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The innate immune response


* Because the human body provides an ideal environment for many microbes, they try to pass your skin barrier and enter. Your immune system is a bodywide network of ... – PowerPoint PPT presentation

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Title: The innate immune response

The innate immune response
Levels of Defence
  • Organisms must continually defend themselves
    against pathogens of many kinds
  • A variety of defence mechanisms have evolved to
    increase the chances of survival in the face of
    these external challenges
  • Defence mechanisms operate at all levels
    external and internal, and involve molecules,
    cells and organ systems.

Non-specifc Defences
  • Non-specific defences are found in all organisms.
  • They are non-specific because they protect
    against a wide variety of pathogenic organisms.
  • They are innate meaning that they are always
    present and are not produced by prior contacts
    with a pathogen.

Invertebrate Defences
  • Invertebrate animals have only innate
    non-specific defence mechanisms.
  • They may respond to any foreign material
    (including a parasite) by producing a capsule of
    connective tissue around the material. Within
    the capsule, phagocytic cells may ingest the
  • Some species of crustaceans produce broad
    spectrum bacteriocidal agents in response to
    infection by bacteria.
  • Both these reactions require the ability to
    recognise and reject non-self materials, but it
    is not known how this occurs in inverterbrates.

Plant Defences
  • Like animals, plants have both molecular and
    cell-mediated defences, and are able to
    distinguish self from non-self.
  • Unlike other organisms, plants have no
    circulatory system or wandering phagocytic cells
    so each cell must fend for itself.
  • Cell wall is first line of defence it provides
    a physical barrier against pathogens.

Plant Defences
  • Secondary substances these are chemicals
    produced by plants, e.g.
  • Antibiotics to protect against bacterial and
    fungal infections
  • Protease enzymes that disrupt the digestive
    functions of herbivores
  • Cellulases and chitinases that kill fungal cells
    by digesting their cell walls
  • Ecdysome insect moulting hormone. Disrupts the
    hormonal balance of parasitic insect larvae
  • Specific examples from textbook include the toxic
    compounds produced by Eucalypt leaves and the
    cytotoxic chemicals produced by some species of
  • Cell mediated defences can involve
    self-destruction of infected or damaged cells.
  • Isolation and encapsulation are also important
    mechanisms for defending against plant parasites
    such as fungi, nematodes, bacteria, viruses and

The immune system has evolved to protect
eukaryotes from microbes
Parasite in red blood cell
SARS virus
Us and them self and non-self
  • Microorganisms protozoans, bacteria, viruses,
    helminths (worms) all express unique molecules
    (proteins, carbohydrates and lipids) that
    distinguish them from other species.
  • These molecular differences are the basis by
    which the immune system discriminates microbes
    from self components.

Recognition of Self and Non-self
  • Some microbial molecules are shared with us.
  • Some microbial molecules are unique to microbes
    but are shared within discrete taxonomic groups
    e.g. LPS in gram negative bacteria. These shared
    molecules are called PAMPs (pathogen associated
    molecular patterns).
  • Some microbial molecules are unique to a
    particular organism e.g. those displayed by one
    strain of influenza virus but not another strain.
  • Unique molecules that can be recognised by the
    immune system are called antigens.
  • The immune system has separate sets of receptors
    for recognising shared and unique molecular
    patterns that are distinct from self molecules.

Markers of self
Every cell in your body carries the same set of
distinctive surface proteins that distinguish you
as self. This set of unique markers on human
cells is called the major histocompatibility
complex (MHC) proteins. There are two classes
MHC Class I proteins, which are on all cells, and
MHC Class II proteins, which are only on certain
specialized cells.
Markers of non-self
SARS virus
Non-self leukocyte
Non-self nerve cell
Epitope Class I MHC protein
Markers of self Major Histocompatibility Complex
Antigenic peptide
Antigenic peptide
Antigenic peptide
Viral infection
MHC Class II
MHC Class I
MHC Class I
Antigen-presenting cell uses MHC Class I or II
Infected cell
Cell membrane
Your immune cells recognize major
histocompatibility complex proteins (MHC) when
they distinguish between self and non-self. An
MHC protein serves as a recognizable scaffold
that presents pieces (peptides) of a foreign
protein (antigenic) to immune cells.
Requirements for an effective defence against
  • Response should not harm the host recognition
    of pathogen presence by recognition of non-self
  • Should be present as soon as exposure to
    pathogens occurs (i.e. at birth)
  • Response must be rapid (pathogens can replicate
  • Response must be appropriate for the pathogen
    (pathogens vary in size, environment, etc)
  • These features evolved early in the development
    of life on Earth and are displayed by the innate
    immune system.

Outcome of the response to microbial invasion by
the innate defences
  • Innate defences remove or control invading
    microbes thus infection resolves
  • OR
  • The microorganism persists and replicates
    because some microbes have evolved to overcome
    the defences of the innate immune system. These
    are pathogens.
  • Additional effector mechanisms are required to
    remove pathogens
  • These are provided by the more recently evolved
    adaptive (specific, acquired, cognate) immune

What is immunity?
  • Protection and resistance from infection by
  • Innate and adaptive immunity have overlapping but
    distinctly different roles in this process.

Where are immune defences required?
  • Sites of microbial infection and normal flora
  • Skin
  • Nose and mouth
  • Respiratory tract
  • Eye
  • Scratch, injury
  • Circulation
  • Urogenital tract
  • Anus

Interactions with microbes
  • Not all microorganisms cause disease some
    microbes colonise their host and aid normal body
  • Suppression of the immune system allows microbes
    that are normally harmless to become pathogenic
    opportunistic infections.
  • Some microbes have evolved to evade the innate
    immune system (pathogens) so the adaptive immune
    system developed later in evolution.

Innate Immune System
  • The innate immune system controls the early
    stages of infection.
  • Characteristics
  • Relatively non-specific receptor molecules on
    cells and in serum recognise PAMPS
  • Rapid because components already present
  • Magnitude constant
  • Acts as a first line of defence (sentinel
  • Comprises
  • Physical barriers
  • Biochemical barriers
  • Serum factors (complement, cytokines etc)
  • Cells (neutrophils, macrophages, NK cells, other)

Physical and biochemical barriers of innate
  • Physical barriers prevent microbial entry.
  • Biochemical barriers control pathogen growth.
  • Normal flora compete with potential pathogens.
  • Skin barrier. Sweat (acidic pH)
  • Clotting also helps protect skin
  • Lysozyme enzyme in saliva, sweat, tears.
    Attacks bacterial cell walls
  • Mucous (respiratory, digestive, urinary
    reproductive tracts) traps pathogens
  • Cilia little hairs that help clear mucous (and
    pathogens) from respiratory tract
  • Alimentary canal lysozyme in saliva, stomach
    HCl kills many pathogens, specialised immune
    areas in the GI tract, very high turnover of
    epithelial cells, antibodies
  • Movement e.g. peristalsis, cough reflex, blinking

Soluble factors the complement system
  • The complement system (complement) is a group of
    plasma proteins which interacts with pathogens to
    mark them for killing.
  • The proteins are activated sequentially in a
  • Multiple triggering events activate the cascade,
  • Binding certain PAMPs on microbial surfaces.
  • Binding antibodies which have bound microbial
    surfaces (associated with the adaptive immune
  • Outcomes
  • Migration of phagocytes to site of infection.
  • Phagocytosis of microbes.
  • Lysis of some microbes.

Other soluble factors
  • Cytokines (including interferons)
  • Small glycoproteins released by body cells a s a
    means of communicating with the immune system
  • Coordinate many aspects of the immune response
  • Usually act locally and only remain active for a
    short time
  • Cytokines act on target cells by attaching to a
    cytokine receptor in the membrane, which sends a
    signal to the nucleus changing the behaviour of
    the cell
  • Different cytokines trigger a variety of
    responses, both non-specific and specific e.g.
    they promote growth and proliferation of
    lymphocytes, induce fever, promote antibody
    responses, activate macrophages
  • Interferons
  • Set of proteins produced by virally infected
    cells to limit the spread of viral infections, by
    inducing a state of resistance in healthy cells.
  • Induced by viruses, bacteria and other signals
    from the immune system

Cells of theinnate immune response
  • Phagocytic white blood cells (leukocytes)
    attracted to a site of infection (chemotaxis) by
    chemicals released by injured cells.
  • Three types
  • neutrophils (short lived)
  • monocytes ( blood)
  • macrophages ( tissue)
  • Cytotoxic cells eosinophil and natural killer
    (NK cells)
  • Inflammatory cells basophil, polymorphonuclear
  • All are derived from pluripotent stem cells in
    bone marrow.
  • All induce inflammation.

Phagocytes and Granulocytes
  • Some immune cells have more than one name
  • Phagocytes are large immune cells that can
    engulf and digest foreign invaders
  • Granulocytes refers to immune cells that carry
    granules laden with killer chemicals.

  • Phagocytes include
  • Monocytes circulate in the blood
  • Macrophages are found in tissues throughout the
  • Dendritic cells are more stationary, monitoring
    their environment from one spot such as the skin
  • Neutrophils are cells that circulate in the
    blood but move into tissues when they are needed.
  • Macrophages are versatile cells besides acting
    as phagocytic scavengers, they secrete a wide
    variety of signaling cytokines (called monokines)
    that are vital to the immune response.

Phagocytes and their relatives
Mast cell
Dendritic cell
  • Functions of Phagocytes
  • Enter an infected site from the circulation
  • Bind, engulf and kill a wide variety of microbial
  • Produce immunomodulatory substances e.g.
    cytokines, chemokines, which regulate the immune
  • Act as first line of defence against infection

Phagocytes in the body
Brain microglial cells
Lungalveolar macrophages
Liver Kupffer cells
Spleen macrophages
Kidneymesangial phagocytes
Blood monocytes
Lymph node resident and recirculating macrophages
Precursors in bone marrow
Jointsynovial A cells
Phagocyte killing mechanisms
  • Acidification pH 3.5-4.0
  • Antimicrobial peptides defensins, cationic
  • Enzymes lysozyme, acid hydrolases
  • Competitors lactoferrin
  • Toxic nitrogen intermediates nitric oxide
  • Toxic oxygen intermediates O2-, H2O2, OH, OCl

  • Neutrophils are both phagocytes and granulocytes
    they contain granules filled with potent
    chemicals. These chemicals, in addition to
    destroying microorganisms, play a key role in
    acute inflammatory reactions.
  • Other types of granulocytes are
  • Eosinophils and basophils these degranulate by
    spraying their chemicals onto harmful cells or
  • Mast cells are twins of the basophil, except
    they are not a blood cells. They release
    granules containing inflammatory mediators to
    augment the action of immune cells and are
    responsible for allergy symptoms in the lungs,
    skin, and linings of the nose and intestinal
  • Blood platelets are cell fragments. These
    fragments contain granules which promote blood
    clotting and wound repair, and activate some
    immune defenses.

Cytotoxic cells
  • Target infected or altered cells, and release
    granules whose contents are toxic.
  • These include
  • Natural killer (NK) cells (kill tumours, virus
    infected cells)
  • Eosinophils (kill parasites)
  • Macrophages (release cytotoxic mediators)

Protective processes
  • Inflammation
  • Infected cells (mast cells) release histamine,
    which is a vasodilator.
  • Causes localised swelling, redness, heat, pain.
    Can also cause high temperature.
  • Brings white cells to the area of infection
  • Phagocytes that invade damaged tissue do their
    work, and are removed by programmed cell death
  • Resolvins (derived from omega-3 fatty acids) are
    a group of naturally occurring substances that
    have been identified as signalling molecules
    involved in dampening down the inflammatory

Protective Processes
  • Preventing blood loss
  • Any injury that damages blood vessels is
    potentially very dangerous, so very efficient
    mechanisms have evolved to prevent the loss of
  • Small arteries constrict in the area around the
    wound to reduce the amount of blood escaping from
    damaged vessels (this involves a nervous
  • Blood platelets become sticky and fragile. They
    clump together to plug the broken part of the
  • Blood coagulates (clots) as a result of a series
    of chemical reactions triggered by the damage to
    cells and the release of platelet contents.
    Soluble blood proteins are converted into
    insoluble protein fibres which entangle blood
    cells and slowly shrink, forming a a more
    permanent seal over the wound.
  • New tissue grows to permanently heal the wound.

Protective Processes
  • Fever
  • Fever is an increase in body temperature
    resulting from a resetting of the body
    temperature set-point in the hypothalamus of the
    brain to a higher level. Temperatures above
    37.8oC are regarded as fever.
  • Fever can be triggered by bacterial toxins called
    pyrogens acting directly on the brain or by
    cytokines released from macrophages stimulated by
    the presence of bacterial substances.
  • Bacteria that infect humans grow best at 37oC so
    fever reduces the growth rate of most bacteria.
  • Moderate increases in temperature increase enzyme
    activity, so fever often improves many aspects of
    the inflammatory response.