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This chapter deals with development of specific immune mechanisms. Objectives are:
1. To become familiar with hall marks of specific acquired immunity i.e. 1) specificity and 2) memory.
2. To study the difference between innate immunity and specific acquired immunity; to understand that establishment of immunity for one organism does not confer protection against another unrelated organism.
3. To acquire knowledge of cells and organs involved in the development of specific acquired immunity.
4. To study clonal selection theory and understand the differences between primary immune response and secondary immune response (anamnestic response).
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When an infectious agent enters the animal body it encounters the elements of innate immune system. If the innate immunity fails, a disease will result and the adaptive immune system is activated. In most cases, the animal recovers and a specific immunological memory is established and a subsequent reinfection with same agent will not cause disease; the animal has specific acquired immunity to the agent.
16.3.1Two broad categories of specific acquired immunity
1) humoral immunity mediated by antibodies and complement.
2) cell-mediated immunity mediated by lymphocytes.
16.3.1.1 Immunopathology
undesirable consequences of immunity.
Immune system
established on the basis of self/non-self recognition.
Tolerance to self antigens breaks down in some cases and results in autoimmune disorders.
Innocuous antigens (eg. pollen) are sometimes recognized and the immune system mounts an inappropriate response leading to hypersensitivity symptoms (allergies).
16.3.1.2 Differences between innate immunity and specific acquired
immunity
Innate Acquired
Effect of repeated resistance not resistance
infection improved improved
factors involved complement, lysozyme, antibody
acute phase proteins
cells involved phagocytes, T cells
natural killer cells
16.3.1.3 Methods of developing specific acquired Immunity
Primary and secondary lymphoid organs and cells involved in the immune system.
16.4.1 Primary Lymphoid Organs
1. Thymus:
Organ found in the anterior mediastinal space (thorax). First lymphoid organ to develop. Absolute size greatest at puberty, thereafter, atrophy occurs slowly. Bilobed organ, each lobule has outer cortex containing immature proliferating lymphoid cells (thymocytes) and inner medulla containing mature cells. Function: educate T cells (maturation). Thymic hormones play a role in maturation.
Neonatal thymectomy - failure to develop cell-mediated immune responses with some reduction in antibody production.
2. Bursa of fabricius and its mammalian equivalent:
In birds B lymphocytes differentiate in the bursa. Mammals have no bursa; fetal liver and fetal and adult bone marrow give rise to B cells. Adult bone marrow also contains many mature T cells and plasma cells, so it is also an important secondary lymphoid organ.
16.4.2 Secondary Lymphoid organs:
(Spleen, lymph nodes, mucosa-associated lymphoid tissue (MALT).
1. Spleen:
Red pulp: storage of erythrocytes, antigen trapping, and erythropoiesis.
White pulp:
contains the lymphoid tissue arranged around a central arteriole - the periarteriolar lymphoid sheath (PALS).
PALS:
composed of T cell and B cell areas. T cells are around the central arteriole while the B cells are found beyond this zone (germinal follicles).
Specialized macrophages are found in the marginal zone - the area surrounding PALS. These and the follicular dendritic cells of the primary follicles present antigen to B cells.
Function of spleen:
to filter blood and remove antigens and old RBC's.
2. Lymph Nodes:
Function:
filter antigen from the tissue fluid and lymph during its passage from the periphery to the thoracic duct.
Cortex contains aggregates of B cells (primary follicles) most of which (secondary follicles) have a site of active proliferation (germinal center).
Paracortex contains mainly T cells.
Medulla contains T cells, B cells and plasma cells.
3. Mucosa-associated lymphoid tissue (MALT):
aggregates of lymphoid tissue are found in the lamina propria and submucosal areas of gastrointestinal, respiratory and urogenital tracts.
Lymphoid tissue associated with gut (GALT) - peyer's patches.
Cells of the immune system arise from pluripotent stem cells through two main lines of differentiation.
1. lymphoid lineage - differentiate into lymphocytes2. myeloid lineage - differentiate into phagocytes (monocytes and neutrophils) and other cells.
Two types based on light microscopy;
1) small lymphocyte - agranular with high N/C ratio and2) large granular lymphocytes (LGL's) with azurophilic granules and low N/C ratio.
Lymphocytes consists of T cells, B cells and Null cells (non-T/ non-B). In general 70% of peripheral blood lymphocytes are T cells and 25% are B cells.
participate in cell-mediated immunity and also provide help to B cells that produce Ig. Mature functional T lymphocytes arise in thymus; have two distinct populations
1) TH subset (CD4+) (helper subset) and2) TC/S subset (CD8+) (cytotoxic/suppressor subset).
Divide in response to mitogens - phytohemaglutinin (PHA) and concanavalin A (Con A). Major secreted products are known as lymphokines.
differentiate into plasma cells that secrete Ig. Mature cells express surface immunoglobulin which acts as specific antigen receptor. Have receptors for Fc of IgG and receptors for C3b; unresponsive to PHA and Con A but divide in response to lipopolysaccharide (LPS).
Pokeweed mitogen (PWM) stimulates the division of both T and B cells.
non T/non B cells that lack the surface antigens or immunoglobulins characteristic of T and B cells.
Killer cells have Fc receptors and also receptors for third component of complement (C3b). They are involved in antibody-dependent cell-mediated cytotoxicity (ADCC) in virus-infected cells and other target cells are killed. Specificity is conferred by the antibody but not by killer cells.
Natural killer cells (NK cells) are mostly derived from large granular lymphocytes (LGLs); are involved in cytotoxicity (natural killer activity) against tumor cells (non-specific).
Orchestration of immune response (or function of various immune cells) depends on communication between interacting cells and soluble molecules known as cytokines. Cytokines include the groups previously called lymphokines, monokines, interleukins and interferons, colony-stimulating factors and tumor necrosis factors.
several have been identified (IL-1 to IL-10).
1) IL-1: secreted predominantly by macrophages but also by other cells such as fibroblasts. Some activities are: proliferation of activated T and B cells, induction of acute phase proteins, stimulation of fever (endogenous pyrogen), in vitro fibroblast growth, and prostaglandin and collagenase release.2) IL-2: secreted by activated T cells that had previously been stimulated by antigen or mitogen. It causes growth and proliferation of activated T and B cells and activation of NK cells.
Please refer to handout for a description of other cytokines.
Evidence suggests that antibodies per se do not occur in invertebrates. The absence of immunoglobulins in invertebrates does not mean that these animals are devoid of internal defense mechanisms. Their defense mechanisms include: Phagocytosis, encapsulation, and chemotaxis.
Hallmarks of acquired immunity: 1) specificity and 2) memory.
A lymphocyte is capable of recognizing one particular antigen. Lymphocytes that recognize a given antigen at a given time are very few. How then an animal generates immune response adequate to counteract an invading microbe?
When an antigen binds to a lymphocyte of appropriate specificity the cell is stimulated to proliferate and mature into effecter cells and longer-lived, antigen specific memory cells.
Secondary immune response (anamnestic response) differs from primary response in the following:
1. response much faster and lasts longer.2. antibody titers are much higher.
3. predominantly an IgG response (IgM in primary response).
4. antibody affinity is much higher.
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2. Essential Immunology
(Ivan Roitt). 3. Immunology (Roitt et
al.).
1.
Veterinary Immunology (Tizzard).
