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Introduction to Immunology

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Title: Introduction to Immunology


1
Introduction to Immunology
2
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)

3
  • Worms ( tapeworm, filaria)
  • Protozoans (leishmania, malaria)
  • Fungi (candida, aspergillus)
  • Bacteria (E.coli, streptococcus, staphylococcus)
  • Viruses (polio, HBV, HCV, Dengue)

4
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

5
  • Mucosal epithelial cells (secrete MUCUS)
  • Epithelial cells of the nasal passage and bronchi
    (cilia)

6
  • 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

7
  • 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)

8
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)
9
  • 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

10
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.

11
  • 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.

12
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
13
  • 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.

14
  • 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.

15
  • 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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17
  • 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.

18
  • 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.

19
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

20
  • 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.

23
  • 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

24
  • 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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