D’YOUVILLE COLLEGE
BIOLOGY 307/607 - PATHOPHYSIOLOGY
Lecture 4 - LYMPHOCYTES & ADAPTIVE IMMUNITY
Chapter 5
1.
Body Defenses:
• nonspecific (innate) immunity:
- skin, mucous membranes, and secretions (e.g., saliva, tears, urine)
represent barriers to entry of microbes
- phagocytes, natural killer cells, acute inflammations, fever, antimicrobial
chemical agents & pH variations obstruct entry or spread of infections (fig. 5 – 1,
table 5 – 1 & ppt. 1)
• specific (acquired) immunity:
- specific for offending agent (antigen) (fig. 5 – 2 & ppt. 2)
- capacity for recognition
- stronger response upon second or later exposures (learning) (fig. 5 – 10 &
ppt. 3)
- vigorous response capability persists (memory)
- exhibits tolerance of 'self'
- function of lymphocytes from lymphoid tissues
- operates collaboratively with nonspecific defenses
2.
Lymphocytes:
three basic types are recognized:
i. T-lymphocytes: progenitors and facilitators of cell-mediated immunity and
facilitators of antibody-mediated immunity (humoral immunity)
- three types of T-cells (distinguished by T-cell receptors & CD4 or CD8):
- two ‘helper’ T-cells (TH1 & TH2) & cytotoxic T- cells (TC)
- helpers express CD4 receptors and are also known as T4 cells
- cytotoxics express CD8 receptors and are also known as T8 cells
- T-cell receptors 'recognize' (bind with) antigens (discussed below) &
CD4 or CD8 facilitate different antigen recognition properties (aid T-cell receptors)
(ppt. 4)
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ii. B-lymphocytes: produce antibody-mediated immunity assisted by TH2cells
- B-cells express receptors that are antibodies (T-cell receptors resemble but
are not identical to antibodies)
- B-cells that have been stimulated by binding antigen may mature into
plasma cells that secrete antibodies (ppt. 5)
iii. NK cells: ‘natural killer cells’ are large granulated lymphocytes that
respond to antibody-coated cells or to surface properties of virus-infected cells or tumor cells
(fig. 5 – 6 & ppt. 6)
3.
Maturation of Lymphocytes:
• lymphocyte clones: both T and B cells bear surface receptors (T cell
receptors or antibodies on B cells)
- receptors on one type of B or T cell are unique and all cells with a
particular specific receptor constitute a clone
- lymphocyte population of the body consists of a billion or more clones,
each with its own unique receptor -- represents recognition for virtually all possible
antigens that may be encountered, including self antigens
• antigens are complex molecules on the surface of microbes as well as normal
body cells; most antigens will have a number of immunogenic features, called
antigenic determinants (epitopes), so more than one lymphocyte clone may respond
to a given antigen
- self-antigens are displayed on the surfaces of normal body cells and are
known as MHC (major histocompatibility complex) antigens; T-cells (helper T-cells )
first responding cells of immune responses must recognize MHC surface receptors
• MHC receptors (proteins) – serve as presenters of endogenous or self-antigens
(on uninfected cells) and also exogenous or foreign antigens (on infected cells)
- class I MHC proteins are produced by all cells and interact with CD8
proteins of cytotoxic T cells (Tc)
- class II MHC proteins are produced only by antigen presenting cells and
interact with CD4 proteins of helper T cells (TH1 & TH2)
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• screening of lymphocyte clones: in the immature immune system,
lymphocyte screening (B-cells in bone marrow, T-cells in thymus gland), eliminates
clones that may attack self, through processes of positive & negative selection
- positive selection entails preservation of only those clones that bind to
MHC receptors; all others are destroyed by apoptosis
- negative selection entails elimination (by apoptosis) of the clones that
have a high affinity for MHC receptors
- resulting lymphocytes exhibit ‘self-tolerance’ and are released to circulate
as lymphocyte traffic (ppts. 7 & 8)
- T cells or B cells that have undergone maturation (positive and negative
selection) in their respective primary lymphoid tissues will be immunocompetent as
well as self-tolerant
- until they have had their first encounter (sensitization) with the antigenic
determinant for which they express specific receptors, they are considered naive
4.
Lymphoid Tissues and Lymphocyte Traffic:
• two primary lymphoid tissues:
- red bone marrow is the repository of stem cells for formation of all
formed elements of the blood: erythrocytes or red cells, leukocytes (neutrophils,
eosinophils, basophils, monocytes & lymphocytes) and platelets)
- site for development of immunocompetence & self-recognition for Blymphocytes
- thymus gland is the site of formation of some T-lymphocytes
- site for development of immunocompetence & self-recognition for T-lymphocytes
• secondary lymphoid tissues: spleen, regional lymph nodes, &
gastrointestinal lymphoid depots (tonsils, Peyer’s patches & vermiform appendix) +
free lymphocytes scattered in various body tissues (fig. 5 – 7 ppts. 9 & 10)
• lymphocyte traffic (ppts. 11 & 12)
- lymphocytes from bone marrow develop further in marrow (B-cells) or
migrate to thymus gland for further development (T-cells)
- competent T-cells & B-cells circulate to secondary lymphoid tissues
(spleen, gastrointestinal depots, regional lymph nodes and other areas that are
strategic locations for encounters with antigens (instigate immune responses)
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- antigen-activated lymphocytes linger in various lymphoid depots and/or
freely circulate in blood