Transcript Ch. 43 - Harford Community College

Ch. 43
The Body’s Defenses
The skin and mucous membranes provide
first-line barriers to infection
• The first line of nonspecific defense
consists of the intact skin and mucous
membranes, mucus, ciliated cells lining
the upper respiratory system, lysozyme,
and gastric juices.
Phagocytic cells, inflammation, and antimicrobial
proteins function early in infection
• The second line of nonspecific defense depends primarily upon
neutrophils and macrophages, phagocytic white cells in the blood
and tissues.
• Natural killer cells mediate lysis of virus-infected cells and tumor
cells.
• Tissue damage triggers a local inflammatory response.
• Injured cells release histamine, a chemical signal that causes
dilation and increased permeability of blood vessels, allowing fluid
and large numbers of phagocytic white blood cells to enter the
tissues.
• The most important antimicrobial proteins in the blood and tissues
are the proteins of the complement system, involved in both
nonspecific and specific defense, and interferons.
• Secreted by virus-infected cells, interferons inhibit virus production
in neighboring cells.
HOW SPECIFIC IMMUNITY ARISES
Lymphocytes provide the specificity
and diversity of the immune system
• A substance that elicits an immune response is called an
antigen.
• The immune system recognizes specific antigens
(molecules belonging to microbes, toxins, transplanted
tissue, or cancer cells) and develops an immune
response that inactivates or destroys that substance.
• B lymphocytes and T lymphocytes recognize antigens
via surface antigen receptors: membrane antibodies for
B cells, and T-cell receptors for T cells.
• Lymphocytes circulate throughout the blood and lymph
and are found in high numbers in lymphatic tissues.
• The great diversity of lymphocytes, each with receptors
of one particular specificity, gives the immune system the
capacity to respond to virtually any antigen.
Antigens interact with specific lymphocytes, inducing
immune responses and immunological memory
• Clonal selection occurs when an antigen
activates a lymphocyte by binding to a specific
receptor.
• In the primary immune response (to the body's
first exposure to an antigen), the lymphocyte
proliferates and differentiates, forming a clone of
short-lived, infection-fighting effector cells and a
clone of long-lived memory cells, all specific for
the antigen.
• Secondary immune responses to that same
antigen, which involve memory cells, are faster
and often protective.
Lymphocyte development gives rise to an immune
system that distinguishes self from nonself
• Lymphocytes develop from pluripotent stem cells in the
bone marrow.
• B cells mature in the marrow, while T cells mature in the
thymus. Self-tolerance develops as lymphocytes bearing
receptors specific for native molecules are destroyed or
rendered nonresponsive.
• Major histocompatibility complex (MHC) molecules are
crucial to T cell function. Class I MHC molecules, located
on all nucleated cells of the body, present antigen
fragments to cytotoxic T cells.
• Class II MHC molecules, found mainly on macrophages
and B cells, present antigen fragments to helper T cells.
• Developing T cells are exposed to class I and II MHC
molecules on cells of the thymus. Only T cells bearing
receptors with affinity for self-MHC molecules reach
maturity.
IMMUNE RESPONSES
Helper T lymphocytes function in both
humoral and cell-mediated immunity
• Humoral, or B cell, immunity, based on circulation of
antibodies in the blood and lymph, defends against free
viruses, bacteria, and other extracellular threats.
• Cell-mediated, or T cell, immunity defends against
intracellular pathogens by destroying infected cells; it
also defends against transplanted tissue and cancer
cells.
• A CD4-bearing helper T cell is activated when its
receptor binds specifically to a class II MHC-antigen
complex on the surface of an antigen-presenting cell
(APC).
• The T cell then secretes interleukin-2 and other
cytokines, which help activate B cells and cytotoxic T
cells.
In the cell-mediated response, cytotoxic T
cells counter intracellular pathogens
• Most cytotoxic T cells are activated by
cytokines and specific binding to class I
MHC-antigen complexes on a target
(infected, transplanted, or cancerous) cell.
• The T cell then secretes perforins, which
form pores in the target cell membrane,
causing the cell to lyse.
In the humoral response, B cells make
antibodies against extracellular pathogens
• B cells are activated by cytokines and specific binding of their
membrane antibodies to extracellular antigens.
• Most of these antigens are proteins or large polysaccharides, each
with multiple epitopes.
• Antibodies, also called immunoglobulin (Ig) molecules, are serum
proteins.
• The variable regions of an Ig molecule bind to a specific epitope; the
constant regions determine the antibody's class.
• The five major immunoglobulin classes are IgG, IgM, IgA, IgD, and
IgE.
• An antibody does not destroy an antigen directly but neutralizes it or
targets it for elimination by opsonization, agglutination, precipitation,
or complement fixation.
• Opsonization, agglutination, and precipitation enhance phagocytosis
of the antigen-antibody complex; complement fixation leads to lysis
of a complement protein-bound bacterium or virus.
Invertebrates have a rudimentary
immune system
• Invertebrates have the ability to distinguish
between self and nonself.
• In many invertebrates, amoeboid cells
called coelomocytes can identify and
destroy foreign substances.
• Experiments with earthworms show that
their defense systems form memory
against tissue grafts.
• Immune Responses video
IMMUNITY IN HEALTH AND DISEASE
Immunity can be achieved naturally
or artificially
• Active immunity occurs when the immune system
responds to a foreign antigen acquired either by natural
infection or artificially, as by immunization.
• In immunization, a nonpathogenic form of a microbe or
part of a microbe generates an immune response to and
immunological memory for that microbe.
• Passive immunity occurs when antibodies are
transferred from one individual to another.
• t occurs naturally, when IgG passes from mother to fetus
or when IgA passes from mother to infant in breast milk,
or artificially, when antibodies from an animal immune to
a disease are injected into another animal, conferring
short-term protection.
The immune system's capacity to distinguish
self from nonself limits blood transfusion and
tissue transplantation
• Certain antigens on red blood cells determine whether a person has
type A, B, AB, or O blood. Antibodies to nonself blood types
(generally IgM) already exist in the body.
• If incompatible blood is transfused, the transfused cells are killed by
antibody- and complement-mediated lysis.
• The Rh factor, another red blood cell antigen, creates difficulties
when an Rh-negative mother carries successive Rh-positive fetuses.
• During delivery of the first Rh-positive infant, the mother's immune
system develops anti-Rh IgG, which can cross the placenta and may
attack the red blood cells of a subsequent Rh-positive fetus.
• The chances of success in organ or tissue transplantation are
improved if the donor and recipient MHC tissue types are well
matched.
• In addition, immunosuppressive drugs help prevent rejection. In
bone marrow transplantation, there is danger of a graft versus host
reaction.
Abnormal immune function can
lead to disease
• In allergies such as hay fever, an allergen, such
as pollen, triggers histamine release from mast
cells, inducing vascular changes and typical
symptoms.
• Sometimes the immune system loses tolerance
for self, leading to autoimmune diseases such as
rheumatoid arthritis and insulin-dependent
diabetes.
• Some people are naturally deficient in humoral
or cell-mediated immune defenses, or both.
AIDS is an immunodeficiency
disease caused by a virus
• Acquired immunodeficiency syndrome
(AIDS) is caused by the direct and indirect
destruction of CD4-bearing T cells by HIV,
the human immunodeficiency virus, over a
period of years.
• AIDS, the final stage of this process, is
marked by low helper T cell levels and
opportunistic diseases characteristic of a
deficient cell-mediated immune response.
• HIV Reproductive Cycle video
• What Causes Infections in AIDS Patients?
video
• Why Do AIDS Rates Differ Across the
U.S.? video