Title: 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/
2The 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
3What 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.
4History impact of immunology on human health
5Why 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
6Reminder 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)
7Immune 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
8Adaptive 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
9Innate 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
10Leucocytes
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.
11Cells Of The Immune System
12Lymphocyte subsets
13Look 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)
14Look 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)
15Look 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
Movie Chemotaxis of human neutrophils (click on
this link)
16(No Transcript)
17Look 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
18Lymphocyte antigen receptors
Each antigen receptor binds to a different
antigen Each cell has only one antigen specificity
19Lymphoid 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
20Lymph 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
21Look for an excellent image of a sectioned lymph
node at the following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l
22Look for an excellent image of a germinal centre
at the following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
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23Spleen white pulp Transverse section
Marginal sinus
B cell corona
Red pulp
Germinal centre
Marginal zone
Periarteriolar lymphocytic sheath (PALS) T cell
area
Central arteriole
24Look for an excellent image of a sectioned spleen
at the following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l
25Lymphocyte 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
26Look for an excellent images of Wuchereria
bancrofti and elephantiasis at the following site
http//www-medlib.med.utah.edu/WebPath/webpath.htm
l
27How 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.
28Bio-assay of cytokines in vitro
Remove cytokine containing supernatant
Which cytokine?
29Specificity of cytokine bioassays
30How 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.
31Cell 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.
32Bio-assay of cell cell contact requirements in
vitro
- Not due to a cytokine Which cell surface
molecule?
- MHC molecules important
33Clonal 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
34Clonal selection theory MacFarlane Burnet 1957
35Clonal selection induces proliferation and
increases effector cell frequency
36Clonal 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
37Clonal nature of adaptive immune response allows
for immunological memory
38Immune effector mechanisms against extracellular
pathogens toxins NEUTRALISATION
NEUTRALISING ANTIBODIES
39Effector mechanisms against extracellular
pathogens OPSONISATION
binding
40Effector mechanisms against extracellular
pathogens COMPLEMENT
Lysis
41Effector mechanisms against intracellular
pathogens CYTOXICITY
Viral infection
Lethal hit
42Effector mechanisms against intracellular
bacteria MACROPHAGE ACTIVATION
Activated macrophage
Resting Macrophage
43Summary
- ? 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)