6.3 Defence against infectious disease Flashcards
1
Q
What happens when the skin is cut?
A
The blood vessels in it are severed and start to bleed
2
Q
What process stops bleeding?
A
Clotting
* changes from a liquid to a semi-solid gel
* Seals up the wound and prevent further loss of blood and blood pressure
* Important because cuts breach the barrier to infection provided by the skin
* Clots prevent entry of pathogens until new tissue has grown to heal the cut
3
Q
Why do blood clots form?
A
To stop blood loss and stop entry of pathogens
4
Q
What release clotting factors in response to a wound?
A
Platelets (small cell fragments) along with damaged tissue
5
Q
What are platelets?
A
- cellular fragments that circulate in the blood
- They are smaller than either red or white blood cells
- When a cur or other injury invovling damage to blood vessels occurs, platelets aggregate at the site forming a temporary plug.
- They then release the clotting factors that trigger off the clotting process
6
Q
What does clotting factors cause?
A
A cascade of reaction, each of which produces a catalyst for the next reaction
Process ends with fibrin (a protein) fibres forming a mesh across the wound site
7
Q
Why must clotting be under strict control?
A
Because if it occurs inside blood vessels the resulting clots can cause blockages
8
Q
What does the cascade of reactions result in?
A
The rapid conversion of fibrinogen to fibrin by thrombin
9
Q
Is fibrinogen and fibrin soluble?
A
Fibrinogen is soluble
Fibrin is insoluble (its fibrous)
10
Q
What is thrombin and what does it do?
A
It is an enzyme that is produced after the release of clotting factors from platelets that converts fibrinogen (soluble) into fibrin fibres (insoluble) that will form a mesh across the wound site to capture the red blood cells and prevent blood loss and entry of pathogens. The resulting clot is initially a gel, but if exposed to the air it dries to form a hard scab
11
Q
How does atherosclerosis cause CHD (coronary heart disease)?
A
Atherosclerosis can lead to blood clots which cause coronary heart disease when they occur in coronary arteries
12
Q
What is a thrombus?
A
A medical name for a blood clot
13
Q
What is coronary thrombosis?
A
The formation of blood clots in the coronary arteries
14
Q
What are the consequences of coronary occlusion?
A
- If a coronary artery becomes completely blocked, an acute myocardial infarction (heart attack) will result
- This is because myocardial tissues require oxygen and nutrients transported via the coronary arteries in order to function
- If the coronary arteries become blocked by a blood clot, part of the heart is deprived of oxygen and nutrients
- Cardiac muscle cells are then unable to produce sufficient ATP by aerobic respiration and their contractions become irregular and uncoordinated
- Fibrillation
- This condition can prove fatal unless it resolves naturally or through medical intervention
15
Q
What is fibrillation?
A
When the wall of the heart makes quivering movements that do not pump blood effectively.
16
Q
What can atherosclerosis cause in coronary arteries?
A
Occlusion
17
Q
What happens to the endothelium of arteries when atheromas develop there?
A
Where atheroma develops the endothelium of the artarteries tends to become damaged and roughened; especially, the artery wall is hardened by deposition of calcium salts. Patches of atheroma sometimes rupture causing a lesion.
18
Q
What increase the risk of coronary thrombosis?
A
- Coronary occlusion
- Damage to the capillary epithelium
- Hardening of arteries
- Rupture of atheroma
19
Q
How are blockages of coronary arteries typically treated?
A
Can insert a closed stent into that artery then expand it with a balloon which widens the artery and compresses the plaque or by-pass surgery (redirecting the blood)
20
Q
What are the stages of CHD?
A
- Formation of atheroma
- Rupture of atheroma
- Platelets activates
- Thrombin
- Fibrinogen converted to fibrin
- Clot
21
Q
What are the risk factors of coronary heart disease?
A
- Age – Blood vessels become less flexible with advancing age
- Genetics – Having hypertension predispose individuals to developing CHD
- Obesity – Being overweight places an additional strain on the heart
- Diseases – Certain diseases increase the risk of CHD (e.g. diabetes)
- Diet – Diets rich in saturated fats, salts and alcohol increases the risk
- Exercise – Sedentary lifestyles increase the risk of developing CHD
- Sex – Males are at a greater risk due to lower oestrogen levels
- Smoking – Nicotine causes vasoconstriction, raising blood pressure
Mnemonic: A Goddess
22
Q
What are some well-known factors that are correlated with an increased risk of coronary thrombosis and heart attacks: (6)
A
- Smoking
- High blood cholesterol concentration
- High blood pressure
- Diabetes
- Obesity
- Lack of exercise
23
Q
What are Erythrocytes?
A
Red blood cells?
24
Q
What are Erythrocytes?
A
Red blood cells?
25
What are microbes that cause disease called?
Pathogens
26
What are the primary defence against infectious disease to the body?
The **first line of defence** against infectious disease are the *surface barriers* that prevent the entry of pathogens into the body
27
What are the surface barriers that prevent the entry of pathogens into the body? (3)
Skin, mucous membranes, sebaceous glands
28
What does the **skin** do in terms of defence against pathogens?
Outermost layer is **tough** and provides a** physical barrier** against the entry of pathogens and** protection against physical and chemical damage**
29
What does **sebaceous** glands do in terms of defence against pathogens?
Are associated with hair follicles and they secrete a chemical called **sebum**, which **maintains skin moisture** and slightly **lowers skin pH**. The lower pH inhibits the growth of bacteria and fungi.
30
Where can mucous membranes be found on the human body?
* Nasal passages and other airways
* The head of a penis
* Foreskin
* Vagina
31
What does mucous membranes do in terms of defence against pathogens?
They are thinner and softer type of skin
* The mucus that these areas of skin secrete is a **sticky solution of glycoproteins**. Mucus acts as a **physical barrier**; pahogens and harmful particles are **trapped** in it and either **swallowed** or **expelled**. It also have **antiseptic properties** because of the presence of the anti-bacterial enzyme **lysozyme**.
32
Overview of Physical and chemical surface barriers
33
What is clotting (haemostasis)?
the mechanisms by which broken blood vessels are required when damaged
34
What are some other primary defenses?
35
What is coagulation cascade?
A complex set of reactions collectively in the process by which blood clots are formed
36
What stimulates the coagulation cascade?
By clotting factors released fro damaged cells and platelets
37
What is the second line of defence against infectious disease?
White blood cells
The innate immune system, which is **_non-specific_** in its response
38
What are the components of the second line of defence?
Principle component: phagocytic white blood cells engulf pathogens by endocytosis and digest them with enzymes from lysosomes
Other components of the innate immune system: inflammation, fever and antimicrobial chemicals (complement proteins)
39
What results in the formation of a white liquid called pus?
When wounds become infected, large number of phagocytes are attracted, resulting in the formation of a white liquid called pus
40
What are the two key properties of the innate immune system?
* It does not differentiate between different types of pathogens (*non-specific*)
* It responds to an infection the same way every time (*non-adaptive*)
41
What is phagocytosis?
the process by which solid materials (such as pathogens) are ingested by a ell (i.e. cell ‘eating’ via endocytosis)
42
Where do phagocytic leukocytes circulate in and where do they go in response to infection?
they circulate in the blood and move into the body tissue (extravasation) in response to infection
43
How do damaged tissue draw white blood cells to the site of infection?
Damaged tissues release chemicals (e.g. histamine) which draw white blood cells to the site of infection (via chemotaxis)
44
How are pathogens engulfed and digested?
During phagocytosis by leukocytes, pathogens are engulfed when cellular extensions (pseudopodia) surround the pathogen and then fuse to form an internal vesicle
Then the vesicle is then fused to a lysosome (forming a phagolysosome) and the pathogen is digested
45
After pathogen is digested, fragments (antigen) may be present on the surface of the phagocyte in order to stimulate what?
The third line of defence
46
What is the third line of defence against infectious disease?
the adaptive immune system, which is _specific_ in its response
47
What is the main difference in the response of the second and third line of defence against infectious disease?
2nd line: not specific
3rd: specific
48
What can the third line of defence able to do that makes its response specific?
* It can differentiate between particular pathogens and target a response that is specific to a given pathogen
* It can respond rapidly upon re-exposure to a specific pathogen, preventing symptoms from developing (immunological memory)
49
What are lympohcytes?
They are a class of leukocyte.
The adaptive immune system is coordinated by lymphocytes and results in the production of antibodies
50
What are B cells and T cells?
B lymphocytes (B cells) are **antibody-producing cells** that recognise and **target a particular pathogen fragment** (antigen)
Helper T lymphocytes (T cells) are **regulator cells** that **release chemicals (cytokines) to activate specific B lymphocytes**
51
What happens after a phagocyte leukocyte engulfs a pathogen and the digested fragments are left on their surface?
* These antigen-presenting cells (dendritic cells) **migrate** to the lymph nodes and **activate specific T cells**
* The helper T cells then **release cytokines** to **activate** the **particular B cell** capable of **producing antibodies specific to the antigen**
* The **activated B cell will divide and differentiate** to form **short-lived** ***plasma cells*** that produce **high amounts of specific antibody**
* **Antibodies will target their specific antigen,** enhancing the capacity of the immune system to **recognise and destroy the pathogen**
* A **small proportion of activated B cell (and activated TH cell)** will develop into **memory cells** to provide **long-lasting immunity**
52
What part of a pathogen is recognized as foreign by the body?
The proteins and other molecules on the surface of pathogens
53
What are antigens?
An antigen is a substance that the body recognises as foreign and that will stimulate a specific immune response
* Any chemical that stimulates an immune respoinse is referred to as an antigen.
54
What is specific immune response?
The production of antibodies in response to a particular pathogen
55
What are antibodies? What are they made of?
An antibody is a protein produced by B lymphocytes (and plasma cells) that is specific to a given antigen and binds to an antigen on that pathogen
* made of 4 polypeptide chains that are joined together by disulphide bonds to form Y-shaped molecules
56
Even though each lymphocyte produces just one type of antibody, how do our bodes produce a vast array of different antibodies?
We have small numbers of lymphocytes for producing each of the many types of antibody. -> too few initially to produce enough antibodies to control a pathogen that has no previously infected the body
But antigens on the pathogen stimulate **cell division** of the small group of lympohocytes that produce the appropriate type of antibody. So then a **large** clone of lymphocytes called **plasma cells** are produced within a few days and they **secrete large enough quantities of the antibody** to control the pathogen and **clear the infection**
57
What does the two functional regions of antibodies do?
A hypervariable region that binds to a specific antigen and another region that helps the body to fight the pathogen
58
What are two ways antibodies help fight the pathogen?
* Makring a pathogen more recognizable to phagocytes so they are more readily engulfed
* Preventing a virus from docking to host cells so that they cannot enter the cells
59
What happens to antibodies after the infection is over?
* Antibodies only persist in the body for a few weeks or months and the plasma cells that produced them are also gradually lost, antigens associated with it are no longer present.
* Some of the lumphocytes produced during an infection are not active plasma cells but instead become memory cells that are very long lived
* These memory cells remain inactive unless the same pathogen infects the body again, in which case they become active and divide to produce plasma cells very rapidly
60
What does having immunity mean?
To either have antibodies against the pathogens or memory cells that allow rapid production of the antibody
61
What does it mean that antigen-antibody interactions are specific?
that each type of antibody recognises a unique antigen (like enzymes and substrates)
62
What are the 3 lines of defence?
1st: Surface barriers
2nd: innate immune system (non specific)
3rd: adaptive immune system (specific)
63
What are antibotics?
compounds that kill or inhibit the growth of microbes (specifically bacteria) by targeting prokaryotic metabolism
64
What are some metabolic features that may be targetted by antibiotics?
key enzymes, 70S ribosomes and components of the cell wall
65
Why do antibiotics target the pathogenic bacteria and not the infected host?
Because the metabolic features that may be targeted by antibiotics arent present in eukaryotic cells (e.g. 70s ribosome, cell wall etc)
66
What do antibiotics do and what are they?
* Block processes that occur in prokaryotic cells but not in eukaryotic cells
* Therefore used to kill bacteria inside the body without causing harm to human cells.
* A chemical that inhibits the growth of microorganisms.
* Most antibiotics are antibacterial.
67
What processes does antibiotic target in prokaryotes? (5)
* Bacterial DNA replication
* Transcription
* Translation
* Ribosome function
* Cell wall formation
68
What is a virus?
* Non living
* only reporoduce when they are inside living cells
* Use chmical processes of a living host cell instead of having a metabolism of their own
* Do not have their own means of transcription or protein synthesis
* Rely on host cell's enzymes for ATP synthesis and other metabolic pathways
* These processes cannot be targeted by drugs as the host cell would also be damaged
69
Why cant viral disease be treated using antibiotics?
They lack a metabolism so they control the host cell completely. These processes that it uses cannot be targetted by drugs as the host cell would also be damaged
70
What do virus do compared to pathogenic bacteria? What cant they be treated with antibiotics?
They do not possess a metabolism (they are not alive) and instead take over the cellular machinery of infected host cells
→ cant be treated with antibiotics and must be treated with specific antiviral agents
71
What if a doctor prescribe antibiotics to viral infections?
* It is inappropriate for doctors to prescribe them for a viral infection
* Contributes to the overuse of antibiotics
* Increases in antibiotic resistance in bacteria
72
What are antivirals?
Drugs that can control viruses by having drugs target their viral enzymes
73
What do antiviral agents target?
There are a few **viral enzymes** which can be used as targets for drugs to control vircuses without harming the host cell.
Only a few dugs have been discovered or developed to control viruses in this way. These are known as antivirals rather than antibiotics
74
What two spectrum can antibiotics be?
Narrow spectrum: effective against specific bacteria
Broad spectrum: effective against many bacteria
75
How may genes confer resistance?
By encoding traits that degrade the antibiotic, block its entry, increase its removal or alter the target
76
What is the consequence of bacteria being able to reproduce at a rapid rate?
resistant strains of bacteria can proliferate very quickly following the initial mutation
77
How may resistant strains be passed?
Resistance to the antibiotic spreads to more and more species of pathogenic bacteria
resistant strains can pass resistance genes to susceptible strains via bacterial conjugation (horizontal gene transfer)
78
What causes the rapid evolution of antibiotic resistance?
* Widespread use of antibiotics, both for treating diseases and in animals feeds used on farms
* Bacteria can reproduce very rapidly, with a generation time of less than an hour
* Populations of abcteria are often huge, increasing he chance of a gene for antibiotic resistance being formed by mutation
* Bacteria can pass genes on to other bacteria in several ways, including using plasmids, which allow one species of bacteria to gain antibiotic resistance genes from another species
79
How is the prevalence of resistant bacterial strains increasing rapidly with human populations?
What are 3 factors?
* Antibiotics are often over-prescribed (particularly broad-spectrum drugs) or misused (e.g. given to treat a viral infection)
* Many antibiotics are freely available without a prescription and certain antibiotics are commonly included in livestock feed
* Multi-drug resistant bacteria are especially common in hospitals (i.e. nosocomial infections) where antibiotic use is high
80
What are the measures required to avoid antibiotic resistance?
* Doctors prescribing antibiotics only for serious bacterial infections
* Patients completing courses of antibiotics to eliminate infections completely
* Hospital staff maintaining high standards of hygiene to prevent cross-infection
* Farmers not using antibiotics in animal feeds to stimulate groth
Pharmaceutical companies developing new types of antibiotics - no new types have been introduced since the 1980s
81
Until when are strains of bacteria with resistance a huge concern?
Strains of bacteria with resistance are usually discovered soon after the introduction of an antibiotic. This is not a huge concern unless a strain develops multiple resistance.
82
What was the first chemical compound found to have antibiotic properties?
Penicillin - identified by Alexander Fleming in 1928
83
Where were many antibacterial antibiotics found in? What is one of the examples?
* Discovered in saprotrophic fungi
* These fungi compete with saprotrophic bacteria for dead organic matter on which they both feed
* By secreting antibacterial antibiotics, saprotrophic fungi inhibit the growth of their bacterial competitors
An example is penicillin
* Produced by some strains of the Penicillium fungus, but only when nutrients are scarce and compeition with bacteria would be harmful
84
How was the discovery of penicillin a fortuitous accident?
it resulted from the unintended contamination of a dish containing *S. aureus*
* A *Penicillium* mould began to grow on the plate and a halo of inhibited bacterial growth was observed around the mould
* Alexander Fleming concluded that the mould was releasing a substance (penicillin) that was killing the nearby bacteria
85
What method did Florey and Chain's team develop on penicillin?
* Developed a method of growing the fungus Penicillium in liquid culture in conditions that stimulated it to secrete penicillin
* They also developed methods for produing reasonably pure samples of penicillin from the cultures
86
How were the medical applications demonstrated by an Australian scientist, Sir Howard Florey, in 1940?
* Working with another scientist (Ernst Chain) and a team of researchers, Florey tested penicillin on 8 deliberately infected mice
* Eight mice were injected with streptococci bacteria that cause death from pneumonia and four of these mice were subsequently injected with doses of penicillin
* The untreated mice died of bacterial infection while those treated with penicillin all survived – demonstrating its antibiotic potential
* Tested on a 43 year old policeman
* Has a life-threatening bacterial infection caused by a scratch on his face
* Given penecillin for 4 days and his condition improved considerably
* Penecillin supply ran out and suffered a relapse and died from the infection
* Larger quantities were produced
* 5 more patients
* All cured but one died
* Small child had infection behind the eye and it weakened the wall of the artery carrying blood to the brain
* Alothought cured from infection, the child died of brain hemorrhage when the artery burst
87
Why would Florey and Chain not be allowed to carry out the tests on penicillin today?
* Strict protocals in minimize risks
* They tested the drug on human patients after only a very brief period of animal testing
* Samples of penicillin were not pure and there could have been side effects from the impurities
* But the patients were all on the point of death and several were cured as a result of the experimental treatment
88
What is HIV and what does it infect?
The **H**uman **I**mmunodeficiency **V**irus (HIV) is a retrovirus that infects helper T cells, disabling the body’s adaptive immune system
* A retrovirus that has genes made of RNA and uses reverse transcriptase to make DNA copies of its genes once it enters a host cell
89
What is a syndrome?
A collection of several diseases or conditions existing together
90
What is AIDS? How does it spread?
Acquitred immune deficiency syndrome (AIDS)
* When the syndrome of conditions due to HIV is present, the person is said to have acquired immune deficiency syndrome (AIDS)
It spreads by HIV infection. Normally only occurs if there is blood to blood contact with an infected person
91
What are the effects of HIV?
* HIV specifically targets the helper T lymphocytes which regulate the adaptive immune system
* The consequence is a progressive loss of the capacity to produce antibodies.
* With a reduction in the number of helper T cells, antibodies are unable to be produced, resulting in a lowered immunity
* Eventually antibody production becomes so ineffective that a group of opportunistic infections strike
* The body becomes susceptible to opportunistic infections, eventually resulting in death if the condition is not managed
92
How can the rate at which helper T-cells are destroyed by HIV be slowed down?
Using anti-retroviral drugs
93
What is meant when a person is said to be HIV-positve?
If antibodies made by the immune systen in the early stages of infection against HIV is detected in a person's body.
94
How can HIV be transmitted? (4)
* exchange of body fluids (including unprotected sex, blood transfusions, breastfeeding, etc.)
* Sexual intercourse, during which abrasions to the mucous membranes of the penis and vagina can cause minor bleeding (i.e. use condoms)
* Transfusion of infected blood, or blood products such as Factor VIII
* Sharing of hypodermic needles by intravenous drug users
95
How may people be immune to HIV infection?
* A small minority of people are immune to HIV infection (they lack the CD4+ receptor on TH cells that HIV requires for docking)
CD4 is **a receptor for HIV**
96
How transnational is HIV and where is it particularly prevalent?
* HIV is a global issue, but is particularly prevalent in poorer nations with poor education and health systems
97
What is a pathogen? What are the 2 category they can be in?
A **pathogen** is a disease causing agent that disrupts the normal physiology of the infected organism
Pathogens can be **cellular** (e.g. parasites, protozoa, bacteria) or **acellular** (viruses and prions)
98
Where can mucous membranes be found on the human body?
* Nasal passages and other airways
* The head of a penis
* Foreskin
* Vagina
