Adaptive Immune System

Question 1

What are the two mechanisms/types of adaptive immune system?

Answer 1

Antibody-mediated

Cell-mediated

Question 2

What is an antigen?

Answer 2

Any molecule that reacts specifically with an antibody or antigen receptor on a lymphocyte.

Question 3

What is an immunogen?

Answer 3

An antigen that can induce an immune response

Question 4

What is antigenicity/immunogenicity?

Answer 4

The relative ability of an antigen to elicit an immune response

Question 5

What are antigenic determinants?

Answer 5

Aka epitopes
They are discreet regions of an antigen molecule specifically recognized by the adaptive immune response
-Stretch of 10 or more amino acids
-3-D structure/protrusion in a molecule

Question 6

What is antibody/humoral immunity?

Answer 6

In response to extracellular antigens, B lymphocytes (B cells; developed in the bone marrow) trigger to proliferate and differentiate into plasma cells called antibodies.
The main cells of humeral immunity are are antibodies that are produced by B-cells. They neutralize free-floating particles (bacteria, toxins, free viruses). They are Y-shaped proteins

Question 7

What are the two functional regions of antibodies?

Answer 7

There are 2 identical arms (Fab) and 1 stem (Fc)
The arms bind to specific antigen
The stem tags antigens for destruction by other immune system components

Question 8

What makes up the body of antigens?

Answer 8

2 light chains
2 heavy chains
Each chain can be divided into two broad regions: the variable region (lots of diversity; allows the antibodies to bind to specific organisms) and the constant region (very little diversity)

Question 9

How are light chains classified?

Answer 9

There are two types of light chains based on the amino acid sequence of the constant regions: lambda and kappa
A given B cell will produce an antibody of only one specificity
Both L chains are identical, so either they will both be L-kappa or L-lambda

Question 10

How are heavy chains classified?

Answer 10

There are five types based on amino acid sequence of the constant region. This different types ‘class’ the antibody type: mu (IgM), gamma (IgG), alpha (IgA), delta (IgD) and epsilon (IgE)

Question 11

Describe IgG

Answer 11

Makes up 75% of serum immunoglobins
Has a basic monomeric structure
Four subclasses, based on amino acid sequence of the C regions of the H chains: IgG1, IgG2, IgG3 and IgG4
-IgG1 is the most prevalent

Question 12

What are the functions of IgG?

Answer 12

Opsonization - enhances phagocytosis, acts as a flag for phagocytes when Fab is bound to antigen and Fc is freely exposed
Neutralizes viruses and toxins
Main antibody type made in secondary response, when body encounters antigen for the second and subsequent times
It also crosses the placenta and provides passive immunity for the fetus from the mother

Question 13

Describe IgM

Answer 13

Monomeric, when attached to B cell surface as a receptor

Pentameric in serum (5 monomers held together by a J chain). It can bind to 10 antigens

Question 14

What are the functions of IgM?

Answer 14

First antibody class produced during primary response and IgG takes over later. IgM levels go down after a week or so following infection
Very efficient against bacteria
Antigen receptor on B cells
Activates part of the innate defences
Agglutinates particulate antigen e.g., bacteria

Question 15

Describe IgD

Answer 15

Monomeric form
Found in serum and on B cell surface as a receptor
Very low amounts (less than 2% of total serum antibodies)
Unknown function (possibly a back-up in case IgG is non-functional or not made)

Question 16

Describe IgA

Answer 16

Primary antibody produced by cells of the mucous membranes
Secretory antibody, found in mucosal secretions (very important)
Low amounts
Monomeric in serum
Dimeric in secretions

Question 17

What are the functions of IgA?

Answer 17

Neutralizes bacteria and viruses by preventing them from attaching to mucous membranes
Passive immunity (breast milk)

Question 18

Describe IgE

Answer 18

Monomeric form, low levels in serum

Antigen receptors are on mast cells (tissues) and basophils (blood)

Question 19

What are the functions of IgE?

Answer 19

Anaphylactic hypersensitivity

Question 20

List the steps of the classical complement pathway

Answer 20

When an antibody binds to an antigen, it activates C1
This converts into C1 qrs. C1 qrs splits C4 and C2 forming C4b2a, which has a C3 convertase enzymatic activity. The remaining events are the same as the alternative pathway

Question 21

What do antibodies do?

Answer 21

They activate phagocytic cells (phagocytes are good at recognizing the constant region of antibodies, which causes activation)
Neutralization (some antibodies can neutralize aka block the action of the pathogen; e.g., they can sometimes suffocate a bacteria by targeting nutrient channels in bacteria)

Question 22

What are T-lymphocytes?

Answer 22

Aka T-cells are apart of cell-mediated immunity
They mature in the thymus
They do not recognize free antigen, rather antigen must be presented by one of the body’s own cells

Question 23

What do T cells do?

Answer 23

They bind to peptide derived from intracellular organisms complexed with major histocompatibility complexes (MHC)
T-cell receptor (TCR) binds to the complex of MHC molecule and peptide. This activates the T-cell, causing it to help macrophages kill intracellular parasites

Question 24

There are two major functional populations of T-cells. What are they and what separates them?

Answer 24

There are cytotoxic T-cells and helper T-cells

They are differentiated by surface markers (cluster of differentiation)

Question 25

What are cytotoxic T-cells?

Answer 25

They have CD8 receptors and they destroy infected or cancerous cells
They recognize antigen presented by MHC class I molecules

Question 26

What are helper T cells?

Answer 26

They have CD4 receptors and they activate B cells (Th2) and macrophages (Th1)
They recognize antigen presented by MHC class II molecules

Question 27

What do T cells do once they are activated?

Answer 27

T cells help macrophages kill intracellular parasites - Th1 cells bind to class II MHC causing the T cell to release macrophage activating factor (IFN gamma) and NO radicals
T cells inhibit intracellular replication of viruses; viral infected cells express class I MHC (which is recognized by cytotoxic T cells

Question 28

What is the immune response against large infectious agents?

Answer 28

Antibody-dependant cellular toxicity (ADCC): Effector cells bind via their surface receptors to antibody molecules, coating the target cells. This causes the activation of effector cells and the release of material that damages the targets

Question 29

What cells are involved in ADCC?

Answer 29

Macrophages, eosinophils, NK cells

Question 30

What is the lymphoid system?

Answer 30

A collection of tissues and organs designed to bring B and T cells into contact with antigens that enter the body. Lymphocytes are highly specific, and only recognize 1 or 2 antigens. This is essential that appropriate lymphocyte encounters, given the amount of antigen to mount an immune response is low

Question 31

Describe the role of the lymphatic vessels

Answer 31

They carry fluid called “lymph” collected from fluid that bathes body’s tissues
As oxygen and blood travel from the heart and lungs through capillaries, this fluid goes into surrounding tissues supplying them with oxygen and nutrients from blood
Most of the fluid re-enters the capillaries and returns to the heart and lungs, but some enters the lymphatic vessels and travels to the lymph nodes, where cells and proteins are removed

Question 32

What are primary lymphoid organs? What is their importance?

Answer 32

Bone marrow and thymus
Hematopoietic stem cells develop into B and T cells
Both B and T cells originate in the bone marrow but only B cells mature here
T cells mature int he thymus
Once mature, lymphocytes gather in secondary lymphoid organs waiting to encounter an antigen

Question 33

What are secondary lymphoid organs?

Answer 33

Sites where lymphocytes gather to collect antigens (lymph nodes, spleen, tonsils, adenoids, appendix)
They are situated at strategic positions in the body to capture antigen (e.g., lymph nodes capture antigens from lymph, spleen captures antigens from the blood)
After lymphocytes make contact with antigen, they proliferate forming clones of cells specific for that antigen

Question 34

Some lymphoid organs are less organized but serve the same function. Give some examples

Answer 34

Mucosal-associated lymphoid tissue (MALT) plays a key role in adaptive immune response that prevents microbes from invading mucosal surfaces
Skin-associated lymphoid tissue (SALT) prevents microbes from invading the skin

Question 35

What differentiates B cells?

Answer 35

They are differentiated by what surface immunoglobulins (antibodies) they carry

Question 36

What happens as lymphocytes matures in the primary lymphoid tissue, with regards to clonal selection and expansion

Answer 36

As lymphocytes mature in the primary lymphoid tissue, a population of cells is generated that are able to recognize a limitless variety of antigens. Each individual cell able to recognize and respond to 1 epitope. The body is estimated to have 1 billion B cells, but only a few will recognize a given epitope

Question 37

What is clonal selection?

Answer 37

Only B cells capable of making the correct antibody bing to the antigen (“selection” of the correct B cell)

Question 38

What is clonal expansion?

Answer 38

The cells that bind the antigen begin dividing and produce populations clones

Question 39

What is somatic mutations? How does this not cause problems elsewhere?

Answer 39

As clonal proliferation takes place, somatic mutation can take place; in the binding region of the B cell, they can “fine tune” it further (via mutations) for better binding
Remember, most lymphocytes require a “second opinion” (accessory signal) from another cell (T helper cell) before activation can occur (helps prevent immune responses against self)

Question 40

What are memory cells?

Answer 40

After the pathogen is cleared from the body, the B cells that underwent clonal selection and expansion go away. But a small subset remain and are banked as memory cells (CD27 B memory cells and surface IgG, IgA or IgE). These are important in subsequent infections (basis of vaccination)

Question 41

Describe the clonal selection and expansion of T cells

Answer 41

It’s a similar process to B cells. When T cells are activated, they can also release cytokines, or have a cytotoxic function.
T cells do not undergo further selection due to somatic mutations
A fraction of clonal expanded T cells differentiate into memory cells (CD45 T memory cells)

Question 42

Why are memory cells important?

Answer 42

They are readily stimulated by antigens (they also interact with antigens better) and result in larger and quicker response. They have a greater combining power; B cels through mutation and selection and T cells through increased expression of accessory adhesion molecules

Question 43

What’s a toxoid?

Answer 43

A toxin protein that is no longer potent. It’s been manipulated in way that it can’t bind with it’s target; it’s inactivated). It can be recognized by B cells and if we get exposed to the real toxin, our memory B cells will kick in and there will be a quick immune response

Question 44

Describe T cell-dependent activation of B cells

Answer 44

A macrophages comes into contact with an antigen. The macrophage digests the antigen and releases most of the byproducts. However, a small part of the antigen is bound with the MHC class II molecule on the surface of the macrophage. The T cell binds with the MHC and this activates the T cell. The T cells can then activate B cells or release cytokines. It will undergo clonal proliferation

Question 45

What are the two main ways of T cell-independent activation of B cells?

Answer 45

Polyclonal activators

Repeating determinants

Question 46

What are polyclonal activators?

Answer 46

Polyclonal activators stimulate a wide variety of B cells independantly of the specific antigen receptors. So if you have an antigen that has multiple epitopes, B cells can bypass the need for T cell activation (you need more than two kinds of B cells)

Question 47

What do repeating determinants do?

Answer 47

They give rise to low-affinity IgM rather than IgG antibody response and they do no induce memory response. One cell can’t do it by itself. There needs to be another cell (T cell, or less commonly another B cell)

Question 48

What is stage I of antibody production?

Answer 48

An antigen is processed by an antigen-presenting cell and it primes a Th cell with a complementary receptor on it’s surface

Question 49

What is stage II of antibody production

Answer 49

A B cell with surface receptors complementary to an epitope on the original antigen captures the antigen on its receptor, internalizes it and, after processing, also present a derived peptide on its surface in association with endogenous MHC class II molecules.
This complex against which the Th cell was originally primed, and recognition of the processed antigen by the primed Th cell causes the production of cytokines and the activation of the B cell, with subsequent activation, proliferation and maturation
Antibodies are produced based on the epitope known to B cells (not T cells)

Question 50

What are cytokines?

Answer 50

Soluble intercellular communication factors (hormones of the immune system)
They are non-antigen specific molecules
They have diverse activity
They have an important role in protection against infectious diseases (contribute to the control of infection and to the development of pathology

Question 51

What differentiates Th cells?

Answer 51

The type of cytokines they produce

Question 52

What do Th1 cells produce?

Answer 52

Interferons (they activate macrophages)

Question 53

What do Th2 cells produce?

Answer 53

Interleukins (they activate B cells)

Question 54

How do Th1 and Th2 cells work together?

Answer 54

Th1 cells produce IFN gamma, which causes the activation of Th 2 cells. They produce interleukins, which activate B cells, which produce antibodies

Question 55

Describe the feedback loops that regulate the immune system

Answer 55

An antigen is presented to to T cells. T cells are activated and they activate B cells. The initial response: B cells produce IgM molecules. IgM stimulates the activation of B and T cells (ensure the continued stimulation; positive feedback loop). Second response: B cells produce IgG molecules. The presence IgG means that most of the antigen has already been neutralized, so IgG inhibits the activation of B cells (negative feedback loop).