Principles of Immunology

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Principles of Immunology UCSC Extension 2008 Inst
ructor Ann Wright, Ph.D. Text T.J. Kindt,
R.A. Goldsby, and B.A. Osborne, 2007. Kuby
Immunology. W.H. Freeman and Co., New York.
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Ch. 1. Overview of the Immune System Immunity
is the state of protection against foreign
organisms or substances (antigens). Vertebrates
have two types of immunity innate and adaptive.
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• Innate first line of defense
• Physical, chemical, inflammatory barriers
• Phagocytic cells
• Molecules that recognize certain classes
• of pathogens
• Adaptive specificity, diversity, memory, and
  self-nonself recognition

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Goals of the immune system Prevent entry of
pathogen Prevent growth of pathogen Kill the
pathogen Eliminate pathogen and repair damage
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Historical perspectives
Ancient Greeks noticed that if people recovered
from the plague, they didnt catch it again
1718 - Lady Montagu - variolation 1798 - Edward
Jenner - vaccination - cowpox Louis Pasteur
(1800s) - vaccine design cholera (in
chickens) anthrax (in sheep) rabies (in dogs)
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Von Behring and Kitasato, 1890 Serum from
immunized animals could be transferred to other
animals and protect them Kabat,
1930s Immunoglobulin (Ig) Passive immunity
Ig from others Active immunity own
Ig Metchnikoff, 1883 Phagocytes could ingest
microbes and were more active in immunized
animals
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What are the components of the immune
response? Innate - less specific and immediate
present before infection cells and
molecules involved Adaptive - more specific,
has memory cells and molecules involved
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Soluble molecules in innate immunity Lysozyme I
nterferon Complement Pattern recognition
receptors (PRRs) Toll-like receptors
(TLRs) Cells in innate immunity Macrophages Neu
trophils Natural killer (NK) cells
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Collaboration between innate and adaptive immunity

• Cytokines
• Chemokines (a subclass) attract specific cells
• Cytokines communicate with cells by signalling

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Adaptive immunity is highly specific.
- Antigenic specificity - Diversity -
Immunologic memory - Self-nonself
recognition Lymphocytes and antigen-presenting
cells cooperate in adaptive immunity. First,
lymphocytes will be described
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Lymphocytes are antigen-specific
(Ag-specific). Produce and display
antigen-binding cell surface receptors Two
major populations - B lymphocytes (B
cells) - T lymphocytes (T cells)
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B cells

• Arise and mature in bone marrow
• Have a unique membrane-bound receptor (an
  antibody molecule) that can bind free Ag
• Antibodies (Abs) are glycoproteins
• Two heavy (H) and two light (L) chains
• N-terminal ends bind antigen (Ag)
• Binding Ag causes B cells to divide and
  differentiate into effector plasma cells (that
  secrete Ab) and memory cells

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T cells

• Arise in bone marrow mature in thymus
• T cells have a unique membrane-bound
  T cell receptor (TCR)
• Subpopulations of T cells
• T helper (Th), CD4 (make cytokines)
• T cytotoxic (Tc), CD8 (kill)
• T regulatory (Treg), CD4 (regulate)

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T cell receptor

• Cannot bind free Ag
• Bind Ag peptide that is bound to cell membrane
  proteins called MHC molecules (Major
  Histocompatibility Complex)
• Two major types of MHC
• Class I MHC on almost all nucleated cells of
  body
• Class II MHC on antigen-presenting cells
  (APCs)
• APCs present Ag fragments to T cells

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Activation of both humoral and CMI requires
cytokines produced by Th cells. B cells need
IL-2 ? plasma cells that make Ab Tc cells need
IL-2 ? cytotoxic T cells that kill Humoral and
CMI have different effector functions. Abs
tag bacteria for destruction, neutralize viruses
and toxins T cells CTLs kill virus-infected
cells, grafts, tumors Th cytokines activate
other cells Antigen-presenting cells interact
with T cells.
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Examples of antigen-presenting cells that can
express class II MHC Macrophages Dendritic
cells B cells
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APCs interact with Th cells

• Two properties of professional APCs
• Express class II MHC molecules on their membranes
• Can produce cytokines that cause Th cells to
  become activated
• APCs internalize Ag, then display Ag peptides on
  their membrane bound to a class II MHC molecule
• APC then produces another signal leading to
  activation of the Th cell

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The antigen receptors of B and T lymphocytes
are diverse. Maturation random rearrangements
of gene segments that encode the cells
antigen-binding receptor (105/cell).
Anti-self clones are eliminated. Thus each
lymphocyte becomes committed to recognizing a
particular antigen. There are 109 (T cells)
to 1010 (B cells) unique Ag specificities.
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Clonal selection theory Main paradigm T and B
cells with different antigen specificities exist
before they encounter antigen. Lymphocytes have
antigen-specific receptors on their
surfaces. Once receptor combines with antigen,
the cells proliferate and differentiate into
clones. Somehow, cells that recognize
self-antigens are prevented from developing
(tolerance).
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Antigen Selection of Lymphocytes Causes Clonal
Expansion Primary response longer lag, lgM
Abs Secondary response more rapid,
heightened, mostly IgG Abs, due to
amplified population of memory cells
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To review The immune reaction consists of
two related activities Recognition of a
specific foreign substance, pathogen or
antigen Response that eliminates or neutralizes
that substance Memory in adaptive immunity,
subsequent exposure to a substance leads to a
faster, more intense response
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Components of immune activation Antigen
recognition by Abs and TCRs Requirement of T
cell help for B cell activation Requirement of
Ag presentation by antigen-presenting cells
(APCs) for T cell activation
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What happens when the immune system
dysfunctions? Allergies and asthma Graft
rejection and graft-vs-host disease Autoimmune
disease Immune deficiency
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