LECTURE 1

INTRODUCTION TO
IMMUNOLOGY
Jan eromski
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
Acute phase proteins
Complement system
Cytokines (chemokines)
Phagocytes (granulocytes,
macrophages)
Natural killer (NK) cells
Dendritic cells
Pattern recognition receptors
(PRR)

Specific (adaptive)
Antibodies
(B lymphocytes)
T lymphocytes and their
subsets

Major differences between innate and acquired

immunity (acc. to U. Koedel & W Pfister 2005)
Innate immune system

Acquired immune system

Lag time (3-4 days) between exposure

and max. response
Immunological memory
Antigen specific
Receptors: generated somatically,
Only in vertebrates,
Recognition of details of molecular
structure,
Imperfect self/non-self discrimination,
Over 100 000 000 000 different
receptors

Immediate maximal response

No immunological memory
Not antigen specific
Receptors: germ line encoded,
In almost all multicellular organisms,
Recognition of conserved molecular
patterns,
Perfect self/non-self discrimination
Only hundreds of 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

Complementinhibitory 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 IMMUNITYPATTERN 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,TNFalpha, 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
cases (year)

Number of
cases in 2004

Diphteria

206,939 (1921)

Measles

894,134 (1941)

37

Mumps

152,209 (1968)

236

Rubella

57,686 (1969)

12

Polio (paralytic) 21,269 (1952)

THANK YOU FOR YOUR ATTENTION !

GOOD LUCK IN STUDYING
IMMUNOLOGY!