IMMUNOLOGY

Definitions and outline structure of

the immune system
Primary function of the immune system is to defend against and

eliminate foreign material, and to minimize any damage that may

be caused as a result of the presence of such material
Pathogen - organism which has the ability to cause disease
Virulence - used to indicate the degree of pathogenicity of a given

strain of microorganism
Attenuation - Reduction in the virulence of a pathogen
Antigen - gives rise to the primary interaction with the bodys immune
system
Immunogen an antigen that elicits an immune response

Definitions and outline structure of

the immune system
Within a given antigen, e.g. a protein, there will be antigenic

determinants or epitopes , which actually represent the antigen

recognition sites for our adaptive immune system
monoclonal antibody - antibody nominally recognizing only a single

antigen and within which only a single common epitope is recognized

polyclonal antibody - an antibody nominally recognizing only a single

antigen but within which a number of different epitopes are

recognized

Definitions and outline structure of

the immune system
The immune system is broadly considered to exhibit two forms of

response:
The innate immune response, which is non - specific, displays no

time lag in responsiveness, and is not intrinsically affected by prior

contact with infectious agent
The adaptive immune response , which displays a time lag in

response, involves highly specific recognition of antigen and affords

the generation of immunological memory

Definitions and outline structure of

the immune system
The adaptive immune system is further subdivided into:
Humoral immunity - the effector cells are B- lymphocytes and where

antigen recognition occurs through interactions with antibodies.

Cell - mediated immunity - the effector cells are T - lymphocytes
In cell - mediated immunity the peptide antigen must be presented to

T - lymphocytes by other cell types (antigen-presenting cells or APCs:

macrophages) in association with a class of plasma membrane
molecules termed major histocompatibility complex (MHC) proteins

Cells of the immune system

Mononuclear phagocytic cells monocytes to macrophages
Granulocyte cell - neutrophil, basophil and eosinophil
Mast cell release numerous initiating factors leading to an

inflammatory response
Natural killer (NK) - elicit cytotoxic actions against host cells infected

with virus and those host cells that have acquired tumour cell
characteristics
B lymphocytes - mature or differentiate in the bone marrow
T lymphocytes - undergo maturation in the thymus

The innate immune system

Innate barriers at epidermal and mucosal surfaces
Innate defence once epidermal or mucosal barriers have been

compromised

Innate barriers at epidermal and mucosal surfaces

Involves a range of non - specific mechanisms

Intact skin
Flow of fluid secretions from tear ducts, the urogenital tract and the

skin (sweat)
Many of these secretions possess bacteriostatic or bactericidal

activity

Innate defence once epidermal or

mucosal barriers have been
compromised
Mononuclear phagocytic cells
Granulocyte cell populations
Phagocytosis
Alternative complement pathway

Mononuclear phagocytic cells

Include monocytes and macrophages
The mononuclear phagocytic cells secrete a wide range of molecules:
lysozyme or cathepsin G
Cytokines - provide innate protective antiviral (e.g. interferon (IFN)

- or - ) and antitumour (e.g. TNF - ) activity against other host

cells
Bioactive lipids - promote the inflammatory response

Granulocyte cell populations

Include the neutrophils, basophils and eosinophils
Neutrophil - the most abundant granulocyte and is the most important

in terms of phagocytosis
Eosinophils - have a specialized role in the extracellular killing of

parasites

Phagocytosis

COMPLEMENT PATHWAYS
i.
ii.

CLASSIC PATHWAY
ALTERNATE PATHWAY

Classic Pathway
Initiation
Binding of C1 complex to Abs bound to Ag
Components
C1 to C9
Stages
i.
ii.
iii.

Recognition
Amplification
MAC

Hundreds of C4 and C2
molecules

Highest conc than any

other complement

C3b: opsonin

Mg++

Intermediate
complex

(12-15)

Alternate Pathway
Initiation
Non-Ab-initiated pathways
Components
Factor B and Factor D
C3, C5 - C9

Alternate Pathway

Stablized by Mg++

6 mins 30 mins

The humoral adaptive immune system

B - lymphocyte antigens
Basic structure of antibody molecule
Clonal selection and expansion
Humoral immune effector functions

B - lymphocyte antigens
A substance or molecule specifically interacting with an antibody, and

which may lead to the further production of antibody and an

immunological response
Molecules

Characteristic

Immunogenicity

Protein

High MW, Complex

structure

Excellent

++++

Polysaccharides
(blood grp Ags)

Large, lack complexity

Must be linked to a
protein or lipid

++

Lipid

Simple structure and low

stability

Must be linked to a
protein or
polysaccharide

Nucleic acid

Simple, flexible, degrades

rapidly

poor

GENERAL CHARACTERISTICS OF
ANTIBODIES
Antibodies
Immunoglobulins
Specific glycoproteins

Most (not all) are found in the gamma-region in

electrophoresis
Hence immunoglobulin

Present in plasma and body fluids (tears, saliva, colostrum)

ANTIBODY STRUCTURE AND

IMMUNOGLOBULIN CLASSES
Five Classes
Differ in MW and sedimentation coefficients
1.
2.
3.
4.
5.

IgM
IgG
IgA
IgE
IgD

ANTIBODY STRUCTURE AND

IMMUNOGLOBULIN CLASSES
Antibodies
All have a common, basic polypeptide structure

Four polypeptide chains linked together by covalent and

noncovalent bonds
w/ identical heavy and light chains

Monomers: IgG, IgD, IgE

Monomer and polymer: IgA
Pentamer: IgM (5 four-chain subunits)

ANTIBODY STRUCTURE AND

IMMUNOGLOBULIN CLASSES
Antibody Molecule
Y shaped

Domain
Basic unit (12)

Chains (linked by disulfide bonds)

Heavy chain (2)
Light chain (2)

Variable (V) region

Constant (C) region

ANTIBODY STRUCTURE AND

IMMUNOGLOBULIN CLASSES
IgG
Has 4 subclasses determined by the

hinge region
Fab region
Mobile and can swing freely
around the hinge region

ANTIBODY STRUCTURE AND

IMMUNOGLOBULIN CLASSES
IgG
CHARACTERISTICS

INCREASED

DECREASED

-Major Ig in normal serum (70

75%)
-Crosses the placenta
-MW: 150,000 D
-SC: 7S
-NV: 800-1800 mg/dL

Infectious diseases
-hepatitis, rubella, IM

Primary and
secondary Ig
disorders

Hematologic disorders
-Polyclonal gammopathies,
monoclonal gammopathies,
ML, Hodgkins Disease

ANTIBODY STRUCTURE AND

IMMUNOGLOBULIN CLASSES
IgM
Pentamer

J-chain (disulfide bond)

Links the 5 subunits in a circular
fashion

ANTIBODY STRUCTURE AND

IMMUNOGLOBULIN CLASSES
IgM
CHARACTERISTICS

INCREASED

DECREASED

-10 % of Ig pool
-Produced early (first) in
immune response
-MW: 900,000 D
-SC: 19S
-NV(mg/dL)
M: 60-250
F: 70 -280

Infectious diseases
-Subacute bctl endocarditis,
leprosy, trypanosomiasis,
malaria, actinomycosis

Primary and Secondary

Ig disorders

Hematologic disorders
-Polyclonal gammopathies,
ML, monoclonal
gammopathies

ANTIBODY STRUCTURE AND

IMMUNOGLOBULIN CLASSES
IgA
Dimer
2 IgA mols joined by J-chain at the Fc portion

ANTIBODY STRUCTURE AND

IMMUNOGLOBULIN CLASSES
IgA
CHARACTERISTICS

INCREASED

DECREASED

-15 20% in Ig pool

-Predominant Ig in
secretions (tears, saliva,
colostrum, milk, intestinal
fluids)
-MW: (dimer) 385,000 D
-SC: (dimer) 11S
-NV: 90 450 mg/dL
-Present in cord blood and
CSF

Infectious diseases
-Tb, actinomycosis

Primary or secondary
Ig disorders

Hematologic disorders
-polyclonal and monoclonal
gammopathies, ML
Liver disease
-Laennecs cirrhosis, chronic
active hepatitis

ANTIBODY STRUCTURE AND

IMMUNOGLOBULIN CLASSES
IgD
-Less than 1% of Ig pool
-Extremely susceptible to proteolysis due
to exposed hinge region and lack of
interchain disulfide bonds bet HCs

IgE
-Can mediate hypersensitivity (allergic)
reactions
- Immunity to invading parasites
- Triggers the release of histamines and
heparin from mast cells and basophils

ANTIBODY SYNTHESIS
Clonal selection
Activation and proliferation of B lymphocytes in response to an

antigen
Production of Ab specifically for that Ag
3-5 days
Antigenicity
Related to portal of entry
IV, intraperitoneal > subcuataneous, Intramascular

ANTIBODY SYNTHESIS
Primary Antibody Response
Four Phases

1.
2.
3.
4.

Lag: no Ab detectable
Log: inc in Ab titer
Plateau: Ab titer stabalizes
Decline: Ab is catabolizes

ANTIBODY SYNTHESIS
Secondary (Anamnestic) Response
Memory response due to subsequent exposure to same Ag
Differs from Primary

Time: shorter lag phase, longer plateau (tenfold), more gradual

decline
Type of Ab
Primary: IgM Secondary: IgG

Ab titer: higher titer

ANTIBODY SYNTHESIS

Cell - mediated adaptive

immune system

T-Lymphocytes Subsets
CD4+ subset
helper-inducer T cell
CD8+ subset
suppressor-cytotoxic T cell
i.
ii.

Helper T Lymphocytes
Cytotoxic T Lymphocytes

T Lymphocyte Subsets
HELPER T LYMPHOCYTES
T-helper (Th) cells
Subsets

i.

Helper T type 1 (Th1)

> for cell-mediated effector mechs

ii.

Helper T type 2 (Th2)

> regulation of Ab production

iii.

Regulatory T (Treg)
> immunoregulatory type of Th cells

T Lymphocyte Subsets
HELPER T LYMPHOCYTES
Function mainly in cytokine production

Th1
IFN: direct and inderect activation of phagos to kill ingested microbes

Th2
IL-4: stimulates IgE production
IL-5: activates eosinophils
Stimulates IgG4 production

T Lymphocyte Subsets
HELPER T LYMPHOCYTES
Reacts w Ag-MHC II complex on APC

Leads to cytokine production

CD4+ TCR

T Lymphocyte Subsets
CYTOTOXIC T LYMPHOCYTES
T-cytotoxic (Tc) cells

Direct destruction of virally infected target cells

CD8+
Interacts w Ag-MHC I complex or MHC-I alone
Virus infected cells or tumor cells

Major effector in allograft organ rejection

Antigen Processing and Antigen Presentation to T

cells
Antigen-Presenting Cells (APCs)
Cells capable of taking up Ags and presenting them to lymphocytes

Dendritic cells, macrophages, B cells, tissue cells

Ag processing pathways
i.
ii.

Endogenous - Tc
Exogenous - Th

Antigen Processing and Antigen Presentation to T

cells

Transplantation rejection
Transplantation is the process of transferring cells, tissues or organs

termed a graft from one location to another

An autologous graft is a transplant between two sites within the same

individual, e.g. skin graft from the thigh to the hand

An allogeneic graft is a transplant between two genetically different

individuals of the same species

A xenogenic graft is a transplant across different species, e.g. pig to

human

Transplantation rejection
Hyperacute rejection occurs within minutes to hours. This should now

be a rare event clinically as recipients are tested (cross - matched)

before transplantation for the presence of antibodies reactive with
cells of the donor
Acute rejection occurs within weeks to months following

transplantation and involves humoral (antibody) and cell - mediated

induced cytotoxicity. Damage may be reversed with early diagnosis
and more aggressive immunosuppressive therapy
Chronic rejection occurs many months or even years following

transplantation.

Hypersensitivity
Defined as an exaggerated response of the immune system leading

to host tissue damage

Type I immediate hypersensitivity . This is also called anaphylactic

or acute hypersensitivity. It involves IgE antibody and is mediated via

degranulation of mast cells for rapid inflammatory reaction
Type II hypersensitivity antibody- mediated cytotoxicity . This is

caused by antibodies that are directed against cell surface antigens.

IgG and IgM are the key antibodies involved that direct cytotoxic
events against the cell surface with which they interact
Type II hypersensitivity disorders include blood transfusion reactions
arising from mismatch of the blood ABO antigens

Hypersensitivity
Type III hypersensitivity complex - mediated . This involves the

formation of large antigen antibody complexes that circulate in the

blood
If this process is compromised for any reason then the antigen

antibody complexes will be deposited in tissue capillary beds that can

lead to a condition termed glomerulonephritis in kidney
Type IV hypersensitivity cell - mediated . This results from

inappropriate accumulation of macrophages at a localized site, and

may or may not involve the presence of antigen