Lecture 2: Diversity and Development

Question 1

Antigen Types

Answer 1

• Exogenous antigens - non-self
- e.g. allergens, surface of foreign cells, toxin, etc

Endogenous antigens

• antigens produced from within the body’s own cells
• e.g. antigens presented by cells that have become infected by bacteria or virus, blood group antigens on RBC, HLA antigens

• Autoantigens
- Normal antigens on cells of the body mistakenly identified as nonself - Causes autoimmune diseases

Question 2

What is antigen epitope?

Answer 2

the part of an antigen molecule which is recognised by the immune system

Question 3

What are poly/multli and monovalent antigens

Answer 3

antigens can be monovalent (one epitope) or multivalent/polyvalent (multiple different epitopes
poly = same)

Question 4

Difference between MHC 1 and MHC 2 STRUCTURE

Answer 4

MHC 1: 3 alpha chains, 1 beta, one cytoplasmic tail, open peptide binding cleft

MHC 2: 2 alpha and 2 beta chains, closed peptide binding cleft, 2 cytoplasmic tails.

Question 5

What chromsome code for MHC

Answer 5

6

Question 6

MHC 1 vs MHC 2

- expressed on what cells and present to what cells

Answer 6

• MHCI

• expressed on all nucleated cells (WBC/plt not RBC)
• present antigens to Tc cells
• NK cell self tolerance

• MHCII
- expressed primarily on APC - present antigen to Th cells

Question 7

What are the 3 antibodies functions

Answer 7

Neutralisation - Antibodies can bind and neutralise the effects of toxins produced by pathogenic microbes

Opsonisation - antigens with antibodies bound to their surface are easily recognised by macrophages

Complement activation – antibodies activate the complement system by coating a bacterial cell

Question 8

Define Affinity

Answer 8

The affinity of the bond is the strength of binding of a single epitope to a single antigen binding site and it is independent of the number of sites.

Question 9

Define Avidity

Answer 9

Avidity is the total binding strength.

Question 10

Exception to affinity and avidity

Answer 10

If the affinity of the antigen-binding sites

in an IgG and an IgM antibody is the same, the IgM molecule (with 10 binding sites) will have a much greater avidity

Question 11

What CD’s do TH, Tc and T reg cells have

Answer 11

TH: CD4 binds to MCH 2
Tc: CD8, Binds to MCH 1
T reg: CD4 and CD25

Question 12

Describe the process of T cell production and POS and NEG selection.

Draw the diagram with the capsule, cortex and medulla

Answer 12

refer to lecture

Question 13

Describe the process of Cytotoxic T cell destruction on infected cell

Answer 13

Have a co-receptor CD8 on their cell surface
* TCR and CD8 bind to MHC class I molecules
* This allows recognition of normal cells that are
infected by a pathogen (also cancers and
transplant tissue.)
* Tc cell becomes activated and produces
molecules that kill the infected cell, destroying
the pathogen in the process (apoptosis)
* Preformed cytotoxic protein (granzymes and
perforin) for quick response
* Fas ligand also capable of inducing apoptosis.
* IFN-γ also released by Tc – inhibits viral
replication, activates macrophages
* Tc can recycle to kill multiple targets

Question 14

What granules do Tc cells have

Answer 14

Granzymes and Perforin (makes holes)

Question 15

Describe Helper T cells

• What receptor?
• Functions
• TH1, TH2 and TH17 functions

Answer 15

• Have co-receptor CD4 on their cell surface.
• TCR and CD4 bind to MHC class II molecules
• Required for almost all adaptive immune responses.
(cell-mediated and humoral immunity)
• Functions:
- control many B cell functions including proliferation and differentiation
- activate B cells to secrete antibodies
- help activate cytotoxic T cells
- help activate macrophages

TH1: activate macrophages and Tc
TH2: Activate B cells
TH17:Recruit neutrophils and macrophages

Question 16

Describe Memory T cells

• What receptor?
• Functions
• process of Memory T cells

Answer 16

~~~
Can be either CD4 or CD8
* Persist after infection
resolved
* Immunological memory -
Quickly expand to large numbers of effector T cells upon re-exposure of antigen
* Faster and more effective response

Question 17

Describe Treg cells

• What receptor?
• Function
• Mechanisms

Answer 17

have CD4, CD25 and intracellular FoxP3

do not activate the immune system
• play a protective role by shutting off the immune
response when it is no longer needed
– maintains immunological tolerance
locate T cells which have escaped neg regualtion and shut them down

Mechanisms:
- suppression by inhibitory cytokines
(IL-10, TGFB, IL-35 and adenosine) 
- suppression by cytolysis
(Granzime and perforin)
- suppression by metabolic disruption
(competition for IL-2 )
- suppression by downregulating dendritic cell
maturation or function

Question 18

B cell maturation Process

Answer 18

Begins with rearrangement of VDJ chain genes of heavy and light chains of antibody
• Firstly heavy chain VDJ rearrangement from Pro-B cell stage to Pre-B cell stage.
• Then light-chain VJ gene re-arrangement from Pre-B-cell to an immature B-cell.
• This commits the immature B-cell to a particular antigenic specificity.
• Immature B cell expresses mIgM on its cell surface.
• At this stage of development, B-cell is still not fully functional.
• Immature B cell leaves the bone marrow and undergo further differentiation in the
secondary lymphoid organs and in the circulation.

The co-expression of IgD and IgM signals full maturation.
• This progression involves a change in RNA processing of the heavy chain primary transcript to
permit the production of two mRNAs (encoding μ chain and 𝛿 chain).
• The mature naïve cell is now ready for exposure to antigens.
• Depending on the nature of the antigen, B cell activation proceeds by two different routes
- one dependent of a Th cell, the other not.

Question 19

Describe the T-cell INDEPENDENT and DEPENDENT process

Answer 19

Independent:
1. Antigen binds to B-cell receptor on B cell and this triggers the b-cell to undergo proliferation and differentation into plasma cells which secrete antibodies.
This is a weaker reaction than that which uses T cells

Dependent:

1. The B-cell acts as a APC where it phagocytoses and presents MCH 2/antigen complex on cell surface
2. The TH cell recognises the MCH2 complex and binds and causes the secretion of cytokines.
3. Cytokine release (IL-4, 5, 6) triggers the B-cell to proliferate and differeniate into both plasma and memory cells.

Question 20

B cell differentiation after activation

Answer 20

Activated mature B cell proliferates and becomes a blasting B cell.
• These B cells form germinal centers in the lymph nodes.
• The germinal center B cells undergo somatic
hypermutation and class switch recombination (antibody
class switching).
• Plasma cells (antibody producing) and long-lived
memory B cells are produced.

Question 21

Describe the process of B-cell class switching

Answer 21

Mature B cells express IgM and IgD as they are the first the heavy chain segments on the Ig locus
During switiching there is cutting of the locus and then rejoining of the locus causing a new heavy chain segment to be at the front

Question 22

Describe the overall process of activation and class switching of B-cells

Answer 22

1. APC presents the MCH2/antigen compelx to TH cells
2. B7 is expressed on APC and this interacts with CD28 on the TH cell causing activation of TH cell
3. Activated TH cell interacts with B cell CD40 ligans and causes activation of B cell proliferation, differeniation and secrete antibodies.
4. The activated TH cell secretes cytokines that determine the class switching, ie IL-4 and IL-5

Question 23

4 characteristics of the adaptive immune response

Answer 23

• Antigen specificity
• Diversity
• Immunologicmemory
• Ability to distinguish between self and non-self

Question 24

Epitopes can either be… DRAW

Answer 24

Linear or conformational