5. Adaptive immunity Flashcards
What activates the adaptive immune response?
Antigen presenting cells which capture, process and present pathogen/tumour antigen to T cells.
Where are APCs usually located in the body?
Strategically located at pathogenic portals of entry:
- skin (SALT)
- mucosal membranes (GALT, NALT, BALT, GUALT)
- lymphoid organs (lymph nodes, spleen) - better organised to maximise interaction between APCs and B/T cells
- blood (plasmacytoid and myeloid DCs)
Name the 2 processes by which APCs capture pathogens.
- phagocytosis
2. macropinocytosis (soluble particles)
Which type of AI will be stimulated by APC recognition of extracellular vs intracellular pathogens?
Extracellular path. recognition stimulates humoral immunity:
- antibodies
- complement
- phagocytosis
Intracellular path. recognition stimulates cell-dependent immunity:
- cytotoxic T lymphocytes
- antibodies
- macrophages
Which APC type present to naïve T cells and where are these found?
- dendritic cells (mucous membranes, lymph nodes, blood)
2. Langerhans’ cells (skin epithelium)
Which APC type present to effector T cells and where are these found?
- macrophages (various tissues)
2. B cells (lymphoid tissues)
Why do macrophages present Ag to effector T cells?
required for proper phagocytosis
Why do B cells present Ag to effector T cells?
required for antibody production
Which cell surface molecule presents processed Ag to T cells?
MHC molecules - via peptide binding cleft
What are the 3 differences between Class I and Class II MHC molecules?
Class I
- found on all nucleated cells (inc. APCs)
- present peptides from intracellular pathogens
- recognised by CD8+ T cells
Class II
- found on DCs, macrophages and B cells (i.e. APCs)
- present peptides from extracellular pathogens
- recognised by CD4+ T cells
Name the chromosome and genes encoding MHC molecules.
HLA (Human Leukocyte Antigen) genes on chromo. 6:
- Class I = HLA-A, HLA-B and HLA-C
- Class II = HLA-DR, HLA-DQ and HLA-DP
Which 2 processes enhance MHC molecule diversity?
- co-dominant expression: both parental genes are expressed, increasing no. of different MHC molecules
- polymorphic genes: different alleles in different individuals - increases presentation of different Ag in a pop.
What are the 2 different antigen processing pathways?
- endogenous (all cells)
2. exogenous (APCs)
Describe the endogenous Ag processing pathway.
i) all viral/tumour Ag and self-Ag are tagged by ubiquitin and degraded by immunoproteasome
ii) peptides transported into ER via TAP1 & 2 (Transporter associated with Antigen Processing) and loaded onto matching MHC-I molecule
iii) MHC-I-Ag complex transported to membrane via vesicle and activates CD8+ T cell
Describe the exogenous Ag processing pathway.
i) exogenous Ag engulfed into vesicle and degraded by endolysosomal enzymes into peptides
ii) endosome fuses with exocytic vesicle which already contains MHC-II molecules and peptides bind to appropriate MHC-II groove by displacing CLIP
iii) MHC-II-Ag complex transported to membrane and activates CD4+ T cell
Why do T cells not respond to self-Ag?
trained not to react during development
What is the difference between elite controller and rapid progressor HIV patients?
Elite controllers/long-term non-progressors: possess HLA genes encoding MHC molecules that present peptides key for virus survival (cannot be mutated)… effective CTL response… normal CD4 T cell count and low viral load
Rapid progressors: low diversity in HLA genes and encode MHC molecules that present less critical peptides that can be mutated… poor T cell recognition… poor CTL response
What causes graft vs host reaction?
HLA molecule mismatch between donor and recipient… organ transplant reaction
Name 2 autoimmune diseases associated with HLA type.
- insulin-dependent diabetes mellitus
2. ankylosing spondylitis
Where do T cells mature?
thymus
What is the Ag receptor on T cells and how is diversity in this generated?
T cell receptor - recognises MHC-Ag complex
via gene rearrangement
Which co-receptors are required by T cells for MHC recognition?
CD3: involved in signal transduction (all T cells)
CD4: MHC-II recognition/signal transduction (TH cells and Treg cells)
CD8: MHC-I recognition/signal transduction (CTLs)
Describe the activation of CD4+ TH cells by APCs.
i) MHC-Ag complex on APC recognised by TCR and CD4 on naïve TH cell (TH0)
ii) TH cell matures, enhancing activation, but full activation also requires co-stimulatory signals:
- interaction between CD80/86 on APC and CD28 on TH cell
- cytokine release from APC
Which 2 cell types can TH0 give rise to according to pathogen type?
- TH2 or TH17 if extracellular path.
- TH1 if intracellular path.
Which T cells will be activated in response to extracellular paths.? How will these act?
APC activates CD4+ TH2 cells and CD4+ TH17 cells.
TH2 acts to:
1) activate eosinophils via IL-5 release… killing of parasites
2) activate B cells via IL-4 release… B cells undergo isotype switching… produce Ab… phagocytosis and complement
3) activate mast cells via IL-4 release… local inflammation and allergies (IgE)
TH17 cells release IL-17… activates neutrophils… phagocytosis
Which T cells will be activated in response to intracellular paths.? How will these act?
APC activates CD4 TH1 cells and CD8 cells.
TH1 acts to:
1) activate B cells via IFNy… B cells undergo isotype switching… produce IgG2-3… pathogen opsonisation, etc.
2) activate macrophages via IFNy… phagocytic activities… kill opsonised paths.
3) completes activation of CD8 CTLs
Activated CD8+ cell matures into CTL… binds via TCR to MHC-I-Ag on infected cells (so no bystander effect)… releases perforin - creates pores in infected cell membrane, and granzymes - enter infected cell and activate apoptosis.
What is the role of the different Ab?
IgM: complement activation
IgG:
- Fc-dependent phagocytosis
- complement activation
- toxin/virus neutralisation
- neonatal immunity (placental transfer)
IgA:
- mucosal immunity
- breast milk
IgE:
- immunity against helminths
- mast cell degranulation (allergies)
A high IgG:IgM indicates what kind of Ab response?
secondary resp.
What is the difference between the primary and secondary Ab resp.?
Primary
- 1st exposure to Ag
- rapid IgM production - less specific
Secondary
- subsequent exposure
- faster and longer
- stronger due to higher Ig affinity caused by isotype switching to IgG
