Viruses and Immune Response Flashcards
(85 cards)
1
Q
what are capsids? what is the structure of a capsid and a unit of nucleic acid called?
A
- protein shell where genetic material of a virus is stored
* a nucleocapsid
2
Q
what are the 3 general shapes of capsids?
A
- helical
- icosahedral
- complex
3
Q
what is the a virion?
A
form a virus takes outside of a cell
4
Q
when virions have an outer lipid membrane, how is this formed?
A
made up of host cell’s plasma membrane, into which virus proteins / glycoproteins are inserted
5
Q
what are the 4 mains routes of viral entry? give examples of each
A
- inhaled droplets - rhinovirus, influenza virus, SARS-CoV-2
- in food / water - hep A virus, norovirus
- direct transfer from other infected hosts ie. body fluids - HIV, hep. B virus, Ebola virus
- bites of vector arthropods - yellow fever virus, Zika virus
6
Q
what are the 3 categories of single-stranded RNA viruses?
A
- +ve sense - like mRNA, directly translated
- -ve sense - complementary to mRNA, converted to +ve using RNA polymerase, then translated
- retrovirus - RNA reverse transcribed to DNA
7
Q
how do viruses replicate?
A
assembly of individual components (not binary fission)
8
Q
what is viral tropism? (3)
A
the ability of a give versus to productively infect a:
• particular cell (cellular tropism)
• particular tissue (tissue tropism)
• a particular host species (host tropism)
9
Q
how is host range of a virus determined?
A
host attachment sites (cellular) and cellular factors (internal environment)
10
Q
give examples of the 4 mains virus types: DNA (6), RNA ss+ (10), RNA ss- (4), RNA ds (1)
A
- DNA : adenovirus, Epstein-Barr virus, herpes simplex 1 + 2, hep. B virus
- RNA ss+: poliovirus, rhinovirus, norovirus, hep. A virus, hep. E virus, dengue virus, yellow fever virus, zika virus, SARS-CoV-2, rubella virus
- RNA ss-: mumps virus, measles virus, influenza virus, Ebola virus
- RNA ds: rotavirus
11
Q
describe the pathology of respiratory viruses eg. coronaviruses, rhinovirus (4)
A
- common cold
- bronchiolitis - progression to coughing, wheezing, breathing difficulties
- croup - harsh brassy, barking cough
- viral pneumonia
12
Q
what are the 3 types of influenza viruses? which cause significant human illness?
A
- A, B and C
* A and B
13
Q
what are symptoms associated with flu (7)
A
fever, chills, headache, muscle pain, fatigue, dry cough, sore throat
14
Q
what are the 2 important surface proteins on influenza A?
A
haemagglutinin and neuraminidase
15
Q
what are the two types of human herpes virus? what are their features?
A
- herpes simplex - cold sores triggered by UV light, stress etc. (persistent due to latent phase)
- Varicella zoster - chicken pox, re-emerges as shingles
16
Q
what is a distinguishing feature of mumps? what complications can it have?
A
- swelling of parotid glands (jaw)
* viral meningitis, infertility
17
Q
what are the common symptoms of measles (4)? what can be a serious complication?
A
- acute rash, cough, fever, conjunctivitis (widespread rash remains while other symptoms decline)
- encephalitis
18
Q
what serious consequences can the rubella virus have?
A
preventable congenital defects (also miscarriage and stillbirth)
19
Q
what can be a serious complication of Zika virus infection during pregnancy?
A
microcephaly
20
Q
what are the 2 ways that viruses enter host cells?
A
- attach to specific receptors to produce a conformational change in capsid proteins / lipid envelope allowing fusion of viral and cellular membranes
- conventional endocytosis (some DNA viruses)
21
Q
how is viral nucleic acid exposed once inside the cell?
A
capsid is shed by viral or host enzymes
22
Q
what is an ‘eclipse phase’
A
period of time where the virus has entered the cell but is not infective because new viral particles have not been assembled
23
Q
describe how mRNA is produced from different virus types: 1. DNA (not reterovirus), 2. RNA ss+, 3. RNA ss-, 4. RNA ds
A
1 - cell’s own RNA polymerase used to transcribe viral DNA
2 - viral RNA acts as mRNA
3 - viral RNA polymerase transcribes -ve strand into +ve strand mRNA
4 - -ve sense strand is transcribed by viral polymerase into mRNA
24
Q
why is a host cell mRNA displaced from ribosomes during viral infection?
A
so viral proteins are synthesised preferentially
25
how does a virus replicate? (3)
1 - viral polymerase is either translated from viral genome or is already present from entry
2 - template strand is synthesised from which new strands of viral DNA / RNA are synthesised
3 - capsomeres (individual unit of capsid) associate with new genetic material to form the nucleocapsid
26
how does a nucleocapsid modify the host cell membrane before budding off?
inserts own envelope proteins and glycoproteins into plasma membrane (localised in part where virus will bud off)
27
describe the lytic pathway (2)
1 - virus goes through replication to produce many more particles
2 - causes host cell lysis and destruction to release particles and infect more cells
28
describe the latent pathway
1 - virus undergoes replication but remains in quiescent state
2 - genetic material either incorporated into host DNA or remains in cytoplasm
3 - a trigger will release the virus from latency
4 - virus will replicate again and release new formed particles
29
what types of mutations are highly common in viruses?
deletion and insertion
30
why are some mutations more common in RNA viruses?
lack ‘proof reading’ mechanisms
31
what is antigenic drift? why is this useful? (3)
* small antigenic changes
* creates new strain of virus (same sub-type)
* reduces the effectiveness of T/B cell immunity
32
what is antigenic shift? (2)
* exchange of genetic material from different origins - gene reassortment (large genetic change)
* results in formation of a new subtype which can result in pandemics (eg. Spanish Flu)
33
why can influenza rapidly generate new strains?
segmented genome (allows genetic reassortment like a human genome where genes are swapped between different chromosomes)
34
what is the structure of HIV? (3)
* single stand RNA retrovirus
* enveloped with gp120 glycoprotein antigen
* high rate of mutation due to many virions that are released at the height of infection and with the low fidelity of reverse transcriptase (does not correct coding mistakes)
35
which cells does HIV usually infect?
cells with CD4 on cell surface: T helper cells, monocytes, dendritic cells
36
where does HIV multiply in the body?
mucosa and draining lymphatic tissues
37
how does HIV enter the cell?
* CD4 has a high affinity binding site for the gp120 glycoprotein
* association causes conformational change that produces a fusion pore for viral entry
38
describe the process of replication for HIV (6)
1 - virus is uncoated by viral protease
2 - DNA copy of RNA synthesised by reverse transcriptase enzyme
3 - viral DNA incorporated into cellular DNA using integrate enzyme (viral DNA now called provirus)
4 - T is activated in response to HIV antigens or another infection, provirus may also be activated -> production of new RNA and proteins
5 - new virions bud off and infect other cells
6 - DNA remains dormant for years in viral reservoirs
39
describe the initial immune response to HIV infection in terms of CD4+ cells (6)
1 - CD4 cells in musical surfaces at sites of entry and in lymphoid tissues are infected
2 - may be considerable destruction of T cells
3 - activation of T cells causes infection to spread
4 - infected and unaffected CD4 T cells destroyed
5 - macrophages attempt phagocytosis, but lose ability to kill / become APCs - also infected
6 - dendritic cells also infected, and may be responsible for spread to lymphoid tissue
40
how do virus specific CD8 T cells try to limit acute HIV syndrome? (2)
* try to reduce viral load (viraemia) by producing interferon-gamma and tumour necrosis factor-alpha (cytokines)
* inhibit HIV replication and block entry to CD4 cells
41
what are the features of HIV antibodies in early infection? (2)
* produced in low level
| * non-neutralising
42
why does HIV become resistant to CD8 T cell actions? (2)
* latency means virus is undetected by immune system
| * high mutation rate, therefore genes that allow HIV to become resistance to CD8 T cells are selected for
43
describe how the humoral response develops as HIV infection becomes chronic (3)
* more neutralising antibodies produced which target entry to cell
* target variable region of gp120, CD4 binding sites, chemokine receptors and transmembrane protein gp41
* antibodies allow some people to control virus - remain symptom free, and maintain high CD4 count
44
what are the features of acute HIV syndrome? (3)
* may experience mild acute illness
* fever, malaise (general unwell feeling)
* initial viraemia (subsides in a few days)
45
describe the clinical features associated with HIV’s progression to a latency phase (3)
* progressive loss of CD4+ T cells in lymphoid tissue + destruction of tissue structure
* circulating CD4+ T cell count declines to under 200 cells / mm3 - classed as having AIDS (normal = 1500)
* patients become more susceptible to opportunistic infections
46
describe the basic clinical features of patients who have progressed to AIDS (2)
* increased infections by microbes usually combated with T-cell immunity (opportunistic infection)
* can also trigger activation of other latent viruses
47
give examples of opportunistic infections that often present in AIDS patients (3)
* Pneumocystis jiroveci - fungal infection, causes pneumocystis pneumonia
* Candidiasis - caused by group of fungi (Candida) in various parts of the body
* toxoplasmosis - parasitic disease caught from infected meat or cat faeces
48
give examples of latent viruses that can be reactivated in AIDS patients (2)
* Epstein-Barr virus - causes mononucleosis (glandular fever), then latency, can cause hairy leukoplakia (oral lesions) and lymphoma in AIDS patients
* TB - caused by mycobacterium tuberculosis (leading cause of death in AID patients)
49
give an example of a malignancy that AIDS patients are more susceptible to
Kaposi’s sarcoma - caused by human herpes virus 8 (HHV-8), presents with pigmented brown lesions
50
give examples of antiretrovirals and how they work (6)
* nucleoside reverse transcriptase inhibitors (NRTIs) - block enzyme required for reverse transcription
* non-nucleoside reverse transcriptase inhibitors (NNRTIs) - block same enzyme in different location (same effect)
* protease inhibitors - block the proteolytic cleavage of viral protein precursors, no new virions can be synthesised
* post-attachment inhibitors - bind to CD4 to prevent HIV from binding to co-receptors after attaching to CD4, so protein cannot enter cell (POST-attachment)
* CCR5 - block CCR5 co-receptor
* integrase strand transfer inhibitors (INSTIs) - blocks integrase which incorporates viral DNA into host DNA
51
what does the U=U aim to spread awareness about? (3)
* undetectable = untransmittable
* it has been proven that people with undetectable viral load cannot pass the disease on even during unprotected sex, and are prevented from developing AIDS
* aims to tackle the stigma associated with having the disease
52
what is PrEP? (2)
* pre-exposure prophylaxis
* medication (antiretrovirals) are taken before being exposed to the virus to prevent the spread - do not need to be taken consistently
53
what is the difference between sterilising and non-sterilising immunity?
* sterilising immunity clears the pathogen completely from the body, allowing recovery
* non-sterilising immunity produces a good immune response, but it is not enough to clear the infection -> leads to chronic infection
54
what are 2 examples of non-sterilising immunity? what is an example of an infection which produces an atypical immune response, but can produce sterilising immunity?
* non-sterilising: HIV and Tuberculosis
| * atypical: Dengue
55
what bacteria causes TB? what are its cellular characteristics?
* Mycobacterium tuberculosis
| * appears G+ or G-, bacillus, forms clusters
56
what property of the bacteria may contribute to TB being hard to diagnose?
• very slow replication rate (18-24 hours)
57
why does TB particularly affect the lungs?
• thrives in high partial pressures of oxygen - usually more prevalent in the superior parts of the lung
58
what type of necrosis does TB cause in the lungs?
• caseous - cheese-like, yellow and crumbly
59
what is a granuloma? (2)
* an aggregation of macrophages, epithelioid cells, T+B cells and fibroblasts
* occurs when immune system attempts to isolate a foreign substance but fails to eliminate it
60
what are epithelioid cells? (2)
* activated form of macrophages
| * aggregate forming multinucleated giant cells
61
what is the basic pathogenesis of TB? (4)
* after entrance of M.tb, 90-95% remain asymptomatic - enters latent phase
* 10% develop active TB
* reactivated eg. HIV infection, smoking, old age
* progression to cavitary TB -> becomes infectious and is spread through coughing
62
what is the initial immune response to TB infection? (3)
* T-cell mediation, macrophages act as controlling cell
* production of interferon gamma
* attempted phagocytosis, but M.tb will survive in cells
63
why can M.tb survive in phagocytes? (3)
* bacterium will coat the phagosome with coronin (actin associated)
* resists post-endocytosis trafficking to lysosome and so is not destroyed
* also resists lysosomal action by pumping protons out of the vesicles to inhibit digestive enzymes
64
what is an example of a genetic risk factor for severe TB infection?
lack interferon gamma receptor, so disease can spread to affect multiple organs
65
what test and vaccine is used to detect / screen for high risk individuals (TB)?
* BCG vaccine (Bacillus Calmette-Guérin) - weakened TB strain
* Mantoux test - Tuberculin (TB proteins) are injected, if high risk (or actively infected), then a hypersensitive reaction will occur causing local inflammation -> diameter of inflammation is measured
66
describe the T-spot test (3)
* interferon gamma release assay
* counts the number of leukocytes that release interferon gamma in a blood sample
* can be used to detect latent TB infection
67
how does dengue spread?
Aedes aegypti - mosquito bites (viral vector)
68
what proportion of people infected with dengue go on to have symptoms?
15% experience mild symptoms, 5% develop severe disease (80% asymptomatic)
70
what cells does dengue infect in the human body? what is a clinical consequence of this?
* white blood cells
| * increased cytokine and interferon release which may be the cause of some symptoms (fever and pain)
71
why is a second dengue infection associated with increased risk of dengue haemorrhagic fever? (3)
* 4 types of dengue strains
* recovery from one strain gives lifelong immunity to that strain
* a second infection from a different strain increases risk of severe disease because antibodies from the first strain actually increase uptake of the virus of the second strain
72
what is the difference between primary and secondary imunodeficiency?
* primary is congenital - results from genetic defects which are inherited from parents
* secondary is acquired as a result of other diseases (eg. HIV, malnutrition, immunosuppression)
73
what is a genetic characteristic of most primary immunodeficiencies?
recessive inheritance
74
what clinical features develop from primary immunodeficiencies? (5)
* recurrent infection in young
* allergy
* autoimmunity
* abnormal lymphocyte proliferation (eg. lymphomas, leukaemias)
* other cancers
75
what is a common consequence of B cell / innate immune deficiency?
pyrogenic (fever-causing) bacterial infections
76
what are 2 common consequences of T cell deficiencies?
* viral and other intracellular microbial infections (unusually severe)
* virus-associated malignancies (eg. EBV-associated lymphomas)
77
what is an example of a severe combined immunodeficiency? what are its features (3)
X-linked SCID (severe combined immunodeficiency disease)
• “bubble boy” - David Vetter
• mutations in cytokine receptors - cytokines cannot bind
• T and NK cells fail, B cells normal but cannot produce efficient antibody responses
78
what is an example of a less severe combined immunodeficiency? what are its features? (3)
Hyper IgM Syndrome
• high IgM (antibody that is produced first), but low of other antibodies (IgM not converted to other forms)
• more susceptible to infection
• fault on T cells -> impaired T/B cell interactions
79
what is an example of a combined immunodeficiency with syndrome features? what are its features? (3)
FoxN1 deficiency
• athymic (no T cells)
• alopecia - syndrome feature
-> caused by lack of hair/thymic epithelium development
80
what are the consequences of faulty antibody function (caused by antibody / humoral deficiencies)? (4)
* recurrent sepsis
* bacterial infections (often airways)
* chronic gastroenteritis
* failure to thrive
81
what type of immunodeficiency is Bruton’s agammaglobinaemia? what are its features? (3)
• humoral defect (antibody deficiency)
* mutation in tyrosine kinase gene
* prevents B cell development
* results in low antibody levels
82
what type of immunodeficiency is IgA deficiency? what are its features (2)
• humoral (antibody deficiency)
* IgA plasma cells do not develop
* often asymptomatic (children sometimes outgrow the deficiency)
83
what type of immunodeficiency is Chronic Granulamtous Disease (CGD)? what are its features? (2)
• congenital defect of phagocytes
* no superoxide burst (used by macrophages to kill bacteria)
* multiple granulomas form, ineffective elimination of bacteria
84
what type of immunodeficiency is chronic mucocutaneous candidiasis an example of?
• defects in innate immunity (multiple causes)
85
what type of immunodeficiency is Familial Mediterranean Fever an example of? what are its features? (2)
• autoinflammatory disorders
* defect in inflammasome regulators
* release too much IL-1 (inflammation attacks)
86
what are the 3 phases of dengue infection? include typical symptoms for each
* febrile: fever, pain, headache and rash
* critical - some progress to critical phase as fever resolves: plasma leakage leading to fluid accumulation and decreased blood supply (can cause shock and haemorrhage)
* recovery phase - fluid reabsorption: may have decreased heart rate and severe itching
