Chapter 18
Lecture Outline*
The Immune System
Eric P. Widmaier
Boston University
Hershel Raff
Medical College of Wisconsin
Kevin T. Strang
University of Wisconsin - Madison
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1
Cells Mediating Immune Defenses
2
Cytokines
3
Nonspecific Immune Defenses
• These defenses recognize some general
property marking the invader as foreign and
they protect the body as the first line of
defense.
• The nonspecific defenses include:
– Physical barriers
– Inflammation
– Interferons
– Natural killer cells
– Complement system
4
Defenses at Body Surfaces
• The body’s first lines of defense against
microbes are the barriers offered by surfaces
exposed to the external environment and their
various antimicrobial secretions.
• Examples: skin and mucous membranes
5
Inflammation
6
Phagocytosis
Fig. 18-2
7
Role of Phagocytosis
Fig. 18-3
8
Oponization
Fig. 18-4
9
Complement System
• The complement system is composed of plasma
proteins that lyse foreign cells, especially bacteria.
• Approximately 30 proteins participate in the
cascades that result in a Membrane Attack Complex
(MAC) on the surface of the invading bacteria.
• The MAC ruptures the bacterial membrane causing
lysis of the bacteria and death of the organism.
10
Functions of Complement
Fig. 18-5
11
Interferons
Fig. 18-6
12
Specific Immune Defenses: Overview
• Lymphocytes recognize specific foreign
molecules called antigens.
13
Lymphoid Organs
Fig. 18-714
Lymphoid Tissues
• Primary Lymphoid organs:
– Bone marrow
– Thymus
• Secondary Lymphoid Organs:
–
–
–
–
–
–
Spleen
Lymph nodes
Tonsils
Adenoids
Appendix
Peyer’s patches
15
Lymphocyte Origins
Fig. 18-8
16
Functions of B Cells and T Cells
Fig. 18-9
17
Lymphocyte Receptors (Antibodies)
Two heavy chains
Two light chains
Constant region—
same within a class
of antibodies
Variable region—
differs
for different
antigens, gives
specificity to
antigen-binding site
Two antigen-binding
sites
Fig. 18-10
18
Antibody Function in Humoral Immunity
• The antibody functions to bind the specifc antigen.
• This leads to inactivation and destruction of the
foreign antigen.
• There are 5 classes of antibodies:
– IgG
– IgM
– IgE
– IgD
– IgA
19
Antibody Functions
• Neutralization
• Agglutination
• Opsonization
• Complement Activation
• Enhanced Natural Killer Cell Activity
20
Major Histocompatibility Complex
(MHC) Molecules
• There are two classes of MHC molecules:
– Class I MHC are expressed on the surface of all
nucleated cells.
– Class II MHC are expressed on the surface of
macrophages, activated B cells, activated T cells, and
thymus cells.
• T cells have antigen receptors which recognize
antigens only when they are associated with MHC
molecules. This is part of the antigen presentation
mechanisms.
21
MHC is the “Self” Recognition
• MHC molecules are unique to each individual
person and are also known as HLA (human
leukocyte antigen).
• These markers are important because they mark
cells as “self” or belonging to that organism.
• Cells that do not match the MHC are foreign and
are responsible for tissue or organ rejection because
they stimulate the immune response to foreign
tissue.
22
Antigen Presentation to T Cells
Fig. 18-11
23
Activation of Helper T Cells
Fig. 18-12
24
Cytotoxic T Cells
Fig. 18-13
25
NK Cells
• NK cells are a class of lymphocytes similar to
cytotoxic T cells, whose major targets are
virus-infected cells and cancer cells; however,
they are not antigen-specific.
26
Development of Immune Tolerance
• Immune tolerance develops during fetal and
early postnatal life due to clonal deletion or
clonal inactivation.
• Autoimmune diseases are caused by failure of
self-tolerance.
27
Defenses Against Bacteria, Extracellular Viruses,
and Toxins
Fig. 18-14
28
Enhancement of Phagocytosis by
Antibodies
Fig. 18-15
29
Activation of Complement
Fig. 18-16
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Defenses Against Virus-Infected Cells
and Cancer Cells
Fig. 18-18
31
Role of IL-2 and Interferon-gamma
Fig. 18-19
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Memory
• Primary immune response: (1st exposure)
– Generally takes 10–17 days to occur after
exposure
– Symptoms of illness occurs during these days
– Antigen-selected B and T cells proliferate and
differentiate into effector cells
• Secondary immune response: (all other
exposures)
– Takes 2–7 days to occur
– Greater response
– Occurs due to memory cells
33
Memory
Fig. 18-17
34
Systemic Manifestations of Infection
Fig. 18-20
35
Factors that Alter the Body’s Resistance
to Infection
• Factors include nutrition, pre-existing disease,
stress, physical exercise, sleep deprivation, and
genetic deficiency.
36
Immunity
• Active immunity is an immune response to vaccine
or pathogen in an individual and gives immunity
because of the production of memory cells.
• Vaccine is the introduction of a microorganism or
its antigens in a form not expected to cause disease,
which induces an immune response including
production of memory cells
37
Immunity
• Passive immunity comes from the
administration of synthetically produced
antibodies.
• This results in no memory cell production, so
there is no long-term memory and immunity.
• Passive immunity can also come from mother
to fetus or baby because antibodies pass in the
placenta (IgG) and breast milk (IgA).
38
Harmful Immune Responses
• Graft Rejection
• Transfusion Reactions
• Allergy (Hypersensitivity)
• Autoimmune Disease
• Excessive Inflammatory Responses
39
Tissue Grafts and Organ Transplantation
• HLA molecules (MHC) stimulate rejection
by inducing immune response, so there must be as close
a match in the MHC between the donor and recipient as
possible.
• The recipient will have to suppress the immune system
pharmacologically to prevent rejection.
– Cyclosporin A
– FK506
40
Transfusion Reactions
• Transfusion reactions are the illness caused when
erythrocytes are destroyed during blood transfusion.
• It is caused by antibodies rather than cytotoxic T cells.
• Erythrocytes do not have MHC proteins, but they do have
plasma membrane proteins and carbohydrates that can
function as antigens.
• The ABO system of carbohydrates is the most important
for transfusion reactions.
• Another group of erythrocyte membrane antigens of
medical importance is the Rh system of proteins.
41
Blood Typing
42
Immediate Hypersensitivity Allergic
Response
Fig. 18-21a
43
Anaphylactic Shock
• Anaphylatic shock is a severe allergic reaction that
results from a massive release of histamine from
mast cells throughout the body. This causes a
massive drop in systemic blood pressure and can
cause circulatory collapse.
44
Autoimmune Diseases
• The immune system treats a part of itself like an
invading pathogen.
• Examples:
– Insulin-dependent diabetes mellitus (type I)
– Lupus
– Rheumatoid arthritis
– Multiple sclerosis
45
Immunodeficiency Diseases
• Immunodeficiency diseases result from weak or
under-active immune systems.
• Examples:
– SCID = severe combined immunodeficiency disease
– Hodgkin’s Disease = cancer of lymphatic system
– AIDS = affects helper T cells
46
Acquired Immune Deficiency
Syndrome (AIDS)
• Human immunodeficiency virus (HIV) infects
and kills helper T cells resulting in impairment
of the immune response to other infectious
organisms.
47