IMMUNOLOGY
that gives rise to the primary interaction with
Thucydides- Described in detail an epidemic.
Variolation- inoculation of live organisms of
smallpox obtained from the diseased pustules
of patients who were recovering from the
disease.
Edward Jenner
Cowpox virus = vaccinia virus
Pasteur- introduced vaccine to commemorate
Jenner’s work.
1979- Eradication of smallpox
Decrease in morbidity and mortality.
 Diphtheria
 Pertussis
 Mumps
 Measles
 Rubella
 Hepatitis A and B
Definitions and outline structure of
the immune system
*primary function- defend and eliminate
foreign material. Minimize damage.
*foreign- is non-self. Not necessarily pathogenic
alone
Allogenic- Withing species
Xenogeneic- between species
Pathogen- ability to cause disease.
Virulence- Degree of pathogenicity
Attenuation- reduction of virulence
Avirulent- completely lose its virulence.
Antigen- a component of the foreign material
the body’s immune system
Immunogen- if an antigen elicits an immune
response.
Antigenic determinants or epitopes-
recognition sites for the adaptive immune
system
 5-20 amino acids
 Linear chain or cluster of amino acid
Antibodies or Immunoglobulins (Ig)- produced
and secreted out by the adaptive immune
system.
 Widely used in vitro diagnostics.
Monoclonal antibody- recognizing single
antigen and a single common epitope.
Polyclonal antibody- recognizing a single
antigen but a number of different epitopes.
Immune system: 2 types of response
a.) innate immune response
 Non-specific
 No time lag
 Not intrinsically infected by prior
contact with infectious agent
b.) adaptive immune response
 Time lag
 Highly-specific recognition
 Generation of immunological memory
Types of adaptive immune response
a.) humoral immunity
 Effector cells- B-lymphocytes
 Antigen recognition occurs through
interaction with antibodies.
1
b.) Cell-mediated immunity
 Effector cells- T-lymphocytes
 Antigen recognition occurs through
peptide antigen.
 T-cells receptors
 Peptide antigen must be introduced to
the t-lymphocytes through major
histocompatibility complex (MHC)
protein.
Cells of the immune system
Progenitor cell population- found in the bone
marrow. Cells involved for the immune system.
 Varies in terms of growth factor.
Principal cells of the innate immune system
1. mononuclear phagocytic cells
 Short lived (>8hrs)
 Monocytes (blood circulation -> tissues)
 Undergo differentiation -> long lived
(macrophage – key effector cell)
2. granulocyte cell
 Neutrophil
 Basophil
 Eosinophil
3. mast cell
 Tissue resident cell
 Triggered by tissue damage or infection
 Initiating factors -> inflammatory
response
o Histamine
o Leukotrienes B4, C4, D4
o Proinflammatory cytokines
 Signals proteins
released by leukocytes
(white blood cells
 Tumor necrosis factor-a
 Chemotactic
substances- interleukin-
8 activation of the alternative
 Responsible for anaphylactic reactions
o Bee stings
o Penicillin
o Nuts
4. natural killer (NK)
 Phenotype
 Like lymphocyte
 lacks recognition receptor
 non-specific
 cytotoxic actions
lymphocytes
a.) B-lymphocytes- mature and differentiate in
the bone marrow before leaving to circulate in
the blood and lymph.
 plasma cell- differentiated lymphocytes.
b.) T-lymphocytes- mature in the thymus.
The innate immune system
Innate barriers at epidermal and mucosal
surfaces
 epidermis and mucosal barrier
 non-specific mechanism
 commensal organism- organism derives
food or other benefits from
another organism without hurting or
helping it
o non-pathogenic
o help prevent colonization of
pathogens
 ex: tear ducts, urogenital tract skin
 secretion posses bacteriostatic or
bactericidal activity due to low ph or
hydrolytic enzymes
o ex lysozyme (peptidoglycan
hydrolase)
Innate defense once epidermal or
mucosal barriers have been compromised
 interstitial tissues and the vascular
compartment rely largely on the
processes of phagocytosis and
complement pathway
2
  mononuclear phagocytic cell and
granulocyte- main cell mediating
phagocytosis
A. Mononuclear phagocytic cells
Monocytes
 short lived (>8hours)
 5% of the circulating leucocytes
population
 Differentiated into macrophage
Macrophage
 Long-lived
 Widely distributed heterogenous
population of cell types
 Kupffer cell
Secretion of mononuclear phagocytic cells
molecules
 Molecules break down or permeabilize
microbial membrane. Extracellular
killings of microorganism.
o Enzymes
 Lysosomes
 Cathepsin G
o Bactericidal reactive oxygen
species
o Cationic proteins
Cytokines
 Innate protective antiviral
o Ex: interferon (IFN)
o Antitumor
 Chemokines – group of cytokines.
Chemoattracts other leukocytes into an
infection or inflammation
 Proinflammation action
 IL-8 attracts neutrophils
 IL-1 and TNF activates endothelial and
leucocytes cells
 IL-1 activation of T-lymphocytes
Bioactive lipids
 Thromboxane
 Prostaglandins
 Leukotrienes
 Promotes inflammatory response by
increasing capillary vasodilation and
permeability.
Mononuclear phagocytic cell receptors
Receptors for chemotaxis
 Receptors for secreted bacterial
peptides
 Ex: formylmethionyl peptide
Receptors for complement proteins
 Leucocytes activator
o C3a and C5a
 Complements protein that serve to coat
o Opsonize
o C3b
 Opsonin triggering enhanced activity of
the phagocyte.
Receptors for promoting adherence
 Lectin receptors – interacts with
carbohydrates moieties
 Fc Domains – non-antigen- recognition
domains or antibodies which opsonize
microorganisms
o Ex: receptors for Fc domain of
IgG is Fcg
 Integrin receptors – for cell-cell
adhesion
o Promoting interaction between
a macrophage and T-
lymphocyte
Receptor for cytokines
 Includes macrophage activation.
o IFN-Y
 Limiting macrophage mobility
o Macrophage inhibitory factor
(MIF)- increases cell retention
at a site of infection
B. Granulocyte cell population
 Basophils, eosinophils, neutrophils
 Short-lived (2-3 days)
Neutrophils
 most abundant (>90% of all circulating
blood granulocyte)
 most important in phagocytosis
 secretion is similar to macrophage
3
  does not present antigen via MHC class  Cationic protein- begin microbial
II proteins membrane degradation
 IL-8 – a neutrophil-specific chemotactic o Defensins
factor that recruits to site of tissue o Reactive oxygen species
infection or inflammation
 Complement protein
o C3a Phagolysosome
o Bacterial formyl methionyl  Fusion of phagosome and lysosome
peptides  Acidic (pH 5)
o Leukotrienes  Active breakdown of microbial structure
 Undergo respiratory burst- effective
generators of reactive oxygen species D. Alternative complement pathway
 Critical role for innate immunity
Eosinophils  Complement system comprises of 20
 Poor phagocytic cells different serum proteins. (“C” & “#”)
 Kills Helminths  Zymogens – compliment protein
 Cant be physically phagocytosed o Proenzyme- require proteolytic
cleavage
Basophils  Suffix “b” – larger fragment compared
 Non-phagocytic cells to “a”. stays associated with a microbial
membrane
C. Phagocytosis  Suffix “a” - smaller fragment. Diffuses
1. chemotaxis away
 Through signals arising from  Cascade sequence – the activation of
compliment proteins (C3a & C5a) the compliment pathway
2. adherence
 At the surface of the phagocyte Resting state
 Through lectin receptors which  Absence of infection
interacts with carbohydrates moieties  Complement proteins are inactive or
o C3b and Fc receptors low level of activation
3. membrane activation
 Of phagocyte actin-myosin contractile Complement pathway
network to extend pseudopodia around  Prevents inappropriate activation of
the attached microbe cascade (when no infection is present)
 Generation of respiratory burst-  Minimizes damage to the host cell
increases the activity of the phagocyte
membrane NADPH oxidase 3 main biological functions of the alternative
 Oxygen -> bactericidal reactive oxygen complement pathway
specie
o Superoxide anion 1. opsonization of microbial membrane
o Hydrogen peroxide  Covalent binding of compliment
o Hydroxyl radicals proteins to the surface of the microbial
o Halogenated oxygen membrane
metabolites  Promotes adherence
4. Enclosure  C3b – complement protein (potent
 Phagosome – membrane vesicle opsonin)

4
2. activation of leucocytes
 Protein acting on leukocytes
 Raising the level of functioning of the
leucocytes in immune defense

3. Lysis of the target cell membrane

 Membrane attack complex (MAC) –
Formation of membrane pores and
microbial lysis