Immune Response to Infection Flashcards
Different pathogen niches
Extra cell
Intracellular
Surface adherent
Intracellular but cystolic
Extra cellular
e.g. Staphylococcus, Streptococcus, Candida, microbiota, worms)
Intracellular
e.g. Salmonella, Chlamydia, Legionella, Coxiella, Plasmodium, helminths)
Surface adherents
(e.g. enteropathogenic & enterohaemorrhagic E. coli)
Intracellular but cystolic
(e.g. viruses, Listeria, Burkholderia, Mycobacterium)
Humoral aspects of innate immunity
Humoral:
Complement, Lectins (collectins, ficolins), Pentraxins, Antimicrobial peptides
How does an immune response to infection start
Tissue damage ( e.g.injury)
Molecular detection of microbes
Intra cellular communication ( interleukins )
Priming the adaptive immune response
How does an immune response to infection end
Clearing infection
Stopping inflammatory cytokines production
Repairing tissue damage
Immune memory
What differences in molecules are there between the innate and the adaptive immune system
Timing of the response Cell types Receptors & ligands Cytokines & chemokines Molecular effector machineries
Uncontrolled activities of phagocytes lead to
Granulomas
Excessive inflammation & inappropriate adaptive immunity
Tissue damage
What helps convert a resting cell to a specialised cell
Gene expression means that the cell is able to better respond to pathogens
Are cytokine responses to pathogens unique
Yes
Phagocyte response to bacteria
Immune response when bacterial mRNA is release • Inflammatory cytokines • Antimicrobial genes • Metabolic genes • Immunomodulatory genes
No immune response if dead pathogen ingested and so no mRNA released
Resolution of inflammation
Phagocyte response to fungi
- Proinflammatory cytokines
- Antimicrobial genes
- Metabolic genes
- Immunomodulatory genes
Phagocyte response to viruses
- Interferon production
- Proinflammatory cytokines
- Antiviral genes
- Immunomodulatory genes
Phagocyte activation and pathogen killing, which interferon is imp?
Interferon gamme (IFN-gamma) is important Induced by microbes & cytokines
Humans lacking IFN gamma or have mutations in these pathways are susceptible to salmenolois and micro bacterial infections
Activated macrophages display enhanced…
Phagocytosis & Migration
Cytokine/chemokine production
Expression of cell surface molecules
Antimicrobial activity
Antigen presentation & T cell activation
“Alternatively” activated macrophages are anti-inflammatory
IFN gamma
Extra cellular bacterial pathogens
IFN alpha/beta
Anti viral
Antiviral genes include
Nucleases
Inhibitors of virus entry & exit
Inhibitors of viral uncoating and replication
Inhibitors of protein translation
Immunomodulatiry roles of interferons
Enhanced T-cell responses
Anti-inflammatory actions
Tissue repair
Every single primary infected cells can produce type 1 interferon
True
Where are types 1-3 interferons produced
Type 3; epithelial cell surfaces
Type 1; produced deeper down
Type 2; only produced in lymphocytes
NK cells
Virus-infected cells are killed by the actions of cytotoxic T lymphocytes (CTLs) or Natural Killer (NK) cells
Cell death removes viral replicative niches
CTLs and NK cells directly kill infected cells (contact-dependent)
Host cells infected with intracellular bacterial pathogens also undergo forms of cell death (contact-independent) - some cytokines can also induce cell death (cytokine-mediated)
So virus can no longer replicate
Type two interferon promotes….
Anti bacterial immunity
Types 1 and 3 interferons promote
Antiviral responses
Soluble effector mechanisms
Complement mediated bacterial destruction Lectin-binding to neutralise cell attachment or entry Iron chelation (siderophores) to prevent replication Antibiotic-like peptides
Cellular effector mechanisms of immunity
Reactive Oxygen and Nitrogen radicals
Acidification and digestion within phagosomes
How do Dcs and macrophages activate T cells
Dendritic cells and macrophages present antigens in combination with MHC-I or MHC-II to T cells.
Cytokines produced by antigen-presenting cells produce a suitable milieu for T-cell activation
E.g. IL-12 promotes T-cell replication
These are specific to the type of pathogen!
T cells provide cytokines that activate phagocytes
E.g. IFNg upregulates MHC-II expression for antigen presentation
Responses are specific to general class of pathogens
Broad classification of T cell function
Phagocyte activation
Enhanced killing of pathogens
Inflammation
Direct killing of infected cells
Removal of replicative niches
B cell activation
Antibody production & affinity maturation
Innate lymphoid cells/gd T cells
A type of early responders (MHC independent actions)
CD4 T cellsz usually in
Bacteria. Cells
CD8 cells usually in
Viral infections
Look at ‘Microbe-specific phagocyte responses induce the appropriate lymphocyte phase’ table in notes
Look at ‘Microbe-specific phagocyte responses induce the appropriate lymphocyte phase’ table in notes
Impact of age on immune cell response
Memory T cells have encountered many diff infections over the period of years. Increased age, decreased immunity
Defect in leukocyte adhesion
Genes involved in migration and adhesion
Chrniicngranulotamous disease
Loss of reactive o2 species
Chédiak-Higashi syndrome
Compromised lysosomes
(SCID)
Reduction in number and function of T cells and B cells
X-linked agammaglobulinaemia
Decreased serum IgG of all types
HIV
Reduced CD4 T helper cells
Irradiation and chemotherapy ( cancer treatment)
Loss of bone marrow precursor
Immunosupression ( graft rejection / chronic disease)
Depletion or impairment of lymphocytes
