4.13 Immune Response to Infection

Question 1

What are the 4 different pathogen niches during infection?

Answer 1

Extracellular – bacteria

Surface adherent – enteropathogenic and enterohaemorrhagic e. coli

Intracellular vacuolar – salmonella, chlamydia, plasmodium, legionella

Intracellular cytosolic – viruses, listeria, bukholderia, mycobacteria

Question 2

How does an immune response to infection start?

Answer 2

Tissue damage occurs
Microbe is detected
Intracellular signalling occurs, leading to interleukin production
Thus the adaptive immune response is primed

Question 3

How does an immune response to infection end?

Answer 3

Pathogen is cleared
Production of inflammatory cytokines is stopped
Tissue repair and remodelling occurs
Memory cells are developed

Question 4

What are the 3 broad differences between innate and adaptive immunity?

Answer 4

Innate – fast acting, first line of defense, germline encoded receptors

Adaptive – slow but long lasting, physical barrier, variable receptors

Question 5

Give examples of physical barriers provided by innate immunity

Answer 5

Epithelial cells
Skin
Mucosa

Question 6

Is complement part of innate or adaptive immunity?

Answer 6

Both

Question 7

What are the key cellular components of innate immunity?

Answer 7

Granulocytes, macrophages, dendritic cells, NK cells

Question 8

What are the humoral components of innate immunity?

Answer 8

Complement, lectins, pentraxins, antimicrobial peptides

Question 9

What are the key cellular components of adaptive immunity?

Answer 9

T cells (killer, reg, helper), B cells, plasma cells

Question 10

What are the humoral components of adaptive immunity?

Answer 10

Antibodies and complement

Question 11

What is the difference in specificity between innate and adaptive immunity?

Answer 11

Innate is less specific – it detects broad pathogen classes via PAMPs

Adaptive is specific – it detects structural details of antigens and non-microbial antigens

Question 12

What is the major difference between innate and adaptive immunity receptors?

Answer 12

Adaptive immunity receptors have a greater diversity

Question 13

Why is there a greater diversity in adaptive immune receptors in comparison to innate immune receptors?

Answer 13

Adaptive immunity receptors are encoded by genes produced from somatic recombination

This produces TCRs and Ig’s with many variations

Question 14

What do adaptive and innate immunity both provide to the body?

Answer 14

Humoral and cellular response

Question 15

List the general sequence of molecular and cellular events of an immune response?

Answer 15

Microbe is detected
Naive host cell undergoes gene expression changes and is activated
Antimicrobial molecules are produced and communicate to nearby cells
This produces an activated and specialised host cell

Question 16

What are the first responders to site of injury?

Answer 16

Neutrophils, then monocytes that differentiate into macrophages

Question 17

What do neutrophils and macrophages do when responding to a site of injury?

Answer 17

Naive cells become activated when interacting with microbes

Phagocytes control infection and limit tissue damage

Question 18

What can uncontrolled activities of first responders lead to?

Answer 18

Excessive inflammation
Tissue damage
Granulomas

Question 19

How do phagocytes and other immune cells identify bacteria?

Answer 19

Cell wall components (e.g. LPS)

Question 20

How do phagocytes and other immune cells identify fungi?

Answer 20

Dectin-1 on phagocytes recognise beta glucans on fungi and signal through SRC tyrosine kinases

Question 21

How do phagocytes and other immune cells identify viruses?

Answer 21

Viral DNA/RNA in cytoplasm

Question 22

How does live vs dead bacteria elicit different immune responses?

Answer 22

Live bacteria causes production of inflammatory cytokines, metabolic genes, antimicrobial genes and immunomodulatory genes

Dead bacteria results in resolution of inflammation

Question 23

What are the common cell surface molecules unique to fungi?

Answer 23

Beta glucans

Question 24

What type of immune response do fungi produce?

Answer 24

Production of inflammatory cytokines, antimicrobial, metabolic and immunomodulatory genes

Question 25

What type of immune response do viruses produce?

Answer 25

Production of inflammatory cytokines, antiviral genes, immunomodulatory genes, and interferons

Question 26

What do interferons do?

Answer 26

Binds IFNRs to activate the anti viral state of the cell Gene transcription occurs to block viral replication, producing 2'5' oligoadenylate synthetase and protein kinase R

Question 27

What do activated macrophages show?

Answer 27

Enhanced: Phagocytosis and migration Cytokine/chemokine production Cell surface molecule expression Antimicrobial activity Antigen presentation and T cell activation

Question 28

Against which 2 classes of pathogens are interferons active?

Answer 28

Viruses and gram negative bacteria

Question 29

What are type I IFNs produced by, and what do they do?

Answer 29

All primary infected cells (mainly plasmacytoid DCs) Promote antiviral response

Question 30

What are type II IFNs produced by, and what do they do?

Answer 30

Lymphocytes only Promote antibacterial response

Question 31

What are type III IFNs produced by, and what do they do?

Answer 31

Epithelial cells Promote antiviral response

Question 32

What do antiviral genes include?

Answer 32

Nucleases Inhibition of viral entry and exit Inhibition of uncoating and replication Inhibition of viral protein translation

Question 33

What are the immunomodulatory roles of IFNs?

Answer 33

Enhance T cell actions Anti inflammatory response Tissue repair

Question 34

How are virus-infected cells killed?

Answer 34

CD8 T cells or NK cells

Question 35

What does cell death remove?

Answer 35

Viral replicative niches

Question 36

Give 2 antimicrobial enzymes that are produced by a cytokine binding to a cytokine receptor leading to the killing of microbes?

Answer 36

Phagocyte oxidase – produces ROS Inducible nitric oxide synthase – produces NO

Question 37

What are the soluble effector mechanisms of innate immunity?

Answer 37

Complement mediated destruction Lectin binding for neutralisation Iron chelation (siderophores) to prevent replication Antibiotic like peptide production

Question 38

What are the cellular effector mechanisms of innate immunity?

Answer 38

ROS and NO from phagocyte oxidase and inducible nitric oxide synthase Acidification and digestion within phagosomes

Question 39

How are T cells activated?

Answer 39

Activated APCs present antigens on MHC to T cells APCs produce cytokines for T cell activation, such as IL-12 for T cell replication T cells produce cytokines that activate phagocytes, such as IFN-gamma that upregulates MHC II expression Cytokines also act in an autocrine manner, such as IFN-gamma causing differentiation into Th1 and IL-17 causing differentiation into Th17

Question 40

How are dendritic cells better able to respond to viral infections than macrophages?

Answer 40

Dendritic cells produce more type I interferons (a, B) during infection

Question 41

How do T cells help B cells produce antibodies?

Answer 41

T helper cells activate B cells with the correct BCR specific to the original antigen

Question 42

What are Th and Tc cells produced in response to respectively?

Answer 42

T helper – bacterial infections, produces cytokines T killer – viral infections, removes viral replicating niches

Question 43

What are some T cell functions?

Answer 43

Phagocyte activation B cell activation Direct killing of infected cells Innate lymphoid cells (gamma-delta T cells in mucosa)

Question 44

What class of T helper cells do macrophages produce and how?

Answer 44

Macrophages respond to **intracellular pathogens** by producing **IFN-gamma** This causes differentiation of T cells into **Th1**

Question 45

What class of T helper cells do eosinophils produce and how?

Answer 45

Eosinophils respond to **parasitic infection** Release of **IL4, 5, and 13** cause differentiation into **Th2**

Question 46

What class of T helper cells do neutrophils produce and how?

Answer 46

Neutrophils are recruited in response to **extracellular bacteria and fungi** Release of **IL-17 and 22** cause differentiation into **Th17**

Question 47

What is the overall sequence of the immune response?

Answer 47

Naive immune cells encounter pathogen and become activated They produce cytokines and phagocytose pathogens They move to lymph nodes to present antigens to specific T cells T cells proliferate and differentiate into effector cells CD8 cells kill pathogens and infected cells, CD4 cells activate B cells B cells differentiate into plasma cells and produce antibodies Phagocytes and complement cascade destroy antibody-opsonised cells

Question 48

What is the difference in serum antibody titre between first and second infections of the same antigen?

Answer 48

Secondary responses has higher antibody levels that are produced more quickly Level after infection reduces slowly and stays higher

Question 49

What is the impact of age on the immune response?

Answer 49

Reduced thymic output thus weakened immune response

Question 50

What kind of genetic dysfunction leads to chronic granulomatous disease?

Answer 50

Loss of ROS production

Question 51

What kind of genetic dysfunction leads to Chediak-Higashi syndrome?

Answer 51

Compromised lysosomes

Question 52

What kind of genetic dysfunction is present in immunosuppression?

Answer 52

Deletion or impairment of lymphocytes

Question 53

What kind of genetic dysfunction is present in HIV?

Answer 53

CD4 T cells are destroyed

Question 54

A genetic dysfunction in the genes controlling what leads Severe Combined Immunodeficiency (SCID)?

Answer 54

Severe reduction in function of B and T cells

Question 55

What genetic disfunction leads to X-linked aggamaglobulinaemia?

Answer 55

Decreased serum IgG

Question 56

To which pathogens are Th1 made?

Answer 56

Intracellular bacteria and protozoa

Question 57

To which pathogens are Th2 made?

Answer 57

Helminths, allergens, venoms

Question 58

To which pathogens are Th17 made?

Answer 58

Extracellular bacteria and fungi