Immunology Flashcards
(469 cards)
1
Q
What does the immune system do?
A
identify + eliminate
- microorganisms
- other harmful substances -abnormal cancer cells
2
Q
How does the immune system identify and eliminate?
A
-Distinguish what is ‘self’ from ‘non-self’ molecules
-Identify ‘danger’ signals
Or combination
3
Q
what must the immune system strike a difficult balance between?
A
- Clearing the pathogen
- Cause accidental damage to the host
4
Q
What does a balanced immune system lead to?
A
Optimal effectiveness
5
Q
What can animmune system under-reaction lead to?
A
- Cancer (HCV, HIV, EBV)
- Infection (Viruses, bacteria, fungi, parasites)
6
Q
What is the internal threat of an immune over reaction?
A
Autoimmune problem (type 1 diabetes, rheumatoid arthritis, psoriasis, multiple sclerosis, lupus, IDB)
7
Q
What is the external threat of an immune over-reaction?
A
Allergic reaction (hay fever, eczema, asthma, sinusitis)
8
Q
List 5 problems associated with the immune system going wrong
A
-Recurrent infections
-Allergy
-Autoimmune disease
-Cancer
T-ransplant rejection
9
Q
Only some multicellular organisms have some form of immune system (T/F)
A
False - all multicellular organisms have some sort of immune system
10
Q
What has been the basis for many major advances in human health?
A
Modulating the immune system
11
Q
Vaccinations are…
A
One of the most important scientific accomplishments of the past century
12
Q
List key achievements of vaccinations
A
- Eradication of smallpox
- 100% decrease in poliomyelitis in North and South America
- 99% decrease in diphtheria, measles, mumps, rubella
- 97% decrease in whooping cough
- Dramatic decline in HiB infections in UK
- Promising early data: HPV infection and cervical cancer
13
Q
What is immune suppression essential for?
A
Treatment of autoimmune disease, allergic diseases + transplantation
14
Q
What does cancer immunotherapy enable the immune system to do?
A
-Recognise target
-Eliminate cancer cells
(Making it a universal answer to cancer)
15
Q
List pathogens points of entry
A
- Digestive system
- Respiratory system
- Urogenital system
- Break in skin
16
Q
List pathogen routes of attack
A
- Circulatory system
- Lymphatic system
17
Q
Each pathogen routes have what kind of barriers to infection?
A
Specific constitutive barriers
18
Q
What happens if defences = breached?
A
Immune system = activated
19
Q
List the constitutive barriers to infection
A
- Skin
- Mucous
- Commensal bacteria
20
Q
Skin is the least important barrier to infection (T/F)
A
False - most important
21
Q
Skin as a physical barrier composed of what?
A
Tightly packed, highly keratinised multi-layered cells
22
Q
What does the skin constantly undergo?
A
Renewal and replacemnt
23
Q
What is the pH of skin?
A
low ph = 5.5 = acidic
24
Q
Skin = low oxygen tension (T/F)
A
True
25
Outline characteristics of sebaceous glands
- Secrete hydrophobic cells
- Lysozyme
- Ammonia
- Antimicrobial peptides
26
Secreted mucous membranes line all body cavities that come into contact with which environments?
- Respiratory
- Gastrointestinal
- Urogenital tract
27
What is the role of mucus?
- Traps bacteria
| - Subsequently removed by ciliated cells
28
What's the role of secretory IgA?
Prevent bacteria + viruses attaching to + penetrating epithelial cells
29
Mucous contains enzymes. Name these and their role
Lysozyme
Defensins
Antimicrobial peptides
Directly kill invading pathogens
30
What does lactoferrin do?
Starve invading bacteria of iron
31
Outline the role of cilia
Traps pathogen directly
| Contributes to mucous removal
32
What is cilia assisted by?
Physical manoeuvres e.g. sneezing + coughing
33
What do 100 trillion bacteria normally do?
Reside at epithelial surfaces
34
How many different microbial species exist?
>500
35
Commensal bacteria exhibit a ______ relationship with the host
Symbiotic
36
List 5 key features of commensal bacteria
- Produces bactericidins - influence other bacteria
- Reduce pH of large bowel
- Compete for essential nutrients
- Synthesis of vitamins - vitamin K, B12
- Produce anti-microbial short chain fatty acids
37
How can commensal bacteria be affected?
- Alterations in homeostasis
- Malnutrition
- Intercurrent infection
- Age
38
Examples of commensal bacteria importance
- Oral candidiasis after oral antibiotics
- Vaginal candidiasis after oral antibiotics
- Clostridium difficile infection after intravenous antibiotics
39
What does eradication of the normal flora with broad-spectrum antibiotics commonly result in?
-Opportunistic infections
40
Explain opportunistic infections
Organisms rapidly colonise an undefended ecological niche
41
Constitutive barriers = _________ effective
Highly
42
If an external defence = breached what is activated?
Immune system
43
How are external defences breached?
By a wound or organism
44
How are constitutive barriers breached during provision of health care?
- Insertion of hardware e.g. intravenous lines
- Antibiotics
- Other therapeutics e.g. anti-acid medication, nasal decongestants, anti-bacterial wipes
45
What are unfavourable pH's which can act as natural barriers?
- Stomach acid
- Sweat
- Saliva
- Urine
46
Where are lysozyme enzymes found?
- Tears
| - Aweat
47
What is the purpose of lysozyme enzymes?
Digests bacterial cell walls
48
What are phagocytic white blood cells?
Leukocytes
49
Macrophages, neutrophils and natural killer cells are?
Leukocytes
50
List the innate/natural immune responses
- Natural barrier
- Soluble components
- Cellular components
51
List the acquired immune response
- Humoral (B cells/ antibody)
| - Cell-mediated T cells
52
Innate/Natural response is adaptive
False - non-adaptive
53
Is acquired response adaptive or non-adaptive?
Adaptive
54
Define innate imunity
- Present continuously
| - Defence mechanism present from birth
55
Define adaptive immunity
-Immunity is induced by presence of foreign material
56
Is innate or adaptive immunity specific?
Adaptive
57
What hours does the rapid innate first response to infection take place?
0-96hrs
58
Does innate immune response have immunological memory?
No
59
Acquired response occurs when?
96hrs+
60
Acquired immunity has immunological memory. Explain what this means
-Subsequent responses are faster + more powerful
61
What is immunological memory the basis of?
-Protective vaccination against infectious diseases
62
Acquired immunity is specific for each antigen encountered
True
63
T cells allow what?
-Self regulating function
64
What can acquired immunity distinguish between?
SELF from NON-SELF
65
Adaptive immunity should act against self molecules
False - should act against non-self molecules
66
Immune System is compromised of 2 arms. What are both are responsible for?
Detecting and destroying the pathogen
67
Both arms of immune response are not essential
False - both essential for maximal protection but work in different ways
68
What is the result when physical barriers = breached?
- Soluble components
| - Cellular components
69
Leukocytes include
- Phagocytic white blood cells
- Macrophages
- Neutrophils
- NK cells
70
What is the complement system?
Proteins that destroy cells
71
What is the effect of the inflammatory response?
- Increases body temp
- Increases capillary permeability
- Attracts macrophages
72
Finish the sentence
| Physical barriers breached
- Pathogens invade
| - Innate Immune Response Initiated
73
What do tissue-resident innate immune cells recognise pathogens as?
- 'non-self'
| - Dangerous
74
What are Phagocytic cells?
Macrophages + Dendritic cells
75
What are killer cells?
Natural killer cells
76
Name another type of cells
Mast cells
77
Where do macrophages reside and what in?
In - exposed epithelial cells
| At - common sites where pathogens invade
78
Macrophages are fast acting. What are they the first line of defence against?
Invading pathogens
79
What are pathogens important in defending against?
- Bacteria
| - Fungi
80
List the 5 functions of macrophages
-Ingest and kill existing pathogens
-Role in antigen presentation
-Induce pro and anti
inflammatory responses
-Clear debris from dead/dying tissue cells
-Promote tissue repair and wound healing
81
What are macrophages called in the liver?
Kupffer cells
82
What are macrophages called in the lungs?
Alveolar macrophages
83
What are macrophages called in the kidney?
Mesangial cells
84
What are macrophages called in the nervous system?
Microglial cells
85
Where are dendritic cells located?
In peripheral tissues
86
What kind of state are dendritic cells in when they are located in the peripheral tissue?
Immature state
87
What do dendritic cells phagocytose?
- Antigens
- Cell debris
- Particles
88
Explain what dendritic cells do?
Process + present materials on the cells via MHC molecules
89
What is the purpose of processing and presenting these proteins?
Initiate T cell immune response + adaptive immunity
90
Natural killer cells are _____ _______ cells
Large granular
91
What do NK cells specifically kill?
- Infected cells
| - Abnormal cancer cell
92
What else can NK cells kill?
- Antibody-bound cells
| - Pathogens
93
Mast cells have a _____ nucleus which is _____ granular
Single
| Highly
94
Where do mast cells reside in?
Tissues
95
What kind of surfaces do mast cells protect?
Mucosal
96
What kind of parasites do mast cells protect against/
Large anti-body coated parasites (those that cannot be phagocytosed e.g. worm)
97
What do mast cells play a key role in?
Mediating allergic responses
98
What happens to mast cells upon activation?
-Release chemicals e.g. histamine, heparin + pro-inflammatory cytokines
99
What do tissue-resident innate immune cells recognise pathogens as?
- 'Non-self'
| - Dangerous
100
What kind of molecules do pathogens express?
'Signature' molecules
101
Are signature molecules found on/in human cells?
No
102
Pathogens are recognised by tissue-resident innate immune cells by
Pathogen associated molecular patterns (PAMP)
103
Pathogen associate molecular patterns are not common to many different pathogens
False - they are common
104
What do innate immune cells express?
Partner receptors to pathogen associate molecular patterns (PAMP)
105
Where are innate immune cells found?
- Cell surfaces
| - Intracellularly for detecting extra + intra cellular pathogens
106
Extracellular bacterial pathogens invade cells
False - do not invade cells
| -proliferate extracellular environment instead
107
What is the extracellular enriched with?
Body fluids
108
What is ingested by macrophages?
- Extracellular bacteria
| - Fungi
109
List the modes of ingestion by macrophages
- Pinocytosis
- Receptor-mediated endocytosis
- Phagocytosis
110
Describe pinoocytosis
Ingestion of fluid surrounding cells
111
Explain receptor-mediated endocytosis
Membrane receptor bound molecules = internalized
112
Receptor mediate endocytosis is an important step in the generation of what kind of immunity?
Adaptive
113
Phagocytosis is key for macrophages. How are intact particles internalised?
Whole
114
Intact particles are internalized whole, but what are they facilitated by?
Opsonisation
115
Phagocytosis is a specific form of what?
Endocytosis
116
Phagocytosis internalise what?
Solid matter
| Including apoptotic cells + microbial pathogens
117
Most cells are capable of phagocytosis
True
118
What truly excels in phagocytosis?
- Professional phagocyte of the immune system
- Macrophages
- Neutrophils
- Immature dendritic cells
119
Outline the 1st stage of phagocytosis
Specific PAMPs expressed on the surface of any different extracellular pathogens are recognised by macrophages
120
The 2nd stage of phagocytosis begins with macrophages rearranging their cytoskeleton. What happens next?
Cell membrane = extend around target
Eventually envelopes it
Pinching off occurs
Form phagosome
121
During the 3rd stage of phagocytosis the vesicle can mature and acidify through fusion with...
Late endosomes + lysosomes
122
What does the fusion of late endosomes + lysosomes form?
Phagolysososme
123
Forming a phagolysosome results in what?
Degradation + digestion of cargo
124
Why does killing occur as a result of phagolysosomes?
Phagolysosomes contain
- Hydrolytic enzymes
- Proteases
- Highly acidic pH
125
What is the final step of phagocytosis?
Cellular debris in form of small soluble molecules = released
126
What also happens in conjunction with the final step?
Pro- inflammatory mediators e.g. TNF alpha = secreted
Promotes acute inflammation
Peptides derived from pathogen = expressed on special cell surface receptors
127
Single phagocytes can ingest more than 1 cellular corpse. This is essential for...
Secretion of pro-inflammatory cytokines
128
Define opsonisation
Coating of pathogens by soluble factors (opsonins)
129
What does opsonisation enhance?
Phagocytosis
130
Give 3 examples of opsonins
- C3b
- C-reactive protein
- IgG/IgM
131
Virally infected cells produce + release small proteins. What are these called?
Intereferons
132
What do interferons play a vita role in?
Immune protection against viruses
133
Why does a virus invade the cells when it infects a person?
To survive + replicate
134
Interferons are host and virus specific
False - host specific but not virus specific
135
Interferons have what kind of general protection?
Anti-viral
136
How do interferons prevent replication of viruses?
Directly interfere with ability to replicate within an infected cell
137
What protects the cell from viral infection?
Cell signals produce anti-viral factors ---> interfere with viral multiplication
138
What else to interferons act as?
Signalling molecules
139
What does interferons acting as signalling molecules allow?
Infected cells to warn nearby cells or viral presence
140
What advantage does warning nearby cells of viral presence give?
Neighbouring cells = increase MHC class 1 molecules upon surfaces increase
141
What does increasing the number of MHC class 1 molecules allow?
T cells surveying the area can identify + eliminate viral infection
142
Outline the 4 steps undertaken by NK cells
- Release perforin protein
- Insert into membrane of target cell
- Form pores = fluid can move in/out of cell
- Cell ruptures (lysis) ---> apoptosis = cell death
143
Natural killer cells are lymphocyres
True
144
What can NK cells recognise and destroy?
Viral or cancerous cells
145
When NK cells come into contact with abnormal cells what happens?
They release cytotoxic molecules
146
What do cytotoxic molecules cause?
Abnormal cells to undergo apoptosis
147
What do NK cells respond to?
Levels of class 1 MHC molecules on cell surface
148
Reduced levels of MHC class 1 leads to killing in what kind of cells?
Virally infected cells
| Cancerous cells
149
Mast cells play a role in degranulation explain
Pre-formed pro-inflammatory substances released
150
Mast cells play a role in gene expression explain
New pro-inflammatory substances produced.
151
Communication between _____ and _____ enhances killing
NK cells
| Macrophages
152
What is macrophage activation enhanced by?
Inflammatory mediators e.g. IFNy
153
List bacteria that can evade phagolysosome killing
- Salmonella
- Straph. aureus
- Mycobacteria
154
What is macrophage activation enhanced by?
Pro-inflammatory mediators e.g. IFN gamma
155
What does macrophage activation lead to?
- Increased MCH-II expression
- Produces toxic reactive
- Oxygen and Nitrogen species
- Increase intracellular bacteria killing
156
List the clinical features of acute inflammation
- Fever
- Liver - Increased synthesis of acute phase proteins
- Bone marrow - Increased production + metabolism of neutrophilia
- Local cellulitis
- Pain
- Redness
- Swelling
157
What is neutrophilia?
A hallmark of acute inflammation
158
What are regarded as innate immune system late events?
- Production of pro-inflammatory mediators
| - Production of chemokines
159
Give examples of pro-inflammatory mediators
- Histamnine
- Leukotrienes
- TNFalpha
160
Chemokines are small insoluble molecules
False - small soluble molecules
161
What do chemokines promote?
Direct movement of cells
162
What do cells normall travel down?
Chemokine gradient
163
Where do cells that normally travel down a chemokine gradient travel to?
Source of chemokine
164
What else do hemokines promote other than directed movement of cells?
-Adhesion of neutrophils + other leukocytes to endothelial cels in infected/ inflamed tissues
165
What are neutrophils critically involved in?
Initiation + maintenance of inflammation
166
Where must neutrophils be able to get to?
Site of injury/ tissue damage from their usual bloody location
167
Why do specific neutrophil mechanisms exist?
Recruit + direct cells to appropriate places
168
Explain the term transendothelial migration
Neutrophil movemnet from blood to tissues through blood vessel wall
169
What is transendothelial migration triggered by?
Pro-inflammatory mediators - alter local vasculature
170
Where do neutrophils circulate?
In bloodstream
171
Where do neutrophils migrate?
Into infected and/or inflamed tissues
172
What kind of nucleus do neutrophils possess?
A multi-loved nucleus
173
Neutrophils have a pink cytoplasm
True
174
What percentage of circulating leukocytes do neutrophils compromise?
50-70%
175
Neutrophils are short lived cells and have a half life of?
6 hours
176
How many neutrophils are released into circulation?
60x10^6/minute
177
When does the number of neutrophils released into circulation increase dramatically?
During inflammation
178
What is the main function of neutrophils?
- Kill pathogen
| - Promote inflammation
179
Do healthy cells have inflammatory mediators?
No
180
Healthy tissue have abnormal vasculature
False - normal
181
Healthy tissues have circulating neutrophils
True
182
What does inflammation promote?
- Vascular changes
| - Recruitment + activation of neutrophils
183
What are the 4 changes to the local vasculature in infected/damaged tissues
- Loss of tight junctions in endothelial cells
- Post capillary venules dilated
- Specific adhesion molecules on endothelial cell surface expressed
- Adhesion molecule receptors on circulating neutrophils activated
184
What does loss of tight junctions between endothelial cells lead to?
Increased vascular permeability
185
List the steps of transendothelial migration
Step 1 - NEED TO DO REVISIT SLIDE !! 11
186
In infected tissues, pathogens release _____ sthat attracts _______
Chemokine-like signals
| Neutrophils
187
WHat do neutrophils use to bind to and phagocytose pathogens?
Pattern Recognition Receptors
188
Name the 2 distinct mechanisms used to kill internalised pathogens
- Phagolysosomal killing
| - ROS-mediated killing
189
Do neutrophils require extra stimulation to kill via ROS-dependent mechanism
NO - already possess ability
190
What do lysozymes do?
Degrade cell wall of some gram +ve bacteria
191
Acidification in phagolysosomal killing
Bactericidal or bacteriostatic
192
Lactoferrin in phagolysosomal killing
Fe binding protein (competitor)
193
Acid hydrolyases in phagolysosomal killing
Further digests bacteria
194
What happens during degranulation?
Anti-bacterial proteins from neutrophil granules released
| Directly into extracellular millieu
195
DEgranulation results in direct killing of what?
Extracellular pathogens - bacteria + fungi
196
Degranulation can result in _____ damage and _____ inflammation
Tissue
| (potentially) systemic
197
How can the tissue damage and systemic inflammation become limited?
By increasing expression of proteinase inhibitors
198
What is the 3rd neutrophil killing mechanism?
NETs
199
What does NETs stand for/
Neutrophil Extracellular Traps
200
What do neutrophils release?
Intracellular structures into extracellular enviroment
201
How do NETs immobilise pathogens?
- Prevent spreading
| - Facilitate phagocytosis
202
What do neutrophils minimise?
Damage to host cells
203
NET formation can be induced by what?
Extracellular bacteria + Hyphal fungi forms
204
NET formation is a form of suicide carried out in order to...
Trap + kill pathogens
205
How do NETs prevent them from from spreading?
Immobilize pathogens
206
What do NETS facilitate subsequent phagocytosis of?
Trapped microorganisms
207
What are NETS composed of?
- Genomic DNA
- Histones
- Granular proteins
- Enzymes
208
Name the granular proteins
- Lactoferrin
| - Cathepsins
209
Name the enzymes
Neutrophil elastase
210
What is PUS made of?
- Neutrophils
- NETS
- Dead bacteria
- Cellular debris
211
What is an abscess?
- Collection of pus
| - Surrounded by membrane of sprouting capillaries, neutrophils + occasional fibroblasts
212
What is responsible for inducing a fever?
-Activated macrophages releasing Pro- inflammatory mediators
213
What type of response is the accute phase response?
Systemic
214
What does an inflammation response result in?
Changes in plasma conc. of specific proteins
215
Activated macrophages release what?
Pro - inflammatory mediators
216
The acute phase response os mediated by liver hepatocytes. What do these produce a variety of?
Acute phase proteins
217
List the roles of C reactive protein?
- Prime certain bacteria - destruction by complement system
| - Prognostic role
218
What kind of protein is a C reactive protein in humans?
- Major
| - Acute
219
What kind of protein is used as a marker for inflammation?
C reactive protein
220
When does CRP increase rapidly?
During inflammation
221
CRP possesses a very short half life. What is the result of this characteristic?
CRP rapidly disappears once inflammation = resolved
222
Name 2 complement system proteins
- MBL
| - C3
223
The complement system is made up of approx how many proteins?
30
224
Where are the proteins of the complement system produced?
In the liver
225
Where do the proteins of the complement system circulate?
In the blood (constitute 10% serum proteins)
226
The complement system enters _______ and ______ tissues
Infected
| Inflamed
227
How are pathogens activated?
Directly or indirectly
228
What happens when the complement system is triggered?
Specific complement proteins = enzymatically activate other complement proteins
229
How do specific complement proteins enzymatically activate other complementary proteins when triggered?
Cascade type reaction
230
How can this be referred to as a very powerful system?
- Rapid amplification
| - 1 upstream molecule activates many downstream molecules
231
Pro-inflammatory cytokines + histamine stimulate what?
Increased
- vascular permeability
- leakage of plasma proteins ----> tissues
232
What are complement proteins made up of?
- Kinins
- Coagulation factors
- Fibrinolytic system
233
An activated complement system creates a cascade of chemical reactions. What does this promote?
- Opsonisation
- Chemotaxis
- Agulation
- MAC production
234
What does the kinin system generate?
- Proteins capable of sustaining vasodilation
| - Physical inflammatory effects
235
What does the coagulation system/ clotting cascade form?
Protective protein mesh over injury site
236
What acts in opposition to the coagulation system?
Fibrinolysis system
237
What is the purpose of the fibrinolysis system?
Counterbalance clotting
| Generate inflammatory mediators
238
What does activation of downstream complement proteins lead to?
- Pathogen killing
- Pathogen opsonisation
- Leukocyte recruitment + inflammation
- Immune complexes removal
239
Name an acute phase protein
Mannose-binding lectin
240
Mannose expression is applicable to human cells
False - not expressed on human cells
241
Why do selective activation arise?
mannose expression = unique to certain pathogens
242
What stops C3b being unstable and rapidly degradable?
Binding to cell surfaces
243
Human cells express inhibitory proteins. What do they prevent?
C3b activating downstream events
244
Pathogens express inhibitory proteins
False - do not express these inhibitory proteins
245
What do the last 5 proteins in a complement cascade do?
Self associate - form membrane-attack complex
246
What inserts into pathogen membranes?
Membrane Attack Complex
247
What do MACs allow?
Extracellular salts + water to enter -----> Microbe swells + bursts
248
What is C3a and C5a AKA?
Anaphylatoxins
249
What do anaphylatoxins promote?
- Vasculature changes
- Acute inflammation
- Leukocyte recruitment
250
How do amphylatoxins promote
- vasculature changes
- acute inflammation
- leukocyte recruitment
1. Activating mast cells - degranulate- release histamine + pro-inflammatory mediators
2. Act on local blood vessels directly
251
Name 2 types of lymphocytes
B cells
| T cells
252
Antibodies are AKA
Immunoglobins
253
What do lymphocytes + antibodies respond to?
Antigens
254
How many and where abouts do Individual B and T cells express antigen receptors?
1 type of antigen receptor
| On cell surface
255
Individual B and T cells express only 1 type of antigen receptor what does this mean for each individual cell?
They can only respond to 1 specific antigen
256
There are plenty of each antigen specific cell within the human body
False - limited number
257
What does he limited number of each antigen-specific cell result in?
Few antigenic specific cells = not sufficient 2 kill + eliminate antigen-carrying pathogen
258
What does each pathogen will express?
Many thousands of different antigens
259
Many thousands of different antigens are expressed. What is the effect of this?
Many 1000's of diff B and T cells can respond to any 1 pathogen
260
Where do B cells mature?
In the bone marrow
261
What are B cells responsible for?
Humoral immune responses
262
What do humoral immune responses produce?
Antibodies that attack pathogens circulating blood and lymph
263
Where do T cells mature?
In the thymus
264
What are T cells responsible for?
Cellular immune responses
265
What do t cells play a key role in?
Defence against intracellular pathogens
266
What are CD4+ T cells regulators for?
ENTIRE immune system
267
What do CD8+ T cells kill?
Virally infected body cells
268
What do B and T cells learn as they develop?
Distinguish self + non-self cells
269
How are B and T cells destroyed?
Reacting to self-antigens
270
What do antigens induce?
Adaptive immune responses
271
Define an antigen
Any substance that causes an adaptive immune response by activating B and T cells
272
Define an antibody
Protein . that bonds to 1 specific antigenic epitope
273
Individual cells/pathogens contain how_____ ______ antigens
Many different
274
What can individual antigens contain?
Many different antigenic epitopes
275
What can each specific antibody bind to?
Only 1 specific antigenic epitope
276
Antibodies are made of a complex of what?
4 polypeptide chains
277
How many heavy and light chains make up the polypeptide chain?
- 2 Light
| - 2 Heavy
278
Each antibody has a unique variable region... WWHat does this bind to?
1 specific antigen
279
What are millions of diff antibodies able to respond to?
Millions of diff antigens
280
What type of glycoproteins fo antibodies have?
Large
| Globular
281
Discuss the structure of antibodies
- Y shaped
- 4 polypeptides
- Held together by disulfide bridges
- 2 identical heavy chains
- 2 identical light chains
- Flexibility at hinge region
282
Where are antibodies normally expressed?
On B cell surface
283
Apart from on B cell surfaces, where else can antibodies be secreted?
As soluble proteins into extracellular fluids
284
What do antibodies provide defence against?
Circulating pathogens
| Bacterial toxins
285
Antibody deficiency diseases are never life threatening?
False - they can be
286
Name 2 B cell antigen receptors
- IgM
| - IgD
287
Why do B cells use membrane bound antibodies?
To recognise antigens
288
1 B cel expresses how many copies of 1 specific antibody?
50,000
289
Diff B cells express diff antibodies
True
290
What forms can antibodies take?
Membrane bound form
| Soluble form
291
What kind of number of PAMPS do non-specific mechanisms have?
Limited
292
What id the effect of non-specific recognition having a limited number of PAMPs?
Common to many diff pathogen
293
In non-specific recognition only a small number of different PRRs are required to stimulate what?
Innate Immune Cell
294
Specific recognition has millions of different antigens. These are _____ to individual pathogenic species
Unique
295
Individual T and B cells of specific recognition express how many specific antigen receptors?
1
296
What do Specific antigen receptors bind to?
1 specific antgenic epitope
297
Where fo antigen-specific T and B cells develop?
Primary lymphoid tissues
298
Name 2 primary lymphoid tissues where antigen specific T and B cells develop
- Bone marrow
| - Spleen
299
Lymphocytes develop initially in the...
Bone marrow
300
Where do lymphocyes mature
- Bone marrow (B cells)
| - Thymus (T cells)
301
Where do t and B cells constantly recirculate between?
- Blood
- Secondary lymphoid tissues
- Lymphatic vessels
302
Where are T and B cells activated?
Secondary Lymphoid Tissues
303
What are T and B cells activated by?
Antigers
304
What are lymph nodes important for?
Monitoring tissue infections
305
What is the spleen important for?
Monitoring blood-borne infections
306
What is mucosal?
Associated lymphoid tissues
307
What is mucosal important for?
Monitoring throat/gastrointestinal tract infections
308
Where does lymph flow and through what vessel?
Through lymph nodes
| Through afferent Lymphatic Vessels
309
Where do B and T cells enter lymph nodes through?
High endothelial venules
310
B cells go through HEV and then immediately go where?
Lymhoid foilicle
311
After T cells go through HEV, where do they stay?
T cell area of lymph nodes
312
What do T cells interact with in the T cell area of the lymph node?
Dendritic cells
313
Where do dendritic cells come through?
The afferent lymph
314
How do lymph and lymphocytes leave the lymph node?
First through medullary sinus
| Then through efferent lymphatic vessels
315
Efferent lymph eventually flows where?
Into blood circulation
| via subclavian vein
316
Where is lymph derived from?
Plasma in tissues
317
How does lymph move?
Via valves
| Movement of smooth muscles in lymphatic vessel walls
318
Where are lymph nodes positioned?
Along lymph vessels
319
What do lymph nodes monitor and why?
Lymph for signs of infection
320
What is lymph formed from?
Fluid that filters out the blood circulation
321
Why is fluid filtered out the blood?
- Nourish cells
| - Remove waste products
322
How is fluid returned to the blood circulation?
- Through venous capillaries
| - Through force of osmosis in the venous blood
323
Why must a portion of fluid containing proteins, cellular debris, bacteria etc. be returned through the lymphatic collection?
Maintain tissue fluid balance
324
REVISE SLIDE 21
LECTURE 4
325
B cells produce specific antibodies in response to what?
Specific antigens
326
What is used to bind to pathogenic antigens?
Membrane bound, antigen-specific IgM
327
B cells _____ _________ and ______ into different types of effector cells upon activation
Proliferate
| Differentiate
328
Nme 2 types of effector cells
Plasma Cells
| Memory B cells
329
What is the role of plasma cells?
Produce + secrete soluble, antigen specific antibodies
330
Explain Memory B cells?
Long lived cells
| circulate round the body continually
331
How do b cells encounter antigens?
Specialised cells within B zone can 'trap' opsonised antigens
332
B cells need to receive 2 signals to become fully activated + clonally proliferate. Name them:
Antigen
| Helper signals from T cells
333
What do B cells express?
BCRs
334
What do the BCRs expressed all have in common?
The same specificity as the parent B cell
335
Where do highly proliferative cells form a secondary follicle?
Within B cell zone (AKA Germinal Centre)
336
What do B cells differentiate into?
Plasma cell
337
Differentiation into plasma cells results in an expanded population of cells. They now have sufficient numbers to be able to deal with what?
Any pathogen that expresses specific antigen on their surface
338
What happens once B cells stop proliferating?
Differentiate into anti-body screening plasma cells
339
What are IgM antibodies?
Initial antibody class that B cells secrete
340
What do secreted antibodies recognise?
Same specific antigen as original parent B cell
341
Initially, low affinity antigen specific IgM antibodies are secreted into what?
Short lived plasma cells
342
What do T cells help the production and secretion of and in what reaction?
'Better' antibodies
| Germinal Centre
343
What do T cells stimulate?
Production of antigen specific memory B cells
344
Where do long-lived plasma cells migrate to?
Bone marrow
345
Why are the antibodies produced with the help of T cells considered better?
High affinity antibodies
346
Antibodies kill/inactivate pathogens through
Recognition function
| Effector function
347
Recognition function involves?
Binding to antigen
348
What is recognition factor mediated by?
Variable region sites
349
Explain the effector function
Clearance mechanism
| mediated interaction of heavy chain constant region with effector molecules
350
What are the effector molecules of the effector function?
Complement
| Fc receptors
351
What kind of microbes do antibodies provide immunological defence against?
Extracellular
| E.g. bacteria/virus
352
How do antibodies provide immunological defence against extracelullar microbes?
Recognise microbe as foreign
| Inactivate/Eliminate microbe
353
What can antibodies bind to?
- Soluble antigens
- Membrane-bound antigens expressed on surface of microbes
- Other immune cells
354
In membrane bound form IgM serves as...
B cell cell antigen receptor
355
What is the function of IgM as a B cell antigen receptor?
B cell activation
356
When is the first Ig type produced + secreted?
During a humoral (adaptive) immune system
357
Where is IgM present?
In plasma + secretory fluids
358
Why does IgM not enter tissues?
It's too large
359
What is the IgM monomer?
BCR
360
What is IgM secreted from?
A pentamer
361
What are the functions of IgM present in plasma + secretory fluids?
Agglutination (immune complex formation)
| Complement system activation
362
Why is IgM good at agglutinating antigens?
Has 10 antigen binding sites
363
What is the term for immune complex formation?
Agglutination
364
What is agglutination mediated by?
Specific antigen binding to IgM and IgG antibodies
365
What does agglutionincrease?
The efficacy of pathogen elimination
366
How does agglutination increase the efficacy of pathogen elimination?
Enhances phagocytosis
367
What do phagocytic cells express?
Fc receptors
368
What can agglutination prevent?
Viruses binding to + infecting host cells
| -AKA 'neutralisation'
369
Define aggulation
- Particles clumping together
| - result of antibodies binding to antigens on surface of 2 adjacent cells/particles etc.
370
Why is phagocytosis an advantage?
Large clumps of bacteria = eliminated in 1 pass
371
What is the classical complement pathway activated by?
Fc antibody region
372
What must each C1 molecule bind to via its globular heads?
AT least 2 Fc sites for a stable interaction
373
When a C1 molecule binds what is the result?
A conformational change within the Fc region of the antibody
374
What is exposed when the C1 molecule changes conformation?
AC1q
375
What is C1q?
Initiating factor of classical complement pathwats
376
C1q binds to antibody Fc regions. What does this activate + lead to?
Activates - classical compliment cascade
| Leads- C3 cleavage + downstream events
377
How does a single IgM pentamer activate Classic pathway?
Binds multiple antigen at once
378
What must several different IgG antibodies bind?
Closely located antigens
379
Why must several different IgG antibodies bind closely located antigens?
To recruit + activate C1 complex
380
What is the most abundant antobody in normal human serum?
IgG
381
What is the function of IgG?
```
Agglutination
Complement System Activation
Foetal Immune Protection
Neutralisation
Opsonisation
Natural Killer cell activation
```
382
What kind of half life does IgG possess?
Longest (20-24 days)
383
List the 4 human subclasses of IgG
IgG1, IgG2, IgG3, IgG4
384
What do the 4 human subclasses contain?
A different heavy chain
385
What are highly homologous?
FIND ANDWER SLIDE ££ PP 4
386
What do ______ differ in (FIND MISSING WORD ON SLIDE 33 PP 4)
- Hinge region
| - Activatte host immune system extent
387
During pregnancy IgG from maternal circulation is transported across what and where to?
- Transported across placenta
| - Directly into foetal blood circulation
388
What is the only antibody that can cross the placenta?
IgG
389
What is IgG uniquely mediated by?
Fc region of IgG antibodies
390
What increases over the course of pregnancy?
IgG levels of maternal origin in foetal circulation
391
What indicates the placenta develops an active transport mechanism for IgG molecules?
End of gestation - foetal IgG levels exceed those in maternal circulation
392
AT birth what do babies have high levels of?
Circulating maternal IgG antibodies
393
What are IgG antibodeis collectively able to recognise?
Range of different antigen specificities
394
Why are the high levels of IgG molecules present at birth essential?
Helps protect neonate against many diff pathogens until full adaptive immune system develops
395
What is transient hypogammaglobulinaemia>
A type of immunodeficiency
396
Why does maternally derived IgG wane over time?
Due to natural half-life of IgG proteins
397
What is neutralisation mediated by?
Antigen binding sites of antibodies
398
How can antibodies neutralise viral infectivity?
- interfere with virus binding to receptor
- block uptake into cells
- prevent uncoating of genomes in endosomes
- cause aggregation of virus particles
399
What is opsonisation initiated by?
Specific antigen binding
400
What do phagocytes express and what do they specifically bind to?
Express Fc receptors
| Bind - constant regions of Ig heavy chain of IgG
401
Opsonisation enhances phagocytosis what is this especially important for?
Encapsulating bacterial species
402
Define phagocytosis
Coating of pathogens by immune proteins to enhance phagocytosis
403
What is the most effective opsonins?
IgG type antibodies
404
What is opsonisation mediated by?
Fc region of IgG
405
What mediates the activation of NK cells?
Fc region of IgG
406
What are good activators of NK cells?
IgG antibodies
407
IgA is the 2nd most abundant Ig type (T/F)
True
408
Where is IgA monomeric form present in?
Serum
409
What is the function of the IgA in monomeric form?
Neutralisation
410
Where is the IgA dimeric form present in?
Secretory fluids
411
What are the functions of secretory IgA?
Neonatal defence
| Neutralisation (@ mucosal site)
412
Why is most IgA present in secreted form?
- Stability to neutralise invading pathogens
- Binds to antigens on pathogen surface
- Prevents attaching to + infecting host
413
What is IgA actively transported across?
Epithelial surfaces
| Into secretions
414
IgA is a primary defence mechanism at what type of surface?
Mucosal
415
IgA is a neutralising antibody. What does this prevent?
Invading pathogens attaching + penetrating epithelial suraces
416
Virus Neutralisation by secretory IgA plays an important role in what?
Protecting mucosal tissues
417
Viruses that spread in the blood are dealth with by what antibodies?
IgG and IgM
418
What antibody types can be secreted across epithelial surfaces?
slgA
419
What are sIgA antibodies transported into to protect GI tract of neonates?
- Colostrum
| - Breast milk
420
What is colostrum?
- Milk Form
- Produced by mammary glands of mammals
- Late pregnancy
- Just prior to giving birth
421
What does colostrum contain?
- Antibodies
| - Help protect newborn against disease
422
Protein concn. in colostrum is substantially higher than in milk (T/F)
True
423
SIgA in breast milk can help protect during periods of what?
Transient hypogammaglobulineaemia
424
What serves as the B cell antigen receptor?
IgD
| -In menbrane bound form
425
WHat is the function of IgD?
B cell activation
426
IgD has what kind of concentrations in blood?
Extremely low
427
What can IgE antibodies trigger?
Allergic responses
428
List 3 allergic responses
Allergy
Asthma
Anaphylaxis
429
What do B cells not require to recognise+ respond to antigens?
- MHC cells
| - Dendritic cells
430
What type pf pathogens do cell - mediated T cells play a key role in defending against?
Intracellular pathogens
431
What's the result of CD4+ T cells?
Key regulators of entire immune system
432
What's the result of CD8+ T cells?
Kill virally infected body cells
433
T cells - _____, _____ & ____ pathogens hiding in infected cells
Attack
Learn
Remember
434
What do T cells recognise?
Antigen fragments
435
T cells defend against what?
'Non-self' body cells
436
Give 2 examples of'non self' body cells
- Cancer cells
| - Transplant cells
437
Give 3 types of T cells?
- Helper T cells
- Killer T cells
- Memory T cels
438
What is the purpose of helper T cells?
Alerts rest of immune system
439
What is the purpose of killer (cytotoxic) T cells?
Attack infected body cells
440
What is the purpose of memory T cells?
Long term immunity
441
T cells only recognise peptide antigens presented to their what?
- TCR molecules
| - MHC molecules
442
B cells require involvement of MHC molecules to 'see' antigen (T/F)
False
443
MHC is the abbreviation for what?
Major Histocompatibility Complex
444
What do MHC molecules display?
Peptide antigens to T cells
445
What are MHC molecules also refererred to as?
Human Leukocyte Antigens
446
MHC molecules can present what?
Different peptides
447
What are MHC molecules encoded by?
Highly polymorphic genes
448
Where are MHC molecules first identified?
Early transplantation procedures
449
T cells only recognise what kind of antigen?
Peptide antigens
450
WHat does a single T cell express?
1000's single antigen receptors
451
A hypervariable region formed by tips of alpha/beta TCR is involved in what?
Antigen binding
452
Hypervariable region is unique to each individual T cell. Hence what does each T cell express?
Unique TCR that binds to only 1 specific peptide antigen
453
How many classes of MHC molecules exist?
2
454
Where is class 1 MHC expressed?
On all nucleated cells
455
What does Class 1 MHC molecules present peptide antigens to?
CD8+ T cellls
456
What does Class 2 MHC express?
Only professional antigen presenting cels
457
Name antigen presenting cells
Dendritic cells
| Macrophages, B cells
458
What do Class 2 MHC molecules present peptide antigens to?
CD4+ T cells
459
What is the first stage of T cell activation?
Particles + antigens derived from pathogens are released by phagocytes
460
What is the main function of dendritic cells?
-Process + present antigens on their cell surface to T cells
461
Where are dendritic cells present in large numbers?
- Tissues in contact with external environment e.g. skin
| - Other epithelial tissues
462
What are dendritic cells called inskin?
Langerhans cells
463
Give an example of epithelial tissue
- Respiratory tract
| - Gut
464
What is the 2nd stage of T cell activation?
Dendritic cells phagocytose pathogen-derived particles + antigens
465
What is the 3rd stage of T cell activation?
Pro-inflammatory TNFalpha stimulates immature tissue-resident dendritic cells = increase co-stimulatory molecule expression
466
What can infected/inflamed tissues cells recognise + phagocytose?
Dendritic cells
467
What do Dendritic cells do in the presence of pro-inflammatory mediators e.g. TNFalpha?
Mature + increase expression of key co-stimulatory surface molecules
468
What is the 4th stage of T cell activation?
Dendritic cells ingest proteins + display small proteins derived from these on their cell surface on complex with MHC proteins
469
What happens after phagocytosing the pathogenic antigens?
- Dendritic cells break proteins down into short peptides
| - Loaded MHC molecules transported to cell surface
