aos3 - immunity

• What is the humoral adaptive response?

  A type of immune response that involves B cells and antibodies
• What do APCs display to T helper cells during the humoral adaptive response?

  Antigens
• What is the role of cytokines in the humoral adaptive response?

  Cytokines activate B cells
• What are the two types of cells that B cells differentiate into?

  1. Plasma cells

  • Produce specific antibodies (short-lived)

  1. Memory B cells

  • Provide immunological memory (long-lived) → faster + greater response upon re-exposure
• humoral adaptive immune response

  1. Initiation - APCs engulf pathogen + present antigen on MHC2 markers → lymph nodes
  2. Clonal selection - antigen of pathogen bind to naive B cell w complementary antibodies on surface + APC display antigen to T helper cells → release cytokines to activate B cell
  3. Clonal expansion - B cell reproduces via mitosis
  4. Differentiation - B cell → plasma + memory B cells
• cell-mediated adaptive immune response

  1. Initiation - APCs engulf pathogen + present antigen on MHC2 markers → lymph nodes
  2. Clonal selection - APC bind to naive T + T helper cells w complementary receptor to antigen + T helper cells release cytokines → activate selected T cells
  3. Clonal expansion - selected T cells proliferate
  4. Differentiation - T cell → cytotoxic + memory T cells
• what are the 2 types of cells that naive T cells proliferate into?

  1. Memory T cells

  • Provide immunological memory (long-lived) → faster + greater response upon re-exposure

  1. Cytotoxic T cells

  • when activated, bind to MHC1 on infected cells → secretes perforin + granzymes → induce apoptosis
• similarities and differences between humoral and cell-mediated response

  part of adaptive immune system, involve T helper cells + cytokines, specific

  humoral: B cells, antibodies, extracellular pathogen

  cell-mediated: T cells, induces apoptosis, intracellular pathogen
• cellular components on innate immune system

  • phagocytes: destroy extracellular pathogen
  • neutrophil - blood, 1st responder
  • macrophages - tissue, APC → release cytokines
  • dendritic cells - tissue, APC → bridge b/w innate + adaptive
  • natural killer: destroy intracellular pathogen → apoptosis - recognise missing/ abnormal MHC1
  • mast cells: release histamine → attract phagocytes
  • eosinophils: granules with toxic chem + histamine → pathogens too big for phagocytes
• non-cellular components of innate immune system

  • interferons: type of cytokine
  • bind to receptor on neighbouring UNINFECTED cells → prevent spread
  • signal neighbouring INFECTED cells → undergo apoptosis
  • activates immune cells (phagocytes)interferons: type of cytokine
  • complement proteins: blood, destory EXTRACELLULAR pathogen via lysis → complement cascade (COLA)
• outcomes of complement cascade

  COLA

  • CHEMOTAXIS - gather near pathogens + attract phagocytes
  • OPSONISATION - bind to pathogen surface → easier for phagocytes to recognise as foreign
  • LYSIS - join together on pathogen surface + forms MEMBRANE ATTACK COMPLEX (MAC) → creates pores → ↑ fluid = lysis
  • AGGLUTINATION - bind pathogens together in same area using antibodies → immune cells attack
• inflammatory response

  inflammatory response: innate response to pathogenic infection (↑ blood flow to infected area)

  1. INITIATION - 1st line surpassed + pathogens enter body, damaged cells release cytokines → signal to mast cells which release histamine
  2. VASODILATION - blood vessels widen + ↑ blood flow = redness + heat = ↑ permeability → swelling
  3. MIGRATION - ↑ signals + permeability → phagocytes (neutrophils, macrophages) → travel to infection site → phagocytosis
• 1st LOD in animals

  physical:

  • intact skin - prevent entry
  • mucous membrane - trap pathogens → expelled

  chemical:

  • lysozyme (sweat, mucus, tears, saliva) - breaks down pathogen
  • stomach acid + digestive enzymes - kills pathogen
  • sebum secreted by skin - protective + anti-microbial film

  microbiological:

  • natural flora - non-pathogenic bacteria → gut, mouth, throat, genital tract
• 1st LOD in plants

  physical: 

  • waxy cuticle - traps pathogen 
  • intact bark - prevents entry
  • stomata - close to prevent entry
  • cellulose cell wall - prevent entry of pathogen 
  • thorns + spikes - protect from grazing animals

  chemical: 

  • secretion of toxin or odour - harmful or unfavourable to pathogens 
  • enzymes - affect pathogen functioning 
  • antimicrobial proteins + enzymes
• phagocytosis


  1. pathogen engulfed by phagocyte in vesicle (phagosome)
  2. lysosomes fuse with phagosome → phagolysosome
  3. lysosome contains lysozyme - digests + destroys pathogen
  4. indigestible material discharged from phagocyte via exocytosis
• antigen


  antigen: molecule presented on surface of plasma membrane → stimulate immune response

  • analogy: antigens = name tag for pathogen → announce presence to immune system
• types of antigens


  self antigens: molecule on surface of own cell

  • self-marker: self antigen → immune system recognises as ‘self’ = doesn't stimulate immune response

  non-self antigens: molecule on plasma membrane → immune system recognises as foreign

  • transplanted cells/organs: contain non-self antigens → lead to immune response = body reject
  • reduce incompatibility - give immunosuppressant drugs or organs from related ppl → ensure markers on transplanted cells as similar as possible to self-markers on recipient’s cells
• MHC markers


  MHC markers: type of receptor proteins present on surface of body cells → distinguish b/w self + non-self
• types of MHC markers

  MHC1: present on all cells

  • differentiate b/w healthy + infected cells (contains intracellular pathogens)
  • healthy cell: bind self-antigens onto MHC1 marker → recognises + leaves alone
  • infected cell: bind non-self antigen onto MHC1 marker → recognise as non-self + initiate an immune response

  MHC2: present on APCs (macrophages, dendritic cells, B cells, T helper cells)

  • APC engulfs pathogen, takes antigen + places onto MHC2 marker → stimulate immune response (T helper cells bind to MHC2 marker)
• pathogen


  disease-causing agent

  • cellular pathogens
  • non-cellular pathogens
• cellular pathogens

  cellular pathogens: living organisms + reproduce independently → extracellular pathogen, undergo cellular functions itself

  • bacteria - plasmid, prokaryote, nucleoid contains DNA, binary fission 
  • fungi - unicellular eukaryote, double stranded linear DNA 
• non-cellular pathogens

  non-cellular pathogens: non-living organisms + require host cell to replicate (intracellular pathogen)+ can't undergo cellular functions itself, not made up of cells

  e.g. virus

  • nucleic acid core (DNA/RNA)
  • can't function outside of host cell
  • replicates by injecting DNA into host cell + uses organelles/energy to transcribe genes
• allergen


  allergen: antigen that causes immune system to produce allergic reaction (hypersensitivity) 
• steps in allergic reaction

  IDENTIFY, IgE ANTIBODIES, PRIMED MAST CELLS, RECOGNISE, ACTIVATE

  1. allergens identified as non-self antigens + harmful
  2. B cells produce IgE antibodies 
  3. IgE antibodies bind to surface receptors of mast cells = primed mast cells
  4. when allergen next encountered - IgE antibodies on primed mast cells recognise allergen + binds
  5. this activates primed mast cells → degranulate + release histamine
  6. inflammation + swelling responses
• lymphatic system

  lymphatic system: acts as transport network (tissues + organs) → monitors for infection

  role:

  • APC recognition (clonal selection) → APC, B cells + T cells (lymphocytes)
  • transports APCs and lymphocytes to lymph nodes → stimulate adaptive immune response
  • production + maturation of B cells + T cells
• lymph nodes

  lymph nodes: small bean-shaped structures located along lymphatic vessels → key site of antigen presentation by macrophages + dendritic cells (if passes first and second line of defence)

  role:

  • where APCs go to present non-self antigens to T helper cellss
  • site of APCs and lymphocytes
  • stores memory cells (B cells and T cells)

  from lymph nodes, activated lymphocytes → enter general circulation in bloodstream to help fight infection
• antibodies

  antibody: antigen-binding proteins produced by B cells (humoral)

  • 2 heavy + 2 light chains → form Y-shaped molecule = quaternary structure
  • constant region: doesn't change b/w antibodies of same class
  • variable region: differs b/w antibodies → antigen-binding site
  • specific + complementary to antigen on pathogen
  • disulphide bridges between two arms → allows flexibility → binding sites form an antigen-antibody complex

  
• function of antibodies

  don't directly destroy pathogens - PIANO

  • Precipitation: bind to soluble antigens → make INSOLUBLE + precipitate = more visible
  • Inflammation: release HISTAMINE → inflammation + complement proteins = COMPLEMENT CASCADE
  • Agglutination: form ANTIGEN-ANTIBODY complexes → clump together = be more visible
  • Neutralisation: antibodies bind to antigens + neutralises it/its toxins (prevent antigen from binding to surface receptors)
  • Opsonisation: form ANTIGEN-ANTIBODY complexes → makes antigens more recognisable to PHAGOCYTES = engulf + destroy
• how are antigen-antibody complexes formed?

  antibody binds to antigen of pathogen
• immunological memory

  secondary response stronger than primary  

  • primary response = initial exposure to antigen: antibodies produced by naive B cells → longer to produce antibodies + levels drop bc plasma B cells die
  • secondary response = re-exposure: antibodies produced by memory B cells which differentiate into plasma B cells → memory B cells activated quicker = more antibodies produced quicker
• source of antibodies (active vs passive)


  active immunity: producing antibodies in response to exposure to particular antigen (long-term immunity → memory)

  passive immunity: receiving antibodies made in another organism (short-term immunity → external antibodies)
• means of gaining immunity


  forms of specific immunity

  natural immunity: antibodies obtained thru natural means (infection)

  artificial immunity: antibodies formed thru deliberate exposure + intervention (vaccination)
• active immunity

  ACTIVE: produced by organism

  
  

  natural active immunity: pathogen enters body naturally

  artificial active immunity: pathogen introduced deliberately (vaccination)

  
  

  advantages:

  • immunological memory → memory cells = faster, greater + more immediate response if re-infected by the same pathogen

  disadvantages:

  • takes longer to become effective
• passive immunity

  PASSIVE: antibodies introduced from external source

  natural: antibodies from mother → fetus (via placenta) ; antibodies from mother → baby (via breast milk) 

  artificial: antibodies is introduced deliberately via injection (antivenom or antiserum) 

   advantages:

  • immediate protection

  disadvantages:

  • injecting antibodies → allergic reactions when sourced from another organism 
  • injecting antibodies = expensive 
• disease

  disease: impairs normal functioning

  • non-infectious disease: can't be transmitted
  • infectious disease: caused by pathogenic agents + can be transmitted
  • emerging diseases: newly identified → may be caused by known variants, but produce new disease characteristics (eg. influenza strains)
  • re-emerging diseases: reappearance of known after a significant decline → once controlled but increased + significant health issues
  • deliberately emerging diseases: developed by man
• how do new diseases emerge

  • antigenic drift: antigens on surface of virus change → genetic mutations 
  • antigenic shift: in cell infected by 2 different viruses, genetic material mixed up → create new hybrid virus 
  • zoonosis: virus originate in other species + transmitted to humans 
• epidemic vs pandemic

  epidemic: widespread infectious disease in restricted geographical area at particular time 

  pandemic: worldwide geographical spread of infectious disease
• IMPACT OF EUROPEAN ARRIVAL ON INDIGENOUS PEOPLE

  • new diseases introduced: chicken pox, influenza, measles, etc
  •  Indigenous people isolated from rest of world → no exposure to diseases = no immunity
  • many susceptible + low herd immunity → spread of new infectious diseases + significant fatalities
  • no access to medical treatment
  • horses (used for travel) act as vectors
  • population reduced by 90% between 1788 to 1900, largely attributed to disease
• identifying viruses

  physical methods (based on size + shape)

  • x-ray crystallography: determines structure
  • electron microscopy: virus images with differing shapes

  immunological methods (based on antigens/antibodies)

  • ELISA test: indicates if organism been in contact with virus

  molecular methods (identify using DNA/RNA)

  • in-situ hybridisation: detect + locate genetic sequences characteristic of particular DNA viruses
  • reverse techniques: identify RNA viruses
  • whole genome sequencing: used to produce vaccine
• how does the ELISA test work?


  1. capturing antigens

  • specific antibodies for antigen bound to base of vial
  • add patient serum to vial → if target (viral) antigen, antigens bind to antibodies = antigen-antibody complex

  2. identifying success:

  • second antibody combined with indicator enzyme → add to vial + binds to antigen-antibody complex
  • add substrate for indicator enzyme
  • substrate converted to product → colour change = positive test