Introduction to Cellular Immunology

1
Introduction to Cellular Immunology Dr. Colin
R.A. Hewitt crah1_at_le.ac.uk
Movie credits The movies of cells are used with
the permission of Dr. James A. Sullivan of Cells
Alive http//www.cellsalive.net/
2
The purpose of this preliminary lecture is to
remind students of the immunology learnt in the
second year, and introduce key concepts that are
required for a full understanding of the later
lectures To use the lecture, click on the
projection screen icon below , then just
click your way through the presentation. Dont
forget to try the online multiple choice
questions at the end to find your strengths and
weaknesses
3
What you should know by the end of this lecture

• ? The basic terms used in immunology
• ? The characteristics and interdependence of
  adaptive and innate immunity
• ? The names and functions of cells in the immune
  system
• ? The structure and function of peripheral
  lymphoid organs
• The purpose of lymphocyte recirculation
• ? How cells communicate in the immune system and
  how this is tested
• ? How the clonal distribution of antigen
  receptors in the immune system allows for
  diverse recognition, self tolerance and memory
• ? That the compartments invaded by pathogens
  require different effector mechanisms of
  immunity.

4
History impact of immunology on human health
5
Why study immunology now?
Infectious diseases Mechanisms of
pathogenicity Vaccine development
Diseases caused by a disturbed immune
system ALLERGY Immune responses to innocuous
materials e.g. ASTHMA AUTOIMMUNITY Anti-self
immunity e.g. MULTIPLE SCLEROSIS GRAFT
REJECTION Immune responses to TRANSPLANTED
TISSUE IMMUNODEFICIENCY Defects in immune
responses e.g. SCID
Manipulation of immunity to treat
disease IMMUNOSUPPRESSION Treatment of immune
diseases IMMUNOREGULATION Immunotherapeutic
interventions
6
Reminder of basic immunological terms
ANTIGENS (Ag) are substances recognised by
ANTIBODIES (Immunoglobulin, Ig, Ab) and T
LYMPHOCYTES (T CELLS) Antibodies are made by B
LYMPHOCYTES (B CELLS) T cells help B cells make
antibodies T HELPER (Th) cells T cells kill
infected cells T CYTOTOXIC (CTL)
7
Immune responses
Skin Mucous membranes rapidly regenerating
surfaces, peristaltic movement, mucociliary
escalator, vomiting, flow of urine/tears, coughing
Cellular and humoral defences lysosyme,
sebaceous/mucous secretions, stomach acid,
commensal organisms,complement proteins,
phagocytosis, NK cells
Cellular and humoral defences Antibodies,
cytokines, T helper cells, cytotoxic T cells
8
Adaptive immunity
Immunity established to adapt to infection
Learnt by experience Confers pathogen-specific
immunity Enhanced by second exposure Has
memory Uses cellular and humoral components
Is poorly effective without innate immunity
Antibodies reflect infections to which
an individual has been exposed- diagnostic for
infection
9
Innate immune response
Inbuilt immunity to resist infection Present
from birth Not antigen-specific 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
10
Leucocytes
Adaptive and innate immunity depends upon
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.
11
Cells Of The Immune System
12
Lymphocyte subsets
13
Look for some excellent low power images and
electron micrographs of the cells at the
following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l

• Resting Lymphocyte
• Activated Lymphocyte
• Plasma cell
• T and B cells are morphologically identical

Movie Cytotoxic T- lymphocyte killing
target (click on this link)
14
Look for some excellent low power images and
electron micrographs of the cells at the
following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l

• Erythrocyte (Red blood cell)
• Blood monocyte
• Platelet (thrombocyte)
• Tissue macrophage

Movie Human macrophage ingesting Candida
albicans (click on this link)
15
Look for some excellent low power images and
electron micrographs of the cells at the
following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l

• Neutrophil

Movie Chemotaxis of human neutrophils (click on
this link)
16
(No Transcript)
17
Look for some excellent low power images and
electron micrographs of the cells at the
following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l

• Eosinophil
• Basophil
• Neutrophil
• Lymphocyte
• Monocyte

18
Lymphocyte antigen receptors
Each antigen receptor binds to a different
antigen Each cell has only one antigen specificity
19
Lymphoid organs
Organised tissue in which lymphocytes interact
with non lymphoid cells Sites of maturation
initiation of adaptive immune responses CENTRAL
LYMPHOID ORGANS PERIPHERAL LYMPHOID ORGANS
Central lymphoid organs THYMUS T cell
maturation BONE MARROW  B cell maturation
Peripheral lymphoid organs LYMPH NODES SPLEEN
WHITE PULP MUCOSAL-ASSOCIATED LYMPHOID TISSUE T
and B cell activation Antigen trapping
20
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
21
Look for an excellent image of a sectioned lymph
node at the following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l
22
Look for an excellent image of a germinal centre
at the following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l
23
Spleen white pulp Transverse section
Marginal sinus
B cell corona
Red pulp
Germinal centre
Marginal zone
Periarteriolar lymphocytic sheath (PALS) T cell
area
Central arteriole
24
Look for an excellent image of a sectioned spleen
at the following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l
25
Lymphocyte recirculation
NAIVE LYMPHOCYTES enter blood, are seeded to
the peripheral lymphoid organs and recirculate
Cells antigens from a site of infection are
trapped in draining lymphoid tissue. Cells
proliferate and re-enter the RECIRCULATING
LYMPHOCYTE POOL to re-seed the peripheral
lymphoid organs
26
Look for an excellent images of Wuchereria
bancrofti and elephantiasis at the following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l
27
How immune cells communicate SOLUBLE MEDIATORS
Infection
CYTOKINES CHEMOKINES Diverse collection of
soluble proteins made by cells that affect the
behaviour of other cells. The balance level of
cytokines and chemokines secreted affects the
outcome of the response
INFLAMMATION Early events involve endothelial
cells and result in the accumulation of fluid,
plasma proteins leucocytes. Later events
involve the activation and maturation of
lymphocytes and other granulocytes.
28
Bio-assay of cytokines in vitro
Remove cytokine containing supernatant
Which cytokine?
29
Specificity of cytokine bioassays
30
How immune cells communicate CELL-CELL CONTACT
Peripheral lymphoid tissues trap
antigen-containing phagocytic cells and
concentrate cells together to promote cell-cell
contact. Cell-cell contact occurs at many stages
of immune responses.
31
Cell surface molecules mediate cell-cell contact
Expression and level of expression controls
cell-cell adhesion Activation can induce
expression. Cell adhesion, migration, antigen
specificity, antigen presentation, costimulation,
helper function, effector function. Cell surface
molecules influenced by activation include
cytokine receptors.
32
Bio-assay of cell cell contact requirements in
vitro
- Not due to a cytokine Which cell surface
molecule?
- MHC molecules important
33
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
34
Clonal selection theory MacFarlane Burnet 1957
35
Clonal selection induces proliferation and
increases effector cell frequency
36
Clonal nature of adaptive immune response allows
for removal of harmful cells
Opportunity to remove harmful specificity at an
early stage of development IMMUNOLOGICAL TOLERANCE
!!!!Cells specific for self antigen!!!!
Antigen receptors recognising self antigens can
be individually purged from the antigen receptor
REPERTOIRE before clonal expansion
37
Clonal nature of adaptive immune response allows
for immunological memory
38
Immune effector mechanisms against extracellular
pathogens toxins NEUTRALISATION
NEUTRALISING ANTIBODIES
39
Effector mechanisms against extracellular
pathogens OPSONISATION
binding
40
Effector mechanisms against extracellular
pathogens COMPLEMENT
Lysis
41
Effector mechanisms against intracellular
pathogens CYTOXICITY
Viral infection
Lethal hit
42
Effector mechanisms against intracellular
bacteria MACROPHAGE ACTIVATION
Activated macrophage
Resting Macrophage
43
Summary

• ? Reminder of 2nd year immunology
• ? Characteristics and components of adaptive and
  innate immunity
• ? Peripheral lymphoid organs lymphocyte
  recirculation
• ? Intercellular communication by cytokines and
  cell-cell contact
• ? Clonal selection Ag recognition, self
  tolerance and memory
• Effector mechanisms

NOW TRY THE MULTIPLE CHOICE QUESTIONS (click on
this link)