8. Immune response to pathogens

Question 1

How does the immune system respond to bacteria?

Answer 1

Complement activation
Macrophage phagocytosis and activation, TH1 activated
Ig production
T helper activation
Innate C’ phagocytosis
Antibody (toxin)
IgA plays important role in organisms that infect mucosal surfaces

Question 2

How does the immune system respond to viruses?

Answer 2

Type I interferon release 
NK lysis 
Macrophage phagocytosis and activation 
Ig production 
Cytotoxic T cell activation 
Complement attack (enveloped viruses)
Phagocytes

Question 3

What is adaptive immunity to viruses?

Answer 3

B cells recognise antigen and its natural state
T cells recognised processed antigen
CD4+T cells provide help to the B cells
T cells activated by two signals (TH2 response)

Question 4

What are the ways in which the immune system responds to pathogens?

Answer 4

Antibody neutralising IgE
Neutrophils, macrophages
Cytotoxic CD8 T cells 
TH2 cells 
ADCC (Antibody Dependant Cell-mediated Cytotoxicity) reactions

Question 5

How does IgG perform its neutralising function?

Answer 5

1. Toxin binds to cell-surface receptor
2. Endocytosis of toxin: receptor complex
3. Dissociation of toxin to release active chain, which poisons cell
4. Neutralising antibody blocks binding of toxin to cell-surface receptor

Question 6

What is in the lytic granules?

Answer 6

Perforin
Granzymes
CTL can also kill their targets by binding of F𝛂s ligand to F𝛂s on target cell
- F𝛂s instructs the target cell to kill itself (apoptosis)

Question 7

What is antigenic drift?

Answer 7

Results from error-prone copying of viral RNA

• responsible for local outbreaks of influenza infections that occur every year of so
• explains why we get flu more than once

Question 8

How are antigens presented by macrophages

Answer 8

1. Phagocytosis and breakdown of bacteria by macrophages induces expression of MHC class II and B7
2. Macrophage delivers a co-stimulatory signal to T-cells recognising bacterial peptide antigen
   - results in proliferation and differentiation of T cells specific for bacterial protein

Question 9

How do bacterial infections lead to the production of the TH2 response ?

Answer 9

1. B cell binds bacterial polysaccharide component of vaccine conjugate
2. Conjugate is internalised and degraded
3. Peptides for the toxoid are presented to the T cell, which activates the B cell
4. Activated B cell differentiates into a plasma cell that produces anti-polysaccharide antibodies
   that bind to bacteria.
5. Encapsulated bacteria cannot be engulfed by neutrophils
6. Antibody bound to bacteria activates complement and bonding of C3b to bacteria
7. Engulfment of bacteria by neutrophils is mediated by Fc receptors and complement receptors
8. Granules fuse with phagosomes, releasing toxic oxygen metabolites that kill bacteria

Question 10

How do antibodies prevent viruses attaching to cell surface?

Answer 10

1. Virus binds to receptor on cell surface
2. Receptor mediated endocytosis of virus
3. Acidification of endosome after endocytosis triggers fusion of virus with cell and entry of viral DNA
4. Antibody blocks binding to virus receptor

Question 11

How do antibodies prevent bacteria attaching to cell surface?

Answer 11

1. Bacteria colonise human cell surfaces by using bacterial adhesins
2. Some species of bacteria become internalised and propagate in internal vesicles
3. Antibodies against adhesins block colonisation and uptake

Question 12

What is the immune response to parasites?

Answer 12

Similar to anti-bacterial mechanisms

1. Neutralising antibody e.g. malaria sporozoite, blocks cell receptor for entry into liver cells
2. Antibody + complement e.g. lysis of blood dwelling trypanosomes
3. Antibody/complement pus neutrophils or macrophages, malaria merozoites
4. Activated macrophages can be effective against many intracellular protozoa, e.g. leishmania, toxoplasma, trypanosoma cruzi
5. CD8+ cytotoxic T cells against parasite infected host cells e.g. pkesmodium infected liver cell
   - IgE
   - Characteristic ADCC reactions

Question 13

What does IgE crosslinking mast-cell surface?

Answer 13

Mast cells have high affinity IgE Fc receptors on their surface that are occupied by IgE molecules
Antigen crosslinking of bound IgE crosslinks the Fc receptors, triggering degranulation of mast cells and release of inflammatory mediators (histamine)
- followed by symptoms of hayfever - type I hypersensitivity

Question 14

What is antibody dependant cellular cytotoxicity (ADCC)?

Answer 14

Neutrophils, NK cells, Eosinophils, and phagocytes all mediate ADCC

• Ligation of the low affinity Fc𝛄RIII (CD16) molecule activates the lytic machinery
• ADCC only triggered by complexes of antibody and antigen, Fc regions form an array sufficient to increase the avidity of the interaction thus avoiding ADCC being triggered by free immunoglobulin