Adaptive immunity Flashcards
Humoral immunity…
Defence against extracellular bacteria and secondary viral infections.
AB binds to BCR on B lymphocytes and turns them into plasma cells which produce soluble AB.
Antibodies
Unique Y-shape
Label materials to kill
Describe the basic Ab structure
Soluble glycoproteins - Immunoglobulins.
Fab
Fc
Hinge
How does structure of the AB reflects its dual role?
AG recognition:
Fab regions (variable in sequence) bind different AGs.
AG elimination:
Fc region - constant in sequence. Bind to complement proteins, FcR on phagocytes and NK cells.
The constant regions are
Same for ABs of a given H chain class or L chain type.
The variable and constant regions encoded…
By separate exons.
What brings about the high diversity in Abs?
Multiple variable region exons in the genome -> RECOMBINE and MUTATE during B cell differentiation -> different AB specificities.
What are the five classes of Immunoglobulins?
M
A
D
G
E
IgG
Main class in serum and tissues.
Important in secondary/memory responses.
It can cross the placenta.
IgM
Important in primary response.
IgA
In serum and in secretions - protection of mucosal surfaces.
IgD
Unknown
IgE
Present at very low levels - involved in allergy and response to parasitic infections.
What are the two light chain types?
Kappa or lambda.
Are the light chain types class restricted?
No - it can either be IgG-kappa or IgG-lambda.
In primary response
IgM and IgG.
In secondary response
IgM and much higher IgG.
Can also include IgA and IgE.
How ABs protect against infection?
Specific binding/Multivalency (Fab):
Neutralise (toxins) IgG;IgA
Immobilise motile microbes IgM
Prevent binding to and infection of host cells.
Form complexes.
Enhance innate mechanisms (Fc)
Activate complement (IgG;IgM)
Bind to FcR:
Phagoctytes (IgG;IgA) enhance
Mast cells (IgE) release inflamm. mediators
NK cells (IgG) enhance killing of infected cells.
ABs can be used in research, diagnostics and therapy
Identify and label molecules in complexes.
Serotype pathogens.
Identify cell types
Humanised AB in therapy.
Her-2 Breast CA -> Herceptin
Cell-mediated immunity
T-cell in thymus
Bind to AG via TCR -> produce CKs; specifically kill infected host cells.
What are the major subpopulations of T-cells?
T helpers (CD4 +ve)
- Help B cells make AB
- Activate macrophages and NK cells
- Help development of Tcytotoxic
T cytotoxic (CD8 +ve)
- Recognise and kill infected host cells.
T regulatory cells (CD4 +ve)
Suppress immune response
TCRs
2 alpha and 2 beta chains.
Multiple V region exons in the genome which recombine during T cell differentiation and give different specificities.
How do T cells recognise AGs?
Via MHC molecules.
What is the MHC?
On Cr. 6
Important in graft rejection
HLA-A, HLA-B, HLA-C
Most polymorphic proteins in man. (1400 alleles of HLA-B locus)
MCH I
HLA-A, HLA-B, HLA-C
On all nucleated cells
AG to CD8 +ve (cytotoxic) T cells
MHC II
HLA-DR, HLA-DP, HLA-DQ
On macrophages, dendritic cells and B cells.
AG to CD4 +ve (helper) T cells.
TCR and MHC I
Cytotoxic T cell recognises peptide bound to MHC I.
Virus-infected cell (viral proteins broken down in cytosol - peptides to ER and bind to MHC I - expressed on surface).
Activated T cells induce apoptosis.
TCR and MHC II
T helper cells recognise this.
Macrophage/dendritic cell/B cell internalise and break down foreign material.
Peptides bind to MHC II in endosome -> cell surface.
Helps B cells make Ab, produce CK that activate/regulate other leucocytes.
What are cytokines?
Small secreted proteins involved in communication between the cells of the immune system.
Produced and act locally.
Bind to cytokine receptors on target cells.
What are the main groups of CKs?
ILs - usually made by T cells
IFNs viral infection alpha and beta, cells activation gamma
Chemokines - cell movement or chemotaxis.
CSF - leukocyte production
IL-1
Source: macrophages, endothelial and epithelial cells..
Induces inflammation, fever and activation of leukocytes.
IL-2
T cells
Stimulates T, B and NK cell growth.
IL-4
TH2 cells and mast cells.
Induces IgE prod.
Promotes Th2 differentiation
IL-8
Macrophages, endothelium, fibroblasts, keratinocytes
Induces neutrophil chemotaxis
IL-10
Monocytes, Th2 Cells
Downregulates Th1 cytokines, MHC II expression
IFN gamma
Th1 cells and NK cells
Activates macrophages and NK cells, increases MCH II expression
TNF alpha
T cells, macrophages and NK cells
Activates neutrophils, endothelial cells, induces cachexia=wasting
Th1 subset produces what?
IL-2, IFN gamma and TNF beta.
Activate macrophages -> inflammation.
Promotes production of cytotoxic T cells.
Induce B cells to make IgG.
Important in intracellular infections.
Th2 subset produces what?
IL-4, -5,-6,-10,-13 activate eosinophils and mast cells.
Induce B cells to make IgE - promotes release of inflammatory mediators (histamine)
Important in helminth infections and allergy.
Tregs produce what?
IL-10, TFG beta - downregulate other T cells subsets
The hygiene hypothesis
Insufficient exposure to certain types of infection (dirt) skews TH1/TH2 balance towards TH2?
But -ve correlation between helminth infections and allergic disease.
Counter regulation hypothesis
Infection protects against allergy by promoting IL-10 and TFG-beta production (upregulates Treg, downregulates TH1 and TH2)
Activation of adaptive immunity in the draining lymph node
Bacterium picked up by macrophages and dendritic cells.
Lymph drain from the infected tissue via afferent lymphatic vessels.
Afferent artery brings blood with naive T cells. Follicular dendritic cells activate T cells.
Plasma cells produce AB.
Efferent vessels carry ABs and effector T cells.
What are the two main lineages of haemtopoiesis?
Myeloid and lymphoid cells.
