Immune Response to Pathogens

Question 1

Give four components of the immediate defence

Answer 1

1. Complement
2. Antibodies
3. Phagocytic cells
4. Antimicrobial peptides

Question 2

How fast does the immediate defence act?

Answer 2

0-4 hours

Question 3

What pathway of complement opsonises pathogens for phagocytosis?

Answer 3

Alternative mainly

Also maybe lectin

Question 4

When can the classical pathway be used?

Answer 4

If natural or specific antibody is present

Question 5

Where is the membrane attack complex used?

Answer 5

Directly destroying Gram-negative bacteria

Question 6

What genetic defects in complement predispose to immune complex disease?

Answer 6

C1q
C1r
C1s
C2
C4

Question 7

What genetic defects in complement predispose to recurrent pyogenic infections?

Answer 7

C3
Factor H
Factor I

Question 8

What genetic defects in complement predispose to Neisseria infections?

Answer 8

C5
C6
C7
C8
Properdin
Factor D

Question 9

How do macrophages and neutrophils recognise pathogens?

Answer 9

Complement, scavenger and other receptors

Question 10

What infection is associated with leukocyte adhesion deficiency (LAD)?

Answer 10

1. Staphylococcus species
2. Enteric gram-negative bacteria
3. Fungal infections, esp. C. albicans

Question 11

What is natural antibody?

Answer 11

IgM

Made without previous exposure to antigens

Question 12

What produces natural antibody?

Answer 12

B-1 cells

Question 13

What are defensins?

Answer 13

Major group of human antimicrobial peptides

Question 14

What do defensins do?

Answer 14

Disrupt cell membranes

Question 15

What are defensins effective against?

Answer 15

1. Gram-negative and Gram-positive bacteria
2. Fungi
3. Parasites
4. Enveloped viruses

Question 16

What produces defensins?

Answer 16

Epithelial cells in skin, respiratory and urogenital tracts

Paneth cells in small intestine

Neutrophils

Question 17

Where are β-defensins produced?

Answer 17

Urogenital tract

Question 18

Where are α-defensins produced?

Answer 18

Paneth cells in small intestine

Question 19

How fast does the induced innate response act?

Answer 19

4 hours to 4 days

Question 20

What is the main component of the induced innate response?

Answer 20

Macrophages

Question 21

What do macrophages do in the induced innate response?

Answer 21

Activated PRRs signal production of pro-inflammatory cytokines

Question 22

What are the pro-inflammatory cytokines?

Answer 22

1. IL-1
2. IL-6
3. IL-12
4. TNF-α

Question 23

What are the six functions of TNF-α?

Answer 23

1. Induces adhesion molecule expression on vascular endothelium
2. Increases vascular permeability
3. Triggers platelet activation and blood clotting
4. Stimulates dendritic cell activation and migration to lymph nodes
5. Stimulates acute phase response
6. Primes newly recruited neutrophils

Question 24

What is the result of increased vascular permeability?

Answer 24

1. Neutrophil migration

2. Inflammatory exudate

Question 25

What pathogens do interferons deal with?

Answer 25

Viruses

Question 26

What is the role of RIG-1-like receptors?

Answer 26

1. Detect presence of viral nucleic acid in cytoplasm of infected cells 2. Induce expression of type 1 interferons

Question 27

What are the type 1 interferons?

Answer 27

IFNα and IFNβ

Question 28

What is the effect of type 1 interferons?

Answer 28

1. Induce antiviral state in surrounding cells by interfering with viral replication 2. Activate natural killer cells

Question 29

What is the role of IFNγ?

Answer 29

Macrophage activation

Question 30

What proportion of lymphocytes do NK cells make?

Answer 30

5-25%

Question 31

What is the role of NK cells?

Answer 31

1. Kill infected host cells | 2. Secrete cytokines that act on macrophages to upregulate phagocytosis and inflammatory cytokine production

Question 32

Which cytokines recruit NK cells to sites of infection?

Answer 32

1. IFNα and IFNβ | 2. IL-12

Question 33

What is the relationship between macrophages and NK cells?

Answer 33

Activate each other

Question 34

What is the effect of NK cells on dendritic cells?

Answer 34

Signals need for initiation of adaptive immunity

Question 35

How fast is the adaptive response?

Answer 35

4 days onwards

Question 36

What four things does the adaptive response require?

Answer 36

1. Dendritic cell activation and migration to secondary lymphoid organs 2. Activation of low frequency T cells 3. Activation and proliferation of antigen-specific B cells by activated T cells 4. B cell differentiation into plasma cells for antibody production, B cell isotype switching and affinity maturation

Question 37

What do CTLs kill?

Answer 37

Cells harbouring intracellular viruses and parasites MHC class I restricted

Question 38

What is the role of TH1 cells?

Answer 38

Activate macrophages via IFNγ

Question 39

What is the role of TH2 cells?

Answer 39

1. Direct IgE production 2. Help eosinophils, basophils, mast cells and B cells resist parasite infections via IL-4

Question 40

What is the role of TH17 cells?

Answer 40

Help neutrophils respond to extracellular bacterial and fungal infections Via IL-17

Question 41

When does specific antibody appear?

Answer 41

5 days post infection

Question 42

What is the first antibody isotype to be produced?

Answer 42

Specific IgM

Question 43

What does IgM do?

Answer 43

1. Recruits complement | 2. Compensates for low affinity with high avidity

Question 44

What does IgE do?

Answer 44

Eosinophil recruitment

Question 45

What does IgG do?

Answer 45

Neutralisation

Question 46

What does IgG1 do?

Answer 46

Opsonisation

Question 47

What does IgA do?

Answer 47

1. Neutralisation | 2. Epithelial transport

Question 48

What are the principle innate mechanisms against extracellular bacteria?

Answer 48

1. Complement activation 2. Phagocytosis 3. Acute inflammatory response

Question 49

What is the principle adaptive mechanism against extracellular bacteria?

Answer 49

Specific antibody

Question 50

What is the role of secretory IgA?

Answer 50

Block binding to epithelial cells

Question 51

What three roles do the CD4+ helper T cells assist with?

Answer 51

1. TH17 cells stimulating neutrophil recruitment 2. TH1 cells activating macrophages 3. Helper T cells required for thymus-dependent antibody production

Question 52

What type of T cell response do helminths induce?

Answer 52

TH2

Question 53

What does the TH2 response involve?

Answer 53

1. IgE 2. IgG1 3. IgG4 4. Eosinophils 5. Expansion of basophils, mast cells and alternatively activated macrophages

Question 54

What do natural killer cells do?

Answer 54

1. Kill virally infected cells | 2. Secrete inflammatory cytokines

Question 55

What does the cell-mediated response to viruses mainly rely on?

Answer 55

1. Cytotoxic T cells | 2. Helper TH1 cells

Question 56

How is protective immunity to viruses established?

Answer 56

Neutralising antibody produced following vaccination or natural infection

Question 57

What do CD4-TH1 cells express to activate macrophages?

Answer 57

CD40L

Question 58

How does Leishmania prevent MAC formation?

Answer 58

Uses a surface protease (gp63) to cleave C3b to iC3b However this increases macrophage uptake as iC3b is an opsonin

Question 59

What is the main innate response to protozoa?

Answer 59

Phagocytosis