Immunology Flashcards
What is SCID?
Severe combined immune deficiency - individual doesn’t have any lymphocytes
What is primary lymphoid tissue?
Bone marrow and thymus
What is secondary lymphoid tissue?
Tonsils, lymph nodes, lymph vessels, liver, spleen, Peyer’s patch (small intestine) and appendix
Define ‘antigen’
Anything which elicits an adaptive immune response
Define ‘self-antigen’
When immune system goes awry and starts recognising own cells as foreign
Define ‘inflammation’
When white cells leave the blood and move into tissues to get rid of pathogens and kill normal tissue in the process as well
How do lymphocytes respond to foreign molecules?
Antigen-specific receptors (BCR/TCR)
How do phagocytes respond to foreign molecules?
Have pattern recognition receptors and Fc receptors which react to PAMP structures on foreign molecules
What are the first cells to respond to an infection?
Neutrophils –> bacteria phagocytosed and killed
Describe how the immune system responds to a nail through the skin
Neutrophils (phagocytose and kill bacteria) –> skin macrophage releases TNF-alpha and IL-1beta to increase stickiness of endothelial by increasing number of adhesion molecules –> lymphocyte recruitment
Name some ‘pathogen-associated molecular patterns’ (PAMPs) that can be recognised by phagocytes
flagella, double-stranded viral RNA, lipoproteins and CpG DNA
What happens if a cell recognises any PAMPs?
Starts to produce pro-inflammatory cytokines
Where do T cells mature?
Thymus
Describe neutrophils
Full of dangerous molecules and die in the tissues e.g. free radicals, collagenase and cytokines
What controls T cell expansion?
IL-2
What happens when T cells are activated?
Clonal expansion (IL-2 needed_ then memory T-cells are produced too
Define ‘epitope’
Portion of an antigen that is recognised and bound by a receptor on an immune cell (antigens can contain many epitopes)
What is the innate immune system?
NK cells, monocytes, granulocytes and dendritic cells
What is the adaptive immune system?
T and B cells
What does TLR4 do?
Present on macrophages and dendritic cells, toll-like receptor 4 binds LPS (a form of PAMP)
What are B cell receptors made of?
They are immunoglobulins/antibodies
What are the 4 different isotopes of antibody?
IgA, IgE, IgM, IgG
What is meant by ‘class switching’?
Given B cell will begin by making IgM and this is the default that must be changed
How are antigens presented to T cells?
By dendritic cells on MHC/HLA complex
What codes for the composition of the TCR?
α-chain locus is on chromosome 14, β-chain locus is on chromosome 7
How is receptor diversity generated in antibodies?
Somatic DNA recombination, mixing and matching within heavy and light chain loci genes, and random mixing and matching of the variable, diversity and joining segments
What codes for the composition of MHC/HLA?
α and β chains in MHC found on chromosome 6
Why is MHC binding termed ‘promiscuous’?
Binds to a range of peptides that can be accommodated in the groove, not just a single peptide
Name two properties of MHC
Polygenic, polymorphic
Define ‘polygenic’
Phenotypes influenced by more than one gene
Define ‘polymorphic’
Occurring in several different forms
Describe MHC Class I
All cells present molecule, and presents antigens to CD8 T cells.
What are the types of MHC Class I?
HLA-A/B/C
Describe MHC Class II
APCs only present this molecule, and antigens are presented to CD4 T cells
What are the types of MHC Class II?
HLA-DQ/DR/DP
Which HLA/MHC molecules are present in coeliac disease?
HAL-DQ2/DQ8
Define ‘central tolerance’
As T and B cells develop (thymus and bone marrow respectively), their receptors are tested for reactivity to self-antigens, if too strong –> destroyed
Define ‘peripheral tolerance’
Self-reactive lymphocytes which escape destruction can be controlled by T regulatory cells
Which molecules target epithelial surface infections?
IgA and antimicrobial peptides
What is a ‘humoral immune response’?
Transformation of B cells –> plasma cells to produce and secrete specific antibodies to pathogen
What do antibodies do?
Neutralise toxins, agglutinate, opsonise (make cell more susceptible to be phagocytosed), activation of complement, antibody-dependent cell killing (NK cells)
Define ‘complement’
Group of proteins present in blood plasma and tissue fluid which combine with antigen-antibody complexes to bring about lysis of foreign cells
What is the response to cytoplasmic infections?
CD8 and NK T cells
What is the response to vesicular infections?
T cell-dependent macrophage activation
What is ‘cell-mediated immune response’?
Response produced when sensitised T cells directly attack foreign antigens and secrete lymphokines
Why can CD8 T cells induce apoptosis?
TCRalphabeta and a CD8 co-receptor
Describe the cell-mediated immune response
Dendritic cells engulf and present antigens –> enter lymph nodes via afferent route –> CD8 T cells leave lymph node via efferent route –> direct cytotoxic activity on invading pathogens –> induce apoptosis in infected cells due to TCRab and CD8 co-receptor
Describe what happens in apoptosis
Nuclear blebbing, alteration in cell morphology, shedding of small membrane vesicles, DNA fragmentation (nuclease enzymes), apoptotic bodies are removed by phagocytic cells
What two enzymes allow CD8 T cells to induce apoptosis?
Perforin and Granzymes
Describe how CD8 T cells induce apoptosis
1) Non-specific adhesion between target cell and CD8 cell
2) TCR-MHC interaction –> specific binding
3) Reorganisation of microtubule-organising centre and Golgi of CD8 cell
4) Lytic granules are released (granzyme and perforin)
5) Cell death of target cell (apoptosis)
What does perforin do?
Modifies target cell by forming pores in cell membrane
What do granzymes do?
Proteases which chop up proteins in target cell
What are natural killer cells?
Innate immune system, don’t have antigen-specific receptors and kill by same means as CD8 T cells (granzyme and perforin)
How are NK cells activated?
By cytokines to cause the release of interferon gamma which increases NK killing efficiency
How do NK cells identify cells to kill?
Missing-self hypothesis - has activating and inhibiting receptors: if cell has MHC Class I receptor then it will recognise as self (inhibitor, even in spite of any activation), if cell doesn’t have MHC Class I receptor –> apoptosis via lytic granule release
What do Th1 cells do?
Drive cell-mediated immunity to activate macrophages
What do Th2 cells do?
Drive humoral immunity to help B cells make antibodies
What do Th17 cells do?
Drive responses to extracellular bacteria
What do T-reg cells do?
Retrain immune responses
What do Th1 cells produce?
IFN-gamma (activates macrophages)
What do Th2 cells produce?
IL-2,4,5,13
When do Th0 cells differentiate into Th1 cells?
presence of IL-12/13 (produced by dendritic cells)
When do Th0 cells differentiate into Th2 cells?
IL-4 (mast cells produce these)
Which clinical issues arise with elevated Th2 responses?
Th2 responses lead to IL-4 production which leads to IgE which causes type I sensitivity disorders
What are cytokines?
Small proteins/glycoproteins that act via specific receptors - can be inflammatory or anti-inflammatory
Define ‘pleiotropy’
Can have multiple effects
What are the 4 attributes of cytokines?
can have multiple effects, different cytokines can do same job, can work together to cause effect, can have opposing effect
Define autocrine transmission
Same cell is target that produced it
Define paracrine transmission
Target cell is nearby to producing cell
Define endocrine transmission
Target cell is distant and molecule travels in circulation
What are chemokines?
Subfamily of cytokines involved in cellular movement (cells migrate towards high concentration); they signal through GPCR
Describe the function of cytokines in inflammation
Macrophages at site of injury/infection –> inflammatory response –> TNF-alpha cytokine and chemokines –> TNF-a increases adhesion molecules and chemokines also activate adhesion molecules to bind to innate cells (neutrophils and monocytes) –> IL-2 cytokine drives T cell proliferation later
When are cytokines pathological?
If there is uncontrolled systemic TNF-a –> septic shock.
Cytokine production uncontrolled –> more and more cytokine in positive feedback (Ebola)
What is involved in type 1 hypersensitivity disorders?
Over-production of IL-3 causes overproduction of Th2 cells –> mast cell degranulation
What is involved in chronic inflammation?
Over-production of Th1 cytokines –> chronic inflammation e.g. Chrohn’s
How may inflammatory conditions be treated?
Anti-TNFa therapy
