ADAPTIVE IMMUNE RESPONSE

types of adaptive immunity

• cell-mediated immunity

• humoral immunity

characteristics of adaptive immunity (4)

• specific

• acquired/ learned

• requires lymphocytes therefore has a memory

• quicker response on second encounter

types of adaptive immunity

• cell-mediated immunity

• humoral immunity

characteristics of adaptive immunity (4)

• specific

• acquired/ learned

• requires lymphocytes therefore has a memory

• quicker response on second encounter

what is adaptive immunity made up of (2)

• cells: T cells - generally target intracellular microbes

• soluble factors/ humoral: B cells - generally targets extracellular microbes

why do we need adaptive immunity (3)

• microbes can evade innate immunity

• intracellular viruses and bacteria ‘hide’ from innate immunity

• need ‘memory’ to specific antigens so response is faster, become sick less often, more likely to survive

the adaptive players

• MALT = Mucosal Associated Lymphoid Tissue

• T cells mature in thymus

• B cells mature in bone marrow

lymphoid tissues of the body

cell-mediated immunity

interplay between:

• infected cells

OR

• APC (macrophages, dendritic cells, B cells)

AND

• T cells

what does cell-mediated immunity require (4)

• intimate cell to cell contact:

to directly recognise and kill infected cells

to control antibody responses via contact w B cells

• Major Histocompatibility Complex (MHC) - everyone has different MHC

• intrinsic/ endogenous/ intracellular antigens

• extrinsic/ exogenous/ extracellular antigens

antigen presentation: dendritic cells and macrophages

dendritic cells:

• phagocytose a non-self organism

• migrate to lymph nodes and present Ag to T cells

macrophages:

• phagocytose a non-self organism

• present Ag at site of infection

T cells: before and after activation

• before activation: naive T cell

• after activation: activated T cell

T Cell Receptor (TCR) structure

• structure is similar to F Igs

• made up of two polypeptide chains (heterodimer)

T cells: T cells that recognise self

• T cells that recognise self are killed in the foetal thymus as they mature during development

i.e. T cell selection

T cells: what do they respond to?

• do NOT respond to soluble antigens, only to antigens presented by MHC

• T cell receptor (TCR) recognises foreign antigens only when in associated w MHC

Major Histocompatibility Complex (MHC)

• MHC display peptides from self or non-self proteins

• in humans MHC molecules (glycoproteins) are coded for by Human Leukocyte Antigen (HLA) genes

Major Histocompatibility Complex (MHC): classes

• MHC I - encoded by HLA (A, B, C genes)

glycoproteins on ALL nucleated cells (not erythrocytes) will express MHC class I

• MHC II - encoded by HLA (DP, DQ, DR genes)

glycoproteins ONLY on APC will express MHC class II

• MHC III genes encode complement proteins

MHC class I and II structure

• class I: display peptides w 8-10 aa

• class I: a heavy chain (alpha 1, 2, 3 domains) and a light chain (beta m)

• class II: display peptides w 13-24 aa

• class II: alpha polypeptide chain and beta polypeptide chain

what is the link between innate and adaptive immunity

antigen presentation via MHC

T cell Ag recognition and activation process (5)

• T cell receptor (TCR) recognises antigen displayed by MHC

• co-stimulatory molecules CD28 on T cell must bind to CD80/ CD86 on APC

• IL-2 secreted by T cell and binds to IL-2R on T cell (autocrine mechanism)

• causes T cell to undergo clonal expansion (cell division)

• also causes T cells to differentiate into effector T cells (Tc, Th, Treg) and memory T cells

functional T cells differentiate into?

• IL-12 high levels = Th1 pathway

• IL-2 low levels = Th2 pathway (helps B cells make antibodies)

cytotoxic T cell (CD8) activation (6)

• APC presents INTRINSIC antigen on MHC class I which binds to naive CD8 T cell

• naive CD8 T cell is activated and differentiates into cytotoxic effector T cell (CTL)

• CTL releases perforins and granulysin - kills infected cell directly w intracellular pathogen

• perforins: form pores in cholesterol-containing cell membranes, initiates cell death via direct lysis and apoptosis

• granulysin: damages cholesterol-poor cell membranes

• CTL secretes IFNγ which activates macrophages

• CTL secretes cytokines which attract more immune cells

• memory CD8 T cells are formed

T helper cell (Th1) (CD4) activation (7)

• phagocytosis of pathogen occurs

• APC presents EXTRINSIC antigen via MHC class II to a naive CD4 T cell

• APC secretes IL-12 which activate naive CD4 T cells to differentiate into Th1 cells

• activated CD4 Th1 cells proliferate (clonal expansion)

• Th1 recognises Ag on infected cells with MHC class II via TCR

• Th1 secretes IFNγ which stops virus spread and increases macrophage activity

• memory T cells are formed

B cells

• B cells express membrane bound Ig (IgM or IgD monomer)

• each B cell can only make one Ab that will only bind to one epitope on one antigen

humoral adaptive immunity: B cell activation (5)

• B cells bind to appropriate Ag and become activated

• activated B cells go to lymph nodes where they proliferate via clonal expansion and differentiate into plasma cells

• plasma cells secrete Ab of same specificity - generally IgM which layer turn into IgG WITH THE SAME Ag SPECIFICITY

• some B cells form memory B cells that last for many years

• re-stimulation of memory B cells leads to a very quick secondary response

B cells: B cells that recognise self

• B cells that recognise self are killed in the bone marrow during foetal development i.e. B cell selection

• we are born w > 10⁹ immature B cells

B cells: antigen presentation (MHC class II)

• B cells present EXTRINSIC Ag to T cells via MHC II (only on APC)

  —

• mIgM or MIgD (Abs) binds Ag

• phagocytosis occurs and the peptide is displayed on B cell surface with MHC II

• T cell receptor of naive Th1 (CD4) binds to MHC II/ peptide surface

• several other co-stimulatory molecules required

how T cells help B cells (7)

• pathogen taken up by APC (macrophage/ dendritic cell) and presented with MHC class II

• naive CD4 T cells bind to EXTRINSIC antigen on APC

• these turn into primed Th2 cells

• Th2 cells bind to B cells presenting the same antigen via MHC class II

• Th2 cell secretes cytokines (IL-4, IL-5, IL-10, IL-13)

• these cause B cell clonal expansion (division)

• B cells differentiate into plasma cells (AFC) and memory B cells (Bm)

actions of antibodies (4)

• binds to microbes and prevent them from binding to and entering cells

• neutralise toxin/ enzymes by binding to the active site

• opsonisation - increases phagocytosis

• activate complement

LINK BETWEEN INNATE AND ADAPTIVE IMMUNITY

adaptive immunity summary diagram

switching OFF the immune response

• when T cells need to be stopped PD-1 will be expressed on cell surface

• when PD-1 encounters and binds to PD-L1 receptor (on APC and other lymphocytes) it tells the T cell to turn ‘off’, inhibiting it from killing other cells

how do some tumour cells avoid being killed by T cells

some tumour cells have PD-L1 on its surface which help it evade being killed by T cells

vaccination: tetanus vaccine (example)

• tetanus toxoid from Clostridium tetani causes muscle contractions/ spasms - interference w neurons

can cause lock jaw

• vaccine: treat purified toxoid in lab w formalin which removes toxicity but maintains epitopes

primary immune response still occurs meaning secondary will be faster

vaccination: principle and diagram