Immune Response to Bacteria, Fungi, and Helminths Flashcards
what are the 4 classes of pathogens
- viruses
- intracellular bacteria, protozoa, parasites
- extracellular bacteria, parasites, fungi
- parasitic worms
what are the major determinants of what kind of effector response is used
size of pathogen
location of pathogen
what are the 4 main effector responses
- cytotoxicity
- intracellular immunity (type 1)
- mucosal and barrier immunity (type 2)
- extracellular immunity (type 3)
cytotoxicity
mediated by NK cells and CD8 T cells
used for viruses
intracellular immunity (type 1)
mediated by ILC1 and Th1 cells
induces macrophage activation
used for intracellular pathogens
mucosal and barrier immunity (type 2)
mediated by ILC2 and Th2 cells
induces eosinophil, basophil, and mast cell activation
used for parasites
extracellular immunity (type 3)
mediated by ILC3 and Th17 cells
induces neutrophil activation
used for extracellular bacteria and fungi
steps of detecting intracellular pathogen
- pathogen binds TLR on macrophage cell surface
- macrophage engulfs pathogen
- bacteria detect a change in pH once inside the phagosome
- bacteria injects proteins to prevent the macrophage from killing it
- macrophages unable to kill pathogen - requires clonal expansion of CD4 T cells
what type of T cells develop in order to combat intracellular pathogens
Th1 cells
main function of Th1 cells
produce IFN-y
also secretes other factors that promote the innate immune response (increase cell accumulation and extravasation)
IFN-y
activates macrophages to be able to kill intracellular pathogens
increases macrophage production of NO and superoxide
how are Th1 cells and CD8 T cells connected
CD4 Th1 cells can increase the ability of dendritic cells to activate CD8 T cells
what innate cells aid in combating intracellular pathogens
ILC-1
NK cells
ILC-1
innate lymphoid cell
- NO TCR
present in the tissues and act like Th1 cells by producing IFN-y before Th1 cells have differentiated
how do cells respond to extracellular pathogens
extracellular pathogens stimulate clinical expansion and differentiation of Th17 cells
main function of Th17 cells
produce IL-17 and IL-22 to increase phagocytosis in order to combat extracellular pathogens
IL-17 and IL-22 function
IL-17:
- recruit neutrophils
- stimulate neutrophil production in bone marrow
IL-22:
- promote antimicrobial peptide secretion at barrier surfaces
- increase epithelial cell turnover
how do neutrophils find the extracellular pathogens
respond to complement gradient (C5a)
how do bacteria prevent detection by neutrophils
bacterial capsules can inhibit complement fixation (C3b) to prevent being detected
what kind of response is required to combat capsulated bacteria
antibody response
ILC-3
innate lymphoid cells
- NO TCR
present in the tissues and act like Th17 cells by producing IL-17 and IL-22
are B cells able to become activated without T cell stimulation
yes - polysaccharide antigens can cross link so many BCRs that the B cell gets activated without T cells
T cells can NOT respond directly to polysaccharide antigens
effect of T independent B cell activation
low affinity antibody for the polysaccharide antigen
IgM only
how can a high affinity receptor for polysaccharide antigens be generated
CD4 Tfh (follicular T helper cells) that help activate B cells specific for non-protein antigens
can ONLY do this if there is a protein component attached to the polysaccharide
steps of generating a high affinity polysaccharide antibody
- B cell binds bacterial polysaccharide bound to protein component
- antigen gets internalized and processed
- peptides from the protein component get presented on MHC II to CD4 Tfh cells
- CD4 Tfh cell activates B cell to produce an antibody against the polysaccharide antigen
are the T and B cells specific for the same antigen during the production of high affinity polysaccharide antibody
no - B cell is specific for the polysaccharide, T cell is specific for the protein component attached to the polysaccharide
what cell type drives almost every aspect of the antibody response
CD4 Tfh cells
- drives germinal center formation and somatic hypermutation of B cells
- produces cytokines associated with Th1, 2, and 17 responses for antibody class switching
how are Tfh cells produced
during clonal expansion of Th cells, each Th cell produced will have a complementary Tfh cell that will stay in the LN to activate B cells
Th cell goes to tissue
Tfh cell stays in LN
what makes helminths different from other extracellular pathogens
too large to be controlled by phagocytosis
must be degraded by toxic mediators
phases of allergic responses
- sensitization - NO allergic reaction
- elicitation - HAS allergic reaction
allergen sensitization
- allergen binds DCs –> presented to T cells in LN
- T cells proliferate and differentiate into Th2 cells which enter circulation
- complementary Tfh cell stays in LN to activate B cells
- B cell proliferates and differentiates into plasma cell
- plasma cell releases IgE antibody which coats mast cells at the tissue site
- mast cells and Th2 cells are primed for next encounter with antigen
allergen elicitation
- subsequent encounter with antigen leads to immediate binding to IgE on mast cell surface
- mast cells degranulate –> release mediators to degrade cuticle
- Th2 cells bind antigen and release IL-4, 5, and 13 to recruit eosinophils, increase peristalsis and epithelial turnover, and promote repair
- basophils bind antigen to release IL-4, histamine, and lipid mediator to degrade cuticle
- eosinophils bind antigen and release toxic mediators to degrade cuticle
ILC-2
innate lymphoid cell that release IL-4, 5, and 13 in response to alarmins secreted by epithelial cells in response to helminth detection
how do Th2 cells promote tissue repair
induce macrophage differentiation into M2 macrophages
M2 macrophages
anti-inflammatory macrophages
release IL-10 and TGF-B to suppress inflammatory response
do eosinophils have a pathogen specific or non-specific response
pathogen specific
express Fc receptors that bind to the back end of IgE antibodies
- pathogen antigen binds to the front end of IgE to cause eosinophil to degranulate
antibody dependent cellular cytotoxicity
Fc receptors allow the eosinophils (some macrophages) to draw the parasite close and release toxic mediators
asthma susceptibility loci
gene regions that are associated with allergies/asthma
involved in hypersensitivity via Th2 cells
atopic hosts
hosts with asthma susceptibility loci
means that they are more likely to develop allergies/asthma
what does a host’s degree of hypersensitivity depend on
amount of IL-4, 10, and IgE produced
more produce = greater hypersensitivity reaction BUT also greater resistance to helminths
how does the environment affect atopy risk
increased exposure to allergens increases risk of developing atopy (hypersensitivity reactions to the allergen)
function of Treg cells
induce tolerance by preventing other T cells from eliminating the pathogen
produce TGF-B and IL-10 to suppress Th1 and Th2 cell responses
why is tolerance to pathogens required in some cases
sometimes a host’s inflammatory response causes more damage than the pathogen itself - Tregs allow the pathogen to exist in the body without immune response
