Immune responses to bacteria

Question 1

What are the stages of bacterial infection?

Answer 1

• Acquisition
• Colonisation
• Penetration
• Spread
• immune evasion
• Damage
• Transmission
• Resolution

Question 2

What natural barriers do we have?

Answer 2

Non-specific
- Physical conditions (dry, acidic), sloughing, microflora, lysozyme, Toxic lipids, lactoferrin, lactoperoxidases, tight junctions, bile, mucin, ciliated epithelia, bile, phagocytes

Adaptive
- Mucosally-associated lymphoid tissue (MALT), SALT, GALT, sIgA

Question 3

What defences do we have in the tissue and blood?

Answer 3

Non-specifc
- transferrin, complement, acute phase proteins, phagocytes, neutrophils

Adaptive
- Abs, macrophage activation, T cells

Question 4

What is the link between adaptive and innate immune system?

Answer 4

• Presentation of APCs to Th cells - get activated to produce cytokines -> help process of adaptive immunity
• B-cells clonally activated, NKs, eosinophils and mast cells
• HMSC will become activated
• Fibroblasts and endothelial cells will start to show special receptors etc

Question 5

What happens to the immune systems of HIV-infected people?

Answer 5

• If someone is HIV infected, their CD4 count will start to drop, and they will become susceptible to more and more infections
• As CD4 goes down, the adaptive immune system cannot function properly -> lots of infections

Question 6

What are PAMPs and PRRs?

Answer 6

• links innate immunity recognition to adaptive immunity via signalling
• Pathogen expresses pathogen associated molecular patterns (PAMPs) eg LPS
• Pattern recognition receptors (PRRs) eg TLR4, recognise these, allowing the organisation and recruitment of immune response in the correct way to give the correct response that will lead to clearage

Question 7

What are the aims of inflammation?

Answer 7

• response to tissue injury - functions to bring serum molecules and cells to site of infection
• Increase blood supply and capillary permeability, allowing migration of cells from blood to tissue eg macrophages and neutrophils
• Get vasodilation, oedema, complement activation, mast cell degranulation, PMN recruitment and clotting

Question 8

What are the 5 signs of inflammation?

Answer 8

Calor (heat)
Dolor (pain)
Rubor (redness)
Tumor (swelling)
Functio laesa (loss of function)

Question 9

What are the main roles of complement?

Answer 9

• Induces inflammatory response
• Promotes chemotaxis
• Increases phagocytosis by opsonisation
• Increases vascular permeability
• Mast cell degranulation
• Lysis of cell membranes (MAC)

Question 10

What are the effects of C3b?

Answer 10

• Where all the pathways come together
• It is an opsonin, so can bind to bacteria, allowing more effective phagocytosis
• Starts recruitment of MAC
• Vasodilator
• Activates phagocytes via CR3 receptor

Question 11

What does C5a do?

Answer 11

• Chemoattractant to attract phagocytes and PMNs

Question 12

What does Factor H do?

Answer 12

• Negatively acts on alternative pathway
• eg Neisseiria have receptors that specifically bind to human factor H - means that we wont recognise it as foreign, complement wont start binding to it, and wont be able to form MAC

Question 13

What protect does a capsule give for bacteria?

Answer 13

• Decrease ability for complement binding and activation
• Decrease ability for opsonisation
• Decreased phagocytosis

Question 14

What are the 4 opsonins?

Answer 14

IgG(1,3), IgM, C3b, CRP

Question 15

What advantage does opsonisation give?

Answer 15

• For opsonisation to occur, macrophage expresses either Fc or C3b (CR3) receptor
• Either of these two interactions will enhance phagocytosis and killing
• Uncoated bacteria are phagocytosed poorly - on coating with Ab, adherence to phagocytes is enhance and increases complement fixing

Question 16

What defences can ciliated epithelial cells provide (mucosal immunity)?

Answer 16

• Always wafting away organisms
• Secrete ferrins, lysozyme and antimicrobial peptides
• IgA production (main Ab at mucosal surface), binds to bacteria, preventing it from binding to epithelial surface
• Can increase IgM release in response to infection - stops bacteria from binding
• increased vascular supply and permeability allows cells to be recruited to deal with infection

Question 17

How do we make Abs for the mucosal surfaces?

Answer 17

• M cells are surveillance cells that sample Ag from the environment
• They present them to the lymphoid follicles, allowing T cell recognition and cytokine production
• Activates B cells to secrete specific IgA

Question 18

What are the antibacterial roles of antibodies?

Answer 18

• Neutralisation of microbes and toxins
• Opsonisation and phagocytosis
• Antibody-dependent cellular cytotoicity - immune complex acts with NK cells and eosinophils to kill microbes
• IgE binds to eFc receptor on eosinophils and mast cells to help destroy parasites
• Complement activation -> lysis, phagocytosis and inflammation

Question 19

What is the different mechanism for bacteria in cytoplasm of cell vs endosome?

Answer 19

• Endosome - not fusing with lysosome, so not being exposed to ROS. Some Ags will be presented -> MHCII -> CD4+ Th –> IFN –> macrophages –> killing
• Cytoplasm - some ags will be presented via MHCI to CD8+ CTL -> kill cell