Acquired Flashcards
Cells of lymphoid cycstem
T (CD4 and CD8)
B
NK
What is the process of formaiton of T cells
Produced in bone marrow
Migrate to Thymus where they mature
How do T cells mature?
Development of T cell receptor
- Cell surface bound protein structure that binds to antigen
TCR binding results in T cell activation and proliferation
TCR testing in thymus - if autoactive - rearrange TCR or undergo apoptosis (clonal deletion)
What can activate a T cell
MHC antigens
Antigen presenting cells
Antigen processing
What are MHC class I cells? What do they present to?
Expressed on all cells
Present to CD8+ T cells
What are MHC class II cells? What do they present to?
Expressed on selected cells such as APCs
Present to CD4+ T cells
What are MHC antigens called in uhmans?
HLA human leukocyte antigens
What do MHC class I cells do
Found on all cells and continuously present broken down peptides .
Constantly proving to the immune system that it is a healthy cell
If a cell becomes infected or a tumour it will start presenting foreign peptides on MHC I molecules stimulating CD8 cells to destroy it
What is cross presentation
Presentation of exogenous material on MHC I receptor
Occurs when APC takes up a cell that contains foreign antigen
Material broken down and presented on MHC II receptor but some debris peptide enters cytoplasm and this is presented on MHC I
CD8 activated and responds
MEchanism of graft rejection
What are MHC class II molecules?
Presented by specialised APCs which take up exogenous pathogens, phagocytose them and present peptide products.
MHC II molecule bind with peptide and travel to cells urface
Antigen/MHC presented to T lymphocytes
How does MHC maximise immunity?
Polygenic - several different MHC class I and II genes
Polymorphic - multiple variants of each gene increasing potential number of peptide combinations that can be presented
What is alloreactivity?
Recognition of non-self tissue from the same species as foreign
2 methods:
1. Recognition of foreign HLA molecule
2. Recognition of presented tissue derived peptide as pathogenic
What are APCs
Dendritic cells
- Myeloid - produce IL12
-Plasmycytoid produce IFN 1
MAcrophages
B cells
CD8 vs CD4 T cells
CD8 recognise MHS class I molecules presented antigens
CD4 recognise MHC class II presented antigens
What do CD8 T cell granules contain
Membrane disrupting proteins - perforin, granulysin
Serine proteases - granzymes
Lysosomal eznumes
Stored effector molecules - FasL - binds to Fas expressing cells to induce apoptosis
What in the role of CD4 cells?
Secreting cytokines to upregulate responses
What do Th1 cells secrete?
IFN - gamma
- Activates macrophages, enhancing antigen presentation to T cells, increasing phagocytosis
IL-12
Drive DC activation and presenation
Express CD40 stimulatory molecule - amplifies response
What do Th2 cells secrete
IL4, IL5 IL6
IL13
Stimulate antibody production and mucous secretion
What do Th17 cells secrete
IL17
What CD4 cells are involved in allergy and parasitic infections
Th2
What is IL 17
Potent neutrophil chemoattractant
What is a cytokine
Cell derived soluble mediator
What are anti inflammatory cytokines?
IL10
TGF beta
Downregulate CD4 cell responses
IL4 (antagonises IFN-ga)
What are functions of cytokines?
Cytotoxic - TNFa
Growth factors - IL4 for B cells
Synergistic to enhance response - IL1 enhances IL8
Clonally expanding cells - IL2 promotes expansion of activated CD4
Cell attractants/chemokines IL8 attracts neutrophils
What are effects of TNFa
Pro-inflammatory
Activate PolyMorphoNuclear leucoytes
Cytotoxic for target cell
Antiviral properties
Anticoagulant
Modulate haematopoiesis
p55 and p75 receptors
Function of IL1
Raise body temperature in response to infectionW
Wat is the function of IL2
Clonal expansion of activated R cell
What is the function of IL4
Th2 cytokine secreted by mast cells and Th2 cells
Activates B cells to differentiation for the process of antibody production
What is the function of IL8
Chemokine
Attracts neutrophils
SEcreted by monocytes, macrophages, T cells, epithelial cells
What are interferons?
Pro inflammatory
Immunomodulatory
Antiviral
IFN alpha/beta
Can be used in chronic hepatitis and MS
IFN gamma upregulates expression of MHC class II on cells secreted by Th1
Activates macrophages and induces NK activity
Formation of B cells
Derived from haemopoietic stem cells in bone marrow
Mature in Bone marrow
Undergo gene rearrangement and receptor testing for autoantigen specificity
- if autoactive - gene editing by RAG genes or clonal deletion
What happens when B cells are activated
Mature into
Plasma cells
Memory cells
What is the function of plasma cells
Produce antibodies
- bind to pathogen and disable
- opsonize pathogen for phagocytosisW
5 classes of antibody
IgA, IgD, IgE, IgG, IgM
What is structure of antibody?
Y shaped
two heavy chains and two light chains
Variable region at two distal arms of Y which bind to antigen
Constant region that does not bind - activates effector cells and complement
What fragments can Ig be cleaved into ? Enzyme?
Papa-in
Fab fragments - antigen binding containing V variable region
Fc fragments - crystallizable and contain C constant region
How can B cells be activated
B cell takes up foreign material and presents it on MHC II antigens
Activated Th2 cell recognises peptide and releases IL4 - activates B cell
Unprocessed antigens (Thymus independent antigens) - significant cross linking of B cell receptors
What is affinity maturation
Increased affinity for antigen presented results in proliferation of B cell and production of new antibody
B cell that has reduced affinity will lack stimulation and will undergo apoptosis
What is the first antibody produced by plasma cell?
IgM
