Adaptive Immunity

Question 1

What is adaptive immunity?

Answer 1

Acquired by experience - you trigger it upon exposure
It is specific for an antigen
It takes a number of days to respond to exposure of a pathogen but subsequent responses are greater in amplitude and more rapid: MEMORY

Question 2

What is the overall process of adaptive immunity?

Answer 2

Establishment of infection, induction of adaptive response, adaptive immune response and immunological memory

Question 3

How can we understand the importance of adaptive immunity?

Answer 3

Looking at HIV
HIV infects CD4 receptors of T-cells
Once the T-cells deplete below a critical level, this leads to AIDs
Due to the weak immune system, you become susceptible to oppotunistic infections

Question 4

What is an antigen?

Answer 4

A protein that causes an immune response in the adaptive immune system

T-cell receptor (TCR) and B-cell receptor (BCR) – both specific for only ONE antigenic determinant

Question 5

What are some properties of B lymphocytes?

Answer 5

Produce antibodies
Humoral immunity
Matures in the bone marrow
Triggered by antigen to differentiate into plasma cells and memory B-cells
Combat bacterial and some viral infections

Question 6

What are some properties of T lymphocytes?

Answer 6

Cell mediated immunity
Starts in the bone marrow then moves to the thymus gland to mature
Combat viruses, fungi, intracellular bacteria and cancerous cells

Question 7

What does immunological memory lead to?

Answer 7

More responder cells available
More efficient antigen recognition/activation
Rapid and effective migration to tissues and lymph nodes
Longer lasting

Question 8

What are the primary and secondary lymphoid tissues?

Answer 8

Primary lymphoid organs:
Bone marrow and Thymus

Secondary lymphoid organs:
Lymph nodes, spleen and mucosal-associated lymphoid tissue (MALT)

Question 9

What are the two stages of differenciation of lymphocytes?

Answer 9

Antigen independent - occurs in the primary lymphoid tissues
Involves the acquisition of an antigen receptor
When T-cells and B-cells leave these tissues they can now respond to antigen

Antigen dependent - occurs in the secondary lymphoid tissues
Corresponds to an antigen-specific response

Question 10

Describe antigen recognition by T-lymphocytes?

Answer 10

It has a T-cell receptor to recognise the antigen (peptide epitope)
T-cells only recognise epitopes of antigens presented to them by Major Histocompatibility Complex (MHC) molecules on the surface of other cells
Antigens presented by MHC molecules are recognised by the T-cell receptor (TCR)

Question 11

What is the issue with the epitope of an antigen?

Answer 11

It is often buried within the antigen, so the antigen mut be broken down into peptide fragments
This allows the epitope to bind to a MHC molcule
The T-cell receptor can then bind to the complex of MHC and the epitope peptide

Question 12

What type of T-cell needs to be discarded?

Answer 12

T-cells that recognise self-antigen as we want to avoid autoimmunity

Question 13

Describe antigen-independent differentiation of T-cells?

Answer 13

Progenitor cells from the bone marrow begin to migrate to the thymus in the eight or ninth week of gestation in humans
Thymocytes (developing T-cells in the thymus) proliferate in the outer layer of the cortex and differentiate into distinct sub-populations of mature T-cells in the inner layer of the cortex
Mature T-cells can then migrate to the secondary lymphoid tissues

Question 14

What is a disorder of T-cells?

Answer 14

DiGeorge syndrome is a developmental defect in which the thymus does not form. Subjects with this disorder have B-cells, but few T-cells

Question 15

What happens to T-cells after antigen-independent differenciation?

Answer 15

The T-cells need T-cell receptors
T-cells are selected for those that have T-cell receptors (TCRs) that can bind to MHC molecules (positive selection)

T-cells are then eliminated when their TCRs recognise self-antigens (negative selection)
Carried out by dendritic cells
Leads to central tolerance

Question 16

What happens in the secondary lymph nodes?

Answer 16

Adaptive immunity is initiated
The fluid is drained at an area of infection before being passed around the lymphatic system in order to reach the T-cells

Question 17

What are the types of adaptive immunity?

Answer 17

Humoral - CD4 helper T-cells and B-cells: Antibodies against extracellular pathogens & their products

Cellular - CD4 helper T-cell and CD8 cytotoxic T-cell: Kill host cells infected with intracellular pathogens

Question 18

Describe CD4 T-cells?

Answer 18

They are helper cells
CD4 is a membrane glycoprotein and is present in the majority of T-cells
They play a central role in coordination of the immune response
There are 5 different types of CD4 T-cells, that interact with different innate cells

Question 19

Describe CD8 cytotoxic T-lymphocytes?

Answer 19

They recognise and bind to a virus infected cell
It programs the target for death, inducing DNA fragmentation
It keeps migrating to a new target until it dies via apoptosis

Question 20

Give an overview of how naive T-cells interact with dendritic cells?

Answer 20

Naïve T-cells are concentrated in the secondary lymphoid tissue
Secondary lymphoid tissues act as a site for antigens (presented by via dendritic cells) to encounter T-cells specific for that antigen
Naïve T-cells that encounter an antigen remain in the lymph tissue and proliferate

Question 21

How are antigens presented to T-cells?

Answer 21

By an antigen presenting cell (APCs)
Antigenic peptides are displayed by MHC molcecules on the APC
These peptides are recognised by the T-cell receptor (TCR)

Question 22

What are the two types of dendritic cells? What is their purpose?

Answer 22

Immature:
Found in the tissues and concentrated in the skin and mucosa
Constantly sampling their environment
Capture antigens for presentation to T-cells

Mature:
Present captured antigens on MHC molecules to T-cells in the secondary lymphoid tissues
Only cells that can present antigen to naïve CD4 + and CD8+ T cells

Purpose:
They take antigens from sites of infection to lymph nodes

Question 23

How do we activated naive T-cells?

Answer 23

Mature Dendritic cells deliver antigenic specific stimulation
Antigenic peptides presented on MHC class I and II molecules
T-cell receptors bind the peptide/MHC complex

Mature Dendritic cells also deliver co-stimulation
B7 is co-stimulatory molecule expressed on mature, but not immature dendritic cell
B7 on dendritic cell binds to CD28 on naïve T- cells
B7 binding provides a second signal that is required to activate naïve T-cells

Question 24

What can happen in the absence of co-stimulation?

Answer 24

An antigen in the absence of co-stimulation can result in T-cells becoming anergic (unresponsive) - this stops cells responding to antigens in the absence of an infection

Question 25

What is a CD4 T-cell effectors function?

Answer 25

CD4 T-cells act via cellular interactions and via the production and secretion cytokines (small proteins that modulate the function of other cells)
They are important for coordination of adaptive immune response e.g.
• The activation of B-cells in secondary lymphoid tissues
• Macrophage activation - mycobacterial infection
• Immunity to intestinal parasites

Question 26

How CD4 T-cells activate B-cells that recognise the same antigen?

Answer 26

1. Antigen capture (by endocytic pathway) and then chopped up by hydrolytic enzymes and presentation by B-cell
2. Antigen recognition by T-cell receptor
3. Help (cytokines and CD40/CD40 ligand) interactions from the T-cell
4. B-cell proliferation/ differentiation

Question 27

How do CD4 T-cells help in macrophage activation and why?

Answer 27

When macrophages take up a pathogen, some bacteria can survive inside them e.g. Mycobacterium tuberculosis - this causes TB

TH1 cells activate infected macrophages: in order to kill the intracellular bacteria
Involves recognition of antigenic peptides presented by MHC class II molecules

Activation of macrophages requires 2 signals provided by TH1 cells

• Priming signal such as the cytokine Interferon-gamma (IFN gamma)
• Second signal such as CD40 ligand (CD40L) which binds CD40 on the macrophage surface

Question 28

How do CD4 T-cells help in immunity to intestinl parasites?

Answer 28

The whipworm embeds in the surface of the surface epithelium of the colon
TH2 cells are required to respond to this
TH2 cells produce IL-13 to induce epithelial cell repair and mucus
IL-5 then recruits and activate eosinophils
They then drive B-cells and mast cells

TH2 also participate in Type I hypersensitivity reactions (allergic responses)

Question 29

What is the function of CD8 T-cell effector cells?

Answer 29

Cytotoxic T-lymphocytes (CTLs) are CD8+ effector T-cells
CTLs kill host cells that are infected with intracellular pathogens (viruses and bacteria) or which are cancerous
They recognise antigenic peptides displayed by MHC class I molecules
They cause cell presenting the antigen (target cell) to die via apoptosis: programmed cell death

Question 30

How do CD8 T-cells kill cells exactly?

Answer 30

Killing is via the secretion of cytotoxic molecules released from CTL granules (stored in the cytoplasm)

Granule secretion is polarised towards the target cell
They secrete perforin and granzymes
Perforin forms pores in the target cell’s plasma membrane through which granzymes enter the cytoplasm
Granzymes induce apoptosis in the target cell
A virus can’t replicate in a dead cell

Therefore important for elimination of intracellular pathogens