Adaptive Immune Response

Question 1

How is the adaptive immune response initiated?

Answer 1

The adaptive immune response is initiated as activated dendritic cells present microbial antigens to t-cells.

Question 2

What are the primary lymph organs?

Answer 2

Thymus and bone marrow.

Question 3

Where do lymphocytes develop?

Answer 3

Bone marrow -> Thymus -> Secondary lymphoid organs

Question 4

What are the three key players of the adaptive immunity? And what are their functions?

Answer 4

• B-cell, produce antibodies
• CD4+ t cell, produce cytokines
• CD8+ t cell, recognise and remove viruses

Question 5

What antigens undergo clonal deletion, selection or expansion?

Answer 5

• Cells that recognize self-antigens undergo clonal deletion

- Cells that recognize foreign antigens undergo clonal selection and expansion

Question 6

What are the two forms of immunoglobulin produced from b-cells?

Answer 6

1. Surface Ig present on b-cell membrane (b-cell antigen receptor + transducer of activation signals)
2. Secreted Ig - plasma cells once the b-cell has activated

Question 7

How do B-cells recognise pathogens?

Answer 7

B-cells bind directly to the pathogen via their antigen receptor. They then release their antibodies.

Question 8

What are the main structural components of an antibody?

Answer 8

1. The fab region - where the antigen binds, has variation due to separate V,D,J
2. Fc constant region - which can be 1/5 isotypes; IgM,D,G,A + E. Will determine if the antibody reacts with the antigen.

Has 2 binding regions, per antibody.

Question 9

How is Ig diversity determined?

Answer 9

• Variability occurs as the variable region’s light chain has Variability and Joining
• While its heavy chain changes in Variability, Diversity and Joining.
• The light chain’s constant region is known as Alpha + Beta.
• Also nucleotides undergo gene deletion and insertion, creating more variability.

Question 10

How are antibody isotypes determined?

Answer 10

Antibody isotypes are determined by the heavy chain constant region.

Question 11

What are the functions of the IgG antibody?

Answer 11

The IgG antibody binds to Fc receptors on monocytes, macrophages and NK cells. This can activate the complement system.
*IgG can cross the placenta
The fab region will neutralize toxins.
The Fc region will cause opsonisation, trigger the classical pathway of the complement cascade and induce the release of cytotoxic products from macrophages/ NK cells.

Question 12

What are the functions of IgE antibodies?

Answer 12

IgE antibodies respond during an allergic response and responds to parasites.
The Fc region triggers the degranulation of mast cells and eosinophils.

Question 13

What are the functions of IgM antibody?

Answer 13

IgM is expressed on naive b-cells. Activate the complement system and forming the membrane attack complex so bacteria + mammalian cells undergo lysis.
The fab region will neutralize toxins.
The Fc region triggers the classical pathway of the complement system.

Question 14

What are the functions of IgA?

Answer 14

IgA is found in mucous secretions in the airways, gut and breast milk.

Question 15

What is the overall process of b-cell activation?

Answer 15

B cells develop in the bone marrow -> undergo gene arrangement + clonal deletion -> mature cells leave the bone marrow -> encounter an antigen -> clonal expansion -> isotype switching -> affinity maturation

Question 16

What is isotype switching?

Answer 16

Isotype switching is when naive b-cells no longer express IgM once activated. With help from Th1 cells the mature b-cells will express IgG or with help from Th2, the mature b-cells will express IgE.
The quanity of IgG and IgE increase with secondary exposure to the same antigen.

Question 17

What are the two major types of t-cells?

Answer 17

CD8+ / Cytotoxic t-cells - Lysis cells infected by the pathogen. Secrete antiviral and inflammatory cytokines (TFNy and TFN alpha)

CD4+ helper t-cells - secrete antiviral and inflammatory cytokines for b-cells, CD8 t cells and macrophages.

Question 18

How do t-cells recognise antigenic peptides?

Answer 18

1. Antigen is broken down into peptide fragments
2. Epitode binds the MHC
3. T-cell receptor binds to the complex of epitode + peptide.

Question 19

How do t-cell receptors differ?

Answer 19

TCR genes can be rearranged, creating different t-cell receptors.
TCR alpha genes can vary V, J and C of gene segments
TCR beta genes can vary V,D, J and C of gene segments

Question 20

What do MHCs do?

Answer 20

MHCs are recognised by t-cell and expresses peptide antigens. The T-cell with receptor binds to the MHC class I with the peptide.

Question 21

What are the two types of MHC molecules? What do they include? And where are the peptides generated?

Answer 21

MHC I - includes; HLA-A, HLA-B, HLA-C
- Peptides are generated by proteolysis in the cytoplasm, load up onto the MHC in the lumen of the ER
MHCII - HLA-DR, HLA-DP AND HLA-DQ
- Peptides are generated in the endosomal network

Question 22

What are the complementarity determining regions (CDRs) of MHCs?

Answer 22

The CDR connect the MHC and peptide. Are visible points on the PCR that recognise the MHC molecule and peptide

Question 23

How do individuals have polymorphic variation in regards to MHCs?

Answer 23

MHCs have polymorphic variation due to haplotype (combination of MHC alleles). Ensures a pathogen is unable to go unrecognized.

Question 24

What are the overall steps in a T-cells life?

Answer 24

T cell progenitors are produced in the bone marrow -> mature in the thymus -> TCR genes are rearranged / t-cell education -> mature cells leave the thymus -> t-cells encounter the LN on antigen presenting cells -> clonal expansion + differentiation -> effector functions -> t-cell memory is established

Question 25

What is t-cell education?

Answer 25

T-cell education is positive and negative selection.
Positive selection: TCR doesn’t bind to self MHC molecules. T-cell dies to remove unreactive t-cells/
Negative Selection: TCR binds to MHC/peptide complexes too tightly. The t-cells die to remove the autoreactive t-cells.

Question 26

What is the purpose of antigen present cells?

Answer 26

APCs are present in tissues, take up antigens and display their peptides on the MHC molecules. This activates naive t-cells via the creation of three signals.
Signal 1: TCR of MHC + antigen
Signal 2: Co-stimulation of CD28: B7 or CD80/86.
Signal 3: Cytokine receptor stimulation
APCs migrate to lympth nodes
T-cells undergo activation, expansion and differentiation

Question 27

What are some variations of CD4+ effector t-cells? And what are there functions?

Answer 27

TH1 Functions:
secrete IFN- y,
activates macrophages to eliminate microbes
stimulates b-cells for IgG subclasses via complement and coating of antibodies.

TH2 Functions:

• Secrete IL-4 triggering b-cells to make IgE
• Secrete IL-5 to activate eosinophils
• Secrete IL-13 for mucous secretion, expelling of microbes and activation of tissue macrophages.

TH17 Functions:
- Secrete IL17 to recruit neutrophils and promote inflammation

Regulatory T-cells:

• Down regulates the immune system
• Prevents autoimmune diseases, maintains homeostasis and regulates response to exposure