Adaptive Immunity

Question 1

What are the different types of antigen-presenting cells?

Answer 1

• Dendritic cells –> present pathogen to naive T cells –> causing T cell responnse against most pathogens
• Langerhans cells –> present pathogen to naive T cells –> causing T cell response against most pathogens
• Macrophages –> present pathogen to effector T cells –> causes phagocytic activities
• B cells –> present pathogen to effector T cells –> causes antibody response (humoral response)

Question 2

What are naive T cells?

Answer 2

• T cells that have not previously encountered the antigen

Question 3

What are effector T cells?

Answer 3

T cells that have previously encountered the antigen and are capable of performing effector functions during an immune response
- Switches antibody production from IgM to IgG

Question 4

What are the three main features of antibody presenting cells?

Answer 4

1) Strategic location
- mucosal membranes, gut/lung
- Skin, langerhans cells
- Blood, plasmacytoid cells
- Lymph nodes, follicular dendritic cells
- Spleen

2) Diversity in pathogen capture mechanisms
- Phagocytosis (whole microbe)
- Macropinocytosis (soluble particles)

3) Diversity in pathogen sensors (PRRs)
- Extracellular pathogens, bacteria/fungi/protoza
- Intracellular pathogens, viruses

Question 5

Where does antigen presentation take place?

Answer 5

• Mucosal associated lymphoid tissue (MALT)
• Lymph nodes
• Spleen

Question 6

What immune response is exerted against extracellular microbes?

Answer 6

INNATE: - complement - phagocytosis
ADAPTIVE: Humoral immunity with antibodies

Question 7

What immune response is exerted against intracellular microbes?

Answer 7

INNATE: - Interferons (prevents viral replication in neighbouring cells) - NK cells
ADAPTIVE: - Humoral immunity - Cell-mediated immunity (with cytotoxic T cell response)

Question 8

What are MHC molecules?

Answer 8

Major Histocompatibility Complex/ Human Leukocyte Antigen (HLA)

Question 9

Where are MHC Class I molecules expressed?

Answer 9

Expressed on all nucleated cells

Question 10

Where are MHC Class II molecules expressed?

Answer 10

• Expressed on antigen-presenting cells (dendritic cells, macrophages, B cells)

Question 11

What class of MHC molecule will be present on a macrophage?

Answer 11

Both Class I and II as they are nucleated but also antigen presenting

Question 12

What types of Class I MHC exist?

Answer 12

MHC A
MHC B
MHC C

Question 13

What types of Class II MHC molecule exist?

Answer 13

MHC DP
MHC DQ
MHC DR

Question 14

What is haplotype?

Answer 14

Set of MHC alleles that are inherited together from one parent and present on the chromosme

Question 15

What are the key features of MHC Class I and Class II molecules?

Answer 15

Co-dominant expression
- Both MHC Class I and II parental molecules are co-expressed in each individual (6 of each class)
Polymorphic genes (different alleles present)
- Different individuals present and respond to different microbes
Presentation of microbial peptides
- Intracellular microbes are presented via MHC Class I molecules (eg. HLA-A, B and C)
- Extracellular microbes are presented via MHC Class II molecules (eg. HLA-DP, DQ, DR)

Question 16

What features are present on MHC Class I and Class II molecules?

Answer 16

Peptide binding cleft
- Variable region with highly polymorphic residues
Broad specificity
- Many peptides presented by the same MHC molecule
Responsive T cells
- MHC class I recognised by CD8+ molecules on T cells
- MHC class II recognised by CD4+ molecules on T cells

Question 17

How does the adaptive immune system deal with extracellular microbes?

Answer 17

• APCs bind with naive CD4+ T cells
• Leads to presentation of microbial peptides via MHC Class II molecules (HLA-DP -DQ, -DR)
• Leads to humoral response

Question 18

How does the adaptive immune system deal with intracellular microbes?

Answer 18

• APCs bind with naive CD8+ T cells
• Presentation of microbial peptides via MHC Class I molecules, (HLA-A, -B, -C)
• Cell mediated immunity

Question 19

Explain the exogenous pathway of processing extracellular microbes?

Answer 19

• Microbes captured by phagocytosis or micropinocytosis
• Degradation in small peptides in the endosome
• Peptide-rich vesicles fuse with vesicles containing MHC Class II molecule
• Formation of peptide-MHC Class II complex if right match
• Occurs only in antigen- presenting cells including dendritic cells, B cells and macrophages
• APCs presents peptides of extracellular pathogens to CD4+ T cells

Question 20

Explain the endogenous pathway of processing intracellular microbes?

Answer 20

• Viral protein present in the cytosol
• Marked for destruction by the proteasome
• Proteasome-generated viral peptide transported to ER by TAP proteins
• Formation of viral peptide-MHC Class I complex if right match
• Occurs in all cell types
• APCs and non-APCs present peptides from intracellular pathogens to CD8+ T cells

Question 21

What is the clinical importance of MHC molecules?

Answer 21

Host can deal with a variety of microbes
- Gene families
- Genetic polymorphism
No two individuals have the same set of MHC molecules
- Not being wiped out by a single microbe/epidemic disease
Different susceptibilities to infections
- Strong vs weak immune response against infectious microbes

Question 22

What clinical conditions are associated with MHC molecules?

Answer 22

MAjor cause for organ transplant rejection

• HLA molecules mismatch between donor and recipiant (Allograft)
• Graft-versus-host reaction (GVH)

HLA association with autoimmune disease

• Ankylosing spondylitis (HLA-B27 in 97% of patients)
• Insulin dependent diabetes mellitus (HLA-DQ2 in 50-75%of patients