Hypersensitivity Reactions Flashcards
Using just a few sentences for each, define innate and adaptive immunity, and list some of the key components of innate immunity. Describe the two types of adaptive immunity. 2. Define naïve lymphocytes, activated lymphocytes, effector lymphocytes, and memory lymphocytes. 3. Describe the function of T-lymphocytes (both CD4+ and CD8+), B-lymphocytes, natural killer cells, macrophages, and dendritic cells. 4. Describe how light chain expression can be used to determine if a B-lymphocyt
Innate (natural) Immunity
refers to pre-existing, nonspecific defense mechanisms present prior to infection that have evolved to recognize microbial pathogens and protect the individual against infection. These defense mechanisms can also recognize nonmicrobial antigens that have been released during cell death or injury. Major components include:
Epithelial barriers Phagocytic cells (neutrophils and monocytes/macrophages) Eosinophils, basophils, mast cells Dendritic cells Natural killer cells (NK cells) Plasma proteins (complement system, mannose-binding lectin, C-reactive protein, lung surfactant)
Adaptive (acquired, specific) immunity
refers to reactive mechanisms that are stimulated by the specific microbe and are capable of recognizing microbial and nonmicrobial substances (antigens). The term “immune response” refers to adaptive immunity.
The adaptive immune system consists of lymphocytes and their products, including antibodies.
There are two types of adaptive immunity:
Humoral immunity: protects against extracellular microbes and toxins. Cell-mediated immunity: protects against intracellular microbes, tumor cells.
Humoral immunity
protects against extracellular microbes and toxins.
Cell-mediated immunity
protects against intracellular microbes, tumor cells.
Naïve 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.
CD4 T cells
helper
secrete cytokines (IL-2 causes proliferation of CD4/CD8 T cells
IFN-Gamma causes activation of macrophages
help B cells become antibody producing plasma cells
CD8 T cells
cytotoxic/ suppressor
kill virus-infected, neoplastic, and donor graft cells
B cells
differentiate into plasma cells that produce imunoglobulins to kill encapsulated bacteria
act as APCs that interact with CD4 cells
NK Cells
Kill virus-infected and neoplactic cells
release IFN-Gamma
macrophages
involved in phagocytosis and cytokine production
Act as APCs to T cells
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 rearrangement studies.
T-cell receptors: 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).
B lymphocytes: 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.
Generative lymphoid organs (primary or central)
sites where T and B lymphocytes mature and become competent to respond to antigens (bone marrow and thymus).
Peripheral lymphoid organs (secondary)
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.
Major Histocompatibility Complex (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)
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 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.
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.
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
HYPERSENSITIVITY REACTIONS
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).
IMMEDIATE (TYPE I) HYPERSENSITIVITY
Defined as 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.
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).
