Intro to Clinical Sciences Flashcards
1
Q
Define inflammation
A
The initial series of tissue reactions to injury which can last from a few hours to a few days
2
Q
Give an example of acute inflammation
A
Appendicitis
Frostbite
3
Q
What is another way of describing acute inflammation?
A
Neutrophil mediated inflammation
4
Q
What are the benefits of acute inflammation?
A
Destroys invading pathogens
Walls off an abscess preventing the spread of infection
5
Q
What are the limitations of acute inflammation?
A
An abscess can compress surrounding structures
Fibrosis can destroy or distort tissues
6
Q
What are the steps of inflammation?
A
Vascular component: dilation of vessels
Exudative component: leakage of fluid
Neutrophil polymorphs: WBCs recruited to the area
7
Q
What are the outcomes of acute inflammation?
A
- Resolution: goes away
- Suppuration: pus formation
- Organisation: healing by granulation to form a fibrous scar
- Progression to chronic inflammation
8
Q
What can cause acute inflammation?
A
Microbial infection
Hypersensitivity reactions
Physical agents
Chemicals
Necrosis
9
Q
What are the 5 cardinal signs of inflammation?
A
Redness/rubor
Heat/calor
Swelling/ tumor
Pain/dolor
Loss of function
10
Q
What are the stages of neutrophil migration in acute inflammation?
A
- Margination of neutrophils: cells flow in plasmatic zone near endothelium
- Adhesion of neutrophils: neutrophils adhere to the endothelium and adhere to each other
- Neutrophil emigration: neutrophils migrate through endothelial walls
- Diapesesis: RBCs escape
- Chemotaxis
11
Q
What are some chemical mediators of acute inflammation?
A
Histamine- vasodilation, adhesion
Thrombin- adhesion
Nitric acid- prolongs permeability
Bradykinin- “”
Prostaglandins- vasodilation, pain, fever, prolonged permeability
Cytokines- local endothelial action, systemic- fever, metabolic permeability
12
Q
What are the systemic effects of acute inflammation?
A
Pyrexia/fever
Malaise
Nausea
Weight loss
Lymph node and spleen enlargement
Anaemia and increased WBC conc
Amyloidosis
13
Q
Define chronic inflammation
A
Subsequent and prolonged tissue response to injury
14
Q
What can chronic inflammation also be defined as (cells)?
A
Lymphocytes
Plasma cells
Macrophages
15
Q
What are some causes of chronic inflammation?
A
Can develop from acute inflammation
Resistance of infective agent such as TB
Endogenous and exogenous material
Autoimmune disease
Granulomatous disease
Transplant rejection
16
Q
What are the effects of chronic inflammation?
A
Fibrosis
Impaired function
Atrophy
Stimulation of immune response
17
Q
How does acute inflammation progress to chronic inflammation?
A
-Suppuration: pus forms and abscess, abscess forms wall from granulation and fibrous tissue, fibrous scar forms in pus
-Indigestible material can not be cleared: such as keratin, necrotic material
18
Q
What are the macroscopic signs of chronic inflammation?
A
-chronic ulcers and cavities
-walls of hollow organs thicken
-fibrosis
-granulomatous inflammation
19
Q
What are the microscopic signs of chronic inflammation?
A
-lymphocytes, plasma cells, macrophages
-macrophage -> giant multinucleate cells
-tissue necrosis (sometimes)
20
Q
What are the roles of the cells involved in chronic inflammation?
A
-T-lymphocytes: cytokines after contact with antigen
-B-lymphocytes: transform into plasma cells -> antibodies
-Macrophages: ingest material and respond to chemotaxis
21
Q
What are 3 different types of macrophages?
A
Kupffer cells in liver
Alveolar macrophages in lungs
Melanophages in skin
22
Q
Define Granuloma:
A
An aggregate of epitheliod histocytes/macrophages surrounded by lymphocytes
23
Q
What are 4 diseases which display Granuloma?
A
Leprosy
TB
Sarcoidosis
Crohn’s disease
24
Q
What can granulomas alongside eosinophils be indicative of?
A
Parasitic infection
25
What is secreted in granulomatous disease that can be used as a marker?
ACE/ angiotensin converting enzyme
26
What are the 2 outcomes of tissue damage?
Resolution: initiating factor removed/ tissue can regenerate or is undamaged
Repair: initiating factor can not be removed/ tissue is damaged
27
Which cells in the body are able to regenerate?
Hepatocytes, pneumocytes, blood cells, gut epithelium, skin, osteocytes
28
Which cells in the body are unable to regenerate?
Myocardial cells, neutrons
29
Define thrombosis
The solidification of blood content that forms in an intact vessel during life
30
Define clot
Coagulated blood outside of the vascular system after death
31
Why does blood not clot all of the time?
Laminar flow: cells travel in the middle of the cells
Endothelial cells: healthy cells are not adhesive
32
Define organisation
The repair of specialised tissue by formation of a fibrous scar
33
What are the stages of thrombus formation?
1. Coronary vasospasm
2. Primary platelet plug
3. Coagulation cascade
34
What causes arterial thrombosis
Atheromatic plaque causes a change in the vessel wall which affects blood flow, causing a thrombus
35
Describe the progression of arterial thrombosis
1. Fatty streak grows causing obstruction
2. Intimal cell loss and fibrin disposition causes platelets to settle
3. Proliferation of smooth muscle cells causes platelet layer to form, traps RBCs
4. Grows and disrupts laminar flow
36
What occurs in venous thrombosis?
Low BP, thrombus begins at valves
37
What is the main cause of venous thrombosis?
Immobility
38
What are the effects of venous thrombosis?
Tenderness (ischaemia) redness and swelling
39
What are the effects of arterial thrombosis?
Distal pulse loss, coldness, pain, paleness, necrosis and gangrene
40
What are the fates of a thrombus?
Resolves by dissolving
Organisation into scar after clearance of thrombus
Intimal cells proliferate and cause thrombus to fuse into a larger vessel
Embolism-fragments break off
41
Define embolism
A mass of material in the vascular system that can lodge in a vessel and block the lumen
42
What are some less common causes of embolism?
Air
Cholesterol crystals
Fat
Tumour amniotic fluid
43
What are the 3 causes of thrombosis outlined in Virchow’s triad?
Change in vessel wall
Change in blood flow
Change in blood constituents
44
What can cause a change in vessel wall?
Smoking
Hypertension
MI
Trauma
45
What can cause changes in blood flow?
Immobility
DVT
AF
46
What can cause changes in blood constituents?
Pregnancy
Oral contraceptives
Cancer
Inherited thrombophlila
47
How does aspirin work and what does it do?
Inhibits platelet aggregation so can prevent thrombosis
48
How does warfarin work and what does it do?
Inhibits vitamin K- many clotting factors dependant on this, can prevent thrombosis
49
Describe the progression of venous thrombosis
Valves naturally protrude into vessel lumen, mostly upstream of thrombosis
Grows by successive deposition via propagation
Fall in BP causes adhesion to endothelial cell walls
Leads to thrombus
50
What occurs during an arterial embolism?
An embolus from the arterial system can travel anywhere downstream- can be due to atheromatous plaque or thrombus in the heart due to AF
51
What type of embolism is a pulmonary embolism?
Venous embolism
52
How does a pulmonary embolism develop?
Embolism travels to vena cava and moves through the heart to lodge in the pulmonary arteries
53
Why can a venous embolism not enter the arterial circulation?
The blood vessels in the lung are too small for an embolus to pass through
54
What are the effects of different sizes of emboli?
-Small: can be lysed in lung or can be organised and cause damage
-Medium: can cause respiratory and cardiac problems that can resolve slowly, or can impair lung function
-Large: can cause sudden death- using from DVT in legs
55
Define ischaemia
A reduction in blood flow to a tissue or organ caused by blockage or obstruction of the blood vessels supplying it
56
What 2 factors determine if ischaemia can be reversed?
Duration of the ischaemic period
Metabolic demands of tissue (eg. Myocytes are vulnerable)
57
Define infarction
Necrosis of part or all of an organ due to the artery supplying it becoming obstructed
58
What is the most common cause of infarction?
Thrombus
59
What type of organs are at greater risk of infarction?
Organs with an end arterial supply (supplied by a single artery)
60
Define gangrene
Whole areas of a limb or region of the gut have their arterial supply cut off and large areas of tissue die
61
Define atherosclerosis
The formation of an atherosclerotic plaques in systemic arteries
62
Does atherosclerosis affect veins/outside of the systemic system? Why?
No- low pressure
63
What are the effects of atherosclerosis?
Cerebral infarction
Carotid atheroma -> TIA
MI
Aortic aneurism
Peripheral vascular disease
Gangrene
64
Outline the progression of atherosclerosis
Birth: no atherosclerosis
Late teens/early adulthood: fatty streaks begin to form
30s-50s: development of atherosclerotic plaques
40s+: complications of atherosclerotic plaques erupt
65
What are the risk factors of atherosclerosis?
High cholesterol (most important)
Smoking
Hypertension
Diabetes
Male sex
Increased age
66
What are the 2 main stages of the development of atherosclerotic plaques?
Endothelial injury
Tissue response to injurious agents
67
Describe the composition of an atherosclerotic plaque
Central lipid core capped by fibrous tissue covered by an arterial endothelium
-collagen for strength (from smooth muscle cells)
-inflammatory cells: macrophages, T lymphocytes, mast cells
-bordered by foam cells- macrophages that have oxidised lipoproteins
68
Where do atherosclerotic plaques usually form?
Branching points and bifurcations
69
Describe the process of the formation of an atherosclerotic plaque
1. Injured endothelial cells increase adhesion of monocytes
2. Lipid accumulation
3. Macrophages engulf LDL and apoptose -> Foam cells
4. Smooth muscle proliferation
5. Fibrous cap forms
6. Plaque rupture and thrombus formation
70
Which effects of atherosclerosis can cause disease?
1.Progressive lumen narrowing
2. Acute atherothrombotic occlusion: plaque rupture leads to coagulation cascade -> ischaemia -> infarction
3.Embolism of distal arterial bed: parts break off and embolism
4. Ruptured abdominal aneurism
71
What can prevent atherosclerosis?
Stopping smoking
Control of BP
Losing weight
Low dose aspirin
Statins
72
What triggers the intrinsic coagulation pathway?
Internal damage to vessel wall
73
Outline the intrinsic coagulation pathway
Factor 12 activated due to collagen contact
Factor 11 activated
Factor 9 activated
Factor 8 leads to common pathway
74
What triggers the extrinsic coagulation pathway?
External trauma causing blood to escape the circulation
75
Outline the extrinsic coagulation pathway
Factor 3 exits the circulation
Factor 7 (tissue factor) is released by damaged cells
Factor VII and III = TF-VIIa complex -> activates factor X
76
Outline the common coagulation pathway
Activated factor X causes factor II (prothrombin) -> IIa (thrombin)
Thrombin converts factor I (fibrinogen) into insoluble fibrin strands
Strands stabilised by factor XIII
77
How are fibrin clots removed after healing has occured?
Plasminogen -> plasmin -> fibrin breakdown
Protein C and S degrade factor Va and VIIIa, slows clotting
Calcium regulates calcium dependant factors
Antithrombin degrades thrombin
78
What are the vitamin K dependant clotting factors?
2, 7, 9, 10
79
Define apoptosis
Non inflammatory controlled cell death without release of harmful products
Chromatin NOT altered
80
What is the difference between apoptosis and necrosis?
Necrosis is unintended cell death in response to cell injury, apoptosis can suppress the results of necrosis
81
Name some inhibitors of apoptosis
Growth factors
Sex steroids
Some viral proteins
Extracellular cell matrix
82
Name some inducers of apoptosis
Glucocorticoids
Free radicals
Ionising radiation
DNA damage
83
Outline the intrinsic apoptosis pathway
Bcl-2: inhibits induction
Bax: enhances apoptosis
Ratio determines if a cell will survive or apoptose
84
Describe the role of the p53 gene in the intrinsic apoptosis pathway
Induces cell cycle arrest and initiates DNA damage repair
Hard to repair damage causes p53 to induce apoptosis via the Bcl-2 pathway
85
Outline the extrinsic apoptosis pathway
FasL or TNF-L activate CSM receptors -> activate caspases
Caspases= death enzymes
86
Outline the execution apoptosis pathway
Caspase 8 causes activation of other caspases
Caspases cause degradation of nuclear proteins and cytoskeletal framework
Dead cells either apoptose or are later phagocytosed
87
Define necrosis
Traumatic cell death which induces inflammation and repair
Chromatin CAN be altered
88
Why does necrosis induce inflammation and repair?
Rupture of plasm membrane releases cell contents which may induce an immune response
89
What are the 4 forms of necrosis?
1.Coagulative: most common, caused by ischaemia which causes protein coagulation
2. Liquefactive: occurs due to lack of stroma in brain
3. Caseous necrosis: seen in TB, soft cheese appearance
4. Gangrene: rotting of tissues
90
Define congenital disease
A disease present at birth
91
Define inherited genetic disease
Caused by an inherited genetic abnormality
92
Define spontaneous genetic disease
Disease caused by a spontaneous mutation eg. Downs syndrom
93
Define acquired disease
Disease caused by non-genetic environmental factors
94
Define Hypertrophy
An increase in cell size without cell division (ie. No increase in number)
95
When is Hypertrophy seen?
Muscle Hypertrophy in atheletes
Uterine smooth muscle Hypertrophy
96
Define hyperplasia
An increase in cell number by mitosis
97
Define atrophy
The decrease in the size of an organ or cell by reduction in cell size/cell number
98
When does atrophy occur?
Development of genitourinary tract (Wolfian and Müllerian ducts)
Muscle atrophy due to loss of innervation or malnutrition
99
Define metaplasia
The change in differentiation from one fully differentiated cell type to another fully differentiated cell type
100
When does metaplasia occur?
Smokers- respiratory epithelium -> squamous epithelium
Barretts oesophagus: squamous epithelium -> columnar epithelium
101
Define dysplasia
Morphological changes seen in cells in the progression to becoming cancer
-not cancer yet but can become cancer
102
What occurs in telomeric shortening?
The telomere at the end of each chromosome shortens each time DNA divides as it is not fully copied
They eventually get so short that the cell is incapable of further division
103
Who is telomere length determined by?
Father
104
What are common complications found in older people?
Sarcopenia
Deafness
Senile dementia
Cataracts
Osteoporosis
Dermal elatosis (wrinkles)
Impaired immunity
105
Define carcinogenesis
The transformation of normal cells to neoplastic cells via permanent genetic alterations or mutations
106
Define neoplasm
Lesion from autonomous abnormal growth of cells which persists after initial stimulus removed
107
What are the 4 features of neoplasia?
Autonomous
Abnormal
Persistent
New growth
108
Define tumour
Any abnormal swelling
-includes: neoplasm, inflammation, Hypertrophy, hyperplasia
109
What 2 things make up a solid tumour?
Neoplastic cells: nucleated cells, synthesise/secrete collagen, mucin, keratin ect
Stroma: neoplastic cells embedded here, provide support and nutrients. Contains fibroblasts, collagen and blood vessels
110
How does vascular supply limit tumour size?
If not vasculated, the growth is limited by nutrient diffusion
Angiogenesis is induced by VEGF
111
What are the features of benign neoplasms?
Localised and non-invasive
Slow growth rate
Resembles normal tissue
Often encapsulated
Expophyic growth
112
How can benign neoplasm cause mortality and morbidity?
Pressure on adjacent structures
Obstruction of ducts
Hormone production (eg. Thyroid)
Transformation to malignancy
Anxiety and stress
113
What are borderline neoplasms?
Neither benign or malignant
Defy classification
Usually treated as malignant
114
What are the features of malignant neoplasms?
Invasive- invade and destroy surrounding tissue
Grow rapidly
Irregular border
Do not resemble parent cell
Increased mitotic activity
Necrosis and ulceration common
Endophytic growth (inwards)
115
What is metastases?
Secondary malignant tumours
116
How do malignant neoplasms cause mortality and morbidity?
Pressure and destruction of adjacent tissue
Metastases
Blood loss from ulcers
Obstruction of flow
Hormone production
Weight loss and debility
Anxiety and pain
117
Define histogenesis
The specific cell or origin of a tumour
118
What are the major categories of origin of tumours?
Epithelial cells = carcinomas
Connective tissues = sarcomas
Lymphoid = malignant neoplasms
119
What are the grades of malignant neoplasms?
Grade 1: well differentiated
Grade 2: moderately differentiated
Grade 3: poorly differentiated
-well differentiated resembles the parent tissue more
-poorly differentiated = more agressive
120
Define papilloma
Benign tumour of non-glandular/secretory epithelium
121
Define adenoma
Benign tumour of glandular epithelium
122
Define carcinoma
Malignant tumour of epithelial cells
123
Define Adenocarcinoma
Malignant tumour of glandular epithelium
124
Define intraepithelial neoplasia
Carcinoma in situ in an epithelium exhibiting malignant cellular features but has not yet invaded the basement membrane
125
Define:
Lipoma
Osteoma
Angioma
Neuroma
Benign tumour of adipocytes
Benign tumour of bone
Benign vascular tumour
Benign tumour of the nerve
126
Define:
Liposarcoma
Osteosarcoma
Neurosarcoma
Chrondrosarcoma
Malignant tumour of adipocytes
Malignant tumour of bone
Malignant tumour of the nerve
Malignant tumour of cartilage
127
What are some malignant tumours that are not carcinomas or sarcomas?
Melanoma: malignant neoplasm of melanocytes
Mesothelioma: malignant neoplasm of mesothelial cells
Lymphoma: malignant neoplasm of lymphoid cells
128
Define carcinosarcoma
Mixed malignant tumours with characteristics of epithelial and connective tissue cells
129
Why can neoplastic cells proliferate endlessly?
Oncogenes
Inactivation of tumour suppressor genes
Abnormal expression of apoptosis inhibiting genes
Telomerase prevents telomeric shortening
130
Define carcinogenic
Malignant neoplasm causing
131
Define oncogenic
Tumour/neoplasm causing
132
What percentage of cancer risk comes from genes vs the environment?
85% is environmental
15% is from genes
133
What are 5 classes of carcinogens?
1. Chemical: most require metabolic conversion
2. Viruses: such as HPV -> cervical cancer
3. Radiation: UV = skin cancer, ionising = more long term effects
4. Biological agents: hormones (oestrogen), parasites, mycotoxins
5. Miscellaneous: asbestos
134
What host factors can induce carcinogenesis?
Race
Diet
Age
Gender
Premaligant lesions (eg ulcerative colitis)
Transplancental exposure
135
What are the events that lead to the progression of a normal cell to cancer?
Initiation: carcinogen induces genetic alteration
Promotion: stimulation of clonal proliferation of the transformed cell
Progression: invasion and it consequences culminate in malignant behaviour
136
Which tumours commonly metastasise to the lungs?
Sarcomas and other cancers
137
Which cancers commonly metastasise to the liver?
GI cancers that drain via portal vein
138
What is the function of the caretaker TSG?
Maintain integrity of the genome by repairing DNA damage
-eg BRCA1 and BRCA2
139
What is the function of the gatekeeper TSG?
Inhibit proliferation or promote the death of cells with damaged DNA
-eg p53
140
Define oncogenes
Genes driving the neoplastic behaviour of cells
141
How can oncogenes be activated?
Mutation resulting in over activity of oncogene
Excessive production of oncoprotein due to gene amplification or increased transcription
142
What are the 3 mechanisms of activation of oncogenes?
1. Translocation: gene is translocated from an untranscribed site to an adjacent actively transcribed gene
2. Point mutation: substitution of a single base leads to a hyperactive oncogene
3. Amplification: multiple copies of the oncogene are inserted into the strand resulting in excessive production
143
What factors affect tumour invasion?
Decreased cellular adhesion: allows carcinomas to escape and metastasise
Secretion of proteolytic enzymes
Abnormal/increased cellular motility
144
What is the function of matrix metalloproteinases?
Most important proteinases in neoplastic invasion
Enzymes secreted by malignant neoplastic cells which enables them to digest surrounding connective tissue
145
What are the 3 major families of proteinases?
Interstitial collagenases: degrade type 1,2, and 3 collagen
Gelatinases: degrade type 4 collagen and gelatin
Stromelysins: degrade type 4 collagen and proteoglycans
146
What counteracts proteolytic enzymes?
Tissue inhibitors of metalloproteinases (TIMPs)
147
Which tissues are the most and least resistant to neoplastic invasion?
Least resistant: perineural space and vascular lamina
Most resistant: cartilage and intervertebral disc fibrocartilage
148
How is invasion recognised in epithelial and connective tissue tumours?
Epithelial: easy as basement membrane shows demarcation
Connective tissue: harder, mitotic activity assessed and evidence of vascular or lymphatic permeation is looked for
149
Define metastasis
The process by which malignant tumours spread from their site of origin to form secondary tumours at different sites
150
What are the stages of metastasis?
1. Detachment of tumour cells
2. Invasion of surrounding connective tissue
3. Intravasation into vessel lumen
4. Evasion of host defence systems
5. Adherence to remote endothelium
6. Extravasation of cells from vessel lumen to surrounding tissue
151
Bone is a site favoured by metastasis of which 5 carcinomas?
KP BLT
Kidney
Prostate
Breast
Lung
Thyroid
152
Describe the haematogeous route of metastasis
Moves via the blood stream to form secondary tumours in organs perfused by the blood that has drained from the tumour
153
Outline the lymphatic route of metastasis
Tumours reach the lymph nodes through an afferent lymphatic channel
154
Outline the transcoelomic route of metastasis
Occurs in pleural, pericardia and peritoneal cavities- tumour causes buildup of fluid (neoplastic effusion)
Fluid contains neoplastic cells and is rich in protein
155
Which route of metastasis is preferred initially by carcinomas?
Lymphatic spread
156
Which route of metastasis is preferred by sarcomas?
Haematogenous spread
157
What is a tumour grade?
Assessment of the degree of malignancy or aggressiveness of a tumour inferred from its histology
158
What are the most important factors contributing to the assessment of tumour grading?
Mitotic activity
Nuclear size, staining and pleomorphism
Differentiation from parent tissue
159
What is determined by tumour staging?
The extent of a tumours spread
160
Describe the TNM tumour grading system
T: denotes size of primary tumour (larger number= larger tumour)
N: lymph node status (larger number= more nodal metastases)
M: extent of distant metastases (larger number = increasing extent)
161
Describe a Germline mutation
-Exist in germ cells
-Can be passed onto future generations
-A person who inherits a germline mutation has the mutation in all the cells of their body
162
Describe a somatic mutation
-Can spontaneously arise in any cells except germ cells at any time during during life
-Limited to descendant of the original cell- not other cells in the body
-Can not be passed from parent to child
163
Why are screening programmes carried out?
Success of treatment more likely due to early diagnosis
People who are most at risk but asymptomatic are examined
164
What screening programmes are carried out in the UK and how are they conducted?
-Cervical cancer: PAP smears/cervical swab]
-Breast cancer: mammograms
-Colorectal cancer: faeces test for occult blood
165
What are the features of innate immunity?
Non specific
Rapid
Instinctive
Phagocytes and NK cells
Lysosomes
Complement system
166
What are the features of adaptive immunity?
Specific
Acquired
Improved by repeat infection
Slower response
Lymphocytes and antibodies
167
Which leukocyte is the most abundant in blood?
Neutrophils (65%)
168
What is the function of neutrophils?
Phagocytosis
Secrete superoxides to kill microbes
Have Fc and complement receptors
169
What shape is the nucleus of a neutrophil?
Multi lobed
170
What is the shape of a monocyte nucleus?
Kidney shaped
171
What are the functions of a monocyte?
Innate: phagocytosis
Adaptive: activate T cells
Differentiate into macrophages in tissue
Have lysosomes
172
What is the function of a macrophage?
Innate: phagocytosis
Adaptive: antigen presentation
Remove foreign and self
Present antigens to T cells
173
Which cell is described as the first line of non-self recognition?
Macrophage
174
What is the appearance of an eosinophil?
Bilobed nucleus
Granules stain red/pink
175
When are eosinophils seen?
Parasitic infection
Allergic reations
176
What is the function of eosinophils?
Release major basic protein (BMP)
-Toxin for helminth worms
-Activates neutrophils and induces histamine release from mast cells -> bronchospasm
177
What is the function of basophils?
Express high affinity IgE receptors
Binding result is degreanulation -> histamine release
Induces allergic reaction
178
Describe the appearance of a basophil
Stain blue/violet for basic dyes
179
What is the difference between mast cells and basophils?
Mast cells are fixed in tissue, basophils circulate around the blood
180
What are mast cells and basophils involved in?
Parasitic infection and allergic reactions
181
Where do T lymphocytes originate and mature?
Originate: bone marrow
Mature: thymus
182
What is the general function of T lymphocytes?
Recognise antigen presenting cells (APC)
Bind to the antigen through TCR receptors
Produce cytokines
183
What are the 4 types of T lymphocytes?
T helper 1
T helper 2
Cytotoxic T cells
T reg
184
What is the function of T helper 1 cells?
-CD4- helps immune response for intracellular pathogens
-Help B cells make antibodies
-Activates macrophages and NK cells
185
What are the functions of T helper 2 cells?
-Help produce antibodies against extracellular pathogens
-Help B cells make antibodies
-Activate macrophages and NK cells
186
Which cells aid the development of cytotoxic T cells?
T helper 1 and 2
187
What is the function of cytotoxic T cells?
CD8 can kill cells directly
188
What is the function of T reg cells?
Regulates immune response and can repress it
189
Where are T and B lymphocytes found?
Blood
Lymph nodes
Spleen
190
What percentage of blood do T and B lymphocytes make up?
T: 10%
B: 15%
191
What is the function of B lymphocytes?
Recognise antigens on APCs
Express antibody on cell surface
Differentiate -> plasma cell
Plasma cell makes antibodies
192
Where do B lymphocytes originate and grow?
Bone marrow
193
What is the resident antigen presenting cell?
Dendritic cell
194
What is the function of dendritic cells?
Detect and digest pathogens before presenting the antigen
Produce cytokines to induce B cell activation
195
Which cells have the capacity to induce an immune response in T lymphocytes?
Dendritic cells
196
Where are dendritic cells found?
In tissue that has contact with the external environment
-ie skin, lining of nose, lungs, stomach, intestines
197
What are some chemical and physical immune barriers?
Skin
Sebum on skin
Mucous membrane
Ph (ie stomach)
198
Define complement system
Complex series of interacting plasma proteins forming an effector system for antibody-mediated immunity
199
Where are complement proteins derived from?
Liver
200
What is the function of the fragments derived from complement protein precursors?
A: minor fragment
-Have important biological properties in fluid phase
B: major fragment
-Bind to triggering complex
-Other cleaves next complement protein
201
What is the main function of the complement protein system?
To remove or destroy antigen, either by direct lysis or by opsonisation
202
What can a complement protein do to kill pathogens?
1. membrane attack complex- makes holes in pathogen
2. Increase chemotaxis
3. Enhance inflammation
3. Induce opsonisation- antigen coated to make it “tastier” to phagocytes
203
What are the 2 phases of complement activation?
Activation of C3 component
Activation of lytic pathway
204
What are the functions of the fragments cleaved from the C3 component?
C3a: enhances inflammation
C3b: mediates opsonisation and lysis- membrane attack complex
205
What are the 3 C3 cleavage pathways?
1. Classic pathway
2. Alternate pathway
3. Lectin pathway
206
Outline the classical pathway of complement activation
1. IgM/ IgG binds to an antigen, causing the binding site on the antibody to be exposed
2. C1q binds to Fc region on 2 adjacent antibodies
3. C1q activation causes C1r+C1s -> C4b2a complex (C3 convertase)
4. C3 convertase cleaves C3 into C3a and C3b
5. Mediated by C1 esterase inhibitor
207
Outline the alternative pathway of complement activation
1. C3 spontaneously cleaved into C3a ad C3b
2. C3b combines with factors D and B to form C3 convertase
3. The C3 convertase can break down more C3
208
Outline the lectin pathway of complement activation
1. Mannose-binding lectin (MBL) binds to mannose on the pathogen
2. Binding generates C3 convertase
3. C3 convertase remains on the surface of the pathogen and cleaves further
209
What activates the classical pathway of complement activation?
Antibody dependent (mostly)
Can be independent when factors react directly with C1
210
What activates the alternate complement pathway?
Complement binds to microbe
Activators are microbial cell surfaces or endotoxins
211
What activates the lectin complement pathway?
Independent of antibodies
Initiates when MBL binds to mannose on bacteria, yeast, or viruses
212
How is the complement pathway controlled?
-Activated components are unstable and decay rapidly
-Several inhibitors e.g. C1 esterase inhibitor
-Cell membrane proteins that accelerate activated component proteins e.g. CD46, CD55
213
What is a PAMP?
Pathogen associated molecular patterns
-General molecular features common to many types of pathogens
- How microbes are recognised by the innate immune system
214
What is a PRR?
Pattern recognition receptor
-Family of proteins that recognise and bind to a variety of pathogen ligands
215
What is the function of PRRs?
Drives cytokine production that increases the likelihood of successful T cell activation
216
What are 3 secreted PRRs and their functions?
-Lectins/collectins: activate complement and improve phagocytosis
-Penetraxins: antimicrobial, activate complement and promote phagocytosis
-Cathelicidin: disrupts microbial membranes
217
Where are toll like receptors found (TLRS)?
Macrophages, dendritic cells and neutrophils
218
What are toll like receptors (TLRs)?
Proteins that recognise and binds to PAMPs such as lipopolysaccharides, viral/bacterial nucleic acids and flagella
219
What occurs when a PAMP binds with a TLR?
-Secondary messengers generated, lead to secretion of inflammatory mediates (IL-1,IL-12, TNF alpha)
-This stimulates immune cell activity
220
What is another function of toll like receptors (TLRs)?
Recognise damage and initiate tissue repair
221
What is the function of nod-like receptors (NLRs)?
-Detect intracellular microbial pathogens
-Release cytokines
222
What does NOD2 recognise?
Muramyl dipeptide (MDP)
223
What does NOD2 do?
-Activates inflammatory signalling pathways
-Can activate anti-viral signalling
224
What condition is linked to non-functioning mutation of NOD2?
Crohn’s disease
225
What is the function of rig-like helicase receptors (RLRs)?
Detect intracellular double stranded DNA and RNA
226
What is the result of activation of rig-like helicase receptors?
Activate interferon production, enabling antiviral response
227
What are the 2 killing mechanisms of macrophages and neutrophils?
O2 dependant
O2 independent
228
Outline the O2 dependent killing pathway?
Reactive oxygen species
-Superoxides: O2- -> -OH (toxic)
-Nitric oxide: vasodilator that increases extravasation (WBC migration to tissue)
229
Outline the O2 independent killing pathway
Enzymes: defensins (disrupt microbial membranes), lysozymes, pH, TNF
230
What are T cells used for in adaptive immunity (broadly)?
Intracellular microbes
231
What are B cells used for in adaptive immunity (broadly)?
Antibodies- extracellular microbes
232
Why is adaptive immunity needed?
Microbes can evade innate immunity
Intracellular pathogens hide from innate immunity
Memory-specific reactions
233
What are cytokines?
Soluble proteins secreted by lymphocytes or macrophages/monocytes that act as inhibitory or stimulatory signals between cells
234
What is an interleukin?
A cytokine that act between cells of the immune system
235
What is a chemokine?
Cytokine that induces chemotaxis of leucocytes
236
What are the common features of cytokines?
-Short half life
-Rapidly degrade
-Can affect multiple organs
237
What is the function of interferons (IFNs)?
Induce an antiviral state in uninfected cells and limit viral infection spread
238
What are the functions of interleukins (ILs)?
Pro inflammatory: IL1
Anti inflammatory: IL10
Can cause division, differentiation, and factor secretion
239
What are the functions of colony stimulating factors?
Direct the division and differentiation of bone marrow stem cells (leukocyte precursors)
240
What is the function of tumour necrosis factors (TNF)
Mediate inflammation and cytotoxic reactions
241
What is the function of TLR2?
Detects gram positive lipopeptides
242
What is the function of TLR4?
Detects gram negative LPS and viral proteins
243
What is the function of TLR5?
Detects flagella
244
What is the function of TLR7?
Detects single stranded RNA
245
What is the function of TLR9?
Detects viruses or bacteria inside cells
246
What is the function of chemokines?
-Direct movement of leukocytes from the blood to tissues or lymph nodes by binding to cell receptors
-Attract leukocytes to the site of infection
247
Describe the process of phagocytosis
1. Chemotaxis + adherence of microbe to phagosome
2. Phagocyte ingest microbe to form phagosome
3. Phagosome fuses with lysosome to form phagolysosome
4. Ingested microbe digested my enzyme, forms residual body of undigested
5. Waste material discharged or presented on surface
248
What are 3 antigen presenting cells?
Dendritic cells
B cells
Macrophages
249
Why is cell to cell contact needed to initiate cell-mediated immunity?
-To control anti body response via B cell contact
-Directly recognise and kill virus infected cell
250
What is the function of major histocompatibility complex (MHC)?
-Initiates T cell response by presenting antigenic peptides
-Prevents immune system from being activated too easily
251
How does MHC regulate immune response
T cells can only react to antigens bound to MHC
252
Which MHCs are intracellular and extracellular?
MHC1: intracellular (ie virus)
MHC2: extracellular (ie phagocytosis)
253
Where are MHC1 found?
All cells except erythrocytes
254
Where are MHC2 found?
On the surface of antigen presenting cells
255
Which cells require an antigen to be associated with MHC1?
Cytotoxic T cells
-Will kill the cell with the intracellular protein
256
Which cells require an antigen to be associated with MHC2?
Helper T cells
-Makes antibodies
257
Define exudate and transudate
The fluid that leaks from blood vessels to nearby tisses
Exudate = protein rich
Transudate = not much protein
258
What is the purpose of a T cell receptor (TCR)?
TCR recognises antigen peptides on a MHC
259
How do T cells recognise antigens?
Respond to antigens bound to MHC
-Cell associated antigens
260
How is T helper cell 1 activated?
1. APC presents MHC II to naive CD4 T helper 1 cell
2. High levels of IL-12 cause naive TH1 -> activated TH1
3. TH1 goes to secondary lymphoid tissue
4. TH1 cells proliferate
261
How are T helper 2 cells activated?
Activated by IL-4
262
What are 4 functions of TH1 cells?
Activate macrophages and NK cells
Activate B cells to make IgG antibodies
Helps cytotoxic T cells
Pro inflammatory
263
What are 4 functions of T helper 2 cells?
Produce IL 4,5,6,10,13
Activates eosinophils and mast cells
Activates B cells to make IgE
Anti-inflammatory
264
Which T cells act intra and extracellularly?
TH1: intracellular
TH2: extracellular
265
How are killer T cells activated?
1. Antigens -> ER -> MHC1 on cell surface
2. Naïve CD8 cells activated by antigen
3. CD8 releases cytokines -> inflammation and macrophage activation
4. CD8 releases perforins and granules in
5. CD8 can also induce apoptosis
266
How are B cells specific?
Each B cell can only make 1 antibody that will only bind 1 epitope (part of antigen that bind to antibody binding site) on 1 antigen
267
What happens to B cells that recognise self?
Killed in bone marrow
268
How are B cells activated?
1. Naïve B cell presents antigen to MHCII
2. APC releases IL1 which activates B cells
3. Activated T helper cell releases IL 4,5,10,13 to induce B cell to divide by clonal expansion
4. B cells ->plasma cells -> memory cells
269
What is an antibody?
Specific protein produced in response to an antigen
270
Define antigen
A molecule that reacts with preformed antibody and specific receptors on T and B cells
271
Define epitope
Part of antigen that binds to antibody/receptor binding site
272
Define antibody affinity
Measure of binding strength between epitope and antibody binding site
273
What is the function of the Fab antibody region?
Binds to different antigens specifically
274
What is the function of the Fc antibody region?
Bind to complement, and Fc receptors on phagocytes and NK cells
275
What is the basic structure of an antibody and how do they impact the function?
2 heavy and 2 light chains
Heavy chain: determines isotope and function
Variable region binds to antigens
Constant regions are the same for a given H or L chain
276
What are the 5 classes of immunoglobulins?
IgG
IgA
IgM
IgE
IgD
277
What is the most abundant antibody?
IgG
278
What are the functions of IgG antibodies?
- Only one to cross placenta
- Important in secondary response
- Activate NK cells
279
What is the most abundant antibody in secretions?
IgE
280
Where are IgE antibodies found?
Saliva
Colostrum
Milk
Bronchiolar and genitourinary secretions
281
What is the function of IgM antibodies?
Involved in primary response- neutralises organisms intravascularly
282
How is IgM structure adapted to its function?
Multiple binding site- good complement activation and lysis/removal of antibody-antigen complexes by phagocytes
283
Where are IgM antibodies found?
Blood
-Too large to cross the endotheium
284
What is the function of IgE antibodies?
Expressed by basophils and mast cells
Binding = histamine release from basophils and mast cells
285
What are IgE antibodies associated with?
Allergic response, hypersensitivity reactions and parasitic infection
286
What is the function of IgD antibodies and where are they found?
Acts as a B-cell antigen receptor
Found on naive B cells
287
Which antibodies are involved in opsonisation?
IgG
288
Which antibodies are involved in immobilising microbes?
IgG
IgA
289
Which antibody immobilises pathogens?
IgM
290
Which antibodies activate complement?
IgG
IgM
291
Define allergy
Abnormal response to harmless foreign material
292
Define atopy
Inherited tendency for overproduction of IgE antibodies to common environmental antigens
293
What are some low affinity IgE receptor expressing cells?
B cells
T cells
Monocytes
Platelets
Neutrophils
294
What is the function of low affinity IgE receptor expressing cells?
Regulate IgE synthesis
Trigger cytokine release by monocytes
Antigen presentation
295
What are the high affinity IgE receptor expressing cell?
Eosinophils
Mast cells
Basophils
296
What are the functions of high affinity IgE receptor expressing cells?
Host defence against parasites
Eosinophils have different granules to the others
Mast cells = only in tissue
297
What are the main effector cells for IgE mediated immunity?
Mast cells
298
Define transudate
Fluids that pass through a membrane or squeeze through tissue or into the EXTRACELLULAR SPACE of TISSUES
299
Outline the development of mast cells
Characterised by requirement of c-kit protein
Immature mast cells circulate- mature do not
Maturing occurs in specific tissue environments
300
What effects does histamine release have?
Vasodilation
Capillary leakage/increased permeability
Bronchoconstriction
301
What compounds are immediately released (preformed) by mast cells?
Histamine
Chemotactic factors
Proteases
Proteoglycans
302
What compounds are released after a few minutes (lipid derived) by mast cells?
Leukotrienes
Prostaglandin
Platelet activating factors
303
What are 3 functions of platelet activating factor (PAF) ?
1. Increases platelet aggregation and degranulation
2. Increases vascular permeability
3. Activated neutrophil secretion
304
What are some indirect activators of mast cells (via IgE)?
Allergens: latex, venom, drugs, pollen
Bacteria/viral antigens
305
What are some direct activators of mast cells?
Cold/mechanical deformation
Aspirin, nitric oxide, preservatives
Complement products
306
What are 3 other cells involved in allergy and their functions?
Lymphocytes: eg. TH1
Dendritic cells: APCs
Neurons: coughing and sneezing
307
What are the effects of anaphylaxis?
Vasodilation
Increased vascular permeability
Low BP
Bronchial smooth muscle contraction
Mucous production
308
What are the symptoms of anaphylaxis?
Skin swelling, itching, reddening
Airways narrowing- wheezing
Vomiting, diarrhoea
Clammy skin
Collapsing or feeling faint
309
What are 3 treatments for allergies?
1. Desensitisation: immunotherapy increasing antigen dose gradually
2. Preventing mast cell activation: beta-2-agonists and glucocorticoids
3. Reducing mast cell products: histamine and prostaglandin antagonists
310
What antibodies are involved in type 1 hypersensitivity reactions?
IgE
311
What antibodies are involved in type 2 hypersensitivity reactions?
IgG/IgM
312
What antibodies are involved in type 3 hypersensitivity reactions?
IgG
313
What cells are involved in type 4 hypersensitivity reactions?
TH1 cells and macrophages
Antibody independent
314
What happens during type 1 hypersensitivity reactions?
1. Th2 activates/recruits B cells, mast cells and eosinophils
2. B cell activation stimulates production of IgE antibodies and activation of T helper cells
3. T helper cells trigger mast cell release of histamine and cytokines
4. This can cause anaphylaxis
315
What is the response time for type 1 hypersensitivity reactions?
Immediate
316
What are 3 examples of type 1 hypersensitivity reactions?
Hay fever
Asthma
Acute anaphylaxis
317
What is an example of a type 2 hypersensitivity reaction?
Haemolytic disease of the newborn
-baby 1: mother us RhD- and baby is RhD+ so antibodies are made slowly
-baby 2: baby is also RhD+ so antibodies destroy baby RBCs = RHESUS DISEASE
318
Describe how type 2 hypersensitivity reactions occur and the consequences
1. Antibody binds to cell surface associated antigens
- causes tissue injury or altered receptor function
319
What occurs during a type 3 hypersensitivity reaction?
1. IgG binds to soluble antigen forming a circulatory immune complex
2. Lumps of complex deposited in skin, lungs, kidneys ect
3. Activates immune response -> inflammation -> damage
320
What are some examples of type 3 hypersensitivity reactions?
Granulatoma
Farmers lung
Malt-workers lung
Mushroom workers lung
Pigeon fanciers lung
APSG- after streptococcal infection
321
What happens during a type 4 hypersensitivity reaction?
1. Antigen activates T helper cells
2. T cells release cytokines which act as inflammatory mediators
3. Activate macrophages to secrete potent mediators
322
How long do type 4 hypersensitivity reactions take to occur?
Several days- aka delayed hypersensitivity
323
What are some times when type 4 hypersensitivity reactions are seen?
TB reactions
Sarcoidosis
324
What is the first line of treatment for anaphylaxis?
IM 500mcg adrenaline
-also anti-histamine, IV fluids ect
325
define rhabdomyoma
benign tumours of striated muscle
326
define rhabdomyosarcoma
malignant tumour of striated muscle
327
define leiomyoma
benign tumours of smooth muscle cell
328
define leiomyosarcoma
malignant tumour of smooth muscle cells
329
define chondrosarcoma
malignant tumours of cartilage
330
What cells are made when T cells interact with MHC1?
CD8
331
What cells are made when T cells interact with MHC2?
CD4
332
What is the function of CD8?
Cytotoxic killing
333
What is the function of CD4?
1. Activates NK cells and macrophages (TH1)
2. Activates B cell differentiation (TH2)
334
What are the sepsis 6?
BUFALO
Blood cultures
Urine sample
Fluids
Antibiotics
blood Lactate
Oxygen
