Immunology Flashcards
Revision of immunology from principles
What is the immune response divided up into?
- Innate/ natural: natural barriers, soluble components and cellular components
- Acquired/ adaptive: humoral (B cells) and cell-mediated (T cells)
What are the main barriers to infection?
- Skin
- Mucous
- Commensal bacteria
How does the skin provide a barrier to infection?
- physical barrier= highly keratinised, multi-layered
- physiological factors= low pH, low oxygen
- sebaceous glands= hydrophobic oils, lysosomes, ammonia, antimicrobial peptides
How does mucous provide a barrier to infection?
lines resp, GI and urogenital surfaces
- physical barrier
- secretory IgAP: prevents bacteria and viruses penetrating epithelial cells
- enzymes: lysosomes, defensives and antimicrobial peptised
- cilia
How does commensal bacteria provide a barrier to infection?
- symbiotic relationship
- makes vitamins K and B12
- makes bactericides
- low pH
- compete for nutrients
- make anti-microbial fatty acids
What are the main components of the innate immune system?
- leukocytes:phagocytic white blood cells, macrophage, neutrophil, natural killer cells
- complement: destroys cells
- inflammatory response: increase temperature, capillary permeability and attract macrophages
What do natural killer cells do?
release perforin, forms pores so fluid moves in and out, cell lysis and apoptosis
What does the complement system do?
- attacks bacteria a fungus
- forms a membrane attack complex
- perforates cells to cause apoptosis
What does the inflammatory response do?
- releases histamines and prostaglandins
- capillaries dilate and become leaky (macrophages, RBCs, platelets and clotting factors)
- increased temperature (decreased bacterial growth, phagocytosis and increased repair)
What is the innate immune system?
present continuously and from birth
What is the adaptive immune system?
induced by the presence of foreign material and is specific
What are the main specific cells of the innate immune system?
- macrophages
- dendritic cells
- natural killer cells
- mast cells
What are the features of macrophages?
develop from monocytes, large pale pink cytoplasm, kidney bean nucleus
What do dendritic cells do?
present in large numbers in tissues, APCs
What do natural killer cells do?
granular, kill infected cells and cancer cells, kill antibody bound cells and pathogens
What do mast cells look like and do?
fried egg appliance, granular, protect mucosal surfaces
What are PAMPs?
pathogen associated molecular pattern which are on the surface of pathogens
What are PRRs?
pattern recognition receptors that are on the surface of cells and intracellular to bind to and detect PAMPs
What is phagocytosis facilitated by?
opsonisation so macrophages can engulf pathogens
What are the main steps of phagocytosis?
- macrophages express PRRs
- PRRs bind to PAMPs
- phagocytic cup engulfs target to form phagosome
- fusion with lysosomes to form phagolysosome
- debris released into extracellular fluid
- pathogen-derived peptides expressed on MHC-II
- pro-inflammatory mediators released eg TNFalpha
What is opsonisation?
coating of pathogens by opsonins to enhance phagocytosis
What do virally-produced interferons activate?
immune cells
signals nearby infected cells to undergo apoptosis
signals nearby uninfected cells to decrease protein synthesis and destroy RNA
What cells to natural killers target?
cells with less MHC-I so virally infected and cancer cells
What happens when mast cells degranulate?
- release pro-inflammatory mediators
- increased acute inflammation
What is macrophage activation enhanced by?
IFNgamma (made by NKC)
increased MHC-II expression
What is neutrophil trans-endothelial migration?
gets neutrophils to the tissues through the blood and is triggered by pro-inflammatory mediators
How does this process of transendothelial migration occur?
- margination
- binding to adhesion molecules on endothelial cells
- migration across endothelial by diapedesis
- movement by chemotaxis
- activation by PAMPs and TNFalpha
What are the three ways that neutrophils can kill?
- Phagocytosis: either phagolysosomal killing or ROS-dependent (reactive oxygen species)
- Degranulation: digestive enzymes which stop replication
- Neutrophil extracellular traps: release of intracellular structures which traps pathogens so macrophages can engulf them
What do macrophages release?
anti-inflammatory particles and stimulate wound healing
What does CRP do?
primes the bacteria for destruction by complement and is used as an inflammation marker
Where do the components of complement come from?
- MBL and C3 are another part of the acute phase response
- complement is made in the liber and enters inflamed tissues and there is a cascade reaction
What are the component proteins that leak out and what is this triggered by?
- kinins, coagulation factors and fibrinolytic leak out
- release is triggered by pro-inflammatory cytokines and histamine that increase permeability
What does C3 split into and what do these cause?
- C3a and C3b
- these cause pathogen killing, opsonisation, leukocyte recruitment and removal of immune complexes
What causes the splitting of C3?
mannose-binding lectin or C3b (human have inhibitory proteins so this doesn’t happen)
What does C3b then cause?
more reactions so C5b made which is the membrane attack complex
What does the MAC do?
causes cell to burst when placed in the membrane
What do C3a and C5a cause?
- acute inflammation
- activate mast cells
- act on vessels
What does C3b do?
acts as an opsonin and causes C5 to split
What are the two types of T cells?
CD4+ T are regulators
CD8+ T are killers
How to T and B cells enter lymph nodes?
transendothelial migration from high endothelial venules
How do B cells recognise antigens?
using membrane-bound antibodies on their surface
What happens when the B and T cells enter the lymph nodes?
- B cells to lymphoid follicle
- T cells to T cell area to interact with dendritic cells
- all leave through medullary sinus and efferent vessels
What are the types of B cells?
- plasma cells: secrete soluble, antigen-specific antibodies
- memory cells: circulate around the body
What happens when an antigen enters a lymph node?
- chemokine attract B cells
- B cells need antigen and helper signals from T cell to be activated
What is the first antibody to be secreted?
IgM
What do antibodies do?
- recognise
- effect so clear with heavy chain region with complement and Fc receptors
What does IgM do?
- B cell activation when on B cell
- first in adaptive response
- agglutination and complement system activation
What do IgG and IgM activate?
complement cascade with Fc region
What does IgG do?
- agglutination
- complement activation
- foetal immune protection (dimeric)
- neutralisation (monomeric)
- opsonisation
- natural killer activation
- transported across placenta
What do IgG and secretory IgA act to do?
neutralise so prevent pathogens from infecting host cells
What do IgG opsonins on pathogen bind to?
Fcgamma receptor on neutrophil and enhance phagocytosis
What is ADCC?
Antibody-Dependent Cell-mediated Cytotoxicity
- activation of natural killer cells by the Fc region of IgG
What are the two types of IgG and their roles?
- monomeric helps with neutralisation
- dimeric helps with neonatal defence and neutralisation
- transported in breast milk to protect neonatal GI tract lining
What is IgD?
B cell receptor for B cell activation
What does IgE do?
allergic response eg allergy, asthma and anaphylaxis
What is the specific state that antigens must be in for T cells to recognise them?
antigens must be presented to the T cells’ TCR by MHC molecules
What do Class I MHC do?
are expressed on all nucleated cells and present peptide antigens to CD8+ T cells
What do Class II MHC do?
expressed only on APCs so dendritic cells and macrophages, B cells
present peptide antigen to CD4+ T cells
What are the steps of inflammation involving dendritic cells?
- debris from phagocyte released
- dendritic cells phagocytise pathogen-derived particles
- TNFalpha stimulates tissue-resident dendritic cells to increase expression of stimulants
- dendritic cells digest proteins and display peptides with MHCs
What do dendritic cells express?
both MHC I and II so both CD4+ and CD8+ can bind
What do Th0 cells do?
IL2 initiates Th0 to be cloned to make more IL2 so CD8+ cells differentiate into killer cells in the T zone
What do Th1 cells do?
- migrate to inflamed tissue to help macrophages
- make IFN gamma to enhance killing by stimulating reactive oxygen species production
What do Tfh cells do?
- form germinal centres
- help B cells survive
What do CD8+ T cells differentiate into?
cytotoxic T cell s which release perforin and granzymes to make cell undergo apoptosis
How is tissue repair stimulated?
- less histamine is produced
- macrophages release anti-inflammatory markers
