MIIM20001 - immunity

Nota:

• -molecule recognised by immune system 

1. dendritic cells

   Nota:

   • - antigen presenting cells > recognise PAMPs via TLR. - MHC I & II expressed - immature forms phagocytic
2. macrophages

   Nota:

   • - present antigen to T cells - highly motile - remove apoptotic/ dead cells/ waste - secrete TNF-a > helps regulate inflammatory response
   1. Phagocytosis

      Nota:

      • - receptors that recognise opsinins which increases adherence of pathogen to phagocytic cell surface - ingested material to lysosome
      1. Danger

         Nota:

         • - NK cells respond to changes in expression of self proteins. - MHC I good recognition
      2. Stranger

         Nota:

         • - recognition of novel microbial structure (PAMPs) - via pattern recognition molecules > mannose receptors > RNA helicases (notice viral RNA structures) - Tol like receptors (TLRs) > TLR4 (LPS - gram negative bacteria) >TLR2 (peptidoglycan - gram positive) >TLR5 (Flagellin)
3. NK cells

   Nota:

   • - important in anti-viral response - directly lyse cells - secrete anti-viral cytokines - activation by peptides
4. mast cells

   Nota:

   • - found only in tissues - 2 types > mucosal > connective tissue - important in response to helminthes
5. cytokines
   1. Interferons (IFN)

      Nota:

      • - blockage of transcription & translation in viral cells - upregulate MHC molecules > impact on adaptive immunity
   2. Chemokines

      Nota:

      • - regulate cell movement
   3. Interleukens (IL)

      Nota:

      • - change permeability of blood vessels
   4. Tumour necrosis factor (TNF)

      Nota:

      • - IL12 - favours strong cell mediated response (CTL & macrophage)
   5. transforming growth factor B

      Nota:

      • - promotes IgA production - IL4 --> igE (helminth immunity)

1. non self and self differentiation
   1. naive T cells

      Nota:

      • - never recognise antigen - need 2 signals for activation >TCR/MHC interaction > co-stimulation (CD28/CD80) - most bodily cells do not express CD80 - no costimulation = death - engagement of TLRs will induce CD80 expression of cell.
2. derived from bone marrow
   1. Primary lymphoid
3. 2 types
   1. humoral

      Nota:

      • - antibody mediated
      1. antibody mediated
         1. B cells

            Nota:

            • - Surface Ig recognition - bind directly to antigen - Bone marrow
            1. memory B cells
            2. plasma cells

               Nota:

               • - mature activated B cell
               1. secrete antibodies
                  1. antigen binding
                     1. epitopes

                        Nota:

                        • - denaturation results in loss of epitopes
                        1. conformational
                        2. linear
                  2. antibodies
                     1. neutralization

                        Nota:

                        • - blocks binding of pathogen to cell surface - causes disruption to conformational changes --> opsinization > changes to cell surface of pathogen increasing phagocytation 
                     2. complement lysis

                        Nota:

                        • - cells coated with antibody and c3b protein > increases binding and phagocytosis - antibody binds through multiple Fc regions. - C1 binds antibody --> produce inflammatory mediators and pore forming mediators
                     3. cellular toxicity (ADCC)

                        Nota:

                        • - NK cells kill cells coated by antibody - do NOT remove free antigen
            3. naive B cells
               1. Ig secretion
                  1. IgM

                     Nota:

                     • - Pentamer - J chain linkage - activate complement - high valency
                  2. IgG

                     Nota:

                     • - Major component of serum - major class in secondary response - bind to Fc receptors expressed by macrophages & monocytes & NK cells. - cross placental activation of compliment ability -
                  3. IgA

                     Nota:

                     • - monomer = surface - dimer = secreted > J chain - mucosal sites - transported across epithelial sites when it has secretory component
                  4. IgE

                     Nota:

                     • - lowest component of serum - actively secreted monomer - important in parasitic response - allergic reaction
               2. IgD

                  Nota:

                  • - low amounts in serum - monomer - structurally similar to IgG - doesn't cross placenta - no gene coding for secretion - secreted via cleavage from cell surface - receptor function - no activation of compliment 
   2. cellular
      1. T cell mediated
         1. cell-cell interaction
         2. T cell

            Nota:

            • -T - cell to T cell surface interaction - don't bind directly to antigen  - Thymus - CD8+/CD4+ - recognise antigen via TCR > unique receptor/ T cell > receptors bind to short linear peptides made via proteolysis > recognised by MHC
            1. MHC
               1. Class I

                  Nota:

                  • - expressed on all nucleated cells - once expressed they are killed by CTL - Bind peptides bound in cytoplasm and in ER lumen
               2. Class II

                  Nota:

                  • - expressed only on B cells or dendritic cells & macrophages - can stimulate T(H) cells. - peptides displayed generated in endosomal network.
            2. education

               Nota:

               • - T cells that survive process express TCR and have low affinity for self MHC molecules - TCR first expressed in thymus - two types of selection
               1. positive

                  Nota:

                  • - TCR has no capacity to bind any self MHC molecule = death
               2. negative

                  Nota:

                  • - TCR binds self MHC too tightly = cell death
            3. Effector
               1. Helper T cells

                  Nota:

                  • - CD4+ - help CTL B cells & macrophages - good motility e.g. survey skin
                  1. Th1

                     Nota:

                     • - cell mediated immunity
                  2. Th2

                     Nota:

                     • - antibody mediated
                  3. Th17

                     Nota:

                     • - inflamation/ autoimmunity
                  4. Treg

                     Nota:

                     • - tolerance
               2. Cytotoxic T Lymphocytes (CTL)

                  Nota:

                  • - CD8+ - kill in response to effected cells - restricted to tissue with initial infection 
               3. NK cells (NKT)

                  Nota:

                  • - don't recognise antigens - activation by glycolipids
            4. memory

1. viral

   Nota:

   • - never Th2 - IFNg and IL12 and IL18 = Th1 (IL2 & IFNg --> strong cell mediated response)
   1. virons

      Nota:

      • - attack via innate factors and antibodies
   2. infected cells

      Nota:

      • - attack via interferons > affect replication life cycle- attack via NK/T cells > lyse infected cells (CD8 secrete cytokines IFNg) - activate macrophages (CD4 IFNg) > helps CD8 cells > helps B cells (class switching)
   3. Virus specific antibodies

      Nota:

      • - neautralise virus - fix complement - enhance phagocytosis via opsinisation - facilitate ADCC
2. bacterial
   1. innate

      Nota:

      • - activation of complement - phagocytosis - activation of phagocytic cells > these secrete cytokines and inflammatory mediators - kill microbes and normal tissue
   2. adaptive

      Nota:

      • - CD4 T cell releases IFNg = Th1 (IL2 & IFNg) - innate cells with IFNg --> cell mediated - innate cells with IL4 = Th2 which is antibody mediated
3. helminthes

   Nota:

   • - never Th1 - release of IL4 by innate cells = Th2 which releases IL4, IL5, and IL6 = class switching to IgE which is a strong antibody mediated response