Immune Response to Bacteria, Fungi, and Helminths

Question 1

what are the 4 classes of pathogens

Answer 1

1. viruses
2. intracellular bacteria, protozoa, parasites
3. extracellular bacteria, parasites, fungi
4. parasitic worms

Question 2

what are the major determinants of what kind of effector response is used

Answer 2

size of pathogen
location of pathogen

Question 3

what are the 4 main effector responses

Answer 3

1. cytotoxicity
2. intracellular immunity (type 1)
3. mucosal and barrier immunity (type 2)
4. extracellular immunity (type 3)

Question 4

cytotoxicity

Answer 4

mediated by NK cells and CD8 T cells

used for viruses

Question 5

intracellular immunity (type 1)

Answer 5

mediated by ILC1 and Th1 cells

induces macrophage activation

used for intracellular pathogens

Question 6

mucosal and barrier immunity (type 2)

Answer 6

mediated by ILC2 and Th2 cells

induces eosinophil, basophil, and mast cell activation

used for parasites

Question 7

extracellular immunity (type 3)

Answer 7

mediated by ILC3 and Th17 cells

induces neutrophil activation

used for extracellular bacteria and fungi

Question 8

steps of detecting intracellular pathogen

Answer 8

1. pathogen binds TLR on macrophage cell surface
2. macrophage engulfs pathogen
3. bacteria detect a change in pH once inside the phagosome
4. bacteria injects proteins to prevent the macrophage from killing it
5. macrophages unable to kill pathogen - requires clonal expansion of CD4 T cells

Question 9

what type of T cells develop in order to combat intracellular pathogens

Answer 9

Th1 cells

Question 10

main function of Th1 cells

Answer 10

produce IFN-y

also secretes other factors that promote the innate immune response (increase cell accumulation and extravasation)

Question 11

IFN-y

Answer 11

activates macrophages to be able to kill intracellular pathogens

increases macrophage production of NO and superoxide

Question 12

how are Th1 cells and CD8 T cells connected

Answer 12

CD4 Th1 cells can increase the ability of dendritic cells to activate CD8 T cells

Question 13

what innate cells aid in combating intracellular pathogens

Answer 13

ILC-1
NK cells

Question 14

ILC-1

Answer 14

innate lymphoid cell
- NO TCR

present in the tissues and act like Th1 cells by producing IFN-y before Th1 cells have differentiated

Question 15

how do cells respond to extracellular pathogens

Answer 15

extracellular pathogens stimulate clinical expansion and differentiation of Th17 cells

Question 16

main function of Th17 cells

Answer 16

produce IL-17 and IL-22 to increase phagocytosis in order to combat extracellular pathogens

Question 17

IL-17 and IL-22 function

Answer 17

IL-17:
- recruit neutrophils
- stimulate neutrophil production in bone marrow

IL-22:
- promote antimicrobial peptide secretion at barrier surfaces
- increase epithelial cell turnover

Question 18

how do neutrophils find the extracellular pathogens

Answer 18

respond to complement gradient (C5a)

Question 19

how do bacteria prevent detection by neutrophils

Answer 19

bacterial capsules can inhibit complement fixation (C3b) to prevent being detected

Question 20

what kind of response is required to combat capsulated bacteria

Answer 20

antibody response

Question 21

ILC-3

Answer 21

innate lymphoid cells
- NO TCR

present in the tissues and act like Th17 cells by producing IL-17 and IL-22

Question 22

are B cells able to become activated without T cell stimulation

Answer 22

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

Question 23

effect of T independent B cell activation

Answer 23

low affinity antibody for the polysaccharide antigen
IgM only

Question 24

how can a high affinity receptor for polysaccharide antigens be generated

Answer 24

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

Question 25

steps of generating a high affinity polysaccharide antibody

Answer 25

1. B cell binds bacterial polysaccharide bound to protein component 2. antigen gets internalized and processed 3. peptides from the protein component get presented on MHC II to CD4 Tfh cells 4. CD4 Tfh cell activates B cell to produce an antibody against the polysaccharide antigen

Question 26

are the T and B cells specific for the same antigen during the production of high affinity polysaccharide antibody

Answer 26

no - B cell is specific for the polysaccharide, T cell is specific for the protein component attached to the polysaccharide

Question 27

what cell type drives almost every aspect of the antibody response

Answer 27

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

Question 28

how are Tfh cells produced

Answer 28

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

Question 29

what makes helminths different from other extracellular pathogens

Answer 29

too large to be controlled by phagocytosis must be degraded by toxic mediators

Question 30

phases of allergic responses

Answer 30

1. sensitization - NO allergic reaction 2. elicitation - HAS allergic reaction

Question 31

allergen sensitization

Answer 31

1. allergen binds DCs --> presented to T cells in LN 2. T cells proliferate and differentiate into Th2 cells which enter circulation 3. complementary Tfh cell stays in LN to activate B cells 4. B cell proliferates and differentiates into plasma cell 5. plasma cell releases IgE antibody which coats mast cells at the tissue site 6. mast cells and Th2 cells are primed for next encounter with antigen

Question 32

allergen elicitation

Answer 32

1. subsequent encounter with antigen leads to immediate binding to IgE on mast cell surface 2. mast cells degranulate --> release mediators to degrade cuticle 3. Th2 cells bind antigen and release IL-4, 5, and 13 to recruit eosinophils, increase peristalsis and epithelial turnover, and promote repair 4. basophils bind antigen to release IL-4, histamine, and lipid mediator to degrade cuticle 5. eosinophils bind antigen and release toxic mediators to degrade cuticle

Question 33

ILC-2

Answer 33

innate lymphoid cell that release IL-4, 5, and 13 in response to alarmins secreted by epithelial cells in response to helminth detection

Question 34

how do Th2 cells promote tissue repair

Answer 34

induce macrophage differentiation into M2 macrophages

Question 35

M2 macrophages

Answer 35

anti-inflammatory macrophages release IL-10 and TGF-B to suppress inflammatory response

Question 36

do eosinophils have a pathogen specific or non-specific response

Answer 36

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

Question 37

antibody dependent cellular cytotoxicity

Answer 37

Fc receptors allow the eosinophils (some macrophages) to draw the parasite close and release toxic mediators

Question 38

asthma susceptibility loci

Answer 38

gene regions that are associated with allergies/asthma involved in hypersensitivity via Th2 cells

Question 39

atopic hosts

Answer 39

hosts with asthma susceptibility loci means that they are more likely to develop allergies/asthma

Question 40

what does a host's degree of hypersensitivity depend on

Answer 40

amount of IL-4, 10, and IgE produced more produce = greater hypersensitivity reaction BUT also greater resistance to helminths

Question 41

how does the environment affect atopy risk

Answer 41

increased exposure to allergens increases risk of developing atopy (hypersensitivity reactions to the allergen)

Question 42

function of Treg cells

Answer 42

induce tolerance by preventing other T cells from eliminating the pathogen produce TGF-B and IL-10 to suppress Th1 and Th2 cell responses

Question 43

why is tolerance to pathogens required in some cases

Answer 43

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