Session 7 ILOs - Adaptive immunity (part 2) and infections on surfaces

Question 1

Describe the antigen receptor present on both B cells and T cells

Answer 1

B cell antigen receptor (BCR):

• Antigen recognition receptor made up of light and heavy chains with a peptide binding site in the variable region
• Can recognise macromolecules or small chemicals aka. can recognise a microbe that hasn’t been processed = KEY DIFFERENCE

T cell antigen receptor (TCR):

• Antigen recognition receptor made up of alpha and beta chains with a peptide binding site in the variable region
• There is a variable region and a constant region
• Only recognises a peptide that has been presented to it by MHC molecules

Question 2

Describe how antigen presenting cells select the appropriate immune response against intracellular vs extra-cellular microbes

Answer 2

B-cell antigen receptors may interact directly with an invading microbe, but TCRs recognise only “processed” antigenic peptides.

Extracellular antigens are pro­cessed for eventual presentation on MHC class II molecules to CD4 + T lymphocytes. The antigen is phagocytosed by the APC and presents the antigen on the surface bound to MHC 2 and presented to TCR = appropriate T cell will proliferate

Intracellular, or endogenous, antigens such as viral proteins are processed by “target cells” for eventual presentation on class I MHC molecules to CD8 + T cells. The antigen is present on the surface in association with MHC 1 and presented to the TCR = appropriate T cell will proliferate

CD8+ T cells recognise peptides presented by MHC Class I molecules, found on all nucleated cells. CD8+ T cells are very important for immune defence against intracellular pathogens, including viruses and bacteria, and for tumour surveillance.

Question 3

Understand the mechanisms leading to B cells and T cells activation

Answer 3

First, an antigen must be recognized; then notice of this recognition (a signal) must be transmitted to the cellular interior, and a response is generated.

B cells - requires multiple signals:
1. BCR engagement from antigen processing and presentation
2. TCR engagement (needs CD4 or CD8 helper cells which act as coreceptors, plus other coreceptors)
3.
Outcome: proliferation and differential of B cells (plasma cells or memory cells), antibody production and heavy chain class switching

T cells:

Outcome: proliferation and differential of T cells (effector cells, CD4+ = t helper cells, CD8+ cells = cytotoxic T cells) and cytokine production

Question 4

Describe the effector mechanisms of cell-mediated immunity and humoral immunity

Answer 4

In both cases, APCs activate naive T CD4+ cells which causes them to release interleukins which have the following effects:

Cell mediated immunity - IL-12 released:
- Defence against intracellular and extracellular pathogens (bacteria, virus, fungus)
- IL-12 released causes naive T CD4+ cells to become T1 helper cells
Outcome:
- Differentiate CD8+ T cells
- Recruit and activate macrophages
- B cells produce IgG or IgA

Humoral immunity - IL4 released and IL-1/IL-6 released:
- Defence against intracellular and extracellular pathogens (parasites, worms)
- IL-4 released causes naive T CD4+ cells to become T2 helper cells
Outcome:
- B cells produce IgE
- Eosinophils kill pathogens
- Mast cells because allergies
- IL-1/IL-6 released causes naive T CD4+ cells to become T17 helper cells
Outcome:
- Neutrophils are recruited and activated

Question 5

Describe the range, importance and origins of surface infections on both natural and prosthetic surfaces

Answer 5

Natural surfaces (skin and mucosal)

• Range of infections: external (e.g. cellulitis, pharyngitis, UTIs etc.) or internal (endocarditis, septic arthritis etc.)
• Importance: some people carry these organisms but they don’t often because disease in the host, except in certain circumstances
• Origins: many places! (e.g. eye, nasopharynx, urethra etc.)

Prosthetic surfaces (valves etc.)

• Range of infections: various (e.g. intravascular lines, prosthetic joints, artificial cardiac valves etc.)
• Importance: can be significant complications of medical interventions (iatrogenic)
• Origins: usually medical interventions (iatrogenic)

Question 6

Describe the importance of the microbiota in this setting with examples for mucosal surfaces

Answer 6

Many people carry these organisms but they don’t often because disease in the host, except in certain circumstances

Examples:
Mouth - Lactobacillus, candida
Nasopharynx - Nesseria menigitidis, streptococcus pneumonia
Stomach - Helicobacter, staphylococci 
Intestine - Lactobacillus, clostridium

Question 7

Describe the pathogenesis of infections at a surface

Answer 7

1. Adherence to the host cells or the prosthetic surface with the help of pili or fimbriae (like velcro)
2. Biofilm formation
   - A colony of bacteria which produce a protective layer of polysaccharides which covers the bacteria
   - Bacteria communicate through quorum sensing
3. Invasion and multiplication of pathogen
4. Host response
   - Pyogenic response (neutrophils produce pus)
   - Granulomatous response (fibroblasts, lymphocytes and macrophages -> nodular inflammatory lesions)

Question 8

Explain a ‘biofilm’ and the implications for an infection on a surface

Answer 8

A biofilm is a glycoprotein protective layer (extracellular matrix) which is produced from a colony of bacteria attached to a surface

Most hospital acquired infections are due to biofilms because they can be life-threatening colonisers of biomedical devices.

Question 9

Describe the management of infected surfaces

Answer 9

Aim of treatment is to sterilise tissue and reduce bio-burden on the tissue. Can use antibacterial drugs, remove the prosthetic material with surgery.

Need to take blood cultures to identify the infecting organism

There are issues with antibacterial penetration into biofilms and the complications of surgery.

The main form of management is prevention! To try to maintain surface integrity, prevent colonisation and remove colonising bacteria, for both natural and prosthetic surfaces.