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Immune system (ii)
 

Immune system (ii)

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    Immune system (ii) Immune system (ii) Presentation Transcript

    • THE IMMUNE SYSTEM (II)
    • The immune system does not design antibodies or T-cell receptors expressly to bind invading antigens
    • The genetic basis of antibody diversity If there are only about 35,000 genes in the entire human genome how is it possible to produce millions of antibodies and T-cell receptors? Due to TWO distinct but complementary mechanisms: 1. DNA rearrangement 2. A high rate of mutations in antibody genes
    • Antibodies are pieced together • there are no genes for entire antibody molecules • instead, the human genome includes many genes that encode a variety of different antibody fragments • these fragments can be pieced together in many millions of combinations
    • Light and heavy chain diversity together yield about 21 billion possibilities.
    • Heavy-chain gene rearrangement & splicing Splice: to join together
    • Independent of exposure to an antigen or pathogen, the immune system generates a repertoire of immune cell lineages or clones [1-8]
    • Those that react with self-antigens (numbers 3, 5, and 8) are deleted shortly after they mature.
    • • every winter, a wave of influenza (flu) sweeps across the world • occasionally devastating flu varieties appear, causing worldwide epidemics, called pandemics CAN WE BEAT THE FLU BUG?
    • - In 1918, the Spanish Influenza, spread across the globe - It infected 20% of the population and killed 5%, which came out to be about 100 million people Think the flu is no big deal?
    • • flu is caused by several viruses Flu viruses • flu virus genes are made up of RNA (mutate rapidly) • 4 or 5 mutations in the same virus may alter the surface antigens enough that the immune system doesn’t fully recognise the virus as the same old flu that was beaten off last year
    • How are flu vaccines against a mutating virus created? Each year, samples of mutated influenza virus from more than 100 sites throughout the world are collected and 3 strains believed the most likely to spread widely are collected
    • Deadly New Strains Bird virus enters pig Human virus enters pig A new strain forms inside pig cells
    • Do people come in close contact with live birds and pigs? Check next two slides!!
    • b ir d v ir u s R N A s t r a n d s p r o t e in s p ik e s h u m a n v ir u s h y b r id h u m a n - b ir d v ir u s fo r m s in p ig a n d m a y in fe c t p e o p le H U M A N B I R D P I G Bird virusHuman virus
    • Use your knowledge of biology to explain the following: The current trivalent influenza vaccine is recommended to people at high risk of exposure to the highly pathogenic H5N1 strain of Avian Influenza Virus even though it is relatively ineffective against this virus. Question: [MAY, 2006]
    • OVERVIEW A) DEFENCE AGAINST MICROBIAL INVASION B) FOUR FEATURES OF THE IMMUNE SYSTEM C) HUMORAL IMMUNITY D) CELL-MEDIATED IMMUNITY E) DISORDERS OF THE IMMUNE SYSTEM F) TYPES OF IMMUNITY G) BLOOD GROUPS and THE RHESUS FACTOR H) ANTIBIOTICS
    • DEFENCE MECHANISMS PASSIVE MECHANISMS ACTIVE MECHANISMS First Line of Defence 1.Skin 2.Mucous membranes NON SPECIFIC INNATE IMMUNITY SPECIFIC ACQUIRED IMMUNITY Second Line of Defence 1.Inflammation 2.Complement Proteins 3.Natural Killer Cells Third Line of Defence 1.Humoral Immunity 2.Cell-Mediated Immunity
    • CELL-MEDIATED IMMUNITY: is directed against any factor that changes a normal cell into an abnormal cell.
    • T cells activate B cells Lymphokines/ Cytokines/ Interleukins
    •  small peptide molecules with various functions  each type of T cell produces a different type of lymphokine Lymphokines:
    • T cells attack:- 1) cells infected by microorganisms, most commonly a virus 2) transplanted organs and tissues 3) cancer-causing cells • T cells do not release antibodies • the whole cell is involved in the attack
    • T Cells arise from: precursor cells in the bone marrow Stem cells of the bone marrow mature in the thymus gland Immature T cells turn either into a cytotoxic cell, helper cell or a suppressor cell Once mature, where do T cells go?
    • T cells: - stay in the blood - migrate to: 1. the tissue fluid 2. lymph nodes 3. other organs e.g. spleen
    •  stem cells develop into thymocytes inside the thymus  at this stage any cells that recognise ‘self’ are destroyed Why is this important? So that the body does not attack itself So that the body does not attack itself
    • T-cell receptors are :  glycoproteins  identical on a surface (about 105 )
    • T-cell receptors: - recognise antigens only if they are combined with self antigens T-cell receptors: - recognise antigens only if they are combined with self antigens self antigens :  are glycoproteins produced by a group of genes called the major histocompatibility complex (MHC)  these proteins are called MHC proteins  are present on the surfaces of most vertebrate cells
    • Three types of MHC proteins B o d y c e lls M a c r o p h a g e s B c e lls T c e lls M H C I M H C I I P r o t e in s o f c o m p le m e n t M H C I I I
    • Role of MHC in T cell function  the genes encoding the MHC proteins are highly polymorphic (have many forms), so that very few individuals in a population possess the same set of alleles  MHC proteins on the tissue cells serve as self markers that enable the individual’s immune system to distinguish its cells from foreign cells, an ability called self-versus- nonself recognition
    • What happens to lymphocytes that bind self-MHC? Killed!! Otherwise they attack the body
    • Antibodies bind to an intact antigen T cell receptors bind to a piece of the antigen displayed on the surface of an antigen- presenting cell T cell receptors bind to a piece of the antigen displayed on the surface of an antigen- presenting cell Difference between antibodies & T cell receptors :
    • Macrophages are antigen- presenting cells.
    • Types of T cellsTypes of T cells FunctionFunction Helper T cellHelper T cell (T(THH oror TTHH-CD4)-CD4) [CD4 is a surface protein] [CD = cluster of differentiation]  Commander of the immune response.  Help B cells differentiate into antibody-secreting plasma cells by secreting lymphokines.  The HIV virus that causes AIDS preferentially infects and destroys TH cells.
    • Types of T cellsTypes of T cells FunctionFunction Helper T cellHelper T cell (T(THH oror TTHH-CD4)-CD4) [CD4 is a surface protein] [CD = cluster of differentiation]  Commander of the immune response [see next slide].  Help B cells differentiate into antibody-secreting plasma cells by secreting lymphokines.  The HIV virus that causes AIDS preferentially infects and destroys TH cells.
    • Central Role of TH Cells: produce interleukins to activate TH, B &TC cells
    • Types of T cellsTypes of T cells FunctionFunction Killer cell orKiller cell or cytotoxic cellcytotoxic cell (T(TCC oror TTCC-CD8-CD8))  Kill tumour cells, body cells infected with viruses and transplanted tissue.
    • Types of T cellsTypes of T cells FunctionFunction Killer cell orKiller cell or cytotoxic cellcytotoxic cell (T(TCC oror TTCC-CD8-CD8))  Recruited by helper T cells.  Kill by a pore-forming molecule called perforin and enzymes.  These enzymes enter the cell through the perforin channels and induce the cell to commit suicide. [see next slide]
    • Cytotoxic T Cells Lyse Infected Cells
    • Natural killer cell Perforin Granzyme Cancer cell is killed NK cells & TC Cells Lyse Infected Cells using perforin & granzymes Cytotoxic T cell BUT they recognise infected cells in a different way…….
    • Natural killer cells kill cells: Cytotoxic T cells kill cells: possessing low levels of MHC class I molecules possessing antigenic fragments bound to MHC class I molecules
    • Types of TTypes of T cellscells FunctionFunction Suppressor TSuppressor T cellcell  Dampens the activity of T and B cells, scaling back the defence after the infection has been checked.
    • Summary of the main stages of the cell-mediated and humoral immune responses.
    • [dendritic cell = antigen presenting cell] What happens when T cells are activated by contact with a specific antigenic determinant?
    • The cytotoxic T cell proliferates [clonal expansion] to produce 1.memory T cells 2.active cytotoxic T cells
    • OVERVIEW A) DEFENCE AGAINST MICROBIAL INVASION B) FOUR FEATURES OF THE IMMUNE SYSTEM C) HUMORAL IMMUNITY D) CELL-MEDIATED IMMUNITY E) DISORDERS OF THE IMMUNE SYSTEM F) TYPES OF IMMUNITY G) BLOOD GROUPS and THE RHESUS FACTOR H) ANTIBIOTICS
    • Two disorders of the immune system: Juvenile diabetes:Juvenile diabetes: an autoimmune disease Juvenile diabetes:Juvenile diabetes: an autoimmune disease AIDSAIDS :: Helper T cell destruction AIDSAIDS :: Helper T cell destruction
    • Autoimmune diseases are produced as the immune system fails to: This failure results in TWO things: This failure results in TWO things: recognise & tolerate self antigens
    • 1. activation of T cells 1. activation of T cells 2. production of autoantibodies by B cells = inflammation + organ damage 2. production of autoantibodies by B cells = inflammation + organ damage
    • Are autoimmune diseases common? • there are over 40 known or suspected autoimmune diseases • affect 5% - 7% of the population PSORIASIS
    • AIDS
    • AIDS: Stands forStands for :: AAcquired IImmune DDeficiency SSyndrome Caused byCaused by::  a retrovirus – HHuman IImmunodeficiency VVirus (HIVHIV)
    • AIDS is a Pandemic disease Pandemic: distributed worldwide and affects many people
    • Why does the HIV attack helper T cells?Why does the HIV attack helper T cells? Recognises the CD4CD4 receptorsreceptors associatedassociated with thesewith these cellscells
    • The course of an HIV infection
    • When is a person considered to have AIDS? When the TWhen the THH cell level has droppedcell level has dropped significantlysignificantly ImmunosuppressionImmunosuppression results in an increase in: opportunistic infections cancers
    • AIDS  The HIV virus doesn’t kill it cripples the immune system • Common diseases that your immune system normally could defeat become life-threatening • Can show no effects for several months all the way up to 10 years
    • How can the progression of the disease be slowed down?
    • How can the progression of the disease be slowed down? Targeting viral enzymes
    • Why is it difficult to develop a vaccine?
    • - lacks proofreading function This leads to mutant virusesThis leads to mutant viruses
    • It is customary to give a cocktail of drugs rather than one drug at a time to an AIDS patient. Why ? More chance to keep virus under control. If a viral enzyme has changed shape, at least virus is prevented from reproducing by another drug.
    • Question: [MAY, 2006] Use your knowledge of biology to explain the following: Despite great progress and advances in medical research, no drug able to effectively destroy the HIV virus has as yet been produced. [5 marks]
    • OVERVIEW A) DEFENCE AGAINST MICROBIAL INVASION B) FOUR FEATURES OF THE IMMUNE SYSTEM C) HUMORAL IMMUNITY D) CELL-MEDIATED IMMUNITY E) DISORDERS OF THE IMMUNE SYSTEM F) TYPES OF IMMUNITY G) BLOOD GROUPS and THE RHESUS FACTOR H) ANTIBIOTICS
    • Two types of acquired immunity:
    • Active antigens received Passive antibodies received Natural Natural active e.g. fighting infection, rejecting transplant Natural passive from mother via milk or placenta Artificial Artificial active vaccination (injection of antigens) Artificial passive injection of antibodies
    • providing immunity artificially Immunisation / VaccinationImmunisation / Vaccination :-
    • ImmunisationImmunisation :- • Whole live microorganism • Dead microorganism • Attenuated (harmless) microorganism • Toxoid (harmless form of toxin) A preparation containing antigenic material:
    • How long does active immunity last? • It depends on the antigen • Some disease-causing bacteria multiply into new forms that the body doesn’t recognize, requiring annual vaccinations, like the flu shot • Booster shot - reminds the immune system of the antigen
    • How long does active immunity last? May last for a lifetime e.g. chicken pox
    • Question: [MAY, 2003] A patient cannot be vaccinated if he or she had been taking immunosuppressive medication within the previous two months. [5 marks]
    • Question: [MAY, 2003] Vaccines rely on production of primary immune response. Antigenic molecules are injected. Individual responds by producing a primary immune response. Immunosuppressive drugs prevent responses by immune system. Especially dangerous if live attenuated forms are injected since recipient cannot respond to defend himself.
    • Question: [MAY, 2012] Use your knowledge of biology to explain the following statement: lactation is important for passive immunity; [5 marks]
    • OVERVIEW A) DEFENCE AGAINST MICROBIAL INVASION B) FOUR FEATURES OF THE IMMUNE SYSTEM C) HUMORAL IMMUNITY D) CELL-MEDIATED IMMUNITY E) DISORDERS OF THE IMMUNE SYSTEM F) TYPES OF IMMUNITY G) BLOOD GROUPS and THE RHESUS FACTOR H) ANTIBIOTICS
    • • A person’s blood type is determined by antigens found on surface of red blood cells Blood Groups
    • • the most important systems include the:  ABO  Rh (rhesus)  MNS Kell Lewis Duffy Kidd More than 30 Blood Grouping Systems in syllabusin syllabus
    • ABO system  ABO blood types = Types A, B, AB and O  Rh factor = Rh positive and Rh negative  the immune system:  is tolerant of its own RBC antigens  makes antibodies that bind to those that differ BUT
    • Antigens [agglutinogens]: are glycoproteins or glycolipids ABO system Antibodies [agglutinins]: specific against blood group antigen A- antigen b- antibody
    • ABO System: four types of blood groups
    • Antigen (agglutinogen) on RBC membrane Agglutinin (antibody) in plasma Blood group A b A B a B AB nil AB nil ab O
    • 45% 40% 11% 4%
    • UNIVERSAL DONORS -blood group O persons -can donate blood to anybody
    • UNIVERSAL RECIPIENTS -blood group AB persons -can receive blood from anybody
    • Blood Transfusion In a transfusion, blood MUSTIn a transfusion, blood MUST be compatible.be compatible. WHY? Otherwise, an antigen- antibody reaction occurs.
    • Donor’s antigens match Recipient’s antibodies Agglutination For blood to agglutinate: A a
    • Recipient Donor O a+b A b B a AB o O a+b - - - - A b + - + - B a + + - - AB o + + + - Key - no agglutination + agglutination Donor (no antigen) Recipient NO Agglutination a b
    • Recipient Donor O a+b A b B a AB o O a+b - - - - A b + - + - B a + + - - AB o + + + - Key - no agglutination + agglutination Donor Recipient Agglutination A a b
    • Recipient Donor O a+b A b B a AB o O a+b - - - - A b + - + - B a + + - - AB o + + + - Key - no agglutination + agglutination Donor Recipient NO Agglutination b A
    • Recipient Donor O a+b A b B a AB o O a+b - - - - A b + - + - B a + + - - AB o + + + - Key - no agglutination + agglutination Donor Recipient Agglutination A a
    • Recipient Donor O a+b A b B a AB o O a+b - - - - A b + - + - B a + + - - AB o + + + - Key - no agglutination + agglutination Donor Recipient (no antibody) NO Agglutination
    • The Rhesus (Rh) Factor Rh+ 85% of the total population: 15% of the total population: Rh- [Rh antigens absent] [Rh antigens present: agglutinogen D])
    • Why called ‘Rhesus factor? The Rhesus factor gets its name from its having first been detected in the blood of the rhesus monkey
    • Rh Dangers During PregnancyRh Dangers During Pregnancy Rh- mother with a Rh+ foetus
    • What is the probability of a child to be Rh+ ? i) Father is rhesus positive (heterozygous) and mother rhesus negative? Rhesus negative: Rh- Rh- Rhesus positive: Rh+ Rh- Parents: Rh+ Rh- X Rh- Rh- Gametes: Rh+ Rh- X Rh- F1 genotype: Rh+ Rh- Rh- Rh- 50%
    • What is the probability of a child to be Rh+ ? ii) Father is rhesus positive (homozygous) and mother rhesus negative? Rhesus negative: Rh- Rh- Rhesus positive: Rh+ Rh+ Parents: Rh+ Rh+ X Rh- Rh- Gametes: Rh+ X Rh- F1 genotype: Rh+ Rh- 100%
    • Rh Dangers During PregnancyRh Dangers During Pregnancy Mother’s blood Foetus’s blood Risk Positive Positive  Positive Negative  Negative Negative  Negative Positive First child  All other children 
    • Can RBC from foetus cross theCan RBC from foetus cross the placenta?placenta? These RBC stimulate antibody production in mother……. YESYES
    • After Protection with anti-DAfter Protection with anti-D Lymphocytes cannot ‘see’ RBC from foetus Anti-D (antibody against rhesus antigen)
    • Rh Dangers During PregnancyRh Dangers During Pregnancy Rh- woman with Rh+ foetus Cells from Rh+ foetus enter mother Woman produces antibodies against Rh+ cells In the next Rh+ pregnancy, antibodies attack foetal RBC How Rh sensitization occurs
    • A Rhesus Baby is usually:  premature  anaemic  jaundiced Haemolytic disease of the newborn Blood of such a baby needs to be completely replaced by a transfusion of healthy blood.
    • Surface antigens Haemolytic disease
    • Surface antigens Opposing antibodies+ + Haemolytic disease
    • Surface antigens Opposing antibodies+ + Agglutination (clumping) Haemolytic disease
    • Surface antigens Opposing antibodies+ + Agglutination (clumping) and haemolysis Haemolytic disease
    • OVERVIEW A) DEFENCE AGAINST MICROBIAL INVASION B) FOUR FEATURES OF THE IMMUNE SYSTEM C) HUMORAL IMMUNITY D) CELL-MEDIATED IMMUNITY E) DISORDERS OF THE IMMUNE SYSTEM F) TYPES OF IMMUNITY G) BLOOD GROUPS and THE RHESUS FACTOR H) ANTIBIOTICS
    • Antibiotics: • compounds produced by a microbe • inhibit the growth of other microbes Sir Alexander Fleming (1955) Penicillium
    • Antibiotics can harm the body Weaken the immune system as they suppress the body’s natural defence system Destroy the beneficial flora in the gut
    • Antibiotics are effective against: BUT NOT EFFECTIVEBUT NOT EFFECTIVE AGAINST:AGAINST: VirusesViruses Bacteria Some fungi Bacteria Some fungi
    • Use your knowledge of biological processes to comment on the following scenario: Medical practitioners sometimes prescribe antibiotics when a person is affected by a viral cold. [MAY, 2003] Antibiotics deal with secondary infections (opportunistic infections) - infections that occur because of a weakened immune system.
    • Question: [MAY, 2003] Use your knowledge of biological processes to comment on the following scenario: Medical authorities often recommend that prescription of antibiotics should be carried out sparingly. Bacteria have high reproductive rates and short generation time Antibiotics effective against normal bacteria Emergence of mutant forms resistant to antibiotics Selection pressure through antibiotic use favours rapid increase in numbers of resistant forms Emergence of disease forms with no cure [5 marks]
    • Antibiotics are not equally effective against all bacteria: An antibiotic will affect only those bacteria which have a particular property in common
    • e.g. penicillin - kills only Gram positive bacteria WHY?WHY? Inhibits formation of peptidoglycan walls. G+ bacteria have a thick peptidoglycan wall. Inhibits formation of peptidoglycan walls. G+ bacteria have a thick peptidoglycan wall. Gram positiveGram positive Gram negativeGram negative
    • BROAD SPECTRUM ANTIBIOTIC: Affect a wide range of microbes NARROW SPECTRUM ANTIBIOTICS: Affect a few species
    • Antibiotics can be: BACTERIOSTATICBACTERIOSTATIC inhibit the growth and multiplication of microbes BACTERIOSTATICBACTERIOSTATIC inhibit the growth and multiplication of microbes BACTERICIDALBACTERICIDAL kill microbes, like penicillin BACTERICIDALBACTERICIDAL kill microbes, like penicillin
    • THE END