LECTURE 1
INTRODUCTION TO
IMMUNOLOGY
Jan Żeromski
20012/2013
Immunology Course Outline
3 student groups
Subjects:
1. 11 lectures – approach to basic and clinical immunology
2. 5 classes – approach to essentials of diagnostic immunology
3. 7 seminars – clinical immunology
Evaluation:
1. Midterm test
2. Basic imm. test Final examination
3. Final test
Detailed schedule on the website: immuno.ump.edu.pl
Recommended books:
• Introduction to Clinical Immunology
Medical University Press, 2009.
• Male, Brostoff, Roth & Roitt
Immunology Mosby, Elsevier
• Chapel:
Essentials of Clinical Immunology Blackwell.
Why medical doctor - practitioner needs
basic knowledge of immunology?
• To understand pathogenesis of several diseases,
• To know principles of laboratory immuno-diagnostic
test selection,
• To be able to read laboratory immunologic reports,
• To be familiar with advantages and risks of treatment
by so-called Biological Response Modifiers
(immunologic drugs),
• To know how to cope with various types of allergy,
• To advice to particular patient proper type of vaccine,
INTRODUCTION TO IMMUNOLOGY
• Immune system (IS): innate and adaptive
immunity
• Development of IS
• Cells and tissues of IS
• Soluble mediators of immunity
• Antigens
• Immunopathology
• Modern approaches to study immunology
Immunologic concept of self
• Recognizing self –whether an encountered molecule is a
part of the body
• Recognizing of absence of self – loss of some surface
molecules such as transplantation antigens in cancer
• Recognizing nonself - such as pathogens or foreign
grafts
• Recognition possible by:
- via pattern recognition receptors
- via somatically generated receptors
Protective barriers of the body
Immunology, 1st Edition. Thao Doan ;Roger Melvold ;Susan Viselli ;Carl Waltenbaugh
Defense mechanisms of skin
Immunology, 1st Edition. Thao Doan ;Roger Melvold ;Susan Viselli ;Carl Waltenbaugh
Defense mechanisms fo mucous
membranes
Immunology, 1st Edition. Thao Doan ;Roger Melvold ;Susan Viselli ;Carl Waltenbaugh
Types of leukocytes
Immunology, 1st Edition. Thao Doan ;Roger Melvold ;Susan Viselli ;Carl Waltenbaugh
TWO TYPES OF IMMUNITY
Non-specific (innate)
•Physical and chemical
agents
•Lysozyme Specific (adaptive)
•Acute phase proteins •Antibodies
•Complement system (B lymphocytes)
•Cytokines (chemokines) •T lymphocytes and their
•Phagocytes (granulocytes,
subsets
macrophages)
•Natural killer (NK) cells
•Dendritic cells
•Pattern recognition receptors
(PRR)
Major differences between innate and acquired
immunity (acc. to U. Koedel & W Pfister 2005)
Innate immune system Acquired immune system
• Immediate maximal response • Lag time (3-4 days) between exposure
• No immunological memory and max. response
• Immunological memory
• Not antigen specific
• Antigen specific
• Receptors: germ line encoded,
• Receptors: generated somatically,
• In almost all multicellular organisms,
• Only in vertebrates,
• Recognition of conserved molecular
• Recognition of details of molecular
patterns,
structure,
• Perfect self/non-self discrimination • Imperfect self/non-self discrimination,
• Only hundreds of different receptors • Over 100 000 000 000 different
receptors
INNATE IMMUNITY
Components of Innate Immunity
• Barriers (epithelia, defensins)
• Circulating effector cells (neutrophils,
eosinophils, basophils, mast cells, NK cells,
monocytes/macrophages)
• Circulating effector proteins (complement,
mannose-binding lectin, c-reactive protein)
• Cytokines (TNF, IL-1- 25)
Receptors of innate immunity
• Pattern recognition receptors (TLRs, NLRs,
Rig-1),
• NK cells: killer activated R.(KAR) and
killer inhibitor R. (KIR),
• Complement receptors (on phagocytic cells)
• Fc receptors – for Fc fragment of Igs
• Scavenger receptors
Complement system
COMPLEMENT SYSTEM – MAIN
STRUCTURAL FEATURES
Consists of about 30 serum proteins marked
by C and arabic number (C1q, C2, C3 etc.)
Many C proteins are zymogens –
proenzymes requiring proteolytic cleavage
Enzymes are often formed from several C
molecules –eg. C4B2a cleaves C3
Activation of C is controlled by regulatory
proteins – eg. DAF, CD59
Complement– bound and Complement – associated
biologically active molecules
C3a i C5a (anafilatoxins) – mediators of
inflammation,
Membrane attack complex (non-enzymatic assembly
of C5b-C9) – responsible for cell lysis
Complement–inhibitory molecules; DAF,MCP, CD59
C receptors (CR) on various cells (B cells monocytes,
neutrophils, some epithelial cells, erythrocytes etc):
EFFECTS OF ACTIVATION OF
COMPLEMENT SYSTEM
Chemotaxis (attraction of cells to sites of
infection
Opsonization (facilitation of phagocytosis)
Increased blood flow
Increased blood vessel permeability
Damage to plasma membranes
Release of inflammatory mediators from mast
cells
BIOLOGICAL EFFECTS OF
COMPLEMENT
Promotion of killing of bacteria
Clearing of immune complexes
The induction and enhancement of
antibody responses
Detrimental if activated on a large scale,
e.g. in Gram negative septicaemia, in
tissue necrosis, in autoimmunity
COLLECTINS (COLLAGEN LECTINS) –
CALCIUM BINDING LECTINS
• Lectins:
proteins binding shugars in non-enzymatic way.
• Collectin family includes:
– mannan binding lectin (MBL),
– Conglutinin (bovine globulin able to react with bound C3)
– lung surfactant proteins A and D and also
– C1q
• MBL binds mannose groups in the bacteria,yeast
fungi, viruses cell walls and then activates serine
proteinases (MASP), able to cleave C4 and C2
analogous to C1q interaction with C1r and C1s.
Effect: C activation
Cytokines
CYTOKINES
SIGNAL TRANSDUCING MOLECULES
Interleukins (IL)
• directing other cells to divide and differentiate
Interferons (INF)
• type I (alpha/beta), type 2-gamma
Colony stimulating factors (CSF)
• directing bone marrow stem cells
Chemokines
• directing cell movement
Other
• TNF, TNF, TGF – involved in inflammation,
cytotoxicity and immunosuppression respectively
CELLULAR MECHANISMS OF INNATE IMMUNITY -
NEUTROPHIL ACTIVATORS
• Bacterially derived N-formylated peptides
(FMLP)
• Defensins (natural antibiotics)
• Products of complement (iC3b)
• Leukotrienes (products od arachidonic acid
metabolism)
• Cytokines ((TNF, IL-8, GM-CSF)
RECEPTORS OF INNATE IMMUNITY-
PATTERN RECOGNITION RECEPTORS
• Expressed on cells of innate immunity
• Encoded in the germline and not by somatic
recombination of genes
• Recognize structures of microbes essential for the
survival and infectivity
• Recognize less than a thousand microbial patterns
(LPS, double stranded RNA, unme-thylated CpG
nucleotides, glycolipids etc.)
TOLL-LIKE RECEPTORS (TLRs)
• Strongly conserved in evolution
• Initially detected in fruit fly Drosophila melanogaster
• Recognize Pathogen-Associated Molecular Patterns
(PAMPs), absent in mammals
• In extracellular portion contain multiple leucine-rich
repeats (LRRs),In intracellular portion show high
homology to IL-1R (TIR domain)
• Exist in families (TLR1-TLR-13)
STRUCTURE OF TOLL-LIKE RECEPTORS
FUNCTIONAL FEATURES OF TLRs
Their stimulation leads to:
1. Augmented inflammatory reaction via activation of
NF-kappa B transcription factor and increased
synthesis of proinflammatory cytokines (IL-1,TNF-
alpha, IL-12)
2. Increased expression of MHC antigens
3. Enhancement of maturation of dendritic cells
4. Induction of apoptosis
FEATURES OF ANTIGEN-
PRESENTING CELLS
• Capacity for antigen uptake and partial
degradation
• Expression of MHC molecules (class I and
class II
• Expression of accesory cell interaction
molecules
• Cytokine secretion (IL-12 and others)
Activated dendritic cell
ADAPTIVE IMMUNITY
ANTIGEN-ANTIBODY BINDING
• Non-covalent
(hydrogen bonding, electrostatic, Van der Waals,
hydrophobic)
• Antibody affinity
the strength of a single Ag-Ab bond
• Ab avidity
the sum of strength of all bonds
• Epitope
antigenic determinant able to bind antibody
determinant (paratope)
ANTIGEN-BINDING MOLECULES
Cell membrane Ig Ab - Antibody
Free Ab in body fluids
T-cell receptors (TCR)
HLA - Human Leucocyte Antigens (MHC) – Major
Histocompatibility Complex - class I
HLA (MHC) class II
Molecules of innate immunity (lectins and others)
MAJOR HISTOCOMPATIBILITY ANTIGENS
• Histocompatibility antigens are cell surface expressed on
all cells (class I) – exception: red blood cells and on
APC, B cells, monocytes/macrophages (class II)
• They are targets for rejection
• They are inherited from both parents as MHC haplotypes
and are co-dominantly expressed
MAJOR HISTOCOMPATIBILITY COMPLEX
(MHC)
Is located on short arm of chromosome 6
It includes 3 regions: class Ia (loci A, B, C) class Ib
(loci E, F, G, H), class II (loci DR, DQ, DP) and class
III
Genes of class Ia and class II are highly polymorphic,
while those of class Ib and class III are not
Polymorphism means occurence of several allelles
ie.genes encoding various qualitatively distinct MHC
antigens located at the same locus
MAJOR FUNCTIONS OF CELLS PARTICIPATING IN
IMMUNE RESPONSES
• B cells - recognize antigens and
produce antibodies
• Plasma cells - produce antibodies
• Th cells - help in immune response,
produce cytokines
• Treg cells - inhibit immune response,
produce cytokines
• Tc cells - kill target cells
• NK cells - able to to kill virally infected
and transformed cells
• Dendritic cells- present antigens to Th cells
Bacterial antigen recognized by antibody
IMMUNOPATHOLOGY
Hypersensitivity – overactive immune
response (IR)
Immunodeficiency – ineffective IR
Autoimmunity – reactivity to self antigens
Graft rejection
Malignancies of the immune system
EFFECTIVENESS OF VACCINES
Disease Number of Number of
cases (year) cases in 2004
Diphteria 206,939 (1921) 0
Measles 894,134 (1941) 37
Mumps 152,209 (1968) 236
Rubella 57,686 (1969) 12
Polio (paralytic) 21,269 (1952) 0
THANK YOU FOR YOUR ATTENTION !
GOOD LUCK IN STUDYING
IMMUNOLOGY!
