ICS Flashcards
1
Q
Define inflammation
A
The body’s response to injury/infection
2
Q
Name the two types of inflammation
A
Acute (neutrophil-mediated inflammation)
Chronic (macrophage/lymphocyte mediated inflammation)
3
Q
Why are neutrophils polymorph?
A
They have polylobed nuclei
4
Q
Where are neutrophil polymorphs made + what is their lifespan?
A
Made in bone marrow, 2-3 days
5
Q
What do neutrophils do?
A
Phagocytosis + contain lysosomes to kill + digest bacteria
6
Q
What are the first cells to arrive at the site of acute inflammation?
A
Neutrophils
7
Q
What are the first cells to arrive at the site of chronic inflammation?
A
Macrophages + lymphocytes
8
Q
What do fibroblasts do?
A
Produce collagenous connective tissue in scarring following some types of inflammation
9
Q
What is the process of acute inflammation?
A
-Injury/infection
-Neutrophils arrive, phagocytose + release enzymes
-Resolution/progression to chronic inflammation
10
Q
Examples of acute inflammation
A
Acute appendicitis, frostbite, Streptococcal sore throat
11
Q
What is the process of chronic inflammation?
A
-Progression from acute/starts as chronic e.g. infectious mononucleosis
-Macrophages + lymphocytes, then fibroblasts arrive
-Resolves if no tissue damage, often repair + scar tissue formation
12
Q
What is the lifespan of macrophages?
A
Months-years
13
Q
What do macrophages do?
A
Phagocytosis + transport material to lymph nodes, also APC to induce secondary immune reactions
14
Q
What is the name of macrophages in the liver?
A
Kupffer cells
15
Q
What is the name of macrophages in bone?
A
Osteoclasts
16
Q
What is the name of macrophages in the brain?
A
Microglial cells
17
Q
What are granulomas?
A
Types of chronic inflammation with collections of macrophages/histiocytes surrounded by lymphocytes-can be due to myobacterial infection e.g. TB/leprosy
18
Q
What do lymphocytes do?
A
Control inflammation + produce antibodies, from B cells-immunological memory-re-infection
19
Q
What are corticosteroids?
A
Anti-inflammatories
20
Q
What is laminar flow?
A
When cells travel in the centre of arterial vessels and don’t touch the sides
21
Q
Give two reasons why clots are rare
A
-Laminar flow
-Endothelial cells that line vessels aren’t ‘sticky’ when healthy
22
Q
What is thrombosis?
A
Formation of a solid mass from blood constituents in an intact vessel in a living person
23
Q
What are the stages of thrombosis?
A
-Platelet aggregation
-Clotting cascade
-Fibrin mesh formation
24
Q
What three factors can cause a thrombosis?
A
-Change in vessel wall
-Change in blood flow
-Change in blood constituents
25
How can smoking lead to a thrombosis?
-Smoking causes endothelial cell injury
-This causes a change in vessel wall + change in blood flow over the injured/absent cells
26
What is embolism?
The process of a solid mass (often a thrombus) in the blood being carried through the circulation to a place where it gets stuck + blocks the vessel
27
What can cause embolisms?
-Thrombus
-Air
-Tumour
-Amniotic fluid
-Fat
-Cholesterol crystals
28
What does aspirin do?
Inhibits platelet aggregation
29
What will happen to a venous embolism?
-Travels to vena cava
-Lodges somewhere in pulmonary arteries ( depends on size)
-Can't reach arterial circulation as lung blood vessels split down to capillaries-too small
30
What will happen to an arterial embolus?
-Can travel anywhere downstream of entry point
31
What is ischemia?
Any reduction in blood flow
32
What is an infarction?
Reduction in blood flow to a tissue so severe that it can't support cell maintenance-so cells die
33
Why is it bad that most organs have end arterial supply?
Only one artery supplying blood-very susceptible to infarction if supply interrupted
34
Which organs have dual arterial supply?
-Liver-HPV + hepatic artery
-Lungs-pulmonary venous + bronchial artery
-Brain-around circle of Willis
35
What is the difference between resolution + repair?
-Resolution=initiating factor removed + tissue undamaged/can regenerate
-Repair=factor still present + tissue damage-can't regenerate
36
What are the two types of wound healing?
-Healing by 1st intention
-Healing by 2nd intention
37
What is healing by 1st intention?
When wound edges can be approximated/brought together e.g. after surgical incision
38
What is healing by 2nd intention?
When wound edges can't be brought together so healing must occur from bottom of wound upwards
39
What are the 4 stages of wound healing?
-Haemostasis
-Inflammation
-Proliferation
-Remodelling
40
Name 6 cells that regenerate
-Hepatocytes
-Pneumocytes
-All blood cells
-Gut epithelium
-Skin epithelium
-Osteocytes
41
Which cells don't regenerate?
-Myocardial cells
-Neurones
42
Define atherosclerosis
The accumulation of fibrolipid plaques in systemic (vs pulmonary) arteries
43
What does atherosclerosis do?
Can cause serious illness by reducing blood flow
44
Describe the time course of atherosclerosis
-Birth-none
-Late teens/early 20s-fatty streaks in aorta, may not progress to atherosclerosis
-30s-50s-development of established atherosclerotic plaques
-40s-80s-complications of atherosclerotic plaques e.g. thrombosis, intraplaque haemorrhage
45
What are the risk factors for atherosclerosis?
-Hypertension
-Hyperlipidaemia
-Smoking
-Poorly controlled diabetes mellitus
46
What is the lipid insudation theory?
Disproved model that suggest atherosclerotic plaques develop from accumulation of lipids in vessel wall
47
What theory describes the pathogenesis of atherosclerosis?
Endothelial cell damage theory
48
How do atherosclerotic plaques form from smoking?
-Free radicals, nicotine, carbon monoxide etc damage delicate endothelial cells
49
How do atherosclerotic plaques form from high blood pressure?
-High blood pressure causes shearing forces on endothelial cells
50
How do atherosclerotic plaques form from high poorly controlled diabetes?
Glycosylation products + superoxide anions damage endothelial cells
51
How do established atherosclerotic plaques develop?
Cumulative damage leads to endothelial ulceration, microthrombi + eventually plaques
52
What are the complications of atherosclerosis?
-Plaque blocks artery=infarct + organ death
-Pieces of plaque can break off + embolise downstream-can cause small embolisms + infarct downstream
53
What is apoptosis?
Programmed cell death-orderly + takes place in single cells, important part of cell turnover
54
Which protein detects levels of DNA damage in cells?
p53
55
Why does a cell 'decide' to apoptose?
When DNA damage is detected
56
How does a cell apoptose?
Cell triggers cascade of activated enzymes that autodigest the cell
57
Name the enzymes involved in cell apoptosis
Caspases
58
When is apoptosis used in health?
-Development-removal of cells during development e.g. interdigital webs
-Cell turnover-removal of cells during normal turnover e.g. cells in intestinal villi at the tips, replaced by cells form below
59
How does cancer affect cell apoptosis?
-Tumour cells often don't apoptose when they should-leads to larger tumours + accumulation of genetic mutations-often due to p53 mutations
60
How does HIV use apoptosis?
HIV virus can induce apoptosis in CD4 helper cells-can make you immunodeficient
61
What is necrosis?
Largescale destruction of many cells by an external factor-causes lots of tissue damage
62
Give 4 examples of necrosis
-Frostbite
-Toxic venom
-Pancreatitis
-Infarction due to loss of blood supply e.g. myocardial/cerebral infarction
63
How does the body react to necrosis?
Has to clear it up by macrophages phagocytosing dead cells + replacing necrotic tissue with fibrous scar tissue
64
What is hypertrophy?
-Increase in the size of an organ due to increase in size of its constituent cells
--Occurs in organs where cells cannot divide
65
Give 2 examples of hyperplasia
-Benign prostatic hyperplasia
-Endometrial hyperplasia
66
What is hyperplasia?
-Increase in size of an organ due to increase in number of its constituent cells
-Occurs in organs where cells can divide
67
Give an example of hypertrophy
Skeletal muscle in body builders
68
Give an example of mixed hypertrophy/hyperplasia
Smooth muscle cells of the uterus in pregnancy
69
What is atrophy?
Decrease in size of an organ due to decrease in size OR number of constituent cells or both
70
Give 2 examples of atrophy
-Alzheimer's dementia
-Quadriceps muscle following knee injuries
71
What is metaplasia?
Change in cell differentiation, from one fully-differentiated cell type to another fully-differentiated type
72
What causes metaplasia?
A consistent change in the environment of an epithelial surface
73
Give 3 examples of metaplasia
-Barrett's oesophagus (squamous->glandular)
-Bronchi after smoking (bronchial epithelium ciliated columnar-> squamous)
-Uterine cervix at puberty (columnar->squamous)
74
What is dysplasia?
Morphological changes in cells in the progression on to the development of cancer (neoplasia)
75
What staining can be used to view dysplasia?
H&E
76
Give an example of dysplasia
Bronchial epithelium in smoking (ciliated->squamous=metaplasia, then development of dysplasia in the squamous epithelium)
77
What is the Hayflick limit?
The limit to how many times a human cell can divide
78
How does telomere length change with age?
Telomere length shortens with age
79
Is telomere length maternally or paternally inherited?
Paternally
80
How does telomere length affect the Hayflick limit?
-At each cell division, telomere length shortens, this means fewer future divisions (shorter length=lower hayflick limit)
81
What is the only definitive method of slowing ageing + why?
Calorie restriction as it reduces metabolic processes
82
How does ageing affect the skin, why + how to reduce it?
-Causes wrinkling of skin (dermal elastosis)
-Caused by UV-B light causing protein cross-linking
-Reduced by wearing high protection sun cream
83
How does ageing affect the eyes, why + how to reduce it?
-Causes cataracts
-Caused by UV-B protein cross-linking
-Prevented by wearing UV sunglasses + can be treated by lens replacement
84
How does ageing affect bones, why + how to reduce it?
-Causes osteoporosis (loss of bone matrix, mainly after menopause)
-Can be prevented by HRT + calcium/vit D supplements
85
How does ageing affect the brain, why + how to reduce it?
-Can cause dementia
-Genetic + lifestyle causes + preventatives
86
How does ageing affect muscles, why + how to reduce it?
-Causes loss of muscle (sarcopenia)
May be caused by reduced levels of GH + testosterone in later life
Can be prevented by regular exercise
87
How does ageing affect the ears, why + how to reduce it?
-Causes deafness due to cells in cochlear not dividing so not replaced when damaged
-Prevented by avoiding high volume sounds
88
What is a granuloma?
An aggregate of epithelioid histiocytes
89
Describe the spread of basal cell carcinomas
They don't spread to other parts of the body-only invade locally
90
How do you cure basal cell carcinomas?
Complete local excision
91
What is a carcinoma?
A malignant tumour of the epithelial cells
92
Name 5 common symptoms of leukemia
-Weight loss
-Fatigue
-Easy bleeding/bruising
-Muscle weakness
-Joint pain/tenderness
93
Describe the spread of general carcinomas
-Spread to lymph nodes that drain the site of the carcinoma
-Can also spread through the blood to bone
94
Name the 5 cancers that most commonly spread to bone
-Breast
-Prostate
-Lung
-Thyroid
-Kidney
95
What are the steps of treatment for breast cancer?
-Confirm breast cancer diagnosis (with biopsy)
-Check if spread to lymph nodes in axilla (then removed)
-Check if spread to rest of body with bone scan (chemo/surgery needed)
96
What is adjuvant therapy?
Extra treatment given after surgical excision
97
What is tamoxifen + what does it do?
-SERM (selective oestrogen receptor modulator)-treatment for breast cancer
98
What is carcinogenesis?
The transformation of normal cells to neoplastic cells through permanent genetic alterations/mutations
99
What is oncogenesis?
The creation of benign + malignant tumours
100
Define carcinogenic
Cancer causing
101
Define oncogenic
Tumour causing
102
Define mutagenic
Acts on DNA
103
What is the latent interval?
Gap between exposure to carcinogen + formation of neoplasm/development of cancer
104
What are the classes of carcinogens?
-Chemical
-Viral
-Ionising/non-ionising radiation
-Hormones, parasites + mycotoxins
Miscellaneous
105
What type of carcinogens require metabolic conversion from pro-carcinogens to ultimate carcinogens?
Chemical
106
Give 4 examples of common chemical carcinogens + where they come from
-Polycyclic aromatic hydrocarbons-smoking/mineral oils
-Aromatic amines-rubber/dye industry
-Nitrosamines-found in treated foods e.g. cured meats
-Alkylating agents-found in chemotherapy drugs
107
What % of cancers are caused by viral carcinogens?
10-15%
108
Give 7 examples of viruses that cause cancer + the cancer they cause
-Human herpes virus 8-Kaposi sarcoma
-Epstein Barr virus-Burkitt lymphoma/nasopharyngeal carcinoma
-Hepatitis B virus-hepatocellular carcinoma
-Human papillomavirus (HPV)-squamous cells carcinomas of the cervix, anus, penis, head + neck
-Merkle cell polyomavirus (MCV)-Merkle cell carcinoma
Human T-lymphotropic virus-adult T-cell leukaemia
-Hepatitis C virus (HCV)- hepatocellular carcinoma
109
How does UV light cause carcinoma?
-Exposure to UVA/UVB, increases risk of basal cell carcinoma/melanoma
110
What is xeroderma pigmentosum?
-Recessive condition that increases risk of developing cancer due to mutations in nucleotide excision repair
111
Give 3 examples of cancer caused by radiation
-Skin cancer in radiographers
-Lung cancer in uranium miners
-Thyroid cancer in Ukrainian children post-Chernobyl
112
Give 3 examples of biological agents that cause cancer
-Hormones e.g. oestrogen increase=mammary/endometrial cancer risk increase
-Mycotoxins e.g. aflatoxin B1=hepatocellular carcinoma
-Parasites e.g. shistosoma=bladder cancer
113
Give 2 examples of miscellaneous carcinogens
-Asbestos
-Metals
114
What host factors affect likelihood of developing cancer?
-Ethnicity
-Diet/lifestyle
-Age
-Gender
-Transplacental exposure
115
How does ethnicity affect your risk of developing cancer?
-Local customs e.g. reverse smoking in SE Asia=increase in oral cancer
-Less skin cancer in those with darker skin
116
How do age + gender affect your risk of developing cancer?
-Increase in age=increase in exposure to carcinogens
-Gender-breast cancer F:M=200
117
How does lifestyle affect your risk of developing cancer?
-Diet/exercise-XS alcohol=increase in mouth, oesophagus, liver, colon and breast cancer
Exercise reduces risk of colon + breast cancer
-Unprotected sex-increases risk of HPV
118
Give an example of how transplacental carcinogenesis affects your risk of developing cancer
-DES (diethylstilboestrol)-prescribed to pregnant women 1940-71 to prevent miscarriage=increase in risk of vaginal cancer
119
What is an invasive carcinoma?
One that has spread to the basement membrane + therefore can metastasise to the rest of the body
120
Name 3 types of carcinoma
-Carcinoma in situ
-Micro-invasive carcinoma
-Invasive carcinoma
121
How do tumour cells evade host immune defence?
-Aggregation with platelets
-Shedding of surface antigens
-Adhesion to other tumour cells
122
Name 2 angiogenesis promoters
-Vascular endothelial growth factor
-Basic fibroblast growth factor
123
Name 3 angiogenesis inhibitors
-Angiostatin
-Endostatin
-Vasculostatin
124
Which tumours most commonly metastasise to the lungs?
Sarcomas. any common cancers
125
Which tumours most commonly metastasise to the liver?
-Colon
-Stomach
Pancreas
-Carcinoid tumours of the intestine
126
Name an antimicrotubule agent
Vinblastine
127
How do antimicrotubule agents work?
They reduce tumour size by binding to micro tubules + stopping them from attaching to chromatin
128
What are 2 drawbacks of conventional chemotherapy?
-Not selective for tumour cells-except they might be dividing faster
-Usually also affects normal dividing cells-cause of hair loss, myelosuppression (decrease in bone marrow activity), diarrhoea etc
129
Name 5 fast dividing tumours
-Germ cell tumours of testis
-Acute leukaemia
-Lymphomas
-Embryonal paediatric tumours
-Choriocarcinomas
130
What is a neoplasm?
A lesion resulting from the abnormal growth of cells after the initiating stimulus has been removed
131
What are 5 characteristics of benign tumours?
-Non-invasive
-Localised
-Low mitotic activity
-Well-circumscribed
-Bland cell morphology
132
What are 5 characteristics of malignant tumours?
-Invasive
-Local + distant spread (metastasis)
-Poorly circumscribed
-Abnormal cell morphology
-High mitotic activity
133
What are benign tumours from secretory/glandular epithelium called?
Adenomas
134
What are benign tumours from non-glandular, non-secretory epithelium called?
Papillomas
135
What are benign tumours from connective tissues (smooth + striated muscle, vascular, adipocytes, bone, nerves) called?
-Leiomyomas-smooth muscle
-Rhabdomyoma-striated muscle
-Angiomas-vascular
-Lipomas-adipocytes
-Osteoma-bone
-Neuroma-nerves
136
What are malignant epithelial tumours called?
Carcinomas
137
What do you call malignant glandular epithelial tumours?
Adenocarcinomas
138
What are malignant tumours from connective tissue called?
Sarcomas (same prefix before sarcoma as for benign)
139
What are malignant tumours with hemopoietic origins called?
Lymphomas, leukaemia/myeloma
140
What are other (not from epithelium, connective tissue or hemopoietic origins) malignant tumours called?
Melanomas/mesotheliomas
141
What 4 ways can we acquire genetic changes?
-Chance-spontaneous mutations
-Hereditary-inherited mutations
-Environment-exposures/toxins
-Micro-organisms-oncogenic viruses/bacteria
142
Give 2 examples of a hereditary inherited genetic mutation that could increase risk of cancer
-Lynch syndrome (aka hereditary non-polyposis colorectal cancer)
-Xeroderma pigmentosa
143
Give 3 examples of micro-organisms that can increase your risk of developing cancer
-Epstein Barr virus
-HPV
-H pylori
144
What are proto-oncogenes?
Genes which promote cell growth + survival-promoting carcinogenesis
145
What are tumour suppressor genes?
Genes which inhibit cell growth + proliferation, can inhibit carcinogenesis
146
What is tumour grading?
Comparing a tumour to its normal counterparts-how much does it resemble them e.g well/poorly differentiated
147
What is tumour staging?
Assessing how much the tumour has spread-looks at lymph nodes + other organs/tissue
148
What does TNM staging stand for?
T-tumour size/depth
N-nodes, has it spread to lymph nodes?
-M-metastases, has it spread to rest of body?
149
Name the 4 modes of metastases
-Direct
-Lymphatic
-Blood vessel
-Transcoeleomic
150
What is a tumour?
Any abnormal swelling (includes neoplasms)
151
What are neoplasms made up of?
-Neoplastic cells
-Stroma
152
Where do neoplastic cells derive form?
Nucleated nuclei
153
What is the stroma in neoplasms?
Connective tissue framework that provides mechanical support + nutrition
154
What are the 3 stages of tumour angiogenesis?
-Cell transforms-avascular tumour nodule
-Vascularised tumour
-Vascularised tumour with central necrosis
155
What size (mm) would a neoplasm without a blood supply be?
<2mm
156
Name 5 ways benign neoplasms cause morbidity + mortality
-Press on adjacent structures
-Obstruct flow
-Produce hormones
-Transform to malignant
-Anxiety
157
Compare the nuclear morphometry of benign + malignant neoplasms
Benign=often normal
Malignant=hyperchromatic + pleomorphic (able to assume diff shapes) nuclei
158
What does anaplastic mean?
Cell type of origin for a tumour cannot be determined
159
Define carcinoma
A malignant epithelial neoplasm
160
What are the top 4 biggest killers in the UK?
-Cancer (42%)
-CVD (22%)
-Respiratory disease (9%)
-Liver disease (6%)
161
What is the purpose of tumour immunology?
To induce clinically effective anti-tumour immune responses that can discriminate between tumour cells + normal cells in cancer patients
162
What are TSAs?
Tumour specific antigens, found only on tumours, from viral antigens, occur as a result of point mutations/gene rearrangements
163
What are TAAs?
Tumour associated antigens
164
Where are TAAs found?
Found on normal + tumour cells-overexpressed in cancer cells
165
What is tumour escape?
When the immune response changes tumours so it can no longer be seen by the immune system
166
What is tumour evasion?
When tumours change the immune response by promoting immune suppressor cells
167
Give an example of active immunotherapy
Vaccination
168
Give 2 examples of passive immunotherapy
-Adoptive cellular therapy (T cells)
-Anti-tumour antibodies
169
Where are dendritic cells found?
Throughout the body:
-Interstitial cells (liver. heart, liver)
-Langerhans cells of epidermis
170
What do dendritic cells do?
APCs-break up pathogens + present piece on surface
171
Name 3 cells that can be used in tumour immunotherapy
-Dendritic cells
-T killer cells
-Macrophages
172
What is passive immunisation?
Administration of pre-formed immunity from one person/animal to another
173
What are the limitations of passive immunisation?
-Only antibody mediated (doesn't work if cell mediated)
-Short-lives
-Possible transfer of pathogens
-'Serum sickness' on transfer of animal sera
174
What are the advantages of passive immunisation?
-Gives immediate protection
-Effective in immunocompromised patients
175
Give 4 examples of passive immunisation
-Human tetanus Ig
-Human rabies specific Ig
-Human hepatitis B Ig
-Varicella zoster Ig
176
What is HNIG?
Human normal immunoglobulin-from pools of 100+ donors, contains antibodies against measles, mumps, varicella, hep A etc
177
What are the 3 approaches to making a vaccine (parts used)?
-Using whole virus/bacterium
-Using parts that trigger immune system
-Using just genetic material
178
What are the 3 types of vaccine given in whole microbe approaches?
-Inactivated vaccine
-Live-attenuated vaccine
-Viral vector vaccine
179
Name 4 limitations of whole killed vaccines
-Organisms grown to high titre in vitro-expensive
-Can cause more adverse reactions
-Immune response not always close to normal response to infection
-Normally need 2+ doses
180
Give 4 examples of bacterial whole killed vaccines
-Diphtheria
-Tetanus
-Pertussis
-Cholera
181
Give 5 examples of viral whole killed vaccines
-Polio
-Influenza
-Hep A
-Rabies
-SARS-Co-V2
182
What are the benefits of live attenuated vaccines?
-Immune response better mimics real infection-better protection
-Better immune response so lower doses needed
-Route of administration may be better (oral)
-Fewer doses required
183
What is attenuation?
Where an organism is cultured in such a way that it does not cause disease when inoculated into humans
184
Limitations of live attenuated vaccines
-Hard to balance attenuation + it still working
-Can reverse to virulence
-Transmissibility
-Live vaccines may not work as well in immunocompromised hosts
185
Give 2 examples of bacterial live attenuated vaccines
-BCG (some protection against TB)
-Salmonella typhi
186
Give 3 examples of viral live attenuated vaccines
-Poliomyelitis
-Vaccinia virus (smallpox)
-MMR
187
Give 3 reasons why it is hard to produce vaccines
-Pathogen hard to grow
-Killed pathogen doesn't work as vaccine )shape changes)
-Some condition have too many strains causing disease
188
What are recombinant protein vaccines?
Genetically engineered vaccines made from bacteria, yeast, insect/mammalian cells
189
Give 3 examples of recombinant protein vaccines on the market
-Hep B surface antigen
-HPV Cervarix + Gardasil
-SARS-Co-V2-Novavax
190
What are live attenuated vector vaccines? Give an example
Safe living attenuated viruses that have inserted genes encoding foreign antigens e.g. SARS-Co-V2
191
What is innate immunity?
Instinctive, non-specific, no reliance on lymphocytes, present from birth
192
What is adaptive immunity?
Specific, acquired/learned immunity, requires lymphocytes, antibodies
193
What 3 layers does contrifuged blood form?
-Plasma-water, electrolytes, proteins, lipids, sugars etc
-Buffy coat/middle layer-leukocytes
-Haematocrit (45%)-erythrocytes, platelets
194
What is serum?
Plasma minus fibrinogen/other clotting factors
195
Name the process by which blood cells are formed
Haematopoiesis
196
What is the progenitor of all blood cells?
Pluripotent haematopoietic stem cells
197
Name 3 polymorphonuclear leukocytes
-Neutrophils
-Eosinophils
-Basophils
198
Name 3 mononuclear leukocytes
-Monocytes
-T-cells
-B-cells
199
What cells produce macrophages?
Monocytes
200
What cells produce plasma cells?
B-cells
201
Name 3 types of T cell
-T-regs
-T-helper cells (CD4)
-Cytotoxic T cells (CD8)
202
What do mast cells do?
Contain histamine-important in allergic reactions
203
What are natural killer cells?
Type of T cell-functions like neutrophil-important in anti-tumour response
204
What are dendritic cells?
Surveillance cells-live in epithelium
205
What is complement?
Series of around 20 proteins made by liver that circulate in an inactive form around the body
206
What are the 3 modes of action of complement?
-Direct lysis
-Attract more leukocytes to site of infection
-Coat invading organisms
207
What are the 5 subclasses of immunoglobulin?
-IgG
-IGA
-IgM
-IgD
-IgE
208
Describe the basic structure of an antibody
--Antigen binding site
-Fab region (recognises non-self)
-Fc region
-Light + heavy chains
-All connected by disulphide bonds
209
What is the most common Ig in human serum?
IgG
210
Where is IgM found + how common is it in serum?
Found in blood-too big to cross endothelium, 10% of serum
211
Which Ig is the main primary immune response?
IgM
212
What is IgA found in?
Mucous secretions e.g. saliva, colostrum, milk, bronchiolar + genitourinary secretions
213
Is IgA a monomer or dimer in humans?
Monomer (dimer in most animals)
214
What is the least common Ig?
IgE
215
Where is IgD found?
Found on mature B cells
216
What cells have receptors complementary to IgE?
Basophils + mast cells
217
What does IgE release?
Histamines in hypersensitivity response + defence against parasitic infections
218
What are cytokines?
Proteins secreted by immune + non-immune cells
219
Give 4 examples of cytokines?
-Interferons (IFN)
-Interleukins (IL)
-Colony stimulating factors (CSF)
-Tumour necrosis factors (TNF)
220
What are chemokines?
Chemotactic cytokines-
Around 40 proteins that direct movement of leukocytes from bloodstream into tissue/lymph by binding to specific receptors
221
Give 3 examples of chemokines
-CXCL
-CCL
222
What do interferons do?
Induce antiviral resistance in uninfected cells-limit spread of viral infection
223
What do interleukins do?
Can cause cells to divide/differentiate/secrete factors. Can be pro-inflammatory or anti-inflammatory
224
What do colony stimulating factors do?
Direct division + differentiation on bone marrow stem cells
225
What do tumour necrosis factors do?
Mediate inflammation + cytotoxic reactions
226
Name 5 physical barriers that contribute to innate immunity
-Lysozyme in tears
-Physical skin barrier + fatty acids
-Low pH of vagina
-Mucus + cilia in bronchi
-Acid + rapid pH change in gut
227
Describe the 7 steps in an inflammatory response
-Stop bleeding (coagulation)
-Acute inflammation
-Kill pathogens, neutralise toxins, limit pathogen spread
-Clear pathogens/dead cells
-Proliferation of cells to repair damage
-Remove blood clot-remodel extracellular matrix
-Re-establish normal structure/function of tissue
228
Name 3 hallmarks of inflammation
-Increased blood supply
-Increased vascular permeability
-Increased leukocyte migration
229
Name the cells that sense microbes in blood
Monocytes + neutrophils
230
Name the cells that detect microbes in tissues
Macrophages + dendritic cells
231
What are PRR?
Pattern recognition receptors-on cells
232
What are PAMP?
Pathogen-associated molecular patterns-on microbe
233
What expresses C-type lectin receptors + what do they do?
-Expressed by macrophages + dendritic cells
-Bind to carbohydrates in a Ca dependent manner
234
What are scavenger receptors?
Group of membrane-bound receptors that mainly recognise lipids
235
What do scavenger receptors do to LDL
Bind + internalise them-if process is dysregulated, it can lead to atherosclerosis
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What are the 3 activation pathways of complement factors?
-Classical-Ab bound to microbe
-Alternative-C' binds to microbe
-Lectin-activated by mannose
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What are the 2 killing pathways present in neutrophils + macrophages?
-O2 dependent
-O2 independent
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How does O2 dependent microbe killing work?
-Reactive oxygen intermediates are used e.g. superoxides->H2O2->OH free radical
-Nitric oxide also causes vasodilation, increases extravasation + anti-microbial
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How does O2 independent microbe killing work?
Enzymes e.g. lysozyme + proteins e.g. defensins + pH are used to kill microbes
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What is the purpose of extravasation?
To get neutrophils from the blood, through the epithelium, into tissue
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What are the steps of extravasation?
-Rolling
-Tethering
-Firm adhesion
-Locomotion
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Where are T + B cells + APC's matured?
-T cells matured in thymus
-B cells matured in bone marrow
-APC's in bone marrow
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What is the secondary lymphoid (where they circulate) for T, B + APC cells?
Spleen, lymph nodes + mucosa and associated lymphoid tissue (MALT)
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What antigens do T cells respond to?
Intracellular presented antigens
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What is T cell selection?
When T cells that recognise self are killed in the foetal thymus as they mature-so adult T cells only recognise foreign bodies
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What do T cell receptors bind to?
MHC-major histocompatibility complex bound to peptide on foreign antigen
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What does MHC do?
Display peptides from self or non-self proteins e.g. degraded microbial proteins on surface-invasion alert
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What are the 2 types of MHC + where are they present?
MHC I-present on all nucleated cells
MHC II-present only on APC
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What is an example of clonal expansion?
T cell division
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What do Th2 cells do?
Antibody production
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What do Th1 cells do?
Secrete interferon gamma-helps kill intracellular pathogens
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Which Igs can B cells bind to?
IgM/IgD
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What is B cell selection?
When B cells that recognise self are killed in foetus in the bone marrow
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Describe the interaction between APC, T cells + B cells
-APC eats + presents antibody to naïve T cell via MHC II
-Th2 cell becomes primed
-TH2 binds to B cell that are presenting the antibody
-Th2 secretes cytokines
-Cytokines cause B cell division + clonal expansion + differentiate into:
-Plasma cells + memory B cells
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What are the primary lymphoid tissues?
-Thymus
-Bone marrow
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What are the secondary lymphoid organs + tissues?
-Waldeyer's ring (tonsils + adenoids)
-Spleen
-Peyer's patch
-Urogenital lymphoid tissue
-Lymph nodes
-Bone marrow
-Bronchus associated lymphoid tissue
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What do antibodies do?
-Neutralise toxins by binding to them
-Increase opsonisation-phagocytosis
-Activate complement
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What are DAMPs?
Damage associated molecular patterns-endogenous molecules created to alert the host to tissue injury + initiate repair
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Give 3 examples of the main PRRs
-Pentraxins
-Lectins
-Collectins
260
What do pentraxins do?
Activate complement + promote phagocytosis
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What do lectins + collectins do?
Bind to carbohydrates + lipids in microbe walls-activate complement + improve phagocytosis
e.g. surfactant proteins A+D
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Name 3 other membrane bound PRRs + where they are found
-Mannose receptors-on macrophages (fungi)
-Dectin-1-on phagocytes
-Scavenger receptors-on macrophages
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What are RIG-I-like receptors (RLRs), give 3 examples?
Receptors that detect viral RNA in the cytoplasm
-RIG-I
-MAD-5
-LGP2
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What do NLRs do?
NOD-like receptors sense cytoplasmic bacterial pathogens + DAMPs + regulate inflammatory + cell death responses
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What is the damage chain reaction?
-Tissue damage leads to inflammation
-This causes the release of DAMPs + then TLRs
-TLRs then trigger pro-inflammatory mediators + increase inflammation, which causes more tissue damage
-Cycle repeats
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What is the cytokine storm?
-Big increase in cytokines, chemokines + interferons
-Causes severe inflammation + tissue damage
-Induced due to genetics of host + persistence of pathogen (evasion mechanisms)
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What do PRRs do?
Detect infection, initiate immunity, eliminate pathogens + hold in check until adaptive immunity develops
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What are the two strategies of immunomodulation?
Agonists (enhance TLR signalling)
Antagonists (inhibit TLR signalling)
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How do agonists enhance TLR signalling?
Adjuvant effect (used with primary Tx e.g. vaccines), stimulate + modify immune response
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How do antagonists inhibit TLR signalling?
Block binding of ligands _ interfere with common signalling pathways
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Antibodies are also known as...
Immunoglobulins
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What antibody mediates type 1 hypersensitivity reactions?
IgE
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What are the hallmarks of ageing on a cellular level?
-Cellular senescence
-Stem cell exhaustion
-Altered intercellular communication
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What are the hallmarks of ageing on a systemic level?
Nutritional dysregulation
Reduced nutrient sensing
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What are the hallmarks of ageing on a molecular level?
-Telomere shortening
-Genomic instability
-Epigenetic alteration
-Mitochondrial dysfunction
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What is immunosensescence?
Dysregulated immune function that contributes to the increased susceptibility of the elderly to infection + possibly to autoimmune disease + cancer
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What happens to the innate immune response with age?
-Less interferons produced
-More inflammatory cytokines produced
-XS inflammation
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What happens to the adaptive immune response with age?
-Less naïve B + T cells
-XS inflammation
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What immune cells are reduced with age?
-Macrophages
-Naive B + T cells
-Dendritic cells
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What immune cells increase with age?
-Memory B + T cells
-MDSCs
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What happens to these immune tissues with age?
-Thymus
-Bone marrow
-Spleen
-Lymph nodes
-Lungs
All decrease output + cell production except lungs-increase infiltration of pro-inflammatory cells + lung damage
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What lifestyle modifications can you make to reduce immunosenescence inflammaging?
-Increase physical activity
-Restrict calories
-Maintain optimal nutrition
-Weight loss
-Modulate gut microbiota e.g. probiotics
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What pharmacological interventions can you perform to reduce immunosenescence inflammaging?
-Reversal of thymic atrophy-IL7 therapy
-Statins
-P13kinase inhibitors
-Antioxidants
-Anti-inflammatories
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What is meningitis?
Inflammation of the meninges-membrane which cover the brain + spinal cord
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What are the infective causes of meningitis?
-Viruses e.g. herpes, influenza, HIV
-Bacteria e.g. meningococcus, pneumococcus
-Other e.g. fungi, protazoa + parasites
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What are the non-infective causes of meningitis?
-Medications e.g. antibiotics, NSAIDs
-Cancers e.g. melanoma, leukemia
-Autoimmune disease e.g. SLE, Behcets
287
Name 6 differential diagnoses of meningitis
-Viral/fungal/TB/drug-induced meningitis
-HIV infection
-Brain tumour
-Sepsis
-Encephalitis
-Brain abscess
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What is invasive meningococcal disease?
Infection with Neisseria meningitidis-carried by 10-24% population-humans=reservoirs
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What are the manifestations of meningococcal disease?
-Meningitis
-Septicaemia
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Which serogroups cause most cases of meningococcal disease?
A, B, C, W, X, Y
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Which serogroups of N.meningitidis are most common in Europe?
B, C, Y
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How is meningitis transmitted + when do cases rise?
-Aerosol droplets/direct contact with upper resp secretion-need prolonged close contact
-Most prevalent in winter
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Who is most commonly affected by meningitis?
Extremes of age, <2 + >60, also spike in adolescence and early adulthood (due to close contact/ social mixing?)
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Name 8 risk factors of meningitis
-Extremes of age
-Immunocompromised
-Smokers
-Cochlear implants
-Cancer
-Sickle cell disease
-Living in overcrowded households
-Cranial anatomical defects
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Name 6 symptoms of meningitis for adults
-Fever
-Stiff neck
-Headache
-Confusion
-Increased sensitivity to light
-Nausea + vomiting
296
Name 6 symptoms of meningitis for babies
-Slow/inactive
-Irritable
-Vomiting
-Feeding poorly
-Bulging fontanelle
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What is Brudzinski's sign?
When child's head is pulled up, knees come up automatically to relieve pressure on meninges
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What are the symptoms of Meningococcal septicaemia?
-Fever + chills
-Fatigue
-Vomiting
-Cold hands + feet
-Rapid breathing
-Petechiae (non-blanching rash)
Later stages = purpura (dark, purple rash)
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Describe the course of meningitis
-Acute onset
-Fulminating infection - occurs suddenly, escalates quickly + can be rapidly fatal
-Prolonged + persistent coccaemia (bloodstream infection)
-Long-term complications
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What are some of the complications of meningitis?
-Deafness/hearing loss
-Seizures
-Motor deficits
-Cognitive impairment
-Blindness
-Amputations
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Is meningitis a notifiable disease?
Yes! Meningitis of any cause + meningococcal septicaemia are notifiable
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What tests would you run on a potential meningitis patient?
-Blood test for blood culture + PCR
-CSF for microscopy
-Throat swab
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When do you notify UKHSA health protection team about meningitis?
When a case is suspected-don't wait for lab confirmation
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What Tx is given for meningitis?
Antibiotics-to stop throat carriage (to stop passing on-doesn't kill infection) e.g. ciprofloxacin, rifampicin
304
What is prophylaxis?
Tx given/action taken to prevent disease
305
Who is included for contact tracing of a case of meningitis?
-Living in same household
-Anyone who slept overnight in household within 7 days
-Intimate kissing contacts (including CPR) within 7 days
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What public health action would be taken after a case of meningitis?
-Chemoprophylaxis of close contacts
-Notify school/uni/nursery
-Standard warning letter
-Offer leaflets
-Media handling
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Give 2 examples of locations for large meningitis outbreaks
-Outbreaks associated with pilgrimage to Hajj
-Epidemics in meningitis belt of Sub Saharan Africa
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Name 5 causes of epidemic meningitis
-Dry season Dec-June-dust laden winds
-Upper resp tract infections due to cold nights
-Decrease in local immunity in pharynx
-Overcrowded housing
-Large population displacement due to pilgrimages + traditional markets
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What is the new meningitis vaccine?
MenAfriVac-new conjugate Men A vaccine developed by WHO/PATH partnership
-Launche din Burkina Faso, Mali + Niger
-Affordable
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What is primary vaccine failure?
When a person doesn't develop immunity from a vaccine
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What is secondary vaccine failure?
When there is an initial response but protection waned over time
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What acts mean doctors have a legal responsibility to notify about certain diseases?
-Health (Control of Disease) Act 1984
-Health Protection Regulations 2010
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What is the role of disease surveillance?
-Outbreak detection
-Early warning
-Forecasting
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