L9 - Immunity against infection Flashcards
Organisms that may cause disease
- Bacteria
- Viruses
- Fungi
- Parasites
Pathogens have evolved ways of escaping host defense mechanisms
Different effector mechanisms needed, dependent on:
- Type of pathogen
- Localisation
- Challenge
- Stage of infection
Host defence mechanisms
Innate defence mechanism
Specific/adaptive defence mechanism
Innate defence mechanism
- Rapid
- Barriers, complement (alternative pathway), phagocytes, NK cells
- Act early: first line of defence
- Non-specific
- Ineffective against many pathogens
Specific/adaptive defence mechanism
- Antibodies & cell mediated immunity
- Takes longer to develop
- Exhibit memory
- Enhances & focuses innate defences
- Less easily evaded by pathogens
What are the types of T helper cells (CD4+)?
TH1
TH2
TH17
TH1 CD4+
Active against intracellular pathogens
Activate macrophages and stimulate cytotoxic T cells (CD8+ cell)
TH2 CD4+
Active against extracellular pathogens
Support antibody production, particularly class-switching to IgE
Also activate eosinophils, basophils and mast cells
TH17 CD4+
Active against extracellular bacteria and fungi, important in attracting inflammatory cells such as neutrophils
Induced early in infection
Difference between gram positive & gram negative bacteria
Thick layer of peptidoglycan in gram positive cell wall
Gram negatives have an outer membrane containing LPS
How do bacteria induce innate responses?
Components of cell walls (eg. LPS, peptidoglycan) can induce innate responses
Bind to Toll-like receptors (TLR) on macrophages
10 TLR genes in humans: receptors recognise distinct molecular patterns on microbes
• Located on plasma membrane and endocytic vesicles
NOD-like receptors (nucleotide binding oligomerization domain (intracellular sensors)
What are PAMPs?
Pathogen-associated molecular patterns
What happens when PAMPs bind to TLRs?
- Produce inflammation
- Promote dendritic cell maturation
- Influence differentiation of T cells
- Activate B cells (TI-1 antigens)
Cellular location of TLR
TLRs in the endosome membrane recognise microbial components that are only exposed after the microbe has been broken down
Phagocytosis often effective against bacteria
Bacteria may have protective capsules
Can be opsonised by antibody/complement
Role of antibodies in bacterial infection
Opsonisation
Complement activation
Bind to & neutralise toxins
Bind to surface structures to prevent mucosal adherence
Opsonisation by antibodies
Bind Fc receptors on phagocytes
Complement activation by antibodies
Promote inflammation via C3a, C5a
Opsonise by binding C3b receptors on phagocytes
Lysis of Gram negative organisms (MAC C5b,C6,C7,C8,C9)
How can gram negative bacteria be killed?
By complement lysis
How do some bacteria survive within phagocytes?
Inhibit lysosome/phagosome fusion
e.g. Mycobacterium tuberculosis
Activated macrophages do what?
- Better at phagocytosis and killing
- More efficient antigen presenting cells
- Stimulate inflammation (cytokines, prostaglandins)
- Macrophages are central to a TH1 response
Example of intracellular bacterium: Mycobacterium leprae
Outcome depends on the type of response
Tuberculoid leprosy: strong TH1 response, few live bacteria, slow progression, granuloma formation
Lepromatous leprosy: strong TH2 and antibody response, large no. of bacteria in macrophages, disseminated infection, fatal
Protection against bacterial infection
Antibodies important in protecting against extracellular pathogens
T cell effector mechanisms protect against intracellular organisms
