Adaptive Immune System Flashcards
What are the two mechanisms/types of adaptive immune system?
Antibody-mediated
Cell-mediated
What is an antigen?
Any molecule that reacts specifically with an antibody or antigen receptor on a lymphocyte.
What is an immunogen?
An antigen that can induce an immune response
What is antigenicity/immunogenicity?
The relative ability of an antigen to elicit an immune response
What are antigenic determinants?
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
What is antibody/humoral immunity?
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
What are the two functional regions of antibodies?
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
What makes up the body of antigens?
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)
How are light chains classified?
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
How are heavy chains classified?
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)
Describe IgG
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
What are the functions of IgG?
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
Describe IgM
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
What are the functions of IgM?
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
Describe IgD
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)
Describe IgA
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
What are the functions of IgA?
Neutralizes bacteria and viruses by preventing them from attaching to mucous membranes Passive immunity (breast milk)
Describe IgE
Monomeric form, low levels in serum
Antigen receptors are on mast cells (tissues) and basophils (blood)
What are the functions of IgE?
Anaphylactic hypersensitivity
List the steps of the classical complement pathway
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
What do antibodies do?
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)
What are T-lymphocytes?
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
What do T cells do?
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
There are two major functional populations of T-cells. What are they and what separates them?
There are cytotoxic T-cells and helper T-cells
They are differentiated by surface markers (cluster of differentiation)
What are cytotoxic T-cells?
They have CD8 receptors and they destroy infected or cancerous cells They recognize antigen presented by MHC class I molecules
What are helper T cells?
They have CD4 receptors and they activate B cells (Th2) and macrophages (Th1) They recognize antigen presented by MHC class II molecules
What do T cells do once they are activated?
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
What is the immune response against large infectious agents?
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
What cells are involved in ADCC?
Macrophages, eosinophils, NK cells
What is the lymphoid system?
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
Describe the role of the lymphatic vessels
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
What are primary lymphoid organs? What is their importance?
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
What are secondary lymphoid organs?
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
Some lymphoid organs are less organized but serve the same function. Give some examples
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
What differentiates B cells?
They are differentiated by what surface immunoglobulins (antibodies) they carry
What happens as lymphocytes matures in the primary lymphoid tissue, with regards to clonal selection and expansion
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
What is clonal selection?
Only B cells capable of making the correct antibody bing to the antigen (“selection” of the correct B cell)
What is clonal expansion?
The cells that bind the antigen begin dividing and produce populations clones
What is somatic mutations? How does this not cause problems elsewhere?
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)
What are memory cells?
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)
Describe the clonal selection and expansion of T cells
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)
Why are memory cells important?
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
What’s a toxoid?
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
Describe T cell-dependent activation of B cells
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
What are the two main ways of T cell-independent activation of B cells?
Polyclonal activators
Repeating determinants
What are polyclonal activators?
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)
What do repeating determinants do?
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)
What is stage I of antibody production?
An antigen is processed by an antigen-presenting cell and it primes a Th cell with a complementary receptor on it’s surface
What is stage II of antibody production
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)
What are cytokines?
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
What differentiates Th cells?
The type of cytokines they produce
What do Th1 cells produce?
Interferons (they activate macrophages)
What do Th2 cells produce?
Interleukins (they activate B cells)
How do Th1 and Th2 cells work together?
Th1 cells produce IFN gamma, which causes the activation of Th 2 cells. They produce interleukins, which activate B cells, which produce antibodies
Describe the feedback loops that regulate the immune system
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).
