Download Introduction to immunology

LECTURE 1
INTRODUCTION TO
IMMUNOLOGY
Jan Żeromski
20013/2014
Immunology Course Outline
3 student groups
Subjects:
1.
2.
3.
11 lectures – approach to basic and clinical
immunology
5 classes – approach to essentials of diagnostic
immunology
7 seminars – clinical immunology
Evaluation:
1.
2.
3.
Midterm test
Basic imm. test
Final test
Final examination
Detailed schedule on the website:
immuno.ump.edu.pl
Recommended books:
•
Introduction to Clinical Immunology
Medical University Press, 2009.
•
Basic Immunology
Abbas et al.. Elsevier 2013
•
Male, Brostoff, Roth & Roitt
Immunology Mosby, Elsevier
•
Chapel:
Essentials of Clinical Immunology Blackwell.
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 (innate recognition)
- via somatically generated receptors (adaptive „
)
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, creactive 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,
EFFECTS OF ACTIVATION OF
COMPLEMENT SYSTEM
 Chemotaxis (attraction of cells to sites of infection
 Opsonization (facilitation of phagocytosis)
 Promotion of killing of microorganisms
 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, unmethylated 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 leucinerich repeats (LRRs),In intracellular portion show
high homology to IL-1R (TIR domain)
• Exist in families (TLR1-TLR-13)
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)
1. Increased expression of MHC antigens
1. Enhancement of maturation of dendritic cells
1. 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)
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
-
• Plasma cells
• Th cells
-
• Treg cells
-
• Tc cells
• NK cells
-
• Dendritic cells-
recognize antigens and
produce antibodies
produce antibodies
help in immune response,
produce cytokines
inhibit immune response,
produce cytokines
kill target cells
able to to kill virally infected
and transformed cells
present antigens to Th cells
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 Number of cases
(year)
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!