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Introduction to Immunology
Prof. Vasantha.V.L
Department of Life Sciences
Christ(Deemed to be University)
Immunity
• Immunity is derived from Latin word immunis Meaning “exempt”
• Immunity-state of protection from infectious disease or resistance to
infections
• Complex defence mechanism found in humans and other advanced
vertebrates against invading pathogen and cancer.
• Functions of immunity
1. Immune defense (Anti infection)
2. Immune surveillance(Anti tumor)
3. Immune Homeostasis(eliminates injured and dead cells)
Historical Perspective
• Earliest Written record about immunity- Thucydides(Historian)
• Plague in Athens during Peloponnesian War(430BC)
• Recovered patients nurse the sick and suffering.
Contd…
• First record to induce immunity by Chinese and Turks (15 century)
• Variolation
• Immunity against small pox
• Dried crust of small pox pustules-Inhale or insert in small cuts.
• 1718 Lady Mary Montague
Popularized Variolation in western
Countries.
Contd….
• Edward Jenner, English physician who was a contributor to
development of the smallpox vaccine(1798).
• introducing fluid from a cowpox pustule into people to protect them
from smallpox.
• Experiment on eight-year-old James Phipps
• Cross reactivity
• Variola virus and Vaccinia virus
• Coined term vaccine derived from vacca ( cow in Latin )
• Technique replaced Variolation
Contd…
• Louis Pasteur
• Working on concept of germ theory proposed by Robert Koch
• Developed vaccine to cholera, anthrax and rabies
• On July 6, 1885, Pasteur vaccinated Joseph Meister, a 9-year-old boy
who had been bitten by a rabid dog
• rabies is a viral disease
• serial passage of a virus through a different species
• Attenuated Vaccine
Edward Jenner experiment
Contd
• Emil Von Behring & Shibasaburo Kitasato in 1890 experimentally
proved serum can transfer immune state from immunized animal to
unimmunized animal.
• Von Behring the Nobel prize in medicine in 1901.
• Researchers called the active agent in serum by different names like
Antitoxin/Precipitin/agglutinin.
• Basis for humoral Immunity,
• Elvin Kabat Isolated this active factor and called as Immunoglobulin
Emil Von Behring Experiment
Cell mediated Immunity
• Elie Metchnikoff demonstrated significance of cells towards immunity.
• Cell mediated immunity
• Antibodies does not participate in this immunity
• Active phagocytic cells in blood (Monocytes and Neutrophils)
• Cell mediated immunity has following functions
Delayed Hypersensitivity,
Immunity in infections caused by obligate and facultative intracellular parasites
Transplantation Immunity
Immunological surveillance and cancer immunity,
• humoral and cell mediated immunity work in coordination for immune response.
Noble prizes for Immunology Research
year Recipient country Research

1913 Charles Richet France Anaphylaxis

1919 Jules Border Belgium Complement-medi
ated bacteriolysis

1930 Karl Landsteiner United States Human Blood

typing
1972 Rodney R. Porter Great Britain Chemical structure
Gerald M. Edelman United States of antibodies
1977 Rosalyn R. Yalow United States Radioimmunoassay
1980 George Snell United States Major
histocompatibility
complex
1984 Cesar Milstein Great Britain Monoclonal
Georges E. Köhler Germany Antibodies
Types of Immunity
Innate Immunity
• Immunity that we are born with.
• Immunity that is naturally present and is not due to prior sensitization
to an antigen.
• Non specific defense mechanism.
• Comes in to play/Action immediately.
• First line of defense.
• The innate immune system has a long evolutionary heritage, with
elements shared by most Invertebrates and even with plants and
insects.
Component of Innate Immunity
• Physical barrier or Anatomical barrier
• Physiological barrier or Physio-chemical barrier
• Inflammatory response
• Cellular barrier
Physical barrier
Physiological Barrier
• Physical and Chemical conditions of an organism
• pH, temperature and soluble proteins in body fluids
• Fever as innate immune response
• Chickens/Avians resistant to anthrax
• Acid pH in stomach, sebum in skin
• Chemical mediators/Soluble proteins present in body fluid
• Complement system, Interferon, Lysozyme.
Complement system
Defensin
1.Mast cell release chemical signal such as
histamine
Extravasation of Neutrophils
Cellular barrier
Gel-Sol Theory
Features of Acquired Immunity
Immunity developing during our life time.
• Second line of defence
• Antigenic Specificity
• Diversity
• Self and Non self recognition
• Immunological memory
B cell and its receptors
Thymus dependent/Independent Antigens
• Ig alpha-61 amino acid, Ig beta-48 amino acids
• protein tyrosine kinases (PTKs).
• Src family of tyrosine kinases (Fyn, Blk, and Lck), activating the
kinases. The activated enzymes phosphorylate tyrosine residues on
the cytoplasmic tails of the Ig-/Ig- heterodimer, creating docking sites
for Syk kinase
• Substrate -phospholipase C gamma 2 (PLCγ2)
Macrophages
• Alveolar macrophages in the lung
• Histiocytes in connective tissues
• Kupffer cells in the liver
• Mesangial cells in the kidney
• Microglial cells in the brain
• Osteoclasts in bone
Macrophages

• TLR2-Gram Positive and yeast cells

• TLR4-Gram Negative
• CO receptor CD14.
• Recognise PAMPS
• LPS, Techoic acid, flagellin etc
• Phagolysosome
• Oxygen dependent and independent mechanism
• MHC II and presents antigenic peptide.
Cytokines secretion by Macrophages
• IL1 –Hypothalamus reset temp
• Internal Pyrogens
• External Pyrogens- Microbes and microbial toxins
• IL8 chemo attractant for neutrophils
• IL-6 stimulate liver cells to produce acute phase proteins and stimulate B
cells to produce antibodies.
• IL12 promotes cytotoxic T cells and cytotoxic killing
• IL10 suppress Tc cells and promotes B cell mediated immunity
• TGF beta reduces the activity is to reduce inflammation by apoptosis of T
cells(Modulate or down regulate immune response) if not aggressive
response leads to hypersensitivity reaction.
Neutrophils
60-75% of circulating WBC
Polymorphnuclear cells(PMN)
Stained by both acidic and basic dyes
Important role in inflammatory response
Migrates to site of infection
Phagocytic cells
Reactive oxygen species are generated in an oxidative burst by
an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
Intracellular granules that contain antimicrobial peptides (α-defensins and cathelicidins), myeloperoxidase,
hydrolytic enzymes (lysozyme, sialidase, and collagenase),
proteases (cathepsin G, azurocidin, and elastase), cationic phospholipase, and metal chelators (lactoferrin)
that are released upon contact with microbes
Azurocidin
• cationic antimicrobial protein of 37 kD
• Chemo attractant and activator of Monocytes and Macrophages.
• Antimicrobial binds to lipid A of bacteria cell wall and facilitates
phagocytosis
• Opsonins.
Cathelicidins
• Cathelicidins are produced as pre-pro-peptides and stored inside granules.
Upon activation of the cell, they are secreted, and the N-terminal
pro-domain which includes the cathelin domain is cleaved off to form the
mature.
• Cathelicidins are directly antimicrobial for many pathogens, including both
Gram-positive and Gram-negative bacteria, fungi, parasites, and enveloped
viruses.
• Cationic cathelicidins can bind and disrupt negatively charged membranes,
leading to cell death. These peptides can also cross membranes and target
intracellular processes like RNA and DNA synthesis, impair functions of
enzymes and chaperones, and can stimulate protein degradation
NETosis
• NETs composed of nuclear contents (DNA and chromatin) mixed with
toxic molecules from intracellular granules and the cytosol and
effectively destroyed.
• Neutrophil extracellular traps (NETs) are complexes of chromosomal
DNA, histones, and granule proteins that are released by neutrophils
and ensnare extracellular microbes
NET
Basophils
• Granulated cells
• Bilobed
• Stained by basic dyes
• Heavily granulated
• 0.5-1% in peripheral blood.
• Helmenths, bacterial and allergic reactions.
• Fixed in tissue as mast cells
• In blood basophils
• Histamine, tryptase, Peroxidases, lipid mediators: prostaglandin and
leukotrienes.
• Vasodilation, and smooth muscle contraction(Edema, hypotension,
bronchial smooth muscle contraction leading to respiratory
dysfunctions.
• Antigen Vs Allergen
• Genetic disposition of HLA
• TH2 cells produces IL4 and IL5
• Class witch B cells to produce IgE.
Treatment
• Cyclic GMP secondary messenger increases.
• Leading to degranulation.
• Cyclic AMP reverse the process by stabilise the membrane and
prevents degranulation.
• Epinephrine.
• Antihistamines such as azatadine, cetirizine, and mizolastine,
• Omalizumab is a humanized monoclonal anti-IgE antibody with a high
degree of human characteristics greater than 95% (IgG1-k).
• It recognizes the constant region of IgE antibodies, Fcε, and prevents
it from binding to the high-affinity FcεR receptors
Dendritic cells

• Antigen presenting cells

• Product of myeloid stem cells
• Endocytosis, pinocytosis, Phagocytosis
• Membrane extended like dendrites of neuron.
• Follicular dendritic cells
• Interdigitating dendritic cells.
• Presents antigenic peptide to T helper cells.
• Tertiary/Diffused lymphatic tissue
• MALT, SALT, BALT, Peyer’s patch, tonsils.