Introduction to Immunology

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Introduction to Immunology Dr. Ofer
Mandelboim
Portions adapted from Drs. David J. Topham and
Colin R.A. Hewitt, web sites, ImmunoBiology by
Janeway Travers
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What you should be aware of by the end of this
lecture

• ? The basic terms used in immunology
• ? The characteristics and interdependence of
  adaptive and innate immunity
• ? The types and functions of cells in the immune
  system
• ? The structure and function of peripheral
  lymphoid organs
• The purpose of lymphocyte recirculation
• ? How cells communicate and recognize antigen
• ? The concept of clonal distribution of antigen
  receptors

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Edward Jenner, the founder of modern
immunology 1796- Introduction of protective
vaccine against small pox based on cow pox (in
Latin - vaccinia )
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History impact of immunology on human health
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Reminder of basic immunological terms
ANTIGENS (Ag) are substances recognized by
ANTIBODIES (Immunoglobulin, Ig, Ab) and T
LYMPHOCYTES (T CELLS) Antibodies are made by B
CELLS T HELPER (Th) cells help B cells make
antibodies CYTOTOXIC T cells (CTL) kill
infected cells
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Immune responses
Skin Mucous membranes rapidly regenerating
surfaces, peristaltic movement, mucociliary
escalator, vomiting, flow of urine/tears, coughing
Cellular and humoral defenses lysosyme,
sebaceous/mucous secretions, stomach acid,
commensal organisms,complement proteins,
phagocytosis, NK cells
Cellular and humoral defenses Antibodies,
cytokines, T helper cells, cytotoxic T cells
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Innate immune response
Inbuilt immunity to resist infection Not
antigen-specific (except from NK cells) Not
enhanced by second exposure Has no memory
Uses cellular and humoral components Is poorly
effective without adaptive immunity Also
involved in the triggering and amplification of
adaptive immune responses
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Adaptive immunity
Immunity adapted to infection Is
antigen-specific Learned by experience
Enhanced by second exposure Has memory Uses
cellular and humoral components Is poorly
effective without innate immunity
Immune memory reflects infections to which
an individual has been exposed
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Leucocytes
Innate immunity is mediated largely by
GRANULOCYTES Adaptive immunity mediated by
LYMPHOCYTES The growth, development and
activities of granulocytes and lymphocytes are
interconnected and often co-operative.
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Cells Of The Immune System
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Lymphocyte subsets
DC, NK
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EOSINOPHIL
RED BLOOD CELLS
Cells of the blood
NEUTROPHILS
MONOCYTE
BASOPHIL
LYMPHOCYTES
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MACROPHAGE
Lymphocytes on the move
Direction of travel
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Lymphoid organs
Organized tissue in which lymphocytes interact
with non-lymphoid cells Sites of maturation
initiation of adaptive immune responses
Central THYMUS T cell maturation BONE MARROW
 B cell maturation
Peripheral LYMPH NODES SPLEEN PEYERS PATCHES T
and B cell activation Antigen trapping
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Lymph node
4. Germinal centre (site of intense B
cell proliferation)
5. Medullary cords (Macrophage plasma
cell area)
3. Secondary lymphoid follicle
6. Efferent lymphatic vessel
2. Primary Lymphoid follicle (B cell area)
Artery
Paracortical (T cell) area
Vein
1. Afferent lymphatic vessel. Lymph, Cells
Ag drained from tissues enters here
Medullary sinus
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LYMPH NODE HISTOLOGY
Germinal centers
Macrophage
Lymphocytes
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Spleen white pulp Transverse section
Marginal sinus
B cell corona
Red pulp
Germinal centre
Marginal zone
T cell area
Central arteriole
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Spleen white pulp
Marginal sinus
Red pulp
Germinal centre
T cell area
Marginal zone
Central arteriole
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Lymphocyte recirculation
NAIVE LYMPHOCYTES circulate from the blood into
lymph nodes through high endothelial venules
(HEV)
EFFECTOR CELLS exit lymph nodes and traffic to
inflamed tissue. MEMORY LYMPHOCYTES re-circulate
from blood into tissue, and then into lymph nodes
through afferent lymphatics. Some may reside in
tissue.
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LYMPHOCYTE RECIRCULATION
Arterial circulation
High Endothelial Venule
LYMPH NODE
Efferent Lymphatic
SPLEEN
Afferent lymphatic
Venous circulation
Dendritic Cell (APC)
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ADHESION MOLECULES IMPORTANT TO LYMPHOCYTE
RECIRCULATION

• CD62L (L-selectin)
• Integrins
• LFA-1
• VLA-4
• VLA-1
• CD44

• Lymph node homing
• Vascular endothelium
• ICAM-1
• VCAM
• ECM
• Tissue binding (ECM)

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Lymphocyte antigen receptors
Each antigen receptor binds to a unique epitope
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Major Histocompatibility Complex  MHC
In mice the MHC is called H-2 Rapid graft
rejection segregated with a cell surface antigen,
Antigen-2 Inbred mice identical at H-2 did not
reject skin grafts from each other MHC genetics
in mice is simplified by inbred strains
In humans the MHC is called the Human Leukocyte
Antigen system HLA Only monozygous twins are
identical at the HLA locus The human population
is extensively outbred MHC genetics in humans is
extremely complex
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MHC molecules
b2M
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Cleft geometry
MHC class I accommodate peptides of 8-10 amino
acids
MHC class II accommodate peptides of 12-20 amino
acids
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Differential distribution of MHC molecules
Tissue MHC class I MHC class II T
cells /- B cells
Macrophages Other
APC Epithelial cells of
thymus Neutrophils
- Hepatocytes - Kidney
- Brain
- Erythrocytes - -
Cell activation affects the level of MHC
expression The pattern of expression reflects the
function of MHC molecules Class I is involved in
anti-viral immune responses Class II involved in
activation of other cells of the immune system
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MHC molecules sample both the intracellular and
extracellular environments
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MHC Summary
T Cells recognize a combination of MHC and
peptide contact points T cells can only be
activated by interaction between the antigen
receptor and peptide antigen in an MHC
molecule Without T cells there can be no
effective immune response

• MHC molecules
• Present antigens to T cells
• Sample extracellular and intracellular antigens
• Class I MHC present intracellular antigens
• Class II MHC present extracellular antigens
• Use anchor residues to tether the peptide
• Fold around the peptide to create a stable
  complex

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Clonal nature of the adaptive immune response
Each lymphocyte expresses a single antigen
receptor specificity.
There are millions of lymphocytes in the body,
and thus millions of different antigen receptors.
Each naive lymphocyte bearing a unique receptor
is the progenitor of a genetically identical
CLONE of daughter cells.
PROBLEM The CLONAL DISTRIBUTION of antigen
receptors means that lymphocytes of a particular
specificity will be too infrequent to mount an
effective response.
A process akin to natural selection, CLONAL
SELECTION raises the clonal frequency of cells
with a particular antigen specificity
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Clonal selection theory MacFarlane Burnet 1957
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Clonal selection induces proliferation and
increases effector cell frequency
No. of cells with useful specificity
No. of cell divisions
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Clonal nature of adaptive immune response allows
for immunological memory
1 response to antigen A
Magnitude of specific response
Days
4
16
12
8
20
64
68
72
Lymphocyte apoptosis
Lymphocyte proliferation to Ag A
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Example humoral effector mechanisms against
viruses OPSONISATION
binding
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Example CD8 T cell mediated virus
elimination CYTOTOXICITY
Viral infection
Lethal hit
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Summary

• ? Characteristics and components of adaptive
• and innate immunity
• ? Peripheral lymphoid organs lymphocyte
  recirculation
• ? Clonal selection Ag recognition and memory