8 - Immunity: Defence Against Disease

40

description

 

Transcript of 8 - Immunity: Defence Against Disease

Page 1: 8 - Immunity: Defence Against Disease
Page 2: 8 - Immunity: Defence Against Disease

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.

Page 3: 8 - Immunity: Defence Against Disease

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)

Page 4: 8 - Immunity: Defence Against Disease

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

Page 5: 8 - Immunity: Defence Against Disease

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

Page 6: 8 - Immunity: Defence Against Disease

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

Page 7: 8 - Immunity: Defence Against Disease

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

Page 8: 8 - Immunity: Defence Against Disease

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

Page 9: 8 - Immunity: Defence Against Disease

Inflammation

Page 10: 8 - Immunity: Defence Against Disease

Inflammation

Page 11: 8 - Immunity: Defence Against Disease

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

Page 12: 8 - Immunity: Defence Against Disease

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

Page 13: 8 - Immunity: Defence Against Disease

Maturation of Lymphocytes

Page 14: 8 - Immunity: Defence Against Disease
Page 15: 8 - Immunity: Defence Against Disease

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)

Page 16: 8 - Immunity: Defence Against Disease

How B & T cells identify foreign material

• B & T cells display– Their own antigens– Receptors for self– Receptors for non-self

Page 17: 8 - Immunity: Defence Against Disease

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

Page 18: 8 - Immunity: Defence Against Disease

Clonal ExpansionAfter replicating some B cells mature in to antibody

producing plasma cells and others mature in to memory B cells

Page 19: 8 - Immunity: Defence Against Disease

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

Page 20: 8 - Immunity: Defence Against Disease

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

Page 21: 8 - Immunity: Defence Against Disease

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

Page 22: 8 - Immunity: Defence Against Disease

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.

Page 23: 8 - Immunity: Defence Against Disease

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

Page 24: 8 - Immunity: Defence Against Disease

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)

Page 25: 8 - Immunity: Defence Against Disease

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

Page 26: 8 - Immunity: Defence Against Disease

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)

Page 27: 8 - Immunity: Defence Against Disease

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

Page 28: 8 - Immunity: Defence Against Disease

Summary of Acquired Immunity

Page 29: 8 - Immunity: Defence Against Disease

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

Page 30: 8 - Immunity: Defence Against Disease

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

Page 31: 8 - Immunity: Defence Against Disease

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

Page 32: 8 - Immunity: Defence Against Disease

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

Page 33: 8 - Immunity: Defence Against Disease

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

Page 34: 8 - Immunity: Defence Against Disease

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

Page 35: 8 - Immunity: Defence Against Disease

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

Page 36: 8 - Immunity: Defence Against Disease

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

Page 37: 8 - Immunity: Defence Against Disease

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

Page 38: 8 - Immunity: Defence Against Disease

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

Page 39: 8 - Immunity: Defence Against Disease

HIV / AIDSVirus

Disruption of HIV-1 lipid surface

Page 40: 8 - Immunity: Defence Against Disease

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