8 - immunity: defence against disease
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What is the Immune System?
• Immunity is all about the body’s ability to distinguish “self” from “non-self”
• Can be broadly separated in to ‘specific’ and ‘non-specific’ immunity.
Non-Specific Immunity
• First line of defence– Prevention: barriers to foreign particles
• Skin (physical barrier including fats and salts)• Mucous membranes (in throat / nose)• Natural secretions (sweat, tears, stomach acid,
milk, semen – all contain antimicrobial agents)• Natural flora (good bacteria)
Second line of defence
Phagocytes and Killer Cells• …are white blood cells• Phagocyctes are produced in the bone
marrow and move to the point of entry of the foreign article and engulf / destroy– Neutrophils (most common WBC)– Monocytes (largest WBC)
• When leaving the blood, mature in to macrophages• Can target free-floating microorganisms• Will ingest and use some parts, excrete the rest
Second line of defence
Natural Killer (NK) cells• … are also white blood cells• Target and destroy body cells that have
been infected by viruses
Other white blood cells• Attach to and destroy multi-cellular
pathogens that are too large to be engulfed
Second line of defence
Complement• 20 different types made in liver and
circulate in an inactive state• Once 1 activated, the rest follow in a
cascade– Stick to invading micro-org and make
identifiable to phagocytes– Stimulate phagocytes– Attract phagocytes to site of infection– Destroy membrane of micro-org
Animation
Second line of defence
Interferon• An infected cell will release interferon that
will stimulate the release of viral resistant proteins by nearby cells
Cytokines• Hormone-like (receptor specific) chemical
messengers used by cells of the immune system
Second line of defence
INFLAMMATION• Release of seratonin causes arterioles around
cut to dilate to increase blood flow and become more permeable to p’cytes
• P’cytes release histamine to attract more p’cytes• Clot forms to contain infection• Pus forms (living & dead WBCs and debris)
– Eventually re-absorbed by cells, excreted vi blood or secreted through skin
Inflammation
Inflammation
Specific Immunity
Third line of defence
• Initiated by foreign particle entering body
• Adaptive & acquired
• Long lasting – often for life
• Recognises, reacts & remembers
• Reacts faster in future occurrences
Cells of the 3rd Line
• Lymphocytes (WBCs produced in bone marrow)– B Cells (mature in bone marrow)
• Plasma cells• Memory B cells
– T Cells (mature in thymus)• Cytoxic T cells• T helper cells
Maturation of Lymphocytes
How B & T cells identify foreign material
• On the surface of every cell, genes code for the production of MHC (major histocompatibility proteins).
• MHC distinguishes “self” from “non-self”– MHC Class 1 (on all cells except RBCs)– MHC Class 2 (only on B & T cells and some
macrophages)
How B & T cells identify foreign material
• B & T cells display– Their own antigens– Receptors for self– Receptors for non-self
B cells and ‘Clonal Selection Theory’• B cells have immunoglobins (Ig)
on their surface• There are millions of different types of
antigens and millions of different types of Igs.
• When an Ig on a B cell interacts with an antigen it results in the proliferation of that type of B cell and its corresponding Ig
• Effectively the antigen is determining what type of Ig becomes abundant in the body
Clonal ExpansionAfter replicating some B cells mature in to antibody
producing plasma cells and others mature in to memory B cells
How much antibody is produced?
• After the body has been exposed to a pathogen, on a subsequent exposure, memory B cells are able to produce large amounts of the specific antibody required, this is what we call immunity.
There is no need for clonal expansion as a small amount of memory B cells are able to produce a large amount of antigen
Structure of an antibody
• 4 polypeptide chains• Heavy chains joined to
light by flexible hinges• Variable binding site• 5 different types of
antibodies (immunoglobins)– IgG, IgD & IgE (1
molecule)– IgA (2 molecules)– IgM (5 molecules)
Heavy chains (long)
Light chains (short)
Hinge
Antigen binding sites
AntibodiesWhen faced with a virus
each binding site can join to a different particle, thereby forming an antigen-antibody
complex and deactivating the virus
Bacteria are much larger than viruses, but a macrophage has
a receptor site for the long-chain end of the antibody and can engulf the entire antibody-
antigen complex
T cells
• B cells are produced in the bone marrow but mature in the thymus.
• Similar to B cells, the body produces millions of varieties of T cells
• When a pathogen is encountered, the T cells with the corresponding binding site will proliferate.
• T cells do not produce antibodies – with phagocytes they form the body’s cellular immunity.
Helper T cells (Th)• After ingesting a pathogen, a phagocyte will use
an MHC class 2 to display the antigenic protein on its surface
• A helper T cell will the appropriate receptor site will bind to the phagocyte and stimulate the proliferation of B cells
Cytotoxic T cells (Tc)
• Uses MHC class 1 & 2 molecules to identify whether a cell contains any ‘non-self’ proteins
• Destroys cells via proteins that punch holes in the cell membrane
• Will ideally destroy a cell before a the contained virus can replicate
• Can’t kill free-floating virus particles (non-cellular agents)
Movement of B & T Cells• Organs
connected by lymphatic vessels
• Memory B & T cells circulate in lymph
• Antigens attacked on site of carried to lymph node
• Swelling of lymph node caused by B Cell expansion
Acquiring Specific Immunity• Active Immunity
– Natural (B & T cell proliferation in response to antigen)
– Induced (Immune response triggered by induced antigen
• A dead microorganism• Attenuated (unable to reproduce) microorganism• Toxoid (artificial low-dose toxin)
– Booster shot on any of the above may be required to maintain immunity (maintain levels of B & T memory cells in lymph)
• Passive Immunity– Natural (mother to foetus / breastfeeding baby)– Induced (administered antibiotic)
Passive Immunity
• Called passive as the antibodies are not made by user
• An advantage is that the user receives a lot of antibodies in a very short space of time
• A disadvantage is that the immunity is temporary as no memory cells are created
Summary of Acquired Immunity
Monoclonal antibody production
• Snake antivenom is produced in rabbits• Rabbit is injected with very small dose of
venom to produce immune response• Doses of venom gradually increased• Blood harvested, antibodies isolated• Rabbit makes more blood with more
antibodies
Immunity – what can go wrong?
• Allergies– Histamine is usually released by mast cells to attract
more phagocytes to an infected area– If IgE is produced against an antigen it can bind to
mast cells– Upon re-exposure to the allergen, large amounts of
histamine can be released, resulting in:• Capillary dilation• Airway constriction• Mucous secretion• Pain• Itching
Facilitates movement of phagocytes in to area
Symptoms of the above
Rh Incompatibility
• Human blood cells have certain marker proteins that belong to either the ABO or Rhesus (Rh) blood group
• Rh is inherited as a dominant allele, so– Rh+Rh+ or Rh+Rh- = Rh positive– Rh-Rh- = Rh negative
• So an Rh- mother can still have an Rh+ child due to the father’s genotype
Rh Incompatibility• During the first pregnancy, at birth the placenta will
detach from the uterine wall and the foetal blood will cause the mother to create Rh antibodies
• During the second pregnancy the mother’s T helper cells will produce antibodies that will cross the placenta and attack the foetus’ RBCs and organs– Resulting in haemolytic disease of the newborn– If untreated, effect will worsen with each subsequent pregnancy
Rh Incompatibility• Treatment
– If, after the first pregnancy the mother gets a large dose of Rh antibodies, she will not have an immune reaction
– Therefore no memory B cells will be present to cause complications in subsequent preganancies
• Other mother-foetus incompatibilities– Blocking factor in the maternal serum will inhibit production of
antibodies against foetal antiges– Placental cells will absorb small amounts of antibody
Auto-immune diseases
• Breakdown of ability to distinguish ‘self ‘from ‘non-self’
• B & T cells attack and destroy own body cells• eg. Multiple sclerosis (MS), approx 1:1000
– Immune system attacks own myelin sheath– Results in short-circuits in the CNS and impaired
communication between CNS and PNS– Sites of damage can vary so symptoms differ– Damage from initial attack/s can be repaired– As more attacks occur scarring (plaques) build up– Once this occurs damage can’t be reversed– Disease is progressive in nature
Multiple Sclerosis
• Diagnosis– Originally had to be done via observations– Now an MRI can be used to find areas of brain with higher water
content (plaques)
• Cause– Unknown but possibly linked to a viruses which have proteins
very simillar to our myelin proteins. Once the immune system disposes if it,, it continues to attack myelin sheath
– Strong linkage with people living in colder climates
• Treatment– Nothing very effective– Cortisone & B interferon can cause mild temporary improvement
Rejection of Organ Transplant
• Only identical twins can be a perfect match
• Recipient and donor typed to match as closely as possible
• Helper T cells are the main immune cell responsible for transplant rejection
• Recipient must take cyclosporin (a helper T cell inhibitor) for the rest of their lives to prevent rejection
Immune Deficiency Disease (IDD)
• Immune system is immature at birth• Once maternal antibodies from placenta and
breast milk wear off, baby is exposed• If immune system dysfunctional, death will occur
not long afterwards• People can be sustained through the donation of
bone marrow (where immune cells are produced)
• Donor and recipient must be typed on ABO, Rh and a number of other MHCs
Acquired Immune Deficiency Syndrome (AIDS)
• Caused by the Human Immunodeficiency Virus (HIV)
• Infects only Helper T Cells and macrophages• Victims will usually die of a disease or infection
that their body could not fight off• HIV can lay dormant for years• Death will usually follow onset of “full-blown”
AIDS• Drugs that affect the membrane lipid bilayer of
the virus can delay death
HIV / AIDSVirus
Disruption of HIV-1 lipid surface
Plants
• Plants have no true immune system• Resistance to infectious agents has evolved
through natural selection• Plants have mechanical barriers to infection
– Cuticle and epidermal cells form barrier– Infection will often enter through stomata
• Plants have chemical barriers to infection– Citrus and mint plants produce oils– Stone fruit plants seal off infection site with “gum’– Other plants have resins, tanins and phenolic
substances