leukocyte
34
What is size of monocyte
14-24 micro metres
35
What is concentration of monocytes in blood and what is % of monocytes amongst other cells of blood
100-700 per mm^3 blood
| 5%
36
What is CD14
Expressed by Monocytes (also dendritic cells, neutrophils (to much lesser extent) and macrophages)
Pattern Recognition receptor
for pathogenic activity and for bacterial lipopolysaccharide (LPS)
37
What are roles of monocytes or macrophages in innate and adaptive immunity
Phagocytosis
| Ag presentation
38
What is main role of monocytes
remove any foreign or dead microbes
39
How do monocytes kill microbes
Have lysosomes containing peroxidase that can kill microbes
40
What receptors are found on monocytes
```
Fc (antibody) receptor
Complement receptors
Pattern Recognition receptors (PRR)
Toll-like receptors
Mannose receptors
```
can bind to all kinds of microbes
41
What cells do monocytes differentiate into
Macrophages
42
What is general lifespan of monocyte
Months
43
What is the main role of macrophages
```
Most often first line of non-self recognition
Remove foreign (microbes) and self (dead/tumour cells)
```
44
What are other features of macrophages
Can bind to all kinds of microbes as have Fc, complement, Scavenger, Toll-like, mannose receptors
Present Ag to T-cells
Have lysosomes containing peroxidase (free radicals)
45
What is general lifespan of macrophages
Months/years
46
Where do monocytes reside and where do macrophages reside generally
Monocytes - blood
| Macrophages - tissue
47
What cells are considered mononuclear leukocytes
B lymphocytes
T lymphocytes
Monocytes
48
What is general size of eosinophil
10-14 micro metres
49
What is concentration of eosinophil and what is percentage in cells of blood
100-400 per mm^3 blood
| 5%
50
What is lifespan of eosinophil
8 to 12 days
51
What is CD125
Expressed by eosinophils
| Alpha subunit of the Interleukin-5 receptor
52
What dyes do eosinophil granules stain for
Granules satin for acidic dyes (eosin)
53
What are roles of eosinophils
Countering Parasitic infections and allergic reactions
54
How do eosinophils counter parasitic infections
Granules contain Major Basic Protein which is a potent toxin for helminth worms
55
How do eosinophils counter allergic reactions
Major Basic Protein activates neutrophils.
| This induces histamine release from mast cells and provokes bronchospasm.
56
Size of basophils
10-12 micro m
57
Conentration of basophils in blood and concentration in blood
20-50 per mm^3 blood
| 0.2% (lowest of cells)
58
What is average lifespan of basophil
2 days
59
Which of these statements regarding basophils is false:
Granules stain for basic dyes
Very similar to mast cells
They are generally 14-20 micro m
They are generally 10-12 micro m
60
What are basophils or mast cells involved in
Immunity to parasitic infections
| Allergic Reactions
61
How are basophils involved in causing allergic reactions
Express high-affinity IgE receptors (FcεR1)
| Binding of IgE to receptor causes de-granulation releasing Histamine (causes allergic reactions)
62
What is size of mast cell
10-14 micro m
63
Where are mast cells found
Only in tissues
| Precursor in blood
64
How are mast cells similar to basophils
Also express high-affinity IgE receptors (FcεR1)
| Binding of IgE to receptor causes de-granulation releasing Histamine (causes allergic reactions)
65
What is a key role of tissue macrophages and give 3 examples
Maintenance of tissue homeostasis through clearance of cellular debris (especially following infection or inflammation):
- Alveolar macrophages (clear microorganisms and debris encountered in air)
- Gut macrophages (bactericidal activity)
- Osteoclasts (giant multinucleate cells that resorb bone)
66
What is size of T lymphocytes
5-12 micro m
67
What is concentration of T lymphocytes in blood and % in blood
300 to 1500 per mm^3 blood
| 10%
68
What is lifespan of T-lymphocytes
hours to years
69
Where do T lymphocytes mature
Thymus
70
What is CD3
T cell receptor complex
71
How do T-lymphocytes play a large role in adaptive immunity
recognise peptide Ag displayed by Antigen Presenting Cells (APC)
72
What are 4 main types of T lymphocytes
T helper 1 (CD4)
T helper 2 (CD4)
Cytotoxic T cell (CD8 - can kill cells directly)
T reg (Fox P3) - regulate immune response (dampens)
73
Where are T lymphocytes and B-lymphocytes found
Blood, Lymph nodes and spleen
74
What is difference between T helper 1 and T helper 2 cells
T helper 1 CD4 - help immune response intracellular pathogens
T helper 2 CD4 - help produce antibodies - extracellular pathogens
75
What is size of B lymphocyte
| What is concentration of them in blood and what % of cell content do they make up
5-12 micro m
300-1500 per mm^3 blood)
15%
76
What is lifespan of B lymphocytes
Hours to Years
77
How do B-lymphocytes play a large role in adaptive immunity
Recognise peptide Ag displayed by Antigen Presenting Cells (APC)
Express membrane bound antibody on cell surface
Differentiate into plasma cells that make antibodies
78
Where do B cells mature?
Bone Marrow
79
What CD proteins are expressed by B lymphocytes
CD19 and CD20
| depends on maturity
80
What % of lymphocytes are Natural Killer Cells?
15%
81
What protein is expressed by Natural Killer cells
CD56
82
Where are natural killer cells found
spleen/tissues
83
Describe appearance of natural killer cells
look like 'large granular lymphocytes'
84
What is purpose of natural killer cells
Recognise and kill:
Virus infected cells
Tumour cells
(by apoptosis)
85
Name 3 kinds of soluble factors
Complement Factors
Antibodies
Cytokines/Chemokines
86
What are 3 main pathways of activating complement factor C'3
Classical - Ab bound to microbe
Alternative -Complement (C') binds to microbe
Lectin - activated by mannose binding to lectin bound to microbe
87
What are immunoglobulins (Ig's)
Soluble Glycoproteins
| Bound to B cells as part of B-cell antigen receptor
88
What are 5 distinct classes of immunoglobulins/antibodies
```
IgG (IgG1-4)
IgA (IgA1 and 2)
IgM
IgD
IgE
```
89
Define Antibody (Ab)
Protein produced in response to an antigen. It can only bind with an antigen that induced its formation (i.e. specificity)
90
Define Antigen (Ag)
A molecule that reacts with preformed antibody and specific receptors on T and B cells.
91
*Define Epitope
The part of the antigen that binds to the antibody/receptor binding site
92
Define Affinity
Measure of binding strength between an epitope and an antibody binging site.
(Higher affinity = better)
93
What is Fab and Fc regions of antibody
Imagine Y shape
Vertical bit is Fc region of only heavy chain parts (binds to Fc receptor of phagocyte)
Two diagonal bits are Fab region of Light chains and parts of heavy chains (with antigen-binding site that binds to epitope of antigen)
**see picture of basic structure of IgG1 with hinge region, variable region etc
94
What is most common Ig in human serum?
IgG
| 70-75% of total Ig in serum
95
Describe the shape of IgG
Light chains of 212 residues
Heavy chains of 450 residues
Hinge region between Fc and Fab regions
(Is like Y shape but Fc region looks circular so is like a gamma symbol)
96
What % of Ig in serum does IgM make up?
10%
97
In which antibodies or immunoglobulins would you find a J chain?
IgM and sIgA (secretory)
| sIgA held together by J chain and secretory component
98
What is shape of IgM
Pentamer
| formation requires J chain
99
Where is IgM mainly found
Blood as too big to cross endothelium
100
Where is monomeric form of IgM (mIgM) found
Present as an antigen-specific receptor on B cells
101
Where are IgMs mainly used?
Mainly primary response - initial contact with Ag
102
What % of Ig in serum does IgA make up?
15%
103
What % of serum IgA is a monomer?
80%
| can also be a dimer, held by J chain
104
Where is IgA found
Predominant Ig in mucous secretions such as saliva, milk, bronchiolar and genitourinary secretions
(sIgA - secretory)
105
What % of Ig in serum does IgD make up?
1%
106
What is mIgD and where is it found?
Transmembrane monomeric form of IgD present on mature B cells
107
What % of Ig in serum does IgE make up?
approx 0.05% (lowest)
108
What cells express IgE-specific receptors with a high affinity for IgE?
Basophils
| Mast cells
109
What is released by binding of IgE to basophils or mast cells
Histamine
| allergic response, also IgE associated with defence against parasitic infections
110
What Ig contains a central carbohydrate unit (Fc')
IgE
111
What are cytokines?
Proteins secreted by immune and non-immune cells
112
Give 4 examples of cytokines
Interferons (IFN)
Interleukins (IL)
Colony Stimulating Factors (CSF)
Tumour Necrosis Factors (TNF alpha and beta)
113
What is role of interferons (cytokine)
Induce a state of antiviral resistance in uninfected cells and limit the spread of viral infection
114
What cells produce IFN alpha and beta (interferons)
Virus infected cells
115
What cells produce IFN gamma
Released by activated Th1 cells
116
What are interleukins (IL)
```
Any of a class of glycoproteins produced by leukocytes for regulating immune responses.
(produced by many cells (>30))
```
117
What is difference between IL1 and IL-10
```
IL-1 = Pro-inflammatory interleukin
IL-10 = Anti-inflammatory interleukin
```
118
What is role of interleukins
Can cause cells to divide, differentiate and to secrete factors
119
What is role of colony stimulating factors
Involved in directing the division and differentiation on bone marrow stem cells - precursors of leukocytes
120
What is role of tumour necrosis factors (alpha and beta)?
Mediate inflammation and cytotoxic reactions
121
What are chemokines?
Chemotactic cytokines
Group of approx 40 proteins that direct movement of leukocytes (and other cells) from the blood stream into the tissue or lymph organs by binding to specific receptors on cells
122
What is role of chemokine?
Attract leukocytes to sites of infection/inflammation
123
Give examples of Chemokines and the leukocytes they attract
CXCL - mainly neutrophils (also T and B lymphocytes)
CCL - monocytes, lymphocytes, eosinophils, basophils
CX3CL - mainly T lymphocytes and NK cells
XCL - Mainly T lymphocytes
124
What chemokine attracts eosinophils
CCL
125
What chemokine mainly attracts neutrophils
CXCL
126
Which chemokines mainly attract T-lymphocytes?
XCL and CX3CL (and CXCL and CCL)
127
What chemokine attracts NK cells
CX3CL
128
What cells do CCL chemokines attract?
Monocytes
Lymphocytes
Eosinophils
Basophils
129
Give differences between Innate and Adaptive immune responses
```
Innate: Non-specific
1st line of defence
Provides barrier to antigen
Present from birth
(no long lasting memory)
```
Adaptive: Specifc
Response specific to antigen
Memory to specific antigen
Quicker Response
(both integrate with each other)
130
Examples of innate immunity
```
Physical and Chemical Barriers (skin - dermis and epidermis, intact skin preventing prevention or growth (low pH) and sebum - skin secretions pH 3-5)
Phagocytic cells (neutrophils, macrophages)
Serum proteins (Complement, acute phase)
```
131
Examples of Physical Barriers (Innate immunity)
Skin (Physical carrier, fatty acids, commensals)
Bronchi (Mucus, cilia)
Gut (acid, rapid pH change)
```
Also:
Lysozyme in tears and other secretions
Commensals in digestive system
Removal of particles by rapid passage of air over turbinate bones
Flushing of urinary tract
Low pH and commensals of vagina
```
132
Examples of Mucous membranes (innate immunity)
```
Saliva
Tears
Mucous secretions
Mucous -entrapment
Cilia - elating removes microbes
Commensal colonies - attachment and nutrients
```
133
Physiological barriers (innate immunity)
```
Temperature (pyrexia)
Fever response (inhibits micro-organism growth)
pH
Gastric acidity (Helicobacter pylori)
Oxygen tension - aerobes/anaerobes
```
134
Define Inflammation
A series of reactions that brings cells and molecules of the immune system to sites of infection or damage
135
What cells sense microbes in blood
Monocytes
| Neutrophils
136
What cells sense microbes in tissues
Macrophages
| Dendritic cells
137
What are PRRs and PAMPs and where are they found
PRR - Pattern Recognition Receptors (on cells) e.g. TLRs
| PAMP - Pathogen Associated Molecular Patterns (on microbe)
138
How do TLRs (toll-like receptors) sense microbes?
TLRs recognise Pathogen-Associated Molecular Patterns expressed by microbes
139
```
What PAMPs (pathogen associated molecular patterns) are detected by each of these PRRs?
TLR2
TLR3
TLR4
TLR7
TLR9
```
TLR2 = Peptidoglycan
TLR3 = Double stranded RNA
TLR4 = Lipopolysaccharide (LPS)
TLR7 = Single stranded RNA
TLR9= Double stranded DNA or CpG DNA
140
What PRRs are expressed by plasmacytoid dendritic cell
TLR7, TLR9
141
Which TLRs/PRRs detect viruses
TLR3, TLR7, TLR9
142
What pathogen is detected by TLR2?
Gram Positive bacteria
143
What pathogen is detected by TLR4?
Gram Negative bacteria
144
What is detected by TLR5
Flagellin
145
What are 3 functions of complements (C')?
- Lyse microbes directly via Membrane Attack Complex
- Increase chemotaxis (C3a and C5a)
- Opsonisation (C3b)
146
*What is meant by opsonisation?
Targeting particles such as bacteria for destruction by a phagocyte
147
What are 2 killing pathways present in polymorphs and macrophages?
O2 - dependent
| O2 - independent
148
Describe O2 dependent pathways of killing
Reactive Oxygen Intermediates (ROI):
* Superoxides (O2 ^-) converted to H2O2 then .OH (free radical)
* Nitric Oxide (NO) - vasodilation increases extravasation but also directly anti-mircobial
149
Describe the O2 independent mechanism of killing
```
Enzymes
Defensins (insert into membranes), lysozyme, pH, TNF
```
150
Give examples of accessory molecules
Acute phase proteins (that are present in blood and increase during infection):
C reactive protein
Mannose binding lectin (MBL)
Surfactant protein-A (SP-A)
151
What is C reactive protein and what is it's function
```
Serum protein produced by liver
Binds to some bacterial cell walls (pneumococci)
Promotes opsonisation
Binds to C1q
Activates C' (complement)
```
152
What is function of Mannose Binding Lectin (MBL)
Binds to lectin on microbes
Promotes Opsonisation (via MBLR)
Activates C'
153
What is the function of Surfactant Protein-A
Binds haemagglutinin in influenza
| Reduces ability of virus to infect cells
154
What is Cell-Mediated Immunity
Immune response that does not involve antibodies, but evolves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes an release of cytokines in response to antigen
155
Do T-cells respond to soluble antigens?
NO
| They only respond to intracellular antigens (presented antigens)
156
Where are t-cells that recognise 'self' eliminated
T cells that recognise ‘self’ are killed in the foetal thymus as they mature (called T cell selection)
157
Describe structure of TCR (T cell receptor)
Similar to Fab Ig's
| Heterodimers are 90% alpha/beta, 10% gamma/delta
158
What does MHC stain for
Major Histocompatibility Complex
159
What is function of MHC
Display peptides from self or non-self proteins (e.g. degraded microbial proteins) on the cell surface
Invasion alert
160
What genes code for MHC 1 and 2 in humans
Human Leukocyte Antigen (HLA) genes
MHC I coded by HLA (A, B and C genes)
MHC II coded by HLA (DP, DQ and DR)
161
What does MHC III code for
Secreted proteins (complement)
162
*What T-cells display MHC class I
MHC I = all cells -> CD8 T cells
163
What T-cells display MHC class II
MHC II = APC only -> CD4 T helper
164
What antigens are detected by MHC I
Intrinsic/Intracellular antigens e.g. virus
165
What antigens are detected by MHC II
Extrinsic/Extracellular antigens (phagocytosis)
166
What antigens are detected by MHC II
Extrinsic/Extracellular antigens (phagocytosis)
167
What is the function of MHC II and their APC
Help B cells make Abs to extracellular pathogens
| Can help directly kill these pathogens
168
Describe the structure of Class I and II MHCs
Class I:
8-10 aa peptide on receptor of 3 alpha units and a beta2m unit
Class II:
13-24 aa peptide on receptor of 2 alpha and 2 beta subunits on APC
169
Upon activation, what is secreted by pDCs (plamsacytoid dendritic cell) in large quantities
IFN alpha
| potent antiviral and pro inflammatory cytokine
170
How does a mature dendritic cell activate naive T cells?
Mature DC provides 3 major signals:
- Presentation of the peptide fragments from the pathogen bound to surface HLA molecules
- Co-stimulation through CD80 and CD86 interacting with CD28 on T-cells
- Secretion of cytokines - e.g. IL-12
* T-cell also secretes IL-2 which binds to IL-2R on T-cells (autocrine) to activate them
Activated T-cell leads to division, differentiation, effector functions, memory
171
What 2 types of T cells can naive alpha/beta T-cells differentiate into?
CD4 or CD8
| CD8 can kill intracellular pathogens directly
172
What 2 cells can CD4 cells mature into and what cytokine determines this
Th1 or Th2 (T-helper)
IL-12
High IL-12 leads to Th1 where as low IL-12 leads to Th2
173
What cytokines are released from Th2 cells and what is the cell's general function?
IL-4,5,10
| Ab production
174
What cytokines are released from Th1 cells?
IL-2
| IFN gamma
175
What is function of IFN gamma
Helps kill intracellular pathogens by activating macrophages
176
What is required to form a cytotoxic t cell (CTL or Tc)
CD8 and MHC I and TCR (t cell receptor)
177
What chemicals released from Cytotoxic T cells lead to apoptosis or pathogen killing?
CTL forms proteolytic granules and releases perforins (apoptosis) and granulysin (killing of pathogen)
178
**Describe Th1 (CD4) activation
- APC presents Ag with MHC II to a naïve CD4 T cell
- Stimulation with high levels of IL-12 activate naïve cells to CD4 Th1 cells
- Th1 cells travel to secondary lymphoid tissue (spleen, lymph nodes)
- Activated CD4 Th1 cells proliferate (clonal expansion)
- Th1 cell recognises Ag on infected cells (with MHC II) via TCR (CD4)
- Th1 secretes INFγ – stop virus spread (apoptosis)
179
Which of the following statements regarding B cells is false:
*B cells express membrane bound Ig (IgM or IgD
monomer)
*Each B cell can only make one Ab that will only bind
one epitope on one Antigen
*We are born with more than 10^9 immature B cells
*B cells that recognise self are killed in spleen
B cells that recognise self are killed in the bone marrow
We ARE born with over 10^9 immature B cells
180
Where are B cells that recognise self killed?
Bone Marrow
181
What Membrane bound Igs are expressed on B cells
IgM or IgD monomer
| mIgM
182
Describe process of B cells presenting Ag to T cells via MHC II
-mIgM (or mIgD) binds Ag
-Phagocytosis
-Peptide displayed on surface with MHC II
-TCR of naive Th (CD4) binds to MHC II
(Lots of other co-stimulatory molecules required)
183
Describe process of forming plasma or memory cells from the APC engulfing the Ag (extrinsic) and presenting it
-APC eats Ag (extrinsic) and presents it to naïve CD4+ T cells (via MHC II)
-These turn into primed Th2 cells
-Th2 cells bind to B cells that are presenting Ag (via MHC II). This Ag
has been captured using the mIgR on cell surface.
-Th2 cell secretes cytokines (IL-4, IL-5, IL-10 and IL-13)
-These cause B cells to divide by CLONAL EXPANSION and differentiate into Plasma cells (AFC) and Memory B cells (Bm)
184
What is an AFC?
Antibody Forming Cell
185
What are primary lymphoid organs of body?
Thymus
| Bone marrow
186
What are secondary lymphoid organs of body?
```
Waldeyers ring (tonsils and adenoids)
Bronchus associated lymphoid tissue
Lymphoid nodules
Peyers Patch
Urogenital Lymphoid tissue
```
187
Give examples of lymphatic vessels important
Thoracic Duct
188
What type of antibody is generally secreted by plasma cells
IgM
| of same specificity of plasma cells, but later these turn into IgG (still keeping same specificity)
189
What is conversion of IgM to IgG called (B cell activation)
Class switching
190
What are 3 functions of antibody
- Neutralise toxin by binding to it
- Increase opsonisation - phagocytosis
- Activate complement
191
Very briefly describe vaccination
(inactive) Toxoid injected to trigger primary antibody response and produce memory B cells.
Then in natural infection secondary antibody response triggered which is much quicker and bigger and destroy toxins and invading organisms.
(Acquired immunity)
192
What 3 layers are formed from centrifuging a blood sample and what is found at each of these layers?
Upper layer:
Plasma - straw coloured liquid
-90% water, also electrolytes, proteins, lipids, sugars etc
Middle Layer: (Thin)
Buffy Coat of White Blood cells
-leukocytes
Lower Layer: (approx 45% of blood)
-Erythrocytes, platelets (Haematocrit)
193
What is serum?
Plasma without fibrinogen and other clotting factors
194
What is source and role of cytokine IL-1
Source - Macrophages, Endothelial and Epithelial cells
| Role - Induces inflammation, fever, activation of leukocytes
195
What is source and role of cytokine IL-2
Source - Tcells
| Role - Stimulates T, B and NK cell growth
196
What is source and role of cytokine IL-4
Source - Th2 cells; mast cells
| Role - induces IgE production; promotes Th2 differentiation (autocrine)
197
What is source and role of cytokine IL-8
Source - macrophages, endothelium, fibroblasts, keratinocytes
Role - Induces neutrophil chemotaxis
198
What is source and role of cytokine IL-10
Source - monocytes, Th2 cells
| Role - Down-regulates Th1 cytokines, MHC II expression
199
What is source and role of cytokine Interferon gamma
Source - Th1 cells, NK cells
| Role - Activates macrophages and NK cells; increases MHC II expression
200
What is source and role of cytokine Tumour Necrosis Factor - alpha (TNF - alpha)
Source - T cells, macrophage, NK cells
| Role - Activates neutrophils, endothelial cells; induces cachexia (wasting away of muscle and body fat)
201
What is cachexia
Loss/Wasting of muscle and body fat
202
What are 3 subgroups of T helper cells and how do they differ?
Th1, Th2, TREG cells
| Differ in the types of cytokines they make
203
What cytokines are produced by Th1 cells?
IL-2
Interferon-gamma
TNF-beta
204
What cytokines are produced by Th2 cells?
```
IL-4
IL-5
IL-6
IL-10 (also TREG cells)
IL-13
```
205
What cytokines are produced by TREG cells?
IL-10
TGF-beta
(down regulates other T-cell subsets)
206
What are functions of Th2 cells?
Activate eosinophils and mast cells
Induce B cells to make IgE - promotes release of inflammatory mediators e.g. histamine from mast cells
Releases IL-4 and IL-13 important in helminth infections and allergy
207
*What are functions of Th1 cells?
Activate macrophages to cause inflammation
Promotes production of cytotoxic T cells
Important in intracellular infections
Induce B cells to make IgG antibodies
208
How does the Fab region of antibody protect against infection?
```
Specific binding/multivalency:
Neutralise e.g. toxins (IgG, IgA)
Immobilise motile microbes (IgM)
Prevent binding to and infection of host cells
Form complexes
```
209
How does Fc region of antibody protect against infection?
```
Enhance Innate Mechanisms:
Activate complement (IgG, IgM)
Bind Fc receptors
```
210
What cells have Fc receptors and which antibodies are each associated to?
Phagocytes (IgG or IgA) - enhance phagocytosis
Mast Cells (IgE) - release inflammatory mediators
NK cells (IgG) - enhanced killing of infected cells
211
Research, Diagnostics, Therapy:
| What is specificity and indication for product OKT3
CD3
| Transplant Rejection
212
Research, Diagnostics, Therapy:
| What is specificity and indication for product Campath
CD52
| Chronic lymphocytic leukemia
213
Research, Diagnostics, Therapy:
| What is specificity and indication for product Herceptin
Her-2
| Breast cancer
214
Research, Diagnostics, Therapy:
| What is specificity and indication for product Remicade
TNF-alpha
| Crohn's disease, rheumatoid arthritis
215
Research, Diagnostics, Therapy:
| What is specificity and indication for product CroFab
Snake venom
| Rattle snake antidote
216
Research, Diagnostics, Therapy:
| What is specificity and indication for product Synagis
RSV
| Respiratory syncytial virus
217
What ligands are recognised by TLR 1/2
Gram positive lipopeptides (exogenous)
218
What ligands are recognised by TLR 3
Double-stranded RNA (exogenous)
| mRNA (endogenous)
219
What ligands are recognised by TLR 4
LPS, pneumolysin, viral proteins (exogenous)
| Heat shock proteins, HMGB1, hyaluronan, fibrinogen (endogenous)
220
What ligands are recognised by TLR 5
Flagellin (exogenous)
221
What ligands are recognised by TLR 2/6
Gram POSITIVE lipopeptides
| Gram negative also noticed by TLR 2
222
What ligands are recognised by TLR 7 or 8
Single-stranded RNA (exogenous)
223
What ligands are recognised by TLR 9
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CpG DNA (exogenous)
DNA, mitochondrial DNA? (endogenous)
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224
What are NLRs
Nod-Like Receptors
(Best known are NOD1, NOD2, NLRP3)
Detect intracellular microbial pathogens
225
What is function of NOD2
Recognises MDP (muramyl dipeptide), a breakdown product of peptidoglycan.
Activates inflammatory signalling pathways.
Can also activate anti-viral signalling
226
What disease can result from non-functioning NOD2 mutation?
Crohn's disease
227
What disease can result from a hyper-functioning NOD2 mutation?
```
Blau syndrome
(Rare; Chronic granulomatous inflammation of skin, eyes and joints)
```
228
What are RLRs
PRR type
Best known are RIG-1 and MDA5 - roles to detect intracellular dsRNA and DNA - viral.
They couple effectively to activate interferon production, enabling an antiviral response.
229
What are 2 groups of PRRs
Secreted and circulating PRRs
| Cell-associated PRRs
230
Give example fo secreted/circulating PRRs
Antimicrobial peptides secreted in lining fluids, from epithelial and phagocytes e.g. Defensins and Cathelicidin
Lectins and Collectins:
Carbohdrate-containing proteins that bind carbs or lipids in microbe walls. Activate complement and improve phagocytosis.
Pentraxins:
Can react with C protein of pneumococci, activate complement and promote phagocytosis
231
Give examples of cell-associated PRRs
Receptors present on cell membrane or in the cytosol of cells
Recognise a broad range of molecular patterns
e.g. TLRs
232
Describe importance of TLR4
| and result of its activation
```
Recognises LPS (lipopolysaccharide), a component present in many Gram-negative bacteria and some Gram-positive.
Activation of TLR4 leads to intracellular signalling pathway NF-κB and inflammatory cytokine production responsible for activating the innate immune system.
```
233
What is NF-κB?
Nuclear factor kappa-light-chain-enhancer of activated B cells
Protein complex that controls transcription of DNA, cytokine production and cell survival.
Involved in cellular responses to stimuli such as stress, cytokines, free radicals, UV irradiation, oxidised LDL and bacterial/viral antigens.
Key role in regulating immune response to infection. Incorrect regulation linked to cancer, autoimmunity, viral infection, septic shock and improper immune development.
234
```
Which of the following is NOT an organ-specific auto-immune disease?
Type 1 diabetes mellitus
Ulcerative colitis
Graves disease
Hashimoto's thyroiditis
Sjorgen's syndrome
```
Ulcerative colitis
235
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Which of the following is a classical PAMP
Interleukin 12
Heat shock protein 70
RIG-I
Lipopolysaccharide
Toll-like receptor 2
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Lipopolysaccharide
236
Which of the following answers is NOT true? Biological therapies for autoimmune diseases...:
are usually delivered with a low dose of the cytotoxic drug methotrexate
have no risk of bacterial infection, unlike conventional treatments
include adalimumab, tocilizumab and retuximab
are immunosuppressive and are always injected
are comparatively very expensive and only prescribed in the NHS once conventional therapies have failed
NOT true:
| Biological therapies for autoimmune diseases have no risk of bacterial infection, unlike conventional treatments
237
Which of the following are features of the adaptive immune response?
Its efficiency is not affected by prior contact with the pathogen
It would not work without B and T lymphocytes
It lacks specificity
It generally distinguishes self from non-self
Its effectiveness is enhanced by complement
It would not work without B and T lymphocytes
238
Which of the following functions of T lymphocytes is true:
T lymphocytes mature in thyroid gland
All T cells secrete cytotoxic materials
T cells respond to proteins on surface of host cells
T cells secrete IgG when they are activated
T cells respond to proteins on surface of host cells
239
What is Hashimoto's thyroiditis
Autoimmune disease in which immune system attacks body's thyroid
aka Chronic Lymphocytic Thyroiditis
240
What is Graves disease
Thyroid autoimmune disease
Most common cause of hyperthyroidism and often results in enlarged thyroid
241
What is Sjorgen's syndrome
Autoimmune disease that affects the body's moisture-producing glands
242
What are primary symptoms of Sjorgen's syndrome
Dry mouth and dry eyes
243
Explain the distinction/difference between Fibrin and fibrous
Fibrin is deposited in BVs and tissues or on surfaces (e.g. in acute inflammation) as a result of the action of thrombin on fibrinogen.
Fibrous describes the texture of non-mineralised tissue of which the principal component is collagen (e.g. scar tissue)
244
Explain the distinction/difference between Monocytes, macrophages and histocytes
Monocytes are newly formed cells of the mononuclear phagocyte system. After a few hours in the blood, they enter tissues and undergo further differentiation into macrophages.
Some macrophages in tissues have specific features and names (e.g. Kupffer cells), others are referred to as histiocytes
245
*Explain the distinction/difference between Granuloma and Granulation tissue
Granuloma is an aggregate of epithelioid histiocytes and feature of some specific chronic inflammatory disorders.
Granulation tissue is an important component of healing and comprises small blood vessels in a connective tissue matrix with myofibroblasts.
246
Explain the distinction/difference between Exudate and Transudate
Exudates hae a high protein content as they result from increased vascular permeability.
Transudates have a LOW protein content as the vessels have normal permeability characteristics.
247
Explain the distinction/difference between Acute and chronic inflammation
in inflammation, acute and chronic denote both the dynamics and character of the process.
Acute inflammation has a relatively rapid onset and (usually) resolution. Neutrophil polymorphs are also the most abundant cell.
Chronic inflammation has a relatively insidious onset, prolonged course and slow resolution. Lymphocytes, plasma cells and macrophages (sometimes with granuloma formation) are the most abundant cells.
248
**Causes of acute inflammation (easy exam q)
- Microbial infections e.g pyogenic (pus causing) bacteria, viruses
- Hypersensitivity reactions e.g parasites, tubercle bacilli
- Physical agents e.g trauma, ionising radiation, heat, cold (frost-bite) - Chemicals e.g corrosives, acids, alkalis, reducing agents
- Bacterial toxins
- Tissue necrosis e.g. ischaemic infarction
249
Essential macroscopic appearances of acute inflammation (and latin translation where appropriate)
- Redness - rubor
- Heat - calor
- Swelling - tumor
- Pain - dolor
- Loss of function is also characteristic
250
What is fibrinolytic system
Generating plasmin which causes fibrin dissolution
| Starts with release of plasminogen activator (t-PA) from endothelial cells. t-PA convert plasminogen to plasmin
251
Define scar
The connective tissue forming a scar and composed chiefly of fibroblasts in recent scars and largely of dense collagenous fibres in old scars.
