Cells : Flashcards

(192 cards)

1
Q

`what is the function of the nucleus ?

A

contains genetic code for each cell and and site of DNA replication

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2
Q

what is the structure of the nucleus ?

A

nuclear envelope - has a double membrane surrounds the nucleus . controls entry and exit of materials .
nuclear pore is large molecule which can pass out of nucleus like mRNA . It prevents DNA from leaving .
nucleoplasm - jelly like material makes up most of nucleus
chromosome - protein bound linear DNA
nucleolus - site of ribosomal reproduction .

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3
Q

mitochondria function ?

A

aerobic respiration to produce ATP

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4
Q

what is the structure of the mitochondria ?

A

Rod shaped
double membrane - controls entry and exit of material e.g glucose
cristae - inside of membrane - forms extensions / projections to increase the SA . means more ATPase enzyme can attach so more respiration
for organelles with high metabolic activity . and require a high supply of ATP to absorb substances by active transport . .

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5
Q

chloroplast function ?

A

site of photosynthesis

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6
Q

structure of chloroplasts

A

-disc shaped
- chloroplast envelope - double plasma membrane surrounds organelle
- granum - stacked up membrane of thylakoids - 1 stage of photosy
stroma - fluid inside ( matrix ) 2 photosy
DNA and ribosomes = quick manufacture of protein - protein synthesis

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7
Q

endoplasmic reticulum has ?

A

has folded membrane called cisternae

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8
Q

RER structure

A

ribosomes on outer surface
for protein synthesis

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9
Q

SER strucutre

A

no ribosomes on n outer layer
lack ribosomes on outside
synthesis and stores lipids & carbs

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10
Q

Golgi apparatus structure :

A
  • has folded membranes to make cisternae
  • secretary vesicles pinch off cisternae
  • modify proteins by adding non protein component - then ‘label
    transport sore and modify lipids and proteins
    ‘ then . and separate them to correct places .
    when vesicles go to cell membrane they fuse to it and secrete content
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11
Q

ribosomes features

A

made of 2 subunits - 70s and 80s
70s in prokaryotic cells small unit
80s in eukaryotic cells large unit

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12
Q

lysosomes features :

A

hydrolyse - phagocytic cells are broken
autolysis - break down dead cells
exocytosis- enzymes to outside cells to destroy material
digest worn out cells for reuse materials .

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13
Q

cell wall features -

A

provide mechanical strength for to prevent cells from bursting
fungi CW made from chitin not cellulose
algae is made of cellulose and glycoproteins

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14
Q

vacuole features

A

make cell turgid
- fluid filled sac surrounded by single membrane called tonoplast .
- contains sugar and AA for temporary food store
pigment colour and petals help attract pollinating insects .

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15
Q

Bacterial cell structure

A
  • flagella
  • cytoplasm
  • capsule
    -ribosomes
  • cell surface membrane
  • circular DNA
  • plasmids
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16
Q

what is purpose of flagella ?

A

Helps with transport and movement - contains a lot of mitochondria

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17
Q

what is purpose of cell wall ?

A

made of Murein - acts as a physical barrier to protect against physical damage

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18
Q

what is purpose of capsule ?

A

contains mucilaginous slime - prevents cell from drying out (NOT IN ALL PROKARYOTES )

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19
Q

what is purpose of cell surface membrane ?

A

controls entry and exit of material

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20
Q

what is purpose of circular DNA ?

A

posses genetic info required for replication of bacterial cells

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21
Q

what is purpose of plasmid ?

A

posses genes which may be helpful/useful for survival of bacterium .

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22
Q

bacterial cell in comparison to eukaryotic cell

A
  • no membrane bound organelles
  • no nucleus
    -smaller
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23
Q

what is purpose of ribosomes in bacteria cell

A

70S proteinsynthesis

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24
Q

what is purpose of cytoplasam ?

A

chemical reactions take place

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25
structure of a virus ?
- capsid - genetic material DNA or RNA - attachment proteins
26
Important info of viruses :
- non living = not independently replicate -not cellular - no organelles - non living = no metabolic reactions - smaller and simpler structure of bacterium
27
what is purpose of genetic material in virus ?
contains either DNA or RNA - to code proteins
28
what is purpose of capsid in virus ?
a protein coat which contains genetic material
29
what is purpose of attachement protein in virus ?
allows viruses to attach to receptors / host cells
30
rule for drawing cell sketches
- use 50 % of paper - sharp pencil -don't shade things in - label line in pencil used with ruler
31
magnification definition ?
measure of how many times a image has been enlarged
32
magnification equation
magnification = image size divided by real size
33
how to convert from cm to mm
x 10
34
convert from mm to um to nm
keep on x by 1000
35
what is eyepeice graticule used for ?
measure size of specimen
36
what to work out in eyepiece graticule
how many eyepiece divisions fit into it and divide by 0.1 by number of divisions to find length of 1 division .
37
where is eyepiece graticule ?
- fits onto eyepiece - transparent ruler with no numbers - see scale when you look through eyepiece
38
where is stage micrometre ?
- placed on stage - microscope slide that has accurate scale -work out value of divisions of graticule at different magnifications .
39
what is meant by resolution ?
the ability to clearly see divisions between organelles and cells .
40
what causes a low resolution ?
long wavelength means image more spread out = low resolution
41
what causes high resolution ?
short wavelength = image less spread out = high resolution
42
what is meant by cell fractionation ?
when cells are broken up and different organelles from those cells are spread out to be studied
43
what is a homogeniser ?
breaks up tissue and cells
44
what is a homogenate ?
all of organelles which we find in cell
45
why is cell fractionation has same conc of h2o as cell ?
prevents h2o entering cell from osmosis = not burst
46
why is cell fractionation buffered ?
to prevent pH changes to prevent damages to organelles and cells
47
Why can electromagnets be used in electron beams ( in SEM OR TEM ) but not optical microscope ?
Electrons are -tively charged so attract to electromagnet . so movement can be affected by electromagnet .
48
2 types of electron microscopes ?
- transmitting electron microscope - scanning electron microscope
49
what are general electron microscope advantages ?
- e- beam is very short wavelength so image is resolved at high resolving power . - e- negatively charged so beam can be controlled by electromagnet
50
why does near vacuum need to be present in e- microscope ?
Specimen needs to be non living as e- are observed or deflected by molecules in air
51
Why is it called transmission electron microscope ?
beam of e- pass physically through specimin
52
what is photomicrograph in TEM ?
image produced on screen of specimin
53
Why TEM produce flat 2D image ?
specimin needs to be really thin to sllow e- to pass through
54
what are limitations of TEM ?
- whole system in vacuum = non living - image is in black and white - specimen is really thin
55
Do specimine need to be thinner or thicker than TEM
Thicker as e- dont penetrate physically through specimine in SEM
56
what do SEM + TEM have in common ?
- both black and white images - have high resolution - both e- microscopes - both are in vacuums - non living - focuses beam using electromagnet
57
compare TEM AND SEM
SEM = 3D TEM =2D SEM = E- dont pass through TEM = e- do pass through SEM - not thin layer TEM = extremely thin layer
58
why in cell fractionation is the cell cold
to reduce enzyme activity
59
what do eukaryotic cells devise by ?
mitosis and meosis
60
what do prokaryotic cells devise by ? ( bacteria cells )
binary fission
61
do viruses go through cell division ?
no as non living
62
cell cycle stages ?
interphase , prophase metaphase , anaphase ,telophase , cytokinesis
63
what is interphase ?
genetic material converts to chromosomes and duplicates cell still carry's out all of its functions eg producing chemicals prepare for cell division breaks down centromere in chromosome - needs enough energy from ATP
64
Prophase ?
chromosomes condense - originally long thin threads which condense , thicken and shorten to chromosomes organelles ( centrioles ) move to opposite side of cell spindle fibre form from one centriole to another nucleolus and nuclear envelope break down - chromosome free in cytoplasm .
65
metaphase ?
chromosomes clearly shown to be made of 2 chromatids - joined together by centromere chromosome arrange to centre of cell
66
anaphase ?
centromeres divide in two and spindle fibres pull individual chromatids apart chromatids move to opposite part of cell an active process which needs energy from respiration ATP
67
Telophase ?
chromosomes become longer and thinner begin to decondense into chromatin spindle fibres disintegrate nucleolus and nuclear envelope reform,
68
cytokenisis ?
cytoplasm divides
69
importance of mitosis ?
+ growth - to have same genetic information to be identical to daughter cell # + repair - if cell is damaged - new cells form and should be identical to +originally broken cell . reproduction :single cell organisms divide by mitosis - produce 2 new daughter cells which are identical to parent organism .
70
process of binary fission for bacteria ?
cell contents double cell membrane grows between 2 dna molecules and divides cells into 2 cell divides into 2 genetically identical cells ( with different amount of plasmids in each )
71
process of division for virus
use attachment proteins to attach to receptor of host cell inject genetic material into host cell nucleic acid replicated in host cell genetic info help produce other components ( capsid and attachment proteins) virus is assembled and can be released ( when cell bursts )
72
why are check points important in mitosis
eg if in replication a gene is misinterpreted - checkpoints will stop the replication there . however if we continue to replicate it it could potentially be dangerous and damage our cells .
73
what is cancer and what causes it ?
genes which regulate mitosis and cell cycle are are damaged leading to uncontrolled growth and division of cells . caused by growth of disordered cells ,
74
what is tumour
a mass of cells which undergo uncontrollable mitosis
75
most common cancer ?
lungs , breast + ovaries , prostate , stomach , pancreas
76
when is tumour cancerous
when it turns from benign to malignant
77
what is more life threatening cancer - benign or malignant ?
malignant as can spread to rest of body
78
link between cancer and mitosis ?
most cell divide by mitosis rate of mitosis can be affected by environment of cell , growth factors , 2 types of genes .
79
chemotherapy ?
drug to cure cancer - disrupts cell cycle by preventing replication of DNA and inhibiting metaphase .
80
issue with chemotherapy ?
cell cycle of fast growing normal cells like hair cells are disrupted
81
what is function of cell membrane ?
controlls what enters and exits cell
82
where is cell membrane located ?
around organelles and cells
83
what are 5 molecules located in membrane ?
- glycoproteins - glycolipids - protiens _ phospholipids - cholesterol
84
phospholipids structure related to cell membrane
hydrophilic head hydrophobic tail 2 fatty acids , i glycerol and 1 phosphate group - water soluble molecules cannot exit membrane mebrane is self sealing
85
cholesterol properties in cell membrane
give membrane mechanical strength and stability fits between phospholipids so more close together + less fluid and more rigid as hydrophobic = create further barrier to polar substances
86
cholesterol functions :
- reduce lateral movement of other molecules - membrane = less fluid at high temp - prevents leakage of water and dissolved ions
87
protein properties in cell membrane
- give mechanical support - protein channels from hydrophilic channels on membrane allowing small charged particles e.g ions
88
what is peripheral proteins purpose in cell membrane :
- dont extend completly through membrane - mechanical support - make glycoproteind and glycolipids - cell recognition as receptors produced
89
what are integral proteins purpose :
- protein carriers / channels involved in transport across cell membrane - span across whole membrane
90
what molecules can pass through cell membrane :
- lipid soluble substances ( hormones ) - very small molecules ( h20 / co2 )
91
what molecules cannot pass through cell membrane :
- water soluble substances ( polar and sodium ions ) - large molecules like glucose
92
what are protein channels :
form tubes for water soluble ions to diffuse tubes are filled with water to allow water soluble ions to pass through membranes ( ONLY OPEN TO PRESENCE OF CERTAIN IONS )
93
what are carrier proteins ?
bind with large molecules( AA and glucose ) to change shape and transport inside cells cause change shape in protein to allow molecule to be released to other side of membrane
94
definition of diffusion :
net movement of particles from an area of high concentration to an area of low concentration until equilibrium is reached . A passive process = no energy needed from ATP
95
what causes movement of molecules by simple diffusion :
kinetic energy allows them to constantly move in fluids
96
to diffuse across membrane what should molecules be ?
lipid soluble small to be able to diffuse across
97
Facilitated diffusion ?
- passive process - membrane proteins help transport molecules - ions and polar molecules can be transported by F Diffusion by carrier proteins and carrier proteins
98
what is water potential ?
pressure exerted by water molecules as they collide with membrane or container
99
what water potential does pure water have ?
0kPa
100
how does a solute effect water potential
the more solute there is the more negative the water potential is
101
definition of osmosis
movement of water from a region of high water potential to an area of low water potential through partially permeable membrane
102
what is a hypertonic solution
positivecells are shrivelled solution has more negative water potential than cells so water moves out of cell
103
what is a isotonic solution
water potentisal is eqyuall outside and inside cell . normal cells no movement of water
104
what is a hypotonic solution of water
cells have a negstive water potential compared to solution so water moves from solution in cell if cell swells it may burst
105
in plant cells plasmolysis
in hypertonic solutions , water moves out of cell until cell surface membrane shrivels and water leaves plant cell by osmosis . protoplast causes cell wall to be more turgid , when water exits cell , protoplast shrinks away from cell .
106
what is the definition of active transport
movement of molecules and ions into or out of cells from a region of lower concentration to a region of hi9gher concentration using ATP and carrier proteins
107
is Active transport a passive or active process and why
a active process as it requires energy from ATP to change shape of a carrier protein in a cell
108
why is active trasnport a selective process
only allows specific molecules and ions through gradient
109
state process of active transport
1. molecule/ion to be transported and bind to receptor of carrier/channel proteins on outside of cell 2. on inside of cell ATP binds to carrier protein and hydrolysed into ADP and phosphate 3. binding of phosphate molecule to carrier protein causes protein causes protein to change shape - opening to inside of cell . 4. molecule or ion is released to inside of cell 5. phosphate molecule is released from the carrier protein and recombines with ADP to make ATP 6. carrier protein returns to original shape
110
what is co trasnport
coupled movement of substances across a cell membrane via a carrier protein
111
what is the lining of the cell surface membrane of epithelial cell called
mammalian ileum
112
process of co transport in sodium pump
co transport 1. na+ moves into blood by active transport from high conc of na in cell and low concentration of na in blood 2. conc gradient now produced 3. na+ by facilitated diffusion from lumen into epithelial cell via carrier protein .as well as carrying a glucose molecule All molecules move down conc gradient in blood by facilitated diffusion
113
what is a pathogen ?
a micro organism which can cause disease
114
what type of people are more vulnerable to illness and infection ?
- people who have a weak immune system - ppl who are on immunosuppressive - elderly ( the more older you are the weaker your immune system gets ) - babies
115
what are primary non - specific defences ?
the bodies first liner to defences ( first opportunity where pathogen comes in contact with body )
116
examples of primary non specific defences ?
- inflammation - goblet cells mucus cilia , oil on body - cuts expulsive reflexes
117
what are examples of expulsive reflexes
- cough and sneeze - vomiting - diarrhoea
118
what are 2 types of defence mechanisms ?
non specific - immediate response for all pathogens ( skin as physical barrier or phagocytosis ) specific - response slower and more specific to pathogen ( cell mediated response T lymphocytes or humoral response B lymphocytes .
119
how are self markers helpful ?
they help us identify which cells are our own and which cells aren't ( so prevents immunes system from destroying it )
120
what happens if body cell recognises self cell as foreign
it will destroy it and cause the cells to be destroyed
121
what are self markers made of and why ?
it made of protein in tertiary structure - as it can be very flexible
122
what can immune system detect as a result of self markers ?
- pathogens - HIV - non self materials ( eg cells from another human DONER ) - toxins ( from bacterium - abnormal body cells eg cancer
123
how does skin protectg against pathogens ?
- form scab ( prevent infection as physical barrier -produce sebum (oil ) inhibits growth of pathogens - secrete fatty acids which can kill pathogens and produce acidic environment
124
how does mucous membrane protect against pathogens ?
- trap pathogens - lysosomes destroy bacterial and fungal cell walls - line bodies openings and act as a barrier - contains phagocytes
125
how does blood clotting protect against pathogens ?
- when we cut skin , opportunity for pathogens to enter bloodstream . - blood clotting allow wound to close up - prevent blood from exiting body
126
how does inflammation protect against pathogens ?
helps remove pathogen from body - immune cells release chemical signals which leads to increase in blood flow to infected area and is treated WBC help isolate any pathogens
127
how does wound repair protect against pathogens ?
repairs skin - prevents pathogens from entering body via barrier -skin repairs - scab dries - side of cut drawn together collagen tissue repair and scab is released
128
how does expulsive reflexes protect against pathogens ?
secrete mucous - traps pathogens and remove from body ( by coughing /sneezing etc )
129
when are lymphocytes made ?
when you are a foetus in womb = less likely to experience non self cells . 1 million lymphocytes are made ( including ones for our own cells ) they then die
130
what causes symptoms of autoimmune diseases ?
lymphocytes affect self cells = produce symptoms of autoimmune diseases ?
131
2 types of WBC in immune response ?
phagocytes and lymphocytes
132
what is phagocytosis ?
the process where pathogens are destroyed and killed
132
process of phagocytosis ?
pathogen release chemical which attracts phagocyte towards it phagocyte has receptors which can detect where pathogen is phagocyte changes shape and engulfs pathogen lysosome fuse with phagosome and secretes it contents lysozyme contents released into phagosome destroys pathogen products are used and absorbed by phagocyte
133
define immunity
ability of organisms to resist infection
134
what is an antigen?
a foreign protein that stimulates an immune response
135
what are lymphocytes
a type of white blood cell with with a larger prominent nucleus .
136
examples of 2 lymphocytes you need to know ?
B and T lymphocytes
137
what do T lymphocytes have on their cell surface membrane ?
receptors
138
what do B lymphocytes have on their cell surface membrane ?
antibodies
139
what is the difference in response between phagocytes and lymphocytes ?
phagocytes = non specific lymphocytes = specific
140
where are b lymphocytes produced and matures
P = bone marrow M= bone marrow
141
where are t lymphocytes produceed and matured ?
p=bone marrow m= thymus
142
what is an APC ?
antigen presenting cell - phagocyte which has antigens of foreign pathogens on outer membrane - helps alert other phagocytes to destroy pathogens
143
what type of immunity do t lymphocytes involve
cell mediated immunity APC
144
what type of immunity do b lymphocytes invove
humoral immunity
145
how do T lymphocytes respond ?
- APC -receptors in helper t cells TH fit exactly on antigen - stimulates t cell to divide by mitosis to form any clones of identical cells - they then differentiate into : + phagocytes to undergo more phagocytosis + memory cells + mutate to b cells ( to produce antibodies ) + cytotoxic killer t cells
146
what do t helper cells do
stimulate response / activity of killer b cells
147
what do cytotoxic t cells do
release protein called perforin . produces whole in cell causes cell death .
148
what type of immunity are b cells involved in ?
humoral immunity ( antibodies soluble in blood )
149
How are b lymphocytes activated ?
b cells are covered with antibodies , binds to complementary antigen on an APC form antigen antibody complex antigens now endocytosed and presented on plasma membrane of b cell Helper t cells receptor's bind to antigens on b cell and stimulate b cells to divide by mitosis forms clones differentiate into plasma cells or memory cells
150
what is purpose of plasma cells ?
can secrete lots of antibodies to destroy antigens .
151
what is purpose of memory cells ?
circulate in blood and tissue fluid for longer period of time then plasma cells . long term immunity against infection . divide rapidly when encounter same antigen to make more memory and plasma cells .
152
what is the definition of an antibody ?
A quaternary structure protein stimulated by b cells which are complimentary to specific antigens .
153
how many chains are antibodies made from ?
4 chains 2 light chains 2 heavy chains
154
what holds the chains of an antibody together ?
the disulphide bridge
155
what is the purpose of the hinge region in an antibody?
gives flexibility to variable region to be able to grip more than one antigen
156
what is the purpose of variable region ?
a specific region which differs between antibodies , its complimentary to a specific antigen .
157
what is agglutination ?
the process of antibodies clumping other antigens so they can undergo phagocytosis quicker . - each variable region on an antibody can bind to 1 complimentary antigen each . - that can be 2 on the same pathogen or 2 on different pathogen - this allows phagocytes to phagocytose those specific antigens quicker .
158
what is a definition of monoclonal antibodies ?
an antibody produced from identical b cells
159
what 2 things can monoclonal antibodies help with >?
- targeting medication - medical diagnoses
160
what are the 2 types of monoclonal antibody therapy used for cancer ?
- direct monoclonal antibody therapy - indirect monoclonal antibody therapy
161
what is direct monoclonal antibody therapy ?
- treatment that enlists your body to fight immune system against disease like cancer . - have complimentary antibody to specific cancer antigen . - form antigen antibody complex which prevents uncontrolled division as other chemicals cannot bind to it to divide - as a result prevents self cells from being damaged .
162
An example of a monoclonal antibody which can fight against treatment ?
Herceptin
163
what is indirect monoclonal therapy ?
a radioactive / cytotoxic drug is attached to monoclonal antibody and kills cancer cells upon attachment
164
advantages of indirect monoclonal therapy ?
- use smaller doses - target specific cells - cheaper / less side effects
165
what can monoclonal antibodies medically diagnose ?
- pregnancy - covid - characteristics in blood
166
how does pregnancy testing work ?
-antigen put in sample on sample pad - mobile antibodies bind to antigen = antigen binds to immobile antibodies - releases dye - those which didn't bind will bind to second set of immobile antibodies and release dye
167
ethical considerations of monoclonal antibodies ? MICE
- harming animals - forced to produce tumour cells -harm / death + taken care of given enough space + watered
168
Taking monoclonal antibodies are a risk , why ?
+ saved many ;ives informed consent - patient knows the benifits and risk of monoclonal antibodies
169
what does the ELISA test stand for ?
Enzyme Linked Immune Sorbent Assay
170
state a brief summary of ELISA test
- use antiboidies to detect presence and quantity of a protein in sample
171
advantages of ELISA test
- detect HIV - can detect pathogens of a disease - can detect quantity e.g drugs
172
state process of antibodies
- apply sample to a surface - wash surface to remove any unattached antigens - add antibody that's specific to antigen ( both will bind ) - wash surface to remove excess antibodies - add second antibodies that bind with first (has enzyme attached) - a solution is added which contains a substrate - a coloured substrate is formed if enzyme reacts with substrate - if colour change occurs = antigen/antibody of interest is present intensity of colour represent how much antigen present .
173
definition of a vaccination ?
introducing small quantities of dead or inactive forms of a pathogen in body to stimulate an immune response
174
what is active immunity
when your immune system makes its own antibodies after being stimulated by an antigen
175
what is active natural immunity ?
after catching a disease
176
what is active artificial immunity ?
after being given a vaccination
177
what is passive immunity ?
when you are given antibodies made by a different organism ( your immune system makes none of it ) .
178
what is passive natural immunity ?
antibodies a babay receives through the placenta or from breast milk
179
what is passive artificial immunity ?
after being injected with antibodies from someone else eg tetanus and hepatitis A and B
180
which type of immunity requires exposure to antigens ?
active passive does not
181
which type of immunity has immediate protection ?
passive as it already gets the complementary antibodies - does not need to wait to form complimentary antigens
182
What type of immunity is short term ?
passive as the antibodies will gradually leave blood active store antibodies as memory cells for long term use
183
which type of immunity produces memory cells ?
active as it first produces its own antibodies which are complimentary by its own immune system .
184
what is a vaccination ?
introduction of appropriate disease antigens into body either by injection / mouth to stimulate immune response
185
what is herd vaccinations ?
herd immunity is when sufficiently large proportion of population has been vaccinated against to make it difficult for pathogen to spread within population
186
what are features of a successful vaccination programme ?
- - economically available in sufficient quantities to immunise most of vulnerable population . - few side effects means of producing , storing and transporting vaccine may be available - possible to vaccinate vast majority of vulnerable population to produce herd immunity - means of administering vaccine properly at right time
187
why may vaccine not eliminate disease ?
- individuals may develop disease immediately after vaccination before immune levels are high enough to prevent it - fail to induce immunity in certain individuals - eg people with defective immune system - - pathogen may mutate frequently - vaccine may become unrecognisable due to new antigens .
188
what type of infections do antibiotics work against ?
bacteria as viruses work in host cells
189
structure of HIV particle ?
- 2 viral RNA strands - proteins which include enzyme reverse transcriptase - a protein coat ( capsid ) enclosing RNA - viral lipid layer -(formed from cell membrane of host cell ) attachment proteins embedded in lipid layer
190
how does HIV replicate ?
- HIV binds to T helper cells - HIV capsid is released inside cell - viral RNA converted to DNA ( reverse transcriptase enzyme ) - viral DNA is integrated into host cell host makes viral proteins - viral proteins released - viral particles infect more t helper cells .
191
how does HIV cause symptoms of AIDS ?
HIV avoids being recognised and destroyed by lymphocytes by repeatedly changing protein coat . - HIV causes AIDS by killing or interfering with normal functioning of T helper cells ( cell mediated immunity / activation of b cells / cytotoxic t cells stimulation / memory cells ) body cannot stimulate immune responses this leads to death