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Immune response to infection Flashcards

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1
Q

What are the 4 different types of resolution of infections?

A
  1. Acute viral infection and clearance e.g. flu
  2. Acute viral infection/clearance and re-infection e.g. RSV
  3. Acute viral infection + chronic infection e.g. HIV
  4. Slow chronic infection e.g. CMV
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2
Q

What is immunological memory to RSV like?

A

It wanes over time so you can get re-infected by the same pathogen

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3
Q

What is immunological resolution to HIV like?

A

There is an acute phase and then the virus is suppressed by the body but it isn’t totally cleared and the viral load then slowly builds up over time

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4
Q

What is immunological resolution to CMV like?

A

There is no acute phase- there is a gradual build up of the amount of virus in the body over time

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5
Q

What are the two main variables that determine how well a virus will spread?

A

Basic reproduction number- how many people does one virus infect
Proportion of infections that occur prior to symptoms

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6
Q

What happens if symptoms are present before being infectious?

A

You can quarantine the subjects

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7
Q

What is an example of a disease where patients are infectious without being ill?

A

HIV

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8
Q

What causes variability in susceptibility/host response to infection?

A

General health and nutritional status
Previous exposure (immunological memory)
Immune deficiencies e.g. SCID, HIV, immunosuppressive drugs
Polymorphisms in innate immune genes
Polymorphisms in adaptive immune genes, particularly HLA

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9
Q

What are the 4 main routes of infection?

A

Airborne
Intestinal
Sexually transmitted
Vector borne

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10
Q

What are the main types of respiratory infection?

A

Virus- Influenza, RSV and RV
Bacterial- M.Tuberculosis, H.influenzae and S. pneumonia
Fungal- Cryptococcus and Aspergillus

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11
Q

What are the main types of faecal oral infection?

A

Virus- Hep A
Bacteria- V.Cholerae, Shigella, E. coli and S. type
Parasite- Ascaris

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12
Q

What are the main type of sexually transmitted infection?

A

Virus- HIV and HPV
Bacteria- T. palladium and N. gonorrhoeae
Fungal- Candida albicans (thrush)

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13
Q

What are the main types of vector infection?

A

Virus- Rabies virus

Parasites- Plasmodium, schistosome and trypanosoma

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14
Q

What are viruses?

A

Obligate intracellular parasites- extremely small

They have a wide variety of life cycles/genetic material and rapid mutation rate

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15
Q

What is the most abundant life form on earth?

A

Viruses

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16
Q

What are bacteria?

A

Unicellular prokaryotes

Can be intracellular or extracellular

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17
Q

How are bacteria classified?

A

They can be Gram-positive or Gram-negative based on cell membrane/cell wall composition

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18
Q

What are fungi?

A

Multicellular eukaryotes. Can be intracellular or extracellular. They often cause opportunistic infections in immunosuppressed individuals

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19
Q

What are parasites?

A

Eukaryotes
Includes:
Protozoa- unicellular
Helminths- multicellular

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20
Q

What are the most common types of infection?

A

Respiratory

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21
Q

What mechanisms for preventing infection at mucosal surfaces?

A

Mechanical- epithelial tight junctions and longitudinal flow of air or liquid

Chemical- Fatty acids, enzymes (lysozyme, pepsin)
Low pH
Antibacterial peptides
Mucus

Microbiological-
Normal flora compete for nutrients/attachment sites.
Production of antibacterial substances

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22
Q

What is mucus produced by?

A

Goblet cells

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23
Q

What does mucus do?

A

It contains mucin glycoproteins and it traps dust and pathogens which are swept upwards

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24
Q

What are proteolytic enzymes produced by?

A

Produced in the stomach (pepsin) and small bowel (trypsin, chymotrypsin and pancreatic proteases)

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25
What do proteolytic enzymes do?
Breakdown large polypeptides into dipeptides and tripeptides. - small peptides are poor immunogens. Enzymes are cytotoxic to pathogens
26
What antimicrobial molecules are there?
Lactoferrin- binds iron and inhibits bacterial growth Lysozyme- cleaves cell wall of Gram-positive bacteria Defensives- 30-40 amino acid peptides that disrupts the cell membranes of bacteria and fungi causing lysis
27
What do commensal organisms do?
They compete with pathogenic bacteria for space and nutrients. They prevent colonisation of the gut by pathogenic bacteria. Commensals are also important in respiratory and genitourinary tracts
28
How do antibiotics affect immune homeostasis?
By killing the commensal microbes that are competing with pathogens
29
What do faecal transplants involve?
Killing the commensals of the GI tracts and then repopulating the GI micro biome using transplanted faeces
30
How effective is the skin as a physical barrier?
There is virtually no invasion by this route. The skin is colonised by potentially pathogenic bacteria. Many pathogens cause disease when the barrier is broken
31
What is the natural state of the digestive system?
It is colonised by large numbers of microorganisms but transient populations can cause a disease
32
At every part of the GI tract, microbes face a hostile environment, what does it face in the oral compartment?
Competition with well adapted normal flora of the mouth and intestine
33
What hostile environment is faced in the stomach?
Acid and secretions
34
What hostile environment is faced in the lower intestine?
Alkaline pH
35
What hostile environment is faced in the intestine?
Peristaltic action of intestine flushes out organisms
36
What hostile environment is faced in the pancreatic enzymes?
Bile salts and lysozyme
37
What is the difference between the male and female genitourinary system?
Male system is sterile | Female system is colonised
38
What is the hostile environment of the genitourinary system?
Flushing mechanisms of urine Acidity of urine Vaginal epithelium
39
What are the three main functions of innate immunity?
Recognition- picks up on infection in the first place Releases inflammatory mediators to recruit other cells to the area Effector function- some of the innate cells are effector cells and can kill other cells
40
How does the early innate part of the immune response link the two arms of the immune response?
Antigen release
41
What are the 4 basic anti-pathogen control strategies?
Prevention of pathogen entry Destruction of pathogen prior to cellular entry Recognition and destruction of infected cells Inhibitor of pathogen products (blocks the toxins produced by viruses) Pathogen sensing in vivo Resident cells detect pathogens Infection is detected by pattern-recognition receptors (PRRs)
42
What is the best known family of PRR?
TLR- They recognise PAMPs and each TLR recognises a different PAMP
43
Name the main TLRs and what do they do?
TLR2- lipopeptide TLR4- LPS TLR9- CpG repeats
44
What does pathogen recognition result in?
Immune response becoming turned on which then leads to: Release of inflammatory mediators Initiation of acute inflammatory response Recruitment/activation/maturation of effector cells
45
What are neutrophils?
Early responding cell in the acute response, preformed, non-specific responders Mainly involved in dealing with bacterial infections
46
How do neutrophils work?
In two ways- Releasing toxic granules Engulfing pathogens
47
How are neutrophils activated?
Recruited by chemokines Primed by cytokines Activated by pathogen contact
48
What are NK cells?
Cytotoxic cells important in killing of infected cells and tumour cells
49
What are the main functions of NK cells in infection?
Lysis of target cells | Secretion of cytokines
50
How do NK cells kill cells?
Granzyme/perforin | FasL/Fas pathways
51
What are NK cells involved in?
Dealing with viral infections (humans that are deficient in NK cell function will suffer severe viral infections)
52
What do macrophages do?
They engulf foreign particles
53
What happens to particles that are engulfed by macrophages?
They are often tagged by an antibody (opsonisation), activated by cytokines especially IFN-gamma. Macrophages kill bacteria in the phagolysosome using a respiratory burst
54
What type of cell are both macrophages and dendritic?
Both are antigen presenting cells
55
How are macrophages and dendritic cells activated?
By the innate immune system stimuli e.g. TLR ligands
56
What acts as a bridge between innate and adaptive immunity?
Macrophages and dendritic cells- they activate T cells
57
How do macrophages cause fever?
They release cytokines
58
How does the process of MHC class I loading occur?
Virally infected cells will produce proteins and some of these proteins will be misfolded. These misfolded proteins are tagged by ubiquitin and driven into the proteasome which processes the protein and produces smaller peptides. The peptides get pumped through TAP and loaded onto MHC class I which translocates to the cell membrane
59
What type of proteins does MHC II present?
MHC class II presents external proteins
60
How does the process of MHC class II loading occur?
There are two intracellular bodies involved: MHC containing lysosome Phagolysosome containing the phagocytosed proteins The external proteins are taken up into a phagolysosome and they get chewed up into smaller peptides The two intracellular bodies then merge and the peptide is loaded onto MHC class II by HLA-DM The loaded MHC class II then moves to the cell membrane
61
What do CD4+ T helper cells do?
They amplify the immune response by initiating the adaptive response and they recruit/activate other cells by cytokines
62
What demonstrates the central role of CD4 lymphocytes
Patients with very low CD4 lymphocyte counts (e.g. HIV/AIDS) have a high risk of opportunistic infections
63
What do CD8+ T cells do?
They are cytotoxic (CTLs)- they kill by releasing granzyes and perforin or by engagement of Fas on target cells by Fas ligand They also produce IFN-g and TNF-a
64
What can CTLs recognise?
Non-self- when MHC class I presents non-self peptides
65
What can NK cells detect?
Missing-self- when there is under expression of MHC class I as a result of virus infection
66
What do B cells do?
They express cognate receptors on their surface and turn into plasma cells-produce antibody Important in prevention of future re-infection Some role in clearance of pathogens
67
What are the two types of B cell?
T cell dependent- require help by CD4+ T cells | T cell independent- highly repetitive polysaccharide antigens
68
What do antibodies do?
They lyse membrane bound virus particles Opsonise particles Coats pathogens with antibody to enhance phagocytosis via Fc receptors on immune cells or via complement Lyse infected cells or pathogens Triggering of inflammation and immune cells Functions often involve complement Neutralise bacterial toxins Bind to epitopes on the pathogen and prevent entry Destroying the pathogen before entry
69
What destroys the pathogen before entry and how?
Membrane attack complex Complement-dependent damage to the cell membranes. This works with bacteria if the membrane can be targeted (Gram-positive bacteria) It also works with enveloped viruses
70
What is antibody depdent cellular cytotoxicity mediated by?
NK cells
71
How does antibody dependent cellular cytotoxicity (ADCC) work?
Antibodies bind to epitopes on the virus infected cell The NK cells binds to the Fc portion of the antibody This results in NK cell mediated lysis of infected cell
72
What does vaccination enhance?
Acquired immunity
73
How does vaccination work?
Vaccine particles are engulfed by APCs, digested into peptides and presented to T cells. The T cells then help B cells to make antibody. So vaccine mimics normal immune responseto a pathogen to allow development of immunological memory without disease. On second exposure, antibody response is much stronger and faster than it was first time around
74
How can pathogens evade the passive immune response?
Antigenic shift and drift lead to epitope escape (immune system can no longer recognise the epitopes) Drift- Small changes in antigens over time Shift- Viruses come from an animal source and it looks totally different to anything previously encountered by humans Anatomical seclusion/hiding Infection of immune cells
75
How does active immune evasion occur?
``` With the innate system: -Interfering with cytokine/chemokine network -Avoiding type I IFN -Alteration of cell cycle/inhibition of apoptosis -Blockade of complement With NK cells With adaptive system: -Interfering with MHC -Inhibition of antibody ```
76
What does HIV target?
CD4+ T cells and antigen presenting cells
77
How does HIV evade the immune system?
HIV particles have coat proteins that are covered by carbohydrate to evade recognition Epitopes in gp41 are masked (important in viral entry) RNA genome undergoes rapid change so both CTL and antibody are evaded- high mutation rate Vaccination increases CD4 T cell infiltrate to the infected area, therefore increasing target cells
78
What are the most important parts of the immune system for dealing with viruses?
Type I IFN | NK, CD8 cells
79
What are the most important parts of the immune system for dealing with bacteria?
Antibody, neutrophils and CD4 cells
80
What are the most important parts of the immune system for dealing with fungi?
CD4 cells | Neutrophils
81
What are the most important parts of the immune system for dealing with parasites?
Mast cells and eosinophils

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