Hypersensitivity Reactions Dr. Nelson 5/5/14 Flashcards
Naive Lymphocytes
Mature lymphocytes which have not yet encountered the antigen for which they are specific for.
Activated Lymphocytes
Differentiate into effector cells, which eliminate the offending organism, and memory cells, which can be reactivated upon second exposure.
Effector Lymphocytes
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Memory Lymphocytes
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Describe the fxn of T-lymphocytes (both CD4+ and CD8+)
CD4+–>secrete cytokines (IL-2–>proliferation of CD4/CD8 T cells, IFN-gamma–>activation of macrophages); help B cells become antibody producing plasma cells.
CD8+–>kill virus-infected, neoplastic, and donor graft cells.
Describe the fxn of B-lymphocytes
Differentiate into plasma cells that produce immunoglobulins to kill encapsulated bacteria (e.g. Streptococcus pneumonia). Act as APCs that interact w/ CD4 cells.
Describe the fxn of NK cells
Kill virus-infected and neoplastic cells. Release IFN-gamma.
Describe the fxn of macrophages
Involved in the phagocytosis and cytokine production. Act as APCs to T cells.
Describe the fxn of dendritic cells
Act as APCs to T cells.
Describe how light chain expression can be used to determine if a B-lymphocyte proliferation is clonal.
Clonal proliferations typically produce or express only one type of immunoglobulin, and thus the light chain will be of either the kappa or lambda type. Sometimes it can be difficult to distinguish a B cell reactive proliferation from a clonal (neoplastic) proliferation; use of Ig (immunoglobulin) gene rearrangement analysis can help.
Describe the use of T-cell receptor gene rearrangement studies and B-cell immunoglobulin gene arrangement studies
Each T cell lymphocyte recognizes a specific cell bound antigen by means of an antigen specific T cell receptor (TCR); clonal (neoplastic) proliferations of T cells can sometimes be difficult to recognize, and use of TCR gene rearrangement analysis can be used to determine if a T-cell proliferation is clonal (neoplastic).
Define generative lymphoid organ
Sites where T and B lymphocytes mature and become competent to respond to antigens (bone marrow and thymus).
Define peripheral lymphoid organs
Sites where the adaptive immune response is initiated (lymph nodes, spleen, mucosal and cutaneous lymphoid tissues (GI tract, respiratory tract, skin); T and B lymphocytes are segregated into different regions in the peripheral lymphoid organs (e.g. in the lymph nodes, B cells are found in the follicles, T cells in the paracortical region; when B cells respond to an antigen get reactive germinal centers in the follicles); spleen responds to blood borne antigens, lymph node responds to antigens in the lymphatic fluid that drains to the lymph node.
Lymphocytes constantly recirculate between tissues and home to particular sites; naïve lymphocytes traverse the peripheral lymphoid organs where immune responses are initiated, and effector lymphocytes migrate to sites of infection and inflammation.
Define MHC
The physiologic function of MHC molecules is to display peptide fragments of proteins for recognition by antigen specific T cells. In humans the MHC complex genes are found on chromosome 6 and are also known as the human leukocyte antigen (HLA) complex as they were initially detected on leukocytes. The MHC gene products are membrane bound glycoproteins which are found on all nucleated cells except mature red blood cells. The HLA system is highly polymorphic (many different alleles of each MHC gene). Key MHC gene products include:
Class I MHC molecules: coded by HLA-A, HLA-B, and HLA-C genes; display proteins that are derived from the cytoplasm (e.g. viral antigens), and are recognized by CD8+ T-lymphocytes and NK cells
Class II MHC molecules: coded by HLA-DP, HLA-DQ, and HLA-DR genes; display antigens that have been internalized into vesicles (such as extracellular microbes and soluble proteins) and are recognized by CD4+ T lymphocytes.
Describe the two uses of HLA testing
- A variety of diseases are associated with the inheritance of certain HLA alleles, and HLA testing can be used to determine disease risk (e.g. 90% of patients with ankylosing spondylitis are positive for HLA-B27).
- HLA testing is also used in the transplantation workup, as close matches of HLA-A, HLA-B, HLA-C, and HLA-D in both the donor and graft recipient increase the chance of graft survival.
Describe the key steps and fxns of cell-mediated immunity
Dendritic cells (DCs) capture microbial antigens from epithelia and tissues and transport the antigens to lymph nodes. During this process, the DCs mature, and express high levels of MHC molecules and costimulators. Naive T cells recognize MHC-associated peptide antigens displayed on DCs. The T cells are activated to proliferate and to differentiate into effector and memory cells, which migrate to sites of infection and serve various functions in cell-mediated immunity. CD4+ effector T cells of the TH1 subset recognize the antigens of microbes ingested by phagocytes, and activate the phagocytes to kill the microbes. CD4+ T cells also induce inflammation. CD8+ cytotoxic T lymphocytes (CTLs) kill infected cells harboring microbes in the cytoplasm. Not shown are TH2 cells, which are especially important in defense against helminthic infections. Some activated T cells differentiate into long-lived memory cells. APC, antigen-presenting cell.
Describe the key steps and fxn of humoral immunity
Naive B lymphocytes recognize antigens, and under the influence of TH cells and other stimuli (not shown), the B cells are activated to proliferate and to differentiate into antibody-secreting plasma cells. Some of the activated B cells undergo heavy-chain class switching and affinity maturation, and some become long-lived memory cells. Antibodies of different heavy-chain classes (isotypes) perform different effector functions, shown on the right.
Define hypersensitivity reaction
Individuals previously exposed to an antigen are said to be sensitized; upon repeat exposure(s), some individuals will develop a pathologic immune reaction to the antigen. These pathologic immune reactions are called hypersensitivity disorders, reactions, or diseases. Some key general points are listed below:
Both exogenous and endogenous antigens may elicit hypersensitivity reactions (e.g., allergic reactions, autoimmune diseases).
The development of hypersensitivity diseases (both allergic and autoimmune disorders) is often associated with the inheritance of particular susceptibility genes (HLA and non-HLA genes).
Hypersensitivity reflects an imbalance between the effector mechanisms of immune responses and the control mechanisms that serve to limit such responses.
Hypersensitivity diseases can be classified on the basis of the immunologic mechanism that mediates the disease (however, multiple mechanisms may be occurring in some diseases).
Define type I hypersensitivity
A rapid immunologic reaction occurring within minutes after an antigen combines with antibody bound to mast cells in individuals previously sensitized to the antigen (allergic reaction). The reaction is typically mediated by IgE antibody-dependant activation of mast cells.
Define atopy
Predisposition to develop localized immediate hypersensitivity reactions.
Describe the mechanisms involved in the immediate and late phase reactions of type I hypersensitivity reactions
Initial exposure to the antigen (allergen) results in activation of B cells with the production of IgE, which attaches to mast cells (this first step is called sensitization). Repeat exposure to the antigen (allergen) results in mast cell degranulation, with the release of chemical mediators, causing vasodilation, vascular leakage, smooth muscle spasm, and recruitment of leukocytes, particularly eosinophils. Eosinophils secrete major basic protein and eosinophil cationic protein, which are toxic to epithelial cells. Activated eosinophils and neutrophils also activate mast cells to release mediators, amplifying and sustaining the inflammatory response without additional exposure to the triggering antigen (late phase reaction).
Immediate reaction (minutes after repeat exposure to allergen)–> vasodilation, vascular leakage, and smooth muscle spasm.
Late phase reaction (2-24 hours after repeat exposure to allergen)–>leukocyte infiltration, epithelial damage, and bronchospasm.
Define localized allergic reaction and list some common examples
- Allergic rhinitis (hay fever)
- Some forms of bronchial asthma (atopic forms)
- Urticaria (hives); can also reflect a systemic reaction, e.g. allergic drug reaction)
- Allergic gastroenteritis (food allergy)
Triggering allergens are numerous and include such things as pollens, molds, house dust, animal dander, foods, medications, blood products, venom from insect bites, etc.
Describe the treatment and prevention of localized allergic reactions
- Avoiding the offending allergen, if possible.
- Use of various medications, such as antihistamines, corticosteriods, agents that inhibit release of histamine from mast cells, leukotriene modifiers (to name just a few).
- In some cases, immunotherapy (desensitization therapy) is also used .
Define systemic anaphylaxis and describe the mechanism and clinical findings in systemic anyphylaxis
Refers to a life threatening systemic allergic reaction typically characterized by vascular shock, widespread edema, and difficulty breathing (massive mast cell activation).
Death can ensue within minutes if untreated (death is usually due to asphyxiation from upper airway edema or respiratory failure due to bronchial constriction/obstruction, and/or shock with cardiovascular collapse). Emergent treatment includes intramuscular epinephrine.
