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Introduction to Immunology
Innate immunity
Cell Biology
Complement system
Antibody dependent responses
Cell mediated immune responses
Immunoregulatory mechanisms
INTRODUCTION TO IMMUNOLOGY
Immunology
Biochemical study of body defenses against
basic sciences
Evolutionary trends from innate to adaptive
immunity
Immunodiagnostics in the treatment and
migration patterns
Paternity identity and criminal
smallpox.
Scientist(s) Contribution
Edward Jenner (1749 – 1823) Experimented with cowpox leading to small pox vaccine in
1796
Lowis Pasteur (1822) Introduced vaccine with the first attenuated virus vaccine.
Paul Ehrlich (1854 – 1915 Believed “humoral immunity” involving antibodies and not
cells.
Wright and Douglas (1903) Demonstrated enhancement of phagocytosis by serum
opsonins indicating a linkage between humoral and cellular
immunity.
Von Behring (1854-1917) and First described diphtheria antitoxin (antibody) – (1890).
Kitasato (1870)
Tiselius and Kobet (1938) Demonstrated that antibody activity resided in the
gamma globulin portion of serum proteins.
Properties)
Cellular (Cells) and Molecular
(Molecules) Immunology
Clinical Immunology: Immunodeficiency;
Allergic and Hypersensitivity; Autoimmune
Diseases; Reproductive Immunology;
Immunohaematology; Tumour Immunology
and ClinicalTransplantation
Classification of Immune Responses
Body defence mechanisms
Innate and adaptive immunity.
memory.
Innate immunity
Constituted by inborn defense
mechanisms
Broad specificity, no memory
Characteristic Features of Immunity
Innate Immunity Adaptive Immunity
antagonisms
Pattern-recognition receptors (PRR)
infectious agents.
High viscosity mucous and beating cilia (upper
enzymes
Prime adaptive immunity.
Physical Barriers To Infection
Defensins
Secreted by epithelial cells (skin, GIT,
genitourinary tract and nasal passages and lungs)
or by recruited leukocytes (neutrophils).
Punch lethal holes facilitated by their positive
charges in penetrating the bacterial membranes.
Cathelicidins
Secreted by epithelial and neutrophils with
secondary alpha helix structures.
Synergistically with defensins confer protection
against microbes.
Microbicidal Mechanisms
Microbicidal mechanisms associated with
Assembly of NADPH oxidase
Upregulation of cytochrome B558 in
Metabolites:
Reactive oxygen intermediates (ROI) Inflammation and intracellular killing
Reactive nitrogen intermediates (RNI) Inflammation and intracellular killing
Eicosanoids, prostaglandins leukotrienes Regulation of inflammation
Platelet activating factor Recruitment and activation of platelets.
Cytokines:
IL-1, TNF-α, IL-6 Inflammation
IFN-α Th1 activation
IL-10 Th1 suppression, Th2 activation
IL-12, IL-18 Activation of NK and T cells
TGF- β Inflammation, tissue repair
Adhesion molecules:
Fibronectin Opsonisation
Thrombospondin Adhesion, phagocytosis
Complement:
C3b, C4b and C2b Opsonisation
Enzymes:
Lysozyme Degrades bacterial cell walls
Collagenase, elactase Matrix catabolism
Natural Killer (NK) Cells
Large granular lymphocytes
Posses CD16, CD56, CD 94, lectin-like
and Ig-like receptors.
Provide early MHC independent
defence against intracellular infections
(herpex group viruses, Leishmania and
Listeria).
Activated by IFN-α and IFN-β in
response to double stranded RNA
viruses.
NK cont
Produce IFN-γ that prime mφ to
secrete TNF and IL-12.
Primed NK cells kill viral and
tumour cells by apoptosis and
recognize target cells that fail to
express class I MHC molecules on
their surfaces.
Inflammation
Represents generalized response to infection
or tissue damage
Designed to localize invading
Redness
Swelling
Inflammation cont
Mast cells initiate inflammation mediated
by granules exocytosed when gram-
negative bacteria derived LPS bind
TLRs.
Released histamine responsible for
redness and swelling associated with
inflammation.
Tumour necrosis factor-alpha (TNF-α )
and chemotactic cytokines secreted by
stimulated mast cells.
Inflammation cont
Reactive oxygen species and nitric oxide
produced by activated phagocytes
Toxic to microorganisms and may also
lead to tissue injury.
Macrophages and monocytes main source
of interleukin-1 (IL-1) causing fever.
Arachidonic acid derivatives (leukotrienes
and prostaglandins) potent mediators of
inflammation
Inflammatory response
Lyses of blood cells and release
Bradykinin and prostaglandin cause the
blood cells
Serotonin from platelets
membranes
Acute phase proteins
Acute phase respones
Leads to elevated production of protective
Histamines
Lysosomal enzymes
Synthetic peptides
antigens
Blood group antigens.
Degree of foreignness
individual
Haemopoitic System
Haemopoiesis occurs
First in the yolk sac and foetal liver at 6 weeks, spleen
adult life.
Lymphoid lineage pathway gives rise to
Thymus-derived (T) and bone marrow derived (B)
lymphocytes
Myeloid stem cells generate
Mononuclear phagocytes (monocytes and
membranes.
Stimulation of B cells lead to the production of
Various immunoglubulins mediating
lymphocytes.
Lymphoid immune system consists of
Primary lymphoid (10 ) organs and
DiGeorge syndrome.
Each lobule organized into
Cortex (infiltrated with rapidly dividing
lymphocytes, thymocytes)
Medulla (containing visible epithelial cells).
differentiation
Secondary Lymphoid Organs
Secondary lymphoid organs
Sites where lymphocytes encounter
antigens
Interact with other cells and enlarge in
Fig. 8 Structure of a Secondary Lymphoid Organ: Refer to text for the details. Source: http://www-immuno.path.com.oc.uk
Lymph Node
Lymph nodes
Encapsulated and packed with lymphocytes,
extensive heterozygosity.
High polymorphism
Genes in the MHC loci exist in different
DRW53
NB. The alleles that have been reported and provisionally given a number pending verification and
official recognition are referred to by the letter “W” before the number such as Aw33(w19).
Inheritance of Haplotypes
MHC genes are co-dominant and the alleles equally
expressed.
Given a simple Mendelian pattern of inheritance,
Distribution of MHC haplotypes in a family: 25%
linked (97%)
Alleles in Linkage Dysequilibrium
A1, B8 AW30 B13 DW1, BW35
A1, BW17 AW33, BW14 DW, BW7
A2, BW12 CW1, B5 DW4, BW15
A2, BW16 CW1, BW16
A11, B5 CW3, BW15
A29, B12 CW4, BW35
CW5, B12
Importance of MHC Antigens
MHC antigens-a group of cell membrane
components
Expressed on cells by certain individuals
in a population referred to as
alloantigens.
Clinical transplantation
Matching donor HLA antigens with
those of recipient to avoid induction of
graft rejection reactions
Patenity identity
HLA gene products of a child compared with
Putative candidates to ascertain the
biological father in a given ethnic or
racial group.
Match between the HLA antigens of
Antigenic mimicry