Adaptive Immunity

Question 1

What is the role of antigen presenting cells

Answer 1

• Only way to activate T cells and issue immune response is through antigen presenting cells
• Capture microbe, process it so it can be recognised, then presenting to T cells

Question 2

What are examples of antigen presenting cells and where are they found

Answer 2

Dendritic cells - lymph nodes, mucous membrane, blood
Langerhans’ cells - skin
Macrophages - various tissue
B cells - lymphoids

Question 3

What is the role of MHC

Answer 3

Main function of MHC is to bind to pathogen and display them for T cells

Question 4

What kind of cells are class 1 and 2 molecules found on

Answer 4

○ Class I molecules - found on all nucleated cells

○ Class II molecules - found on dendritic cells, macrophages, B cells

Question 5

What genes code for class 1 and 2 molecules

Answer 5

§ Class 1 molecules - presented by HLA-A, HLA-B, HLA-C (chromosome 6)
§ Class 2 molecules - presented by HLA-DR, HLA-DQ, HLA-DP (chromosome 6)

Question 6

What type of pathogens do class 1 and 2 molecules present

Answer 6

§ Class 1 molecules - present peptides from intracellular microbes (virus, bacteria, protozoa)
§ Class 2 molecules - present peptides from extracellular microbes (bacteria, parasites, worms, fungi)

Question 7

What type of receptors recognize class 1 and 2 molecules

Answer 7

§ Class 1 molecules - recognized by CD8+ T cells

§ Class 2 molecules - recognized by CD4+ T cells

Question 8

How and why are MHC proteins diverse

Answer 8

• The more diverse, the more microbes able to be presented
○ Co-dominant expression - both parental genes are expressed to increase number of different MHC molecules
○ Polymorphic genes - different alleles among different individuals to increase presentation of different antigens

Question 9

What is the structure of MHC molecules

Answer 9

○ Peptide binding cleft - variable region with highly polymorphic residues
○ Broad specificity - many peptides presented by the same MHC molecule
○ Responsive T cells - CD8+ and CD4+ T cells

Question 10

Explain the processing and presentation by MHC

Answer 10

○ Both self and non-self (viral) peptides are presented and will be degraded
§ Our cells are programmed to not target self protein (presented molecules not targeted for destruction)
○ All peptides from the same microbe are presented by different MHC molecules
• Endogenous pathway - Proteasome produces antigenic peptide and processed in ER
○ MHC class 1 in ER move through vesicles to cell surface and express
• Exogenous pathway - pathogen will always be contained within vesicle, form antigenic peptide and form an endosome
○ Endosome fuses with MHC class 2 complexes that match with antigen

Question 11

Describe the difference in MHC for slow and rapid progressors of HIV

Answer 11

○ Slow progressors - MHC molecules present key peptides for the survival of the virus (unmutated), leading to effective T cell response
§ Virus will not mutate protein needed for its own fitness
○ Rapid progressors - MHC molecules present mutated peptides (less critical peptides for the virus)
§ Poor recognition by T cells - poor T cell responses
§ Don’t have antigen presenting cells to prevent virus

Question 12

What are some clinical problems of MHC molecules

Answer 12

○ Susceptibility to infections depends on the types of MHC microbes
○ Major cause for organ transplant rejection
§ HLA molecules mismatch between donor and recipient
§ Graft-versus-host reaction
○ HLA association and autoimmune disease

Question 13

How are T-helper cells activated

Answer 13

• Right peptide recognised by right TCR is the first step - assisted by cytokines
○ Co-stimulatory signals enhance the interaction from the naïve T cells
○ Then activates T helper cells

Question 14

Explain the T cell responses against intracellular microbes

Answer 14

○ Activate TH1 cells
○ Antigen presenting cells (CD8) tell cytotoxic T lymphocytes what the antigen looks like
§ Finds MHC presented on all virus and kills it
○ Also stimulates B cell to produce antibodies and macrophages to undertake phagocytic activities

Question 15

Explain the T cell responses against extracellular microbes

Answer 15

○ Activates TH2 and TH17 cells
○ TH2 cells involved in stimulation of B cells and production of antibodies, leading to phagocytosis and complement
§ Also involved in allergic reactions (IgE) and killing of parasites
○ TH17 involved in stimulations of phagocytosis through neutrophils

Question 16

Which receptor type and T-helper cells are involved in humoral and cell-mediated response

Answer 16

Humoral - CD4 activate TH2 and TH17
Extracellular microbes targeted
Antibody production and phagocytosis
Cell mediated - CD4 activate TH1 - antibody production, complement, macrophages (phagocytosis)
CD8 tell cytotoxic T cells what antigen looks like
Intracellular microbes targeted

Question 17

What is the significance of the IgG:IgM ratio

Answer 17

Ratio of IgG to IgM is high in secondary response and low in primary response
Primary response produces high IgM
Secondary response produces high IgG
High IgG shows person better equipped for pathogen (vaccinated)

Question 18

What is the role of the different immunoglobulins

Answer 18

• IgG involved in phagocytosis, complement activation, neonatal immunity, toxin/virus neutralization
○ IgG transferred to foetus for protection for first few months against all microbes mother exposed to
○ A faster, stronger, longer duration and higher affinity response
• IgE - mast cell degranulation (allergies)
• IgA - found in breast milk, mucosal immunity
IgM - complement activation