Introduction to Immunology

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Introduction to Immunology
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1 The Need

• The Ubiquitous Enemy
• Microbes
• Extracellular (survive on animals and plants by
  releasing digestive enzymes directly and
  absorbing food or growth on living tissues)
• Intracellular (infect cells, whereby survive,
  replicate and utilize host energy sources)

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• Worms ( tapeworm, filaria)
• Protozoans (leishmania, malaria)
• Fungi (candida, aspergillus)
• Bacteria (E.coli, streptococcus, staphylococcus)
• Viruses (polio, HBV, HCV, Dengue)

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2 External Defenses

• Physical Barriers
• Microbe or parasite must attach or penetrate the
  epithelial layers of the body
• Organisms enter through active or passive means
• Burrow through the skin
• Ingested with food
• Inhalation
• Penetration through an open wound
• Irrespective of the route, physical barriers must
  be crossed in each tract involved

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• Mucosal epithelial cells (secrete MUCUS)
• Epithelial cells of the nasal passage and bronchi
  (cilia)

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• Secretions
• Provide a hostile environment for microbial
  habitation
• Some substances directly kill the microbe
  (lysozyme- bacterial cell wall)
• Some act by interference with ion channels (NaCl)
• Musus (Mucin) coats surface of epithelial cells
  and makes it difficult for microbes to contact
  and bind them

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• Tears and saliva contain IgA (antibodies)
• Also secreted by respiratory tract
• Gastrointestinal tract
• Genitourinary tract
• Peptide antibiotics
• Small peptides
• Secreted by gastrointestinal, respiratory
  epithelia and phagocytes
• Conserved through species
• Most primitive defense mechanism against microbes
• Molecular weight 3-5kD
• Effective against gram positive and negative
  bacteria
• Cecropins (cause lysis)
• Maganins (cause lysis)
• Defensins (interfere with ion channels)

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Secretions at Epithelial Surfaces Secretions at Epithelial Surfaces Secretions at Epithelial Surfaces
Site Source Specific Substances Secreted
Eyes Lacrimal Glands Lysozyme, IgA, IgG
Ears Sebaceous Glands Waxy secretions- cerumen
Mouth Salivary Glands Digestive enzymes, Lysozyme, IgA, IgG, lactoferrin
Skin Sweat Glands Sebaceous Glands Lysozyme, NaCl, short chain fatty acids
Stomach Gastric Juices Pepsin, rennin, acid (pH 1-2)
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• Microbial Products and Competition
• Nonpathogenic bacteria
• Found on skin, mouth, reproductive and
  gastrointestinal tract
• Prevent pathogens from colonizing at the site
• Prevent attachment
• Compete for nutrients
• Release antibiotic substances like colicins and
  short chain fatty acids (E.coli)
• Gut Flora also performs
• Degrading waste matter
• Lactobacilli help to make the environment acidic,
  thus preventing growth of microbes

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3 Immune Defense

• Immune System
• The immune system has a mobile force of cells in
  the blood stream which are ready to attack the
  invading microbe wherever it enters the body.
• Although many of the cells of the immune system
  are separate from each other they maintain
  communication through cell contact and molecules
  secreted by them.
• One from the dysfunction is IMMUNODEFICIENCY
  which can result form infection with the human
  immunodeficiency virus (HIV) causing AIDS.
• On the other hand, the immune system can be
  hypersensitive to a microbe (or even to a
  substance such as pollen) and this itself can
  cause severe tissue damage sometimes leading to
  death.

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• Innate versus Adaptive Systems
• First line defense
• This is called the innate immune system since
  it is present at birth and changes little
  throughout the life of the individual.
• The second line is the
• Adaptive immune system
• The key difference between the two systems is
  that the adaptive system shows far more
  specificity and remembers that a particular
  microbe has previously invaded the body.
• This leads to a more rapid expulsion of the
  microbe on its second and third time of entry.

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Characteristics Cells Molecules
Natural Immunity Responds rapidly Has some specificity No memory Phagocytes and macrophages Natural Killer cells Mast cells Dendritic cells Cytokines Complement Acute phase proteins
Adaptive Immunity Slow to start Highly specific Memory T and B cells Antibodies Cytokines
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• Interaction between Innate and Adaptive Immunity
• Macrophages are phagocytic but produce important
  cytokines that help to induce the adaptive
  immune system are activated by antibodies,
  molecules of the adaptive system.
• These chemical mediators can either be cell bound
  or released as localized hormones, acting over
  short distances.
• Cells of both systems have a large number of
  surface receptors some are involved in
• adhesion of the cells to blood endothelial walls
  (e.g. leukocyte function antigens LFA-1),
• some recognize chemicals released by cells (e.g.
  complement, cytokine and chemokine receptors) and
  others
• trigger the function of the cell such as
  activation of the phagocytic process.

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• Clonal Selection
• When an antigen is introduced into an individual,
  lymphocytes with appropriate receptors seek out
  and bind the antigen and are triggered to
  proliferate and differentiate into the effector
  cells of immunity (i.e., they give rise through
  division to large numbers of cells).
• All members of this clone of cells are specific
  for the antigen initially triggering the response
  and they, or their products, are capable of
  specifically reacting with the antigen or the
  cells that produce it and to mediate its
  elimination.
• In addition, there are a much larger number of
  cells specific for the immunizing antigen late in
  the immune response.
• These cells are able to respond faster to
  antigen challenge giving rise the memory
  involved in immunity.

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• That is, individuals do not usually get infected
  by the same organism twice, as their immune
  system remembers the first encounter and protect
  against a second infection by the same organism.
• In particular, when antigen is introduced into an
  individual, B cells with receptors for that
  antigen bind and internalize it and receive help
  from T cells.
• These B cells are triggered to proliferate,
  giving rise to clones of daughter cells. Some of
  these cells serve as memory cells, others
  differentiate and become plasma cells.

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• T and B cells and Cell Co-operation
• The lymphocytes selected for clonal expansion are
  of two major types, B cells and T cells, each
  giving rise to a different form of immunity.
• T lymphocytes mature under the influence of the
  thymus and, on stimulation by antigen, give rise
  to cellular immunity.
• The B lymphocyte population matures mainly under
  the influence of bone marrow and gives rise to
  lymphoid populations which, on contact with
  antigen, proliferate and differentiate into
  plasma cells.
• These plasma cells make a humoral factor
  (antibody immunoglobulin) which is specific for
  the antigen and able to neutralize and / or
  eliminate it.

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• The development of the immune response to an
  antigen also requires cell co-operation.
• T and B cell populations, as well as macrophages,
  interact in the development of specific immunity.
  
• In particular, subpopulations of T cells regulate
  (e.g. help) humoral and cellular immune
  responses.
• Although immune responses to most antigens
  (especially proteins) require cell co-operation,
  some antigens (T-independent)are able to initiate
  an immune response in the absence of T
  lymphocytes.

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4 Antigens

• The Range of Antigens
• The first stage of removing an invading organism
  from the body is to recognize it as Non Self.
• An antigen is any substance that induces an
  immune response by proliferation of lymphocytes
  and production of specific antibodies
• Includes
• Proteins
• Nucleic acids
• Carbohydrates
• Lipids

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• The Structure of Antigens
• Antibodies produced against an antigen are not
  directed towards the whole molecule
• Rather, they are directed towards specific
  portions called
• Antigenic determinants or
• Epitopes
• For a protein an antibody binds 3-6 amino acids
• For carbohydrates, they bind to 5-6 sugar
  residues, atleast

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• Therefore most large molecules are
  Multideterminant.
• And can bind to many different antibodies at the
  same time.
• The structure/folded conformation of the
  antigenic molecule plays an important role in
  antibody binding
• Thus residues close to each other in linear
  sequence might not be included in antibody
  binding
• While residues far apart may be involved.

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• All antigens might not elicit the same type of
  immune response
• Some might elicit a strong while others a weak
  immune response.
• This is determined by
• Health
• Genetics and
• Age of an individual

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• Very small molecules that can be viewed as single
  antigenic determinants are also incapable of
  eliciting an immune response
• They are referred to as Haptens
• The can be attached to larger carrier molecules
• And in this form they are able to induce the
  production of antibodies with the help of T cells
• It is therefore necessary to distinguish between
  immunogens and other molecules that react with
  antibodies but do not elicit an immune response

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