immune response

The immune response is mounted by cells of the immune system in response to invasion by pathogens. Immune responses are classifed as passive or active, innate or adaptive, and cellular or humoral.

activation B : activation T : active/passive : adaptive immune response : anergy : autoimmune : blood : cells : cellular immune response : cellular participants : classification : costimulation : danger hypothesis : humoral immune response : humoral participants : innate immune response : pattern recognition receptors : phagocytes : molecular participants : self-other : surface receptors

The immune system is intimately connected with the hematologic system since white blood cells (leukocytes, including B- and T-lymphocytes) are key players in the lymphoid system. Cellular participants in the immune and inflammatory responses include :
phagocytic cells (dendritic cells, monocytes and macrophages, and granulocytes)
antigen presenting cells (dendritic cells, macrophages, B lymphocytes, helper T cells)
antibody producing cells (plasma cells)
cytotoxic cells (CTL, NK)
● regulatory cells (APCs, helper T cells, regulatory T cells)
● cells-in-waiting (memory B cells, monocytes)
● chemical releasing cells (basophils, eosinophils, neutrophils; mast cells - histamine, cytokines; hepatocytes - complement proteins)

Anergy toward self-targets operates as one self-tolerance mechanism to control the autoreactive cells found in disease-causing autoimmunity. Immune responses ideally distinguish between self and other. In 1994, Polly Matzinger proposed an alternative to the widely established concept that the immune system primarily discriminates self from non-self. This alternative hypothesis suggested that the immune system is mainly adapted to recognize and respond to signals generated in a 'dangerous' situation that involves cell damage (Matzinger, 1994). This model, which became known as the 'danger' hypothesis, is based on the idea that the crucial signals for the initiation of immune responses are endogenous, not exogenous (Matzinger, 2001). According to this hypothesis, the power lies with the tissues: the activation state of APCs would depend on the health of cells in their neighbourhood. Accumulating evidence suggests that both exogenous and endogenous adjuvants contribute to the initiation of immune responses by activating APCs (Rock et al, 2005).[s=fft]

Immune responses are classifed as passive or active, innate or adaptive, and cellular or humoral.

Passive measures to prevent pathogenic incursions are provided by physical barriers to invasion – the skin, secretions, and ciliary action. Should pathogens pass beyond the physical barricade, then active innate and adaptive immune reactions mount a defense.

Innate immune responses employ phagocytic cells that are circulating or tissue emplaced – granulocytes, monocytes, dendritic cells, macrophages, and B lymphocytes. The early, innate response also employs chemical responses – chemical-mediated inflammation; the complement cascade; antimicrobial peptides; and, pattern-recognition receptors (PRR), including toll-like receptors. The innate system is considered to constitute an evolutionarily older defense strategy, and it is the predominant immune system exhibited by plants, fungi, insects, and primitive metazoa.

An induced, adaptive response begins when foreign or pathogenic substances (antigens) are 'recognized' by cells of the lymphoid system, stimulating a co-ordinated cellular/humoral response depending upon the nature of the pathogen.

Surfaces of cells of the immune system are coated with proteins and receptors that participate in cellular signal transduction, enabling regulatory interaction:
clusters of differentiation – a defined subset of cellular surface receptors (epitopes) on B and T lymphocytes that identify cell type and stage of differentiation, and which are recognized by antibodies.
B cell receptors (BCR) comprising one of thousands of distinct immunoglobulin superfamily molecules generated through VDJ recombination.
T cell receptors (TCR) with heterodimers of α and β chains or γ and δ chains with Ig-like domains. Each TCR originates in a single allele and binding with a single specificity (CDR3 for antigens and CDR1-2 for MHCs).
major histocompatibility complex (MHC) molecules of classes I, II, and III, participate in lymphocyte recognition and antigen presentation.

B lymphocytes perform the humoral immune response , and are activated when naïve B cells encounter their specific, cognate antigen. Secreted cytokines promote the proliferation of single clones of B cells that express that immunoglobulin surface receptor (BCR) that already possesses VDJ recombination-generated affinity for the antigen.

Costimulation involves ligand-receptor interactions at the surfaces of a responder lymphocyte and an "accessory" cell – APCs for activation of T cells, and helper T cells for activation of B cells. Assisted by costimulation from helper T cells, B cells may undergo differentiation into plasma cells, which secrete copious quantities of the monoclonal antibody, or into memory B cells, which are primed for rapid response to a repeated exposure of the priming antigen.[]diagram B[]

T lymphocytes participate in the cellular immune response, and are (first signal) activated by engagement of their surface receptor (TCR), which ensures antigen specificity and MHC restriction of the response. Delivery of first signal (TCR engagement) in the absence of costimulation by second signaling results in apoptosis or anergy. Synergistic signaling by (second signal) costimulatory molecules is also necessary to sustain and integrate TCR signaling to stimulate optimal T cell proliferation and differentiation. []diagram T[]

In addition to antibodies produced by plasma cells, a number of molecule types participate in the humoral response, including:
complement cascadeanaphylatoxins and opsonins
coagulation factors
● lysozyme, phospholipase
interleukin-1 (IL-1), inflammatory kinins
● iron-binding lactoferrin and transferrin

▲ф activation B : activation T (activation B : activation T : activation complement cascade ) : active/passive : adaptive immune response : anergy ф anergy ф antibodies ф antigen ф APCs ф autoimmunity : autoimmune ф B cells ф basophils : blood ф blood ф CD : cells : cellular immune response : cellular participants ф cellular response : classification ф CD ф cellular response ф clonal selection ф complement system ф costimulation : costimulation ф cytolysis ф cytotoxicity : danger hypothesis ф dendritic cells ф eosinophils ф granulocytes ф helper T cell ф hematopoiesis ф humoral immunity ф HIV/AIDs : humoral immune response : humoral participants ф immune cytokines ф immune response ф immune tolerance ф inflammatory response : innate immune response ф killer T cells ф leukocytes ф leukocyte adhesion cascade ф lymphocytes ф lymphokines ф lymphoid system ф macrophages ф MHC ф migration : pattern recognition receptors : phagocytes ф phagocyte ф plasma cells ф receptors ф signaling ф surface receptors : molecular participants : self-other : surface receptors ф surface receptorsT ф T cells ф thymus V ф vaccines ф VDJ recombination▲ф

Tables  Complement Receptors  Cytokines  Fc receptors  Immune Cytokines  Immunoglobulins  Interferons  Scavenger Receptors  Toll-like Receptors

Toll, A New Piece in the Puzzle of Innate Immunity. Wright SD. [Free Full Text Article] J Exp Med. 1999 Feb 15;189(4):605-9.

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