Immunology Review

• 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

Low molecular weight substance that is incapable of stimulating antibody production unless it is bound to a larger carrier molecule.

Determinant site on an antigen.

• 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.

• 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)

Inate immunity, the nonspecific defenses with which one is born, such as intact skin, mucous membranes, secretions, phagocytes, and complement.

Natural immunity

• 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.

• Humoral immunity
• Cellular immunity

• Humoral immunity is antibody-mediated immunity involving B lymphs and plasma cells.
• Provides defense against extracellular pathogens.

• 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.

• Immunity that develops following exposure to an antigen.
• It involves specific responses by T lymphocytes, B lymphocytes, plasma cells

• 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.

• Short-term protection by antibiodies develop in another individual.
• Ex: Maternal antibodies that protect newborns and immunoglobulin injections.

Active immunity

Passive immunity

Active immunity

Passive immunity

Active immunity

Active immunity

Passive immunity. Antibodies are already formed.

• 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.

Monocyte

• Bone marrow and thymus
• Sites of antigen-independent differentiation of lymphocytes.

• Spleen, lymph nodes, and mucosal-associated lymphoid tissue (MALT), and tonsils.
• Sites of antigen-dependent activation and differentiation of lymphocytes.

Bone marrow

CD 19, 20, 21

• 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.

8:1

• In the thymus.
• They are produced in the bone marrow and travel to the thymus where further maturation takes place.

• CD 2,3,4
• CD4 cells are known as T4 cells/helper inducer cells.
• CD8 cells known as T8 or suppressor/cytotoxic cells.

2:1

Orchestrate the immune response by activating B cells and cytotoxic T 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).

• 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.

• 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.

• 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.

• Heavy chain
• IgG has gamma chains
• IgM has mu
• IgA has alpha
• IgD has delta chains
• IgE epsilon chains

• Fab fragment
• It consists of one light chain and 1/2 of a heavy chain. Each immunoglobulin has two Fab fragments

• 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.

• 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.

IgM

The J or joining chain

IgA

IgM

IgG

IgG

IgA

IgG

IgG and IgM

Fc portion

• 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.

• IgM
• Sulfhydryl compounds break the disulfide bonds of the J chain of the IgM molecule but leave the IgG molecule intact.

IgA

IgE

• Four
• IgG1, IgG2, IgG3, and IgG4
• Differ in number and position of the disulfide  bridges between the gamma chains.

Basophils and 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.

IgG

Antibodies and other serum proteins that attach to foreign substances and enhance phagocytosis

• It is involved in:
• Opsonization
• Chemotaxis
• Cell lysis
• mediation of inflammation

• - Classical pathway:
• Activated by antigen-antibody reactions
• - Alternative pathway:
• Bacteria, fungi, viruses, some parasites, and tumor cells

Mg²⁺ and Ca²⁺

Cell lysis.

C3

C1

• C5b, C6, C7, C8, C9
• Complex becomes inserted into the target cell membrane, causing lysis

Chemical messengers produced by stimulated cells that affect the function of other cells.

Chemicals given off by antigen-stimulated T cells that regulate the function of other cells.

Cytokines produced by T cells and other cells that inhibit viral synthesis or act as immune regulators.

Cytokines produced by T cells or machrophages that stimulate other cells.

IL-1

• Human Leukocyte antigens
• Present on all nucleated cells of the body and play an important role in graft rejection.

• RBCs
• They are nonnucleated

• Class I HLA antigens
• Class II antigens are much more restricted in their distribution.

The genes that control expression of the HLA antigens.

• 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.

• 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.

• 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.

• Bone marrow
• Because immunologically reactive tissue is transplanted, potentially fatal graft vs. host disease can result.

Potentially fatal disease in which transplanted immunocompetent cells recognize that host as foreign and attack.

• 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.

A heightened state of immune responsiveness that causes tissue damage in the host.

• 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

T-lymphocytes

• 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.

• 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

• 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