Immune response to infection Flashcards
What are the 4 different types of resolution of infections?
- Acute viral infection and clearance e.g. flu
- Acute viral infection/clearance and re-infection e.g. RSV
- Acute viral infection + chronic infection e.g. HIV
- Slow chronic infection e.g. CMV
What is immunological memory to RSV like?
It wanes over time so you can get re-infected by the same pathogen
What is immunological resolution to HIV like?
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
What is immunological resolution to CMV like?
There is no acute phase- there is a gradual build up of the amount of virus in the body over time
What are the two main variables that determine how well a virus will spread?
Basic reproduction number- how many people does one virus infect
Proportion of infections that occur prior to symptoms
What happens if symptoms are present before being infectious?
You can quarantine the subjects
What is an example of a disease where patients are infectious without being ill?
HIV
What causes variability in susceptibility/host response to infection?
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
What are the 4 main routes of infection?
Airborne
Intestinal
Sexually transmitted
Vector borne
What are the main types of respiratory infection?
Virus- Influenza, RSV and RV
Bacterial- M.Tuberculosis, H.influenzae and S. pneumonia
Fungal- Cryptococcus and Aspergillus
What are the main types of faecal oral infection?
Virus- Hep A
Bacteria- V.Cholerae, Shigella, E. coli and S. type
Parasite- Ascaris
What are the main type of sexually transmitted infection?
Virus- HIV and HPV
Bacteria- T. palladium and N. gonorrhoeae
Fungal- Candida albicans (thrush)
What are the main types of vector infection?
Virus- Rabies virus
Parasites- Plasmodium, schistosome and trypanosoma
What are viruses?
Obligate intracellular parasites- extremely small
They have a wide variety of life cycles/genetic material and rapid mutation rate
What is the most abundant life form on earth?
Viruses
What are bacteria?
Unicellular prokaryotes
Can be intracellular or extracellular
How are bacteria classified?
They can be Gram-positive or Gram-negative based on cell membrane/cell wall composition
What are fungi?
Multicellular eukaryotes. Can be intracellular or extracellular. They often cause opportunistic infections in immunosuppressed individuals
What are parasites?
Eukaryotes
Includes:
Protozoa- unicellular
Helminths- multicellular
What are the most common types of infection?
Respiratory
What mechanisms for preventing infection at mucosal surfaces?
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
What is mucus produced by?
Goblet cells
What does mucus do?
It contains mucin glycoproteins and it traps dust and pathogens which are swept upwards
What are proteolytic enzymes produced by?
Produced in the stomach (pepsin) and small bowel (trypsin, chymotrypsin and pancreatic proteases)
What do proteolytic enzymes do?
Breakdown large polypeptides into dipeptides and tripeptides. - small peptides are poor immunogens. Enzymes are cytotoxic to pathogens
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
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
How do antibiotics affect immune homeostasis?
By killing the commensal microbes that are competing with pathogens
What do faecal transplants involve?
Killing the commensals of the GI tracts and then repopulating the GI micro biome using transplanted faeces
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
What is the natural state of the digestive system?
It is colonised by large numbers of microorganisms but transient populations can cause a disease
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
What hostile environment is faced in the stomach?
Acid and secretions
What hostile environment is faced in the lower intestine?
Alkaline pH
What hostile environment is faced in the intestine?
Peristaltic action of intestine flushes out organisms
What hostile environment is faced in the pancreatic enzymes?
Bile salts and lysozyme
What is the difference between the male and female genitourinary system?
Male system is sterile
Female system is colonised
What is the hostile environment of the genitourinary system?
Flushing mechanisms of urine
Acidity of urine
Vaginal epithelium
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
How does the early innate part of the immune response link the two arms of the immune response?
Antigen release
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)
What is the best known family of PRR?
TLR- They recognise PAMPs and each TLR recognises a different PAMP
Name the main TLRs and what do they do?
TLR2- lipopeptide
TLR4- LPS
TLR9- CpG repeats
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
What are neutrophils?
Early responding cell in the acute response, preformed, non-specific responders
Mainly involved in dealing with bacterial infections
How do neutrophils work?
In two ways-
Releasing toxic granules
Engulfing pathogens
How are neutrophils activated?
Recruited by chemokines
Primed by cytokines
Activated by pathogen contact
What are NK cells?
Cytotoxic cells important in killing of infected cells and tumour cells
What are the main functions of NK cells in infection?
Lysis of target cells
Secretion of cytokines
How do NK cells kill cells?
Granzyme/perforin
FasL/Fas pathways
What are NK cells involved in?
Dealing with viral infections (humans that are deficient in NK cell function will suffer severe viral infections)
What do macrophages do?
They engulf foreign particles
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
What type of cell are both macrophages and dendritic?
Both are antigen presenting cells
How are macrophages and dendritic cells activated?
By the innate immune system stimuli e.g. TLR ligands
What acts as a bridge between innate and adaptive immunity?
Macrophages and dendritic cells- they activate T cells
How do macrophages cause fever?
They release cytokines
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
What type of proteins does MHC II present?
MHC class II presents external proteins
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
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
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
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
What can CTLs recognise?
Non-self- when MHC class I presents non-self peptides
What can NK cells detect?
Missing-self- when there is under expression of MHC class I as a result of virus infection
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
What are the two types of B cell?
T cell dependent- require help by CD4+ T cells
T cell independent- highly repetitive polysaccharide antigens
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
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
What is antibody depdent cellular cytotoxicity mediated by?
NK cells
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
What does vaccination enhance?
Acquired immunity
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
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
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
What does HIV target?
CD4+ T cells and antigen presenting cells
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
What are the most important parts of the immune system for dealing with viruses?
Type I IFN
NK, CD8 cells
What are the most important parts of the immune system for dealing with bacteria?
Antibody, neutrophils and CD4 cells
What are the most important parts of the immune system for dealing with fungi?
CD4 cells
Neutrophils
What are the most important parts of the immune system for dealing with parasites?
Mast cells and eosinophils
