Immune System 3

Question 1

B cell activation and antibody production ?

Answer 1

• mature B cells enter a secondary lymphoid tissue
• in absence of its sepcific antigen, the B cells leave the lymph node and recirculate
• Naive B cells encounter an antigen
  in a secondary lymphoid tissue
• when this happens, antigen-specific B cells are futher activated by T helper cells
• some activated B cells proliferate in primary follicle + differentiate in plasma cells (secrete IgM)

Question 2

What happens to activated B cells after they migrate to secondary lymphoid follicles?

Answer 2

• mature more slowly
• after diffferentiation they tranform into plasma cells secreting high-affinity antibodies (IgG, IgA)
• also develop into memory B cells
• activation of memory cells produces quicker + stronger response

Question 3

structure of T cell receptor (TCR)?

Answer 3

• made of 2 polypeptide chains chains α and β
• each chain has variable + constant regions
• each V chain contains 3 CDRs
• TCR complex also includes CD3 complex proteins and the ζ chain(zeta), which are required for signal transduction.

Question 4

What are the key differences between MHC class I and class II molecules?

Answer 4

• different structures and expression patterns
• present polypeptides from different sources

Question 5

What are the two types of MHC molecules and their key differences?

Answer 5

• MHC class I = expressed on all nucleated cells
• binds TCR of CD8+ T cells
• MHC class II = expressed on APC
• binds TCR of CD4 T helper cells

Question 6

Why are MHC molecules important in immune response?

Answer 6

• MHC molecules are polymorphic, meaning they have many genetic variants, which play a role in transplant rejection and diversity in immune responses.

Question 7

How are endogenous antigens presented to CD8+ T cells?

Answer 7

• intracellular endogenous antigens are presented by MHC class I molecules
• antigens must be procesed into peptides before binding MHC
• MHC Class I molecules present the peptide on the cell surface (all nucleated cells have MHC-I molecules)
• CD8+ cytotoxic T cells recognize the antigen and can kill the infected cell.

Question 8

How are exogenous antigens presented to CD4 T helper cells ?

Answer 8

• Exogenous (extracellular) antigens are internalised and
  presented by MHC class II
• proteins must be processed to peptides before binding MHC
• The MHC Class II-peptide complex is presented on the surface of the APCs for recognition by CD4+ T helper cells.

Question 9

Similarities + differences in T + B cell development ?

Answer 9

• Both originate from bone marrow stem cells.
• Both rearrange receptor genes to produce a unique receptor (TCR for T cells).
• Both express a pre-receptor before full maturation.
• Both undergo negative selection to eliminate self-reactive cells.
• T cells develop in the thymus, not the bone marrow.
• T cells undergo positive selection (eliminate non-functioning cells)

Question 10

What can an immature T cell recognize when it leaves the bone marrow and migrates into the thymus?

Answer 10

• Can recognise self MHC and respond to
  a foreign peptide (defence)
• Can recognise and respond to self MHC
  plus self peptide (danger!) = negative selection
• No recognition of self-MHC (useless) = positive selection

Question 11

What happens during positive selection of T cells ?

Answer 11

• selects T cells that can recognize self-MHC and has a TCR that can bind to self-MHC molecules
• Occurs when the TCR of double-positive
  (CD4+CD8+) T cells recognise MHC
  molecules expressed on cortical epithelial cells
• Only 1 - 2% capable of recognising
  own MHC will be selected
  – Vast majority of T cells with non-
  binding TCR die via apoptosis

Question 12

what happens during negative selection ?

Answer 12

• eliminates cells with a TCR binding tightly to self-peptides
• TCR od CD4 or CD8 cells recongnises MHC on dendritic cells/macrophages with high affinity
• T cells with high-affinity TCRs for self-peptide-MHC complexes undergo apoptosis
• T cells with moderate-affinity TCRs for self-peptides survive and mature.

Question 13

How do T cells become effector T cells + their function after ?

Answer 13

• T cells acquire effector functions in secondary lymphoid tissues after encountering antigen on dendritic cells and after the interaction of co-
  stimulatory molecules (e.g., CD28-B7).
• CD8+ T cells acquire cytotoxic activity. They kill the cells bearing the MHC I –peptide complex
• CD4+ T cells (helper TH cells) mainly function by secreting cytokines–> effects on other cell types

Question 14

What happens to T cells after acquiring effector functions?

Answer 14

• No longer require co-stimulation
• Change of location
• exit lymph nodes and enter tissues at infection sites via activated endothelial cells.

Question 15

2 ways to activate CD8+ T cells ?

Answer 15

• Requires high levels of co-stimulator activity (e.g. IL-2)
  1. Direct activation from infected cells presenting MHC I/peptide complexes.
  2. Help from CD4+ T cells via cytokine release.

Question 16

What happens to CD8+ T cells after activation?

Answer 16

• Exit the lymph nodes + enter bloodstream
• Enter infection sites to eliminate the pathogen.

Question 17

3 mechanisms of killing by CD8+ T cells ?

Answer 17

1. Secretion of cytotoxic granules
   ▪ perforin = polymerises in membrane
   ▪ granzymes (proteases) enter cell
2. Fas ligand on T cell interacts with
   Fas on target -> cell to die
3. CTLs can also secrete cytokines
   ▪ Secrete IFNy (as NK cells)
   ▪ Inhibits viral replication
   ▪ Upregulates MHC class I expression
   and antigen presentation
   ▪ Increases macrophage phagocytosis
   of dead cells
   - both 1 and 2 induce apoptosis

Question 18

what are the types of specific CD4+ T helper cells ?

Answer 18

• TH1: active against intracellular pathogens
• TH2: active against extracellular pathogens
• TH17: active against extracellular pathogens
• TFH & Treg: regulatory functions
• Recognise MHC II peptides complexes presented by APC cells

Question 19

What is the function of Tʜ1 cells?

Answer 19

• active against intracellular bacteria and certain viruses
• Release cytokines to activate macrophages to increase their intracellular killing of pathogens.
• Help the macrophages

Question 20

What is the function of Tʜ2 cells ?

Answer 20

• active against extracellular parasites and allergens
• Release cytokines
• Support antibody production, particularly class-switching toIgE, leading to activate mast cells.
• Also activate eosinophils.
• Help the B cells

Question 21

what is the function of Tʜ17 cells ?

Answer 21

• Active against extracellular bacteria and fungi
• Induced early in infection.
• Release cytokines to amplify neutrophilic responses (phagocytosis).
• Help the neutrophils

Question 22

what is the function of TFH cells ?

Answer 22

• Supporting B cells maturation
• present in lymph nodes where they stimulate IgM production during the primaryresponse
• support isotype switch to IgG, IgA etc during the secondary response

Question 23

what is the function of Treg cells ?

Answer 23

• Regulatory cells
• Only type that can inhibit antigen presentation to T cells, blocking their activation (potential role in autoimmunity)

Question 24

How do Cytotoxic T cells (CTL or CD8+) recognize and respond to viral infections?

Answer 24

• recognise viral peptide + MHC class I
• Kill virus infected cells
• release IFNγ = induces resistance to the viral replication in the cells