Immuno 11 - Immunity to Bacteria Fungi Parasites Flashcards
what is infection
why does disease occur
Infection: invasion of host tissues by organisms Infection ≠ Disease
Disease occurs because:
* An infectious agent damages organs, tissues or cells in the host
or
* It is the result of the immune response against the pathogen
(remember the previous lecture material Re: sickness‐inducing cytokines and danger signals [e.g., IL‐6, IL‐1, TNF‐α and HMGB1], hallmarks of inflammation, etc)
…and often it is a combination of the two
*Disease due to infection is not the norm
*Well‐adapted microorganisms do not damage the host, nor do they induce robust immune responses
*It is in the interest of microorganisms to avoid being noticed
*They can best exploit the host’s resources if they avoid causing damage or triggering an effective immune response
infectious disease in animals vs humans
- In human medicine a patient sees
their physician when they experience symptoms of disease - Something unique to production
animal medicine… - It is industry practice to monitor various production parameters (e.g., milk yield, time‐to‐market, etc)
- In many cases, underlying infections can be detected as unexpected decreases in these parameters
- The animals may not even feel sick (i.e., if human, they wouldn’t bother
seeking medical attention) - But the animals get treated anyways
to boost production
innate antmicrobial immunity (bacteria)
Some mechanisms include:
* Complement cascade triggered by alternate or lectin pathways, or antibody‐mediated
- Phagocytosis
- Natural killer (NK cells) as a result of some intracellular bacteria up‐regulating NK‐activating ligands (e.g., NKG2D) on the cell surface
- Lysozyme in blood can digest bacterial cell walls
- Iron sequestration (needed for bacterial growth)
tuberculosis; M tuberculosis survives in alveolar macrophages
- Immunity to Mycobacterium tuberculosis is governed in many species by the availability of vitamin D
- M. tuberculosis is detected on
macrophages by TLR 1/2 - TLR1/2 signaling up‐regulates the
expression of vitamin D receptors on
macrophages - Binding of vitamin D to this receptor
up‐regulates vitamin D hydroxylase, which in turn increases production of
the antibacterial cathelicidins that kill
M. tuberculosis
adaptive antimicrobial immunity (bacteria)
- M1 macrophages are important against bacteria
-Antibodies are critical effectors against extracellular bacteria (this is most of them)
Some antibody‐mediated mechanisms include:
*Neutralizing bacterial toxins before they bind to their receptors
*Opsonization (coating bacteria and promoting their phagocytosis via Fc receptor‐mediated uptake)
*ADCC (Ab‐dependent cellular cytotoxicity)
* CD8+ cytotoxic T cells are important against intracellular bacteria
fever/stress and heat shock proteins
- HSPs are induced in bacteria in response to heat (e.g., fever) and stress (e.g., following phagocytosis)
- HSPs are potent danger‐associated molecular patterns that activate a large # of cells in the immune system
the effect of immune response bias on disease
- The differences in blood lymphocyte‐derived IL‐2, IFN‐γ (i.e., associated with a Th1 response), and antibody production between sheep with the paucibacillary (PB) form (mild) and sheep with the multibacillary (MB) form (severe) of Johne’s disease (caused by Mycobacterium avium subspecies
paratuberculosis) - Note that there is a marked tendency for the T cells from animals with the PB form (few bacteria/lesion) of the disease to produce more Th1
cytokines than those with the MB form (many bacteria/lesion) - As expected with a Th1 immune response bias, animals with the PB
form also produce fewer antibodies
(which is typical for an intracellular pathogen)
the effect of immune response bias on johnes disease
- The two forms of Johne’s disease
in sheep - (A) Section of terminal ileum from a case of multibacillary Johne’s disease (associated with a Th2 immune response bias), showing abundant acid‐fast organisms within large infiltrating macrophages
- (B) Section of terminal ileum from a case of paucibacillary Johne’s disease (associated with a Th1 bias), showing very few acid‐fast bacteria and a significant lymphocyte infiltration
- Ziehl‐Nielsen stain
evasion of immune responses by bacteria
Examples of mechanisms:
*Producing modified PAMPs that don’t activate TLRs
*Blocking TLR signaling pathways
*Redirecting TLR signaling pathways from proinflammatory to anti inflammatory pathways
*Secrete proteins/enzymes to block/degrade defensins
*Blocking phagocytic receptors
*Secrete proteins/enzymes to block/degrade complement
*Kill phagocytic cells (secrete leukotoxins)
*Prevent intracellular destruction after phagocytosis (and live happily inside the cell)
*Encapsulation (host proteins can’t bind efficiently)
*Endonuclease‐mediated degradation of neutrophil extracellular traps (NETs)
*Inhibit polarization of macrophages to M1 phenotype
mechanisms of antifungal immunity
There are three main types of fungal infections:
* Primary skin/other surfaces
* Primary, lungs
* Secondary/opportunistic
-The main effectors are: NK cells, Th17 cells and a Th1 response (which promotes induction of granulomas to
isolate fungi)
-Note that neutrophils and other phagocytes often cannot fully engulf fungi due to their size
parasitemia and antibody cycles (due to antigenic variation)
- The time course of Trypanosoma congolense parasitemia in an infected calf
- Each parasitemic peak represents the development of a new, antigenically original population of organisms
-cyclic parasitemia. mutate which allows selection of more types
helminth infections
- A Th2 response (i.e., against extracellular pathogens) is required for elimination of helminths
- IgE is the most effective antibody isotype against helminths
- Eosinophils represent another
critical defense mechanism (usually activated indirectly by IgE binding to mast cells)
-Some of the molecules released from eosinophils that cause damage to the cuticle of parasitic helminths
the antibody response against helminths
-A Toxocara canis larva after incubation in specific antiserum. Serum antibodies bind and precipitate antigens in the saliva and excretions of this larva. This precipitate may block these pores and kill the larva. The immune precipitates at the oral and excretory pores are indicated by arrows. Antibodies can also block helminthic proteases
The IgE response to Helminths
-The mechanisms involved in the self cure reaction against intestinal helminths. In essence, the animal mounts an allergic response to the salivary antigens of attached nematodes. This acute inflammatory response causes the worms to detach from the intestinal wall and pass out in the feces
evasion of the immune response by helminths
Some mechanisms:
* Secretion of proteins that block:
‐neutrophil proteases
‐neutrophil chemoattractants
‐oxidation
‐complement proteins
- Capture host proteins that inhibit complement activation and embed them in their outer lipid bilayer
- Low antigenicity (i.e., don’t express very many immunogenic molecules)
- Adsorbing host antigens to block their own immunogenic antigens
- Gradual antigenic variation
- Interfere with antigen processing
- Promote/recruit regulatory T cells
- Induce immunosuppressive cytokines
