Immunology - Humoral and Cell-Mediated Immunity

Question 1

What mediates humoral immunity?

Answer 1

Antibodies

Question 2

What are the 2 regions and their roles in antibodies?

Answer 2

Fab region - Antigen binding
Fc region - Antigen elimination (binds Fc receptors)

Question 3

Explain the 4-chain structure of antibodies
- What 2 types of chains make this up?
- Molecular weights (kD)
- What joins these chains?

Answer 3

Light (L) chain - 25kD
Heavy (H) chain - 50kD

2 Heavy chains and 2 Heavy chains
- Joined by S-S bridges

Question 4

Which regions within antibodies are variable and constant?
- Role and traits of variable and constant regions

Answer 4

Variable (V) region - Bind antigen; Differ between antibodies with different specificities
Constant (C) region - Same for antibodies of a given H or L chain class type

Question 5

What encodes Variable and Constant regions?
How can new specificity be achieved?

Answer 5

These regions are encoded by separate exons

Multiple V region exons can recombine during B cell differentiation to give rise to new variable region and specificity

Question 6

What are the 4 understood Immunoglobulin classes?
- What is each important in?
What structural feature sets each class apart?

Answer 6

They all differ in the amino acid sequence of the heavy chain

IgG (γ) - Main class in serum and tissues; Secondary response
IgM (µ) - Primary response
IgA (α) - In serum and secretions which protect mucosal surfaces; Secretory component protects them proteolysis
IgE (ε) – Very low concentrations; Allergy and protection against large parasites

Question 7

What are the 2 light chain types?
- Give 2 examples of a nomenclature of an antibody including light chain type

Answer 7

Kappa (κ)
Lambda (λ)

e.g. IgGκ, IgGλ

Question 8

Characteristics of a primary and secondary response?

Answer 8

Primary - Slow and small response of antibody production
Secondary - Very rapid and massive production of IgG

Question 9

Explain class switching in secondary response and how it provides flexible response?

Answer 9

B cells can switch from IgM to IgG, IgA or IgE after antigen stimulation depending on type and route of infection
Same V region gene recombines with different C region genes
- Same antigen specificity linked to different Fc functions

This all allows for flexible response Flexible response

Question 10

Distribution of 4 Immunoglobulin classes in the body?
- One has 2 types with different distribution

Answer 10

IgG - Serum and extracellular blood; Can cross placenta
IgM - Usually restricted in blood
IgA monomer - Blood and extracellular fluid
IgA dimer - Mucosal secretions, saliva, breast milk
IgE - Mainly associated with mast cells beneath epithelial surfaces e.g. Respiratory tract

Question 11

What is affinity maturation?
- How does this happen? (2 ways)

Answer 11

• Somatic hyperstimulation of V region genes in B cells responding to antigen
• Mutations increasing binding affinity are selected

Question 12

Effects of all Immunoglobulin classes on pathogens? (3 effects)

Answer 12

Complement mediated lysis (bacteria and enveloped viruses)
Enhancement of phagocytosis (opsonisation)
Enhanced killing of infected cells by NK cells

Question 13

Specific effects of IgA on pathogens? (3 effects)
- Specify monomeric, dimeric or both

Answer 13

Block adherence
Neutralise toxins
Agglutination of bacteria, inhibiting movement (dimeric IgA)

Question 14

Specific effects of IgG on pathogens? (3 effects)

Answer 14

Block adherence
Neutralise toxins
Block uptake of nutrients

Question 15

Specific effects of IgM on pathogens? (2 effects)

Answer 15

Block adherence
Agglutination of bacteria, inhibiting movement

Question 16

How do antibodies activate complement (“Classical Pathway”)?
- Why is IgM better than IgG at activation

Answer 16

C1q interacts with 2 Fc regions
- IgM (pentamer) better activator than IgG
Activation leads to opsonisation, inflammation and cell lysis

Question 17

How do antibodies like IgG and IgA monomer act as opsonins?

Answer 17

They bind bacterial Fc receptors and direct pathogen toward the Fc receptors on phagocytes

Question 18

What do infected host cells express on their cell surface?
How can NK cells take advantage of this?
This is called ADCC, which means?

Answer 18

Infected host cells express foreign proteins on their cell surface (e.g. virus envelope proteins)

Allows specific recognition by NK cells with appropriate receptors; These then induce apoptosis

This is called Antibody Dependent Cell-Mediated Cytotoxicity (ADCC)

Question 19

How does the Thymus influence things like class switching and B cell response?
- Name of antigens?
What is the name of antigens which are not influenced by the thymus?

Answer 19

B cell response and class switching require T cell help; These are matured in the Thymus
- Thymus-dependent

Thymus-independent (TI) antigens; Induce B cell response in absence of T cells

Question 20

Which lymphocytes mediate Cell-Mediated immunity?
Traits of these lymphocytes?

Answer 20

T cells
Mature in Thymus
Bind antigen through specific T cell receptors

Question 21

What are the 2 major subpopulations of T lymphocytes?
- Receptor type
- Roles of each

Answer 21

T Helper Cells (CD4 +ve)
- Help B cells make antibody
- Activate macrophage and NK cells
- Help development of cytotoxic T cells

T Cytotoxic Cells (CD8 +ve)
- Recognise and kill infected host cells

Question 22

What is a TCR and what part of an antibody is it similar to?
- What happens with exons like they do in antibodies?

Answer 22

T Lymphocyte Receptor (TLR) is similar to antibody Fab arm
- Exons which encode V region recombine during T cell differentiation (somatic recombination)

Question 23

How do T cells recognise antigen?
- How does this differ to B cells
What is an APC?

Answer 23

T cells can only recognise host cell-associated processed antigen
- Unlike B cells which can recognise free antibody

APC - Antigen Presenting Cell

Question 24

What is the MHC and what does it do?
Which cells express MHC I and II and what do they both do?

Answer 24

Major Histocompatibility-Proteins (MHC) – Transports processed antigen to the surface of host cells

MHC I - Expressed by all nucleated cells; Display ENDOgenous peptides to CD8 +ve (type?) T cells

MHC II - Expressed by Macrophages, Dendritic (very specialised) cells and B cells; Display EXOgenous peptides to CD4 +ve (type?) T cells

Question 25

How does the MHCI work?
How does this interact with CD8 T cells?

Answer 25

Viral proteins of infected cell are broken down in cytosol and transported to ER, bind MHCI and are presented on the surface

CD8 (cytotoxic) T cells recognise surface peptides bound to MHCI and induce apoptosis

Question 26

How does MHCII work?
How does this interact with CD4 T cell?

Answer 26

Macrophage/Dendritic cell/B cell internalise and break down foreign material
Peptides bind to MHCII and are presented on the surface

CD4 (helper) T cells recognise surface peptides and help B cells make antibody as well as produce cytokines to activate other leucocytes

Question 27

What are ‘naïve’ CD4 cells and what do they develop into?
What decides what they develop into?

Answer 27

Naïve CD4 cells recognise Peptide-MHCII and differentiate into different subsets of CD4 cells which produce different cytokines

Different types are induced by different pathogens and facilitate different immune functions

Question 28

What are the 5 different CD4 cell subtypes?

Answer 28

TH1
TH2
TH17
TFH
TReg

Question 29

What do CD8 T cells do once activated and bind target cells?
How do some viruses evade CD8 cells?

Answer 29

They release granzymes (proteases) into target cell via perforin channel, inducing apoptosis

Viruses can down regulate MHCI expression to evade CD8 cells

Question 30

What is generated in Cell-mediated immunity to help with secondary responses?

Answer 30

Memory T and B cells