Lecture 26: Infection and Immunity Flashcards
Immunity and infection factors influencin this?
Microbial Factors:
- Type of organism
- Amount of organism
- Route of entry
- Virulence
Host Factors:
- Integrity of innate barriers
- Adaptive immune competence
- HLA, Ig and TCR genes
- Previous exposure
- Other concurrent infection
Pathogens and their antigens? Viruses? Bacteria? Parasites?
Viruses:
- Lytic or integral cycle
- Capsid antigens
- Internal structural components (HLA I)
- Metabolic products (HLA I)
Bacteris (and Fungi):
- Extracellular (eg. S aureus) or intracellular (eg. M tuberculosis)
- Structural changes
- Metabolic products and toxins
Parasites:
- Large (multicellular) - slower
- Life cycle changes
- Radical changes in antigenicity
Antibodies are effective against?
Cytotoxic T cells are effective against?
Effective against antigens outside cells of the body:
- Viruses - (IgA, IgG, IgM)
- Toxins - (IgG, IgG)
- Extracellular bacteria - (IgA, IgM, IgG)
- Parasites - (IgE, IgA)
Intracellular protein antigens:
- Virus infections
- tumour cells
- Transplanted organs
Recognisable bacterial pathogens? Lead to?
PAMPs - Pathogen-Associated Molecular Patterns
Local inflammation
- vascular permeability changes
- Phagocytoc recruitment
- Acute Phase Protein (APP) induction
- Local temperature changes
All leading to phagocytosis and complement activation
Complement Cascade Pathways?
Classical - Antigen-antibody complexes (C1,2,4)
Alternative - Pathogen surfaces (C3b, Factor B, Factor D)
Both make a C3 convertase enzyme that breaks C3 into C3a and C3b and C5 into C5a and C5b.
The a parts cause vasodilation, mast cell activation and chemotaxis
Late complement factors are used to attack the membrane lysing it.
How do AB and complement deal with bacteria? Bacteria strategies to avoid?
Prevent adherence or reduce mobility
Enhance bacterial destruction (complement)
Enhance phagocytosis (opsonisation)
Capsuel resistant opsonisation (eg. Haemophilus influenzae)
Intracellular growth (eg. Mycobacterium tuburculosis)
Mucosal Immunity?
IgA is the main class of antibody in the mucosa that block adherance and opsonisation
In the submucosal area there are lots of mast cells that have hgh affinity regions for the Fc region of IgE. These cells release vasoactive and chemotactic factors that cause IgG and complement levels to rise along with neutrophils and eosinophils.
Antibody-dependent Cellular Cytotoxicity and natural killing activity?
Done through a small population of NK cells through Fcγ receptor (CD16) on the NK cell
Natural Killing activity is through the killer-activating and killer-inhibitory receptor on the NK cell
Details of NK recognition and killing
Killer-activating receptors bind to a ubiquitous molecule on the normal cell and the killer-inhibiting receptor binds to HLA Class I molecule.
In an Abnormal cell (tumour or infected) - often with down-regulated HLA I the killer-inhibitory receptor does not bind and so the NK cell gets no inhibitory signal but still the activating signal.
1-5% of blood mononuclear cells and not classical B or T cells so no antigen priming required. Killing can be increased by IL-2 and IFN-γ (so are important in viral infections and some cancers)
What parts are effective against acute viral infections and at what points?
proinflammatory cytokines in infection?
IL-1, IL-6 and TNF-α
- In the early phase of infection inducing acute phase proteins
- Increase body tempertature (fever) to increase cell metabolism
- TNF-α triggered by bacterial LPS
- Tissue repair promotion (bone resorption, fibroblast prolif, collagenase synthase and leukocyte adhesion)
- T and B cell activation
Chemokines and interferons in infection?
Chemokines
- Aid chemotaxis (eg. neutrophils)
- Direct effector cell traffic
Interferons
- Induce transient antiviral state
- Activate NK cell activity
- Upregulate MHC expressio (improves cytotoxic T cell Killing)
