adaptive immune system

T cell mediated

• antigen is brought to lymphoid tissue by dendritic cells where it is processed and presented through the afferent lymphatic

• t cells enter lymphoid tissue via hev and examine the dendritic cells present in the paracortex

• t cells express tcr that can recognise foreign peptides displayed by MHC

• immunological synapse

MHC class i

• protein antigens in the cytoplasm are digested to peptide fragments

• these are transported int he ER where new MHC molecules are being synthsised

• the foreign peptides are loaded onto empty MHC class i then transported to the cell surface allowing recognition by CD8 t CELLS

• all nucleated cell express this

cd8 t vs cd8 4t

• only interact with mhc class i peptides

• detect intracellular infection

• cd4 with mhc class ii

• detect etracellular

what antigen receptors do T cells have

T cell receptors on T cell

surface immunoglobulin on B cell

MHC class ii pathway

• protein antigens in the extracellular fluid are eaten by specialist phagocytic cells

• lysosomes fuse with the phagosome releasing acid hydrolases that digest the protiens into peptide fragments

• new mhc class ii synthesied which travel via the golgi to meet with endocytic pathway and the foreign peptide fragments are loaded onto the empty MHC class ii molecules

  • so unlike class i the complexes are not formed inside of the ER

• mhc class ii peptide complexes then transported to the cell surface allowing recognition by CD4 t cells

• only APCs (dendritic, macrophages and B cells ) express class ii, these also express class i

T cell mediated

• naive t cells are in surveillance mode and visit difderent secondary lymphoid using blood to lymph node via HEV and efferent lymph for transportation

• if it recognises an antigen it stops circulating and starts to proliferate (clonal expansion)

• following a period of proliferation and further diferentiation most t cell clones leave the LN via the efferent lymph enter teh bloodstream and search for the infectious oganism

• change their cell surface homing molecules and start looking for sites of inflammation rather than lymphoid HEVs

CD8 Killer (Cytotoxic) T cells

• what do they do to the infected cell via what mechanism

• what 3 ways can this occur

• viral proteins in the cytoplasm of infected cells are processed via the MHC class i pathway and expressed on the cell surface marking the cell as infected

• MHC class I peptide complex can e recognised by a CD8 killer T cell which forces the infected cell to apoptose via the caspace cascade before replication is complete

• this can occur by

  • release of perforin and granzymes

  • stimulation of apoptosis via the Fas/Fas ligand interaction

  • production of cytotoxic cytokines eg tumour necrosis factor

CD4 helper t cells

when naive CD4 T cells are activatedfor the first tie in a LN they must decide what typeof T helper cell they become

can differentiate in th type 1 or th type 2 cells which have different function

stimulate B cells to secret e antibodies

• IgG systemic protection

• IgA mucosal

CD4 Th1 cells

• how do macrophages interact with these cells

• how do these effector t cells respond

• which type of infections is it important

• macrophages interact with th1 via MHC class ii presentation of antigen detected by TCR

• these effector T cells respond by secreting cytokines particularly IFN gamma that activated macrophages

• important in vesicular infections where pathogens deliberately infect macrophages

IFN gamma effects on macrophage function

• Stimulates the RESPIRATORY BURST.

Production of high levels of OXYGEN FREE RADICALS, NITRIC OXIDE & ANTI-MICROBIAL PROTEASES, resulting in an increased capacity for killing pathogens.

• Increased production and fusion of lysosomes with endosomes results in increased digestion of endogenous pathogens

CD4 th2 cells

• how do they interact with the TH2 cells

• how do the th2 effector cells respond

• what does this stimulate

• what influeces what type of antibody the b cell makes

interact with TH 2 cells via the MHC class ii peptide: TCR engagement

these effector t cells respond by secreting B cell growth factors particularly IL4

th2 cells timulate B cells to mature into plasma cells that begin to secrete antibodies

cytokines produced by the th2 cells inluence what type of antibody the b cell makes via class switching

B cell and antibody mediated immunity

• b cell expresses surface immunoglobulin

• upon recognition of antigen in secondary lymphoid tissues B cells become activated and start to proliferate

• then they differentiate into plasma cells

  • either remain in the lymph node moving locally to the medullary cords

  • leaev the lymph node to migrate to the bone marrow

• IgM is the first antibody produced which functions to neutralise viruses, agglutinate bacteria and is a potent trigger of the complement cascade upon binding to microbial antigen

• B cells also present antigen (MHC II peptide) to helper t cells which respond by secreting cytokines to stimulate further B cell differentiation via paracrine effect

• with T cell help B cells can class switch the type of antibody they produce and start secreting IgG instead of M

• further cytokine signals can modify this antibody response in favour of IgA or IgE

what is IgG

• what can it trigger

• what does it act as and what does it enhance

• how is it produced

• a potent virus neutralising antibody

• can trigger complement activation

• acts as an opsonin and can enhance phagocytosis of bacteria by macrophages and neutrophils that express Fc-gamma receptors

• produced after recieing Th2 cell help - class switching

what is IgA

• what is it produced byb

• function

• where can it be found

• produced by plasma cells in the MALT

• it is a dimer that is actively transported across mucosal epithelial surfaces and functions to bind to pathogens or toxins, preventing their harmful effects on epithelial cells

• thus it neutralises toxins and interferes with pathogens ability to attach and infect via the mucosal route

• important component of colosrum and milk for neonatal health

IgE

• when is it produced

• what happens to it

• how does this help the immune response

• produced during helminth parasite infections

• specifically adsorbed onto the surface of mast cells which express Fc- epsilon receptors

• coating their surface with IgE enables these cells to seek out and bind to parasites more effectively, triggering degranulation and histamine release

• however abnormal production of IgE to environmental antigens is often the cause of allergy

where do MHC class I vs II present peptides generated from antign in

• 1 is cytoplasm

• 2 is tissue fluid

regulatory t cells

• produce immunosuppressive cytokines such as IL 10

• ensure response is appropriate and minimise collateral damage to host cells

which part of the antigen binds to the antigen

• fragment antigen binding

• variable region

what does the constant region do

• fc

• biological effects

what are the basic functions of the antibody

• neutralisation - antibody prevents adherance

• opsonisation- antibody promotes phagocytosis

• complement activation- antibody activates complement which lyses bacteria

igg

igd

ige

iga

igm

immunoglobulin M

• first antibody produced in the immune response

• pentameter- binds 10 antigens at once

• agglutinin

• good at triggering the complement cascade

degranulation of mast cells

• mast cells have receptors for IgE

• when ige binds to the antigen this triggers degranulation of the mast cell

phases of antibody response

• LAG phase

  • first 5-7 days

• LOG phase

  • IgM more than IgG (7-14 days)

• PLATEAU

  • can last months or years

path of naive vs effector t cell

naive goes through the high endothelial venule to the lymph node

effector t cell goes through inflamed endothelium to infected tissues

how do killer t cells kill

• release perforins, granzymes, cytotoxic cytokine

• perforins create holes in the cell outer membeane

• granzymes cause a cascade leadin to apoptosis

dendritic cell migration

• PRR detect PAMPs

• they stop engulfing and upregulate MHC for antigen presentation

• enter the lymphatic vessels

which APC is used

• dendritic cell- naive T cell

• CD4 T helper t1 tend to use the macrophage as an APC as this allows cell to cell communication.

  • interferon gamma is produced to super activate the macrophage

• T helper type 2 tend to use B cells

  • produce cytokines to enable the B cell to class switch, IgM to IgG, then to others eg IgA if in MALT