What is an antigen?
- Foreign substance that stimulates an immune response, immunogen.
- Large, complex molecules with a molecular weight at least 10,000.
- Proteins and polysaccharides are best antigens
What is a hapten?
Low molecular weight substance that is incapable of stimulating antibody production unless it is bound to a larger carrier molecule.
What is an epitope?
Determinant site on an antigen.
What is an antibody?
- Immunoglobulin produced in response to an antigen.
- Antibodies are produced by plasma cells (transformed B lymphocytes)
Initial force of attraction between a Fab site on an antibody and a determinant site on the corresponding antigen.
Overall binding strength that keeps an antibody and an antigen together. It is a measure of the overall stability of an antigen-antibody complex.
What are the three distinct phenomena of antigen-antibody reactions?
- Primary phenomenon: Initial antigen-antibody binding
- Secondary phenomenon: Formation of complexes to produce precipitation, agglutination, or complement fixation
- Tertiary phenomenon: Reaction of the body to immune complexes (inflammation, phagocytosis, chemotaxis, complex deposition)
What is natural immunity?
Inate immunity, the nonspecific defenses with which one is born, such as intact skin, mucous membranes, secretions, phagocytes, and complement.
Some individuals do not react to poison ivy. What type of immunity do they have?
How does skin contribute to resistance to disease?
- Keratinization of the upper layer of the skin and constant renewal of the skin's epithelial cells provide a physical barrier to microorganisms.
- Lactic acid from sweat and fatty acids from sebaceous glands maintain the skin pH around 5.6 which is inhibitory to most microorganisms.
What are the two branches of the immune system?
- Humoral immunity
- Cellular immunity
What is humoral immunity?
- Humoral immunity is antibody-mediated immunity involving B lymphs and plasma cells.
- Provides defense against extracellular pathogens.
What is cellular immunity?
- Cellular immunity involves T lymphocytes and defends against tumor cells
- Intracellular pathogens like viruses, fungi, and mycobacteria.
- Graft rejections and type IV hypersensitivity reactions are examples of cellular immunity.
What is adaptive or acquired immunity?
- Immunity that develops following exposure to an antigen.
- It involves specific responses by T lymphocytes, B lymphocytes, plasma cells
What is active immunity?
- Development of a specific antibody by an individual who has been exposed to an antigen.
- The immunity acquired in the course of an infection or following immunization is active immunity.
- Provides long-term protection.
What is passive immunity?
- Short-term protection by antibiodies develop in another individual.
- Ex: Maternal antibodies that protect newborns and immunoglobulin injections.
Injection of an attenuated antigen should result in the development of which type of immunity?
Administration of an antitoxin is an example of which type of immunity?
The Hepatitis B vaccine is an example of which type of immunity?
Administration of hepatitis B immune globulin (HBIG) is an example of which type of immunity?
Administration of the tetanus toxoid is an example of which type of immunity?
The antibodies that develop following acute hepatitis B are an example of which type of immunity?
Which type of immunity affords immediate protection?
Passive immunity. Antibodies are already formed.
What role does the macrophage play in the immune response?
- Initiates the immune response by phagocytizing, processing, and presenting the antigen to the T lymphocytes.
- It also secretes cytokines and is involved in the destruction of microorganisms, intracellular parasites, and tumors.
Which cell is the precursor of the macrophage?
What are the primary lymphoid tissues?
- Bone marrow and thymus
- Sites of antigen-independent differentiation of lymphocytes.
What are the secondary lymphoid tissues?
- Spleen, lymph nodes, and mucosal-associated lymphoid tissue (MALT), and tonsils.
- Sites of antigen-dependent activation and differentiation of lymphocytes.
Where do B lymphocytes develop?
Which CD (Clusters of differentiation) markers are associated with B cells?
CD 19, 20, 21
What are memory B lymphocytes?
- Cells in a clone of stimulated B cells that do not differentiate into plasma cells, but revert to a resting state in the lymphoid follicles.
- Responsible for the accelerated secondary response.
What is the normal T cell:B cell ratio?
Where do T lymphocytes develop their identifying characteristics?
- In the thymus.
- They are produced in the bone marrow and travel to the thymus where further maturation takes place.
Which CD markers are associated with T cells?
- CD 2,3,4
- CD4 cells are known as T4 cells/helper inducer cells.
- CD8 cells known as T8 or suppressor/cytotoxic cells.
What is the normal CD4:CD8 ratio?
What role do CD4 cells play in the immune response?
Orchestrate the immune response by activating B cells and cytotoxic T cells.
What are natural killer (NK) cells?
- Large granular lymphocytes that destroy target cells by an extracellular nonphagocytic mechanism referred to as a cytotoxic reaction.
- In first line of defense against virally-infected cells and tumor cells.
- When activated by IL-2, they are called lymphokine-activated killer cells (LAK).
Following an antigen challenge, what is the lag or latent phase?
- Time it takes for antibody to be detected following exposure to an antigen.
- Time varies depending on the individual and antigen, but is usually around 5-7 days.
How do primary and secondary response differ?
- Secondary (anamnestic) response, accelerated response. Antibody titer increases more rapidly, plateaus higher, and remains elevated longer. IgG is the predominant antibody.
- Primary: IgM is produced first, followed by IgG after class switching.
Describe the immunoglobulin molecule.
- Four chain polypeptide
- Composed of 2 identical heavy chains (alpha,delton, epsilon, gamma, or mu)
- 2 identical light chains (kappa or lambda).
- The chains are help together by disulfide bonds.
Which part of the immunoglobulin molecule determines the immunoglobulin class?
- Heavy chain
- IgG has gamma chains
- IgM has mu
- IgA has alpha
- IgD has delta chains
- IgE epsilon chains
What is the name of the region of the immunoglobulin molecule that creates the antigen-binding site?
- Fab fragment
- It consists of one light chain and 1/2 of a heavy chain. Each immunoglobulin has two Fab fragments
What is the Fc fragment?
- Crystallizable fragment, consisting of the carboxy-terminal halves of the two heavy chains.
- Each immunoglobulin molecule has one Fc fragment.
- It has no antigen binding ability, but it does bind complement.
What is the antigen recognition unit?
- The amino-terminal ends of the heavy and light chains (Fab fragment) known as hypervariable region.
- Region is unique to a specific antibody and forms the antigen-binding site.
Which immunoglobulin is a pentamer?
In the IgM molecule, what holds the five monomeric units together?
The J or joining chain
Which other immunoglobulin class has a J chain?
Which immunoglobulin is produced first in an immune response?
What is the predominant antibody in a secondary response?
Which immunoglobulin is present in highest concentration in normal serum?
Which immunoglobulin is present on mucosal surfaces and serves as the first line of defense against antigens?
Which immunoglobulin can cross the placenta?
Which immunoglobulin bind complement?
IgG and IgM
Where does complement attach to the immunoglobulin molecule?
Which immunoglobulin is most efficient at initiating the complement cascade?
- IgM, because it has multiple binding sites.
- Only takes one IgM molecule attached to two adjacent antigenic determinants to initiate the complement cascade, whereas at least two molecules of IgG are required.
Which immunoglobulin is destroyed by sulfhydryl compounds like DTT (dithiothreitol) and 2-ME (2-mercaptoethanol)?
- Sulfhydryl compounds break the disulfide bonds of the J chain of the IgM molecule but leave the IgG molecule intact.
Which immunoglobulin is present in saliva, tears, and other secretions?
Which immunoglobulin binds to mast cells and is responsible for symptoms of allergies?
How many IgG subclasses are there?
- IgG1, IgG2, IgG3, and IgG4
- Differ in number and position of the disulfide bridges between the gamma chains.
Which cells have surface receptors for the Fc portion of IgE?
Basophils and mast cells
What are mast cells?
- Tissue cells related to basophils.
- Found mainly in the skin and lining the respiratory and GI tracts.
- Involved in type I hypersensitivity reactions. Cross-linking of surface-bound IgE by a specific allergen causes release of histamine and heparin.
Which immunoglobulin is long-lasting?
What are opsonins?
Antibodies and other serum proteins that attach to foreign substances and enhance phagocytosis
What role does complement play in the immune response?
- It is involved in:
- Cell lysis
- mediation of inflammation
How are the two complement pathways activated?
- - Classical pathway:
- Activated by antigen-antibody reactions
- - Alternative pathway:
- Bacteria, fungi, viruses, some parasites, and tumor cells
Which ions are required in the complement cascade?
Mg2+ and Ca2+
What is the end product of complement activation?
Which complement component is present in highest concentration in serum and a key component in both the classical and alternative pathways?
In the classical pathway, which complement component is the first to bind?
Which complement components comprise the membrane attack unit?
- C5b, C6, C7, C8, C9
- Complex becomes inserted into the target cell membrane, causing lysis
What are cytokines?
Chemical messengers produced by stimulated cells that affect the function of other cells.
What are lymphokines?
Chemicals given off by antigen-stimulated T cells that regulate the function of other cells.
What are interferons?
Cytokines produced by T cells and other cells that inhibit viral synthesis or act as immune regulators.
What are interleukins?
Cytokines produced by T cells or machrophages that stimulate other cells.
Which interleukin is produced primarily by macrophages and activates T and B lymphocytes?
What are HLA antigens?
- Human Leukocyte antigens
- Present on all nucleated cells of the body and play an important role in graft rejection.
Which cells do not possess HLA antigens?
- They are nonnucleated
Which HLA antigens are expressed on all nucleated cells?
- Class I HLA antigens
- Class II antigens are much more restricted in their distribution.
What is the major histocompatibility complex (MHC)?
The genes that control expression of the HLA antigens.
What are class I gene products?
- HLA-A, HLA-B, HLA-C antigens that are found on all nucleated cells.
- Class I molecules present antigen to CD8 (cytotoxic) T cells.
- Appropriate class I molecule is required for the interaction of the cytotoxic T lymphocyte with the target cell.
What are class II gene products?
- HLA-DR, HLA-DQ found on B lymphocytes, macrophages, dendritic cells, and endothelial cells.
- Class II molecules are involved in antigen recognition by CD4 (helper) T cells. The T helper cell recognizes a foreign substance on the cell surface of a macrophage only when it is complexed to an appropriate class II antigen Class I and Class II antigens play a major role in transplantation.
What is an allograft?
- Transplantation of an organ or tissue from an individual of the same species.
- Allografts differ from the host genetically and must be matched as closely as possible.
Of all types of tissue transplants, which is the one where matching is most critical?
- Bone marrow
- Because immunologically reactive tissue is transplanted, potentially fatal graft vs. host disease can result.
What is graft vs host disease (GVHD)?
Potentially fatal disease in which transplanted immunocompetent cells recognize that host as foreign and attack.
How is rejection of transplanted tissue minimized?
- Histocompatibility testing prior to transplantation
- Administration of immunosuppressive drugs such as cyclosporine and steroids and therapy directed against T lymphocytes.
- OKT3 (an antibody to the epsilon chain of the CD3 antigen on T cells) and thymoglobulin (rabbit polyclonal antiserum to thymocytes) are used to deplete T cells.
- In successfully treated patients, the number of CD3 cells is very low or even undetectable.
What is hypersensitivity?
A heightened state of immune responsiveness that causes tissue damage in the host.
What are the four types of hypersensitivity reactions?
- Type I anaphylactic:
- Release of mediators from mast cells and
- basophils. Symptoms are immediate. Key
- reactants: IgE. Ex: Anaphylaxis, hay,
- Fever, asthma, food allergies.
- Type II Cytotoxic:
- Cytolysis due to antibody and
- complement. Symptoms are immediate.
- Key reactant: IgG, IgM, complement.
- Ex: Transfusion reactions, HDNB, ITP,
- Goodpasture's syndrome
- Type III Immune complex:
- Deposition of ag-ab complexes.
- Symptom are immediate.
- IgG, IgM, complement. Ex: serum
- sickness, SLE, RA
- Type IV Cell Mediated: Release of
- lymphokines from ag-stimulated T cells
- Delayed symptoms. T-lymphocytes
- Contact dermatitis, PPD
Which cells are involved in contact dermatitis such as poison ivy?
What are the two broad categories of autoimmune diseases?
- Systemic and organ-specific.
- Examples of systemic autoimmune disease: RA, SLE, scleroderma.
- Examples of organ-specific autoimmune disease: Hashimoto's throiditis, Graves' disease, pernicious anemia, Addison's disease, insulin-dependent diabetes mellitus, myasthenia gravis, MS, ITP, Goodpasture's syndrome.
Name the target tissue(s) for each of the autoimmune
- RA=Joints, lungs, skin
- SLE=Skin,joints, kidneys, brain, heart, lungs
- Scleroderma= Skin, gut, lungs, kidney
- Hashimoto's throiditis=thyroid
- Graves' disease=thyroid
- Pernicious anemia=gastric parietal cells
- Addison's disease=Adrenal gland
- Insulin dependent diabetes mellitus= pancreas
- Myasthenia gravis= nerve-muscle synapses
- Autoimmune hemolytic anemia= RBCs
- Idiopathic thrombocytopenic purpura= platelets
- Goodpasture's syndrome=kidney,lung
Name the autoimmune disease associated with each of the following antibodies:
- Rheumatoid factor=RA
- Antinuclear antibodies=SLE
- Parietal cell antibody= Pernicious anemia
- Intrinsic factor antibody= Pernicious anemia
- Insulin antibody= Insulin-dependent diabetes mellitus
- Islet cell antibody= Insulin-dependent diabetes mellitus
- Antithyroglobulin antibody=Hashimoto's thyroiditis
- Thyroid-stimulating hormone receptor antibody= Grave's disease