Infection 6 - Adaptive Immunity (Part 1 - Recognition Phase)

Question 1

The two important cell types in the adaptive immune response are APC’s + T cells. What are the 4 APC’s and 2 T-cell cell types?

Answer 1

• APC’s = dendritic cells, langerhans cells, B-cells + macrophages
• T-cells = naive (never encountered the pathogen) + effector (have encountered the pathogen + capable of performing effector functions)

Question 2

What is the role of APC’s?

What type of T-cells do the 4 APC’s present the pathogen to?

Answer 2

Present antigens from pathogens on MHC molecules on their surface to initiate adaptive immune response by taking antigen to lymphatic system for T-cell recognition.

• Dendritic + langerhans to Naive T-cells
• Macrophages + B-cells to Effector T-cells

Question 3

What are the key features of APC’s?

Answer 3

1) Strategic locations - e.g.: mucosal membranes, skin, blood, lymph nodes + spleen.
2) Diversity in PRR’s - looking for different PAMP’s and can recognise extracellular pathogens (bacteria, fungi + protozoa) and intracellular pathogens (viruses)
3) Diversity in pathogen capture mechanisms - phagocytosis (whole microbes) + macropinocytosis (soluble particles)

Question 4

Pathogens are presented by Major Histocompatibility Complex (MHC) molecules. What kind of cells express type 1 and type 2 MHC molecules?

What kind of microbial peptides do each class present?

Answer 4

1) Type l = antigen-presenting cells (dendritic cells, macrophages + B-cells) - present microbial peptides from intracellular pathogens (viruses)
2) Type ll = All nucleated cells (e.g.: macrophages) - present microbial peptides from extracellular pathogens (fungi, bacteria, parasites)

Question 5

Describe the processing of intracellular microbes via the endogenous pathway (viruses)

Answer 5

• Intracellular microbes (viruses) are presented by APC’s on MHC class l molecules.
• APC’s express viral peptides on MHC class 1 after being marked for destruction by proteasome
• Presentation to naive CD8+ T-cells causes activation in lymphoid tissue, these search and kill infected cells as any infected cell will express viral peptides on MHC class 1 molecules

Question 6

Describe the processing of extracellular microbes via the exogenous pathway (bacteria, fungi + protozoa)

Answer 6

• Extracellular microbes (bacteria, fungi + protozoa) are presented by APC’s on MHC class ll molecules
• Microbes captured by phagocytosis, peptide-rich vesicles fuse with vesicles containing MHC class ll molecules.
• APC’s present peptides of extracellular pathogens to CD4+ T-cells

Question 7

Which molecules recognise MHC class l and class ll molecules?

Answer 7

Class l = recognised by CD8+ molecules on T-cells

Class ll = recognised by CD4+ molecules on T-cells

Question 8

How do antigen presenting cells activate the right adaptive immune response?

Answer 8

• MHC molecules have a peptide binding cleft (for antigens) with a variable region with highly polymorphic residues.
• Therefore, many peptides can be presented by the same MHC molecules
• Everyone had different sets of MHC molecules therefore people have different susceptibilities to infections

Question 9

What are the 2 major clinical problems associated with MHC molecules?

Answer 9

1) Major cause for organ transplant rejection - HLA (human leukocyte antigen) molecules mismatch between donor and recipient
2) HLA association with autoimmune disease - in ankylosing spondylitis + T1DM (insulin dependent diabetes mellitus)