INTRODUCTION TO IMMUNOLOGY 1

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DR. CROSDALE O. PUGHIKUMO
MBBS, PGDM, FMCPath (Haem), MSc.

COLLEGE OF HEALTH SCIENCES

NIGER DELTA UNIVERSITY
 INTRODUCTION 2

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 Immunology is the discipline concerned with the protective mechanisms against
disease-producing foreign agents and micro-organisms (pathogens).
 The immune system also contributes to the control of malignancies.

 It is also responsible for the phenomenon of allergy, hypersensitivity and

transplant rejection.
 The immune system has 2 main arms:
 A. Innate or non-specific immunity
 B. Adaptive or specific immunity.
 INNATE IMMUNITY 3

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 This involves the natural mechanisms that provides the first line of defence
against the invasion of pathogens.

 They are divided into 3 main groups:

 A. Barriers to infection.

 B. Cellular components.

 C. Serum proteins & the Complement system.

 A. Barriers to infection 4

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 1. Physical & mechanical barriers.
 Skin.
 Mucosal membranes.
 Tight junctions between cells.
 Flushing action of tears, saliva & urine.
 High oxygen tension in the lungs.
 In the respiratory tract, mucus is secreted to trap micro-organisms, they are
then mechanically expelled by: beating cilia, coughing & sneezing.
 2. Chemical barriers 5

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 Acidic pH in the stomach & vagina.

 Lactic acid & fatty acids in sebum from the sebaceous glands maintain the skin
pH 3 & 5.

 Enzymes like lysozyme in saliva, sweat & tears.

 Pepsin in the GIT.

 3. Biological barriers 6

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 Normal flora protects the host by:

 Competing with pathogenic bacteria for nutrients & attachment sites.

 Production of anti-bacterial substances.

 B. Cells of innate immunity 7

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 They consist of:

 Phagocytes.

 Natural killer cells.

 Degranulating cells.
 1. Phagocytes 8

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 Macrophages & neutrophils engulf & destroy pathogens.
 Macrophages are long-lived sentinel cells located strategically at likely sites of
infection.
 Upon infection, they release cytokines which recruit the short-lived but more
actively phagocytic neutrophils.
 Complement proteins like C3a & C5a are also chemotactic for neutrophils.
 Neutrophils constitute 45-70% of WBCs.
The mononuclear phagocyte system (MPS) 9

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 Monocytes are the other major phagocytes.
 They constitute 2-8% of WBCs & circulate in the blood for about 8 hours before
migrating into the tissues where they differentiate into macrophages.
 Some macrophages become adapted for specific functions in particular tissues, e.g
Kupffer cells, glial cells, mesangial cells.
 Monocytes also differentiate into osteoclasts & microglial cells.
 Macrophages can be activated by cytokines like IFN-ɣ, Complement, products of
blood coagulation, direct contact with the target.
 Macrophages stimulate the specific immune system.
 They can also act as antigen-presenting cells (APCs).
 Natural killer cells 10

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 NK cells do not require T cells to kill pathogens.
 They use cell-surface receptors to identify cells modified by viruses or
malignancy.
 NK cells can destroy Ab-coated cells irrespective of MHC molecules (Antibody
depependent cytotoxicity-ADCC).
 This killing is initiated by cross-linking of receptors for the Fc portion of IgG1 &
IgG3.
 NK cells induce apoptosis in target cells by activation of FAS or TNF (Tumour
necrosis factor) receptors initiating a sequence of caspases; release of perforins &
granzymes from their granules.
 De-granulating cells 11

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 Basophils & Mast cells.

 Mast cells are believed to be differentiated basophils in tissues.

 Basophils constitute < 1% of WBC in circulation while mast cells are found in
tissues.

 Mast cells occur in aggregates close to blood vessels in connective tissues, skin &
mucosal membranes.
 Basophils & Mast cells contd. 12

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 They act by discharging their granule contents triggered by cross-linking of
receptors for Fc portion of IgE.

 Cross-linking results in calcium influx which induces release of mediators from

the granules. E.g., Heparin, histamine, leukotrienes

 Leukotrienes from the granules is chemotactic to eosinophils.

 Thus in type I hypersensitivity reaction (allergy), basophils & mast cells mediate
the early phase while eosinophils mediates the late phase.
 Eosinophils 13

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 They constitute 2-6% of T.WBCs.
 Mostly reside in tissues.
 They are vital in the immunity against parasitic infections.
 They act by extra-cellular degranulation releasing major basic protein (MBP),
cationic proteins, peroxidase & perforin-like molecules.
 Peroxidase generates hypochlorous acid.
 MBP damages the parasites’s outer surface.
 Cationic protein acts as a neurotoxin.
 C. Soluble proteins 14

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 They can be divided into:
 1. Anti-microbial serum agents, &
 2. Proteins from immune cells.
1. Anti-microbial serum agents 15

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 i. Acute phase proteins:
 Following infection or tissue injury, macrophages & endothelial cells release
cytokines; IL-1, IL-6 & TNF-α into the circulation.
 The liver responds by increasing the secretion of acute phase proteins (APP) or
acute phase reactants (APR).
 It is accompanied by fever, leucocytosis, thrombocytosis, catabolism of muscle
proteins & fat deposits.
 The major APPs are C-reactive protein (CRP) & Serum amyloid A (SAA).

 APP contd. 16

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 Others are:
 Complement proteins.
 Fibrinogen.
 Αlpha1-Antitrypsin.
 Ceruloplasmin.
 Haptoglobulin.

 Plasma levels of some proteins reduce during the acute phase response:
 Albumin.
 Transferrin
 c-reactive protein 17

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 Actions:

 It binds to the polysaccharide cell wall of bacteria & fungi.

 It activates Complement via the classical pathway.

 It opsonises for phagocytosis.

 ii. Secreted agents 18

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 Ii.Lysozyme:
 A bactericidal enzyme found in mucus, saliva, tears, sweat gland & breast milk.
 It cleaves peptidoglycan present in the bacterial cell wall.

 iii. Lactoferrin:
 An iron-binding protein that competes with micro-organisms for iron which is an
essential metabolite.
 iv. The Complement proteins 19

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 A group of 20 pro-enzymes.
 Activated in an enzyme cascade.
 The products have the following effects:
 Enhancement of phagocytosis by opsonisation (C3b).
 Mediates lysis of target cells (MAC).
 The alternative pathway can be activated by non-specific mechanisms.
 Mannan-binding lectin also activates the Complement system.
2. Proteins from cells of the immune system 20

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 Interferon-α: Produced by virus-infected cells against other viruses.
 Interferon-β: induces a state of viral resistance in neighbouring cells by:
 Inducing genes that destroys viral DNA.
 Inducing MHC class I expression.
 ADAPTIVE IMMUNITY 21

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 This is a highly specific system dependent on recognition of exogenous materials
as foreign (antigenicity).

 Lymphocytes play a central role, but it also rely on the MPS for presentation of
Ags to T-lymphocytes.

 Some other components of the innate immune system like Complement proteins
are also involved.
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 The adaptive immune system is divided into 2 arms:

 1. Humoral immunity: B-cells produce antibodies specific to invading antigenic

substances.

 2. Cell-mediated immunity: T-cells function as cytotoxic cells directly killing

foreign & abnormal cells.
CELLS OF THE ADAPTIVE IMMUNE SYSTEM 23

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 LYMPHOCYTES
 They are derived from the lymphoid stem cell (LSC) in the bone marrow.
 Constitute 20-45% of the WBCs.
 There are 3 types: B-cells, T-cells & NK cells.
 Most are small (6-9μmD), about 3% are large (9-15μmD).
 Large lymphocytes are usually activated B-cells & NK cells.
 T- LYMPHOCYTES 24

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 Immature T-cells migrate from the bone marrow to the thymus where they mature.
 This involves proliferation, TCR gene re-arrangement with a wide range of Ag.
specifities, acquisition of surface markers (CD2, CD3, CD4 or CD8).
 In the thymus, T cells reactive to self Ags are deleted by apoptosis in the process
of self-tolerance.
 The surviving mature T cells then migrate to peripheral lymphoid tissues & the
general circulation in search of specific Ags.
 If they encounter a corresponding Ag, direct cytotoxicity is initiated via cytotoxic
T cells (CD8) or indirectly by activation of B cells or macrophages.
 Subsets of T cells 25

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 A. T Helper cells (TH cells):
 They help other lymphocytes perform their effector functions by secreting
cytokines.
 They also activate macrophages to mount a granulomatous inflammatory response
(delayed hypersensitivity).
 They are characterised by CD4 in addition to pan T cell markers- CD2, CD3 and
TCR.
 c. Suppressor T cells (TS cells) 26

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 They are said to be responsible for moderating & switching off the immune
response when the initiating stimulus is removed.
 They are also CD8 positive.
 B- LYMPHOCYTES 27

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 They are derived from precursors in the bone marrow where they also mature.
 They can mature into Ab-producing plasma cells when stimulated by specific Ags.
 The resulting Abs (Igs) are divided into 5 structural classes: IgG, -A, -M, -D, -E
which are secreted into the circulation.
 Igs are also produced by mature B cells & displayed on their surfaces.
 Once activated, the B cells undergo mitotic division to produce a clone of Ab-
producing B cells & plasma cells.
 Plasma cells produce & secrete large quantities of Igs.
 Basis for specificity 28

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 Antigen-presenting cells (APCs) including B-cells & macrophages control the
activation of T-cells.
 The specificity is due to the unique structure of antigenic receptors on the
lymphocytes.
 These are:
 Surface immunoglobulins (Igs) on B-cells, &
 T-cell receptors (TCR) on the surface of T-cells.
 The genes for these receptors are re-arranged by DNA splicing to generate diverse
structures.
 Terminologies 29

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 Antigen (Ag): An organism, molecule or part of a molecule that is recognisable by
the specific immune system.
 Epitope: smallest individual identifiable part of an Ag capable of being bound by
a receptor.
 Immunogens: contain epitopes that both induce a specific positive immune
response & are the targets of that response. Not all antigens are immunogens.
 Haptens: small, normally non-immunogenic molecules usually of non-biologic
origin, that behaves like synthetic epitopes. They are antigenic & can bind to
receptors but cannot on their own induce a specific immune response & hence are
not immunogenic.

 Immunologic memory 30

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 A few B cells of the same clone mature into memory cells.
 They are long-lived circulating lymphocytes.
 Capable of quickly responding to subsequent challenge by the same Ag.
 This is the secondary immune response .
 It explains the life time immunity which follows many common infections.
 It is also the principle behind vaccination.
 Immunogenicity predictors 31

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 1. Size: Proteins > 10KDa are more immunogenic.
2. Complexity: Complex proteins with numerous, diverse epitopes are more
immunogenic than simple peptides with few epitopes.
 3. Conformation & accessibility: Epitopes must be visible & accessible to the
immune system.
 4. Chemical properties: Protein immunogens have to be enzymatically cleavable
by phagocytes. L-amino acid containing polypeptides are usually better
immunogens compared to D-amino acid containing polypeptides. Many
carbohydrate, steroids & lipids are poor immunogens.
Differences between innate & adaptive immune systems 32

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Characteristic Innate immunity Adaptive immunity
1. Nature Natural Acquired
2. Speed of onset Slow Rapid
3. Specificity Non-specific Highly specific
4. Cellular components Different types Mainly T & B cells
5. Complexity Simple system Highly complex
6. Memory Not involved Important component
Components of innate & adaptive immunity 33

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Innate system Adaptive system
Cellular components Monocytes, macrophages B-cells, Plasma cells
Neutrophils T-cells.
Eosinophils
Basophils, Mast cells
NK cells

Secreted components Complement Antibodies

Cytokines Cytokines.
Lysozyme
APPs
Interferons
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BUCKLEUP AND HIT THE
GROUND RUNNING!!!