Immunology Flashcards
functions of the immune system
to identify and eliminate microorganisms
what does the immune system detect?
- self and non-self
- danger signals
what can happen when the immune system goes wrong?
- recurring infections
- allergy
- autoimmune diseases
- cancer
- transplant rejection
three ways of modulating the immune system
- vaccination
- immune suppression
- cancer immunotherapy
natural barriers
- skin
- mucous membranes
- commensal bacteria
describe how skin is a line of defence
- physical barrier: tightly packed, highly keratinised cells
- physiological barrier: pH 5.5 and low oxygen tension
- sebaceous glands
describe how mucous is a natural barrier
- mucous membranes line all body cavities
- cilia to trap bacteria
- releases enzymes that kill the invading pathogen.
how are commensal bacteria a natural barrier?
compete with pathogens for resources
provision healthcare methods that breach natural barriers are?
- insertion of ‘hardware’
- antibiotics
other natural barriers
- elimination via coughing, sneezing, etc.
- sweating has lysosomes
- unfavourable pH
Three sections of the innate immune system
- leukocytes
- complement system
- inflammatory response
define innate immunity
defence mechanism present from birth that has a rapid response and is non-specific.
define adaptive (acquired) immunity
induced by presence of foreign material. Ability to distinguish self and non-self
innate immune cells that recognise non-self pathogens
- macrophages
- dendritic cells
- NK cells
- mast cells
describe macrophages
develop from circulating monocytes. Involved in phagocytosis, antigen presentation and inflammatory response.
describe dendritic cells
present in large numbers in tissues in contact with the external environment. Involved in antigen-presenting cells
describe NK cells
large granular cells that kill infection and abnormal cells
mast cells
defence against parasites and protect mucosal surfaces
name the receptors on pathogens and innate immune cells
PAMPS- pathogen associated molecular patterns
PRRs- pattern-recognition receptors
three ways pathogens can be ingested by macrophages
- pinocytosis (ingestion of fluid surrounding cells)
- receptor- mediated endocytosis
- phagocytosis
describe the action of macrophages in phagocytosis
- macrophages express PRRs
- bind to PAMPs
- pinch off to form a phagosome
- lysozyme release lysosomes that forms a phagolysosome
- debris is released
- MHC-II expressed on receptors
- pro-inflammatory mediators released
define opsonisation
coating of pathogens using opsonins to enhance phagocytosis
innate immune system against intracellular viruses
the infected cells release interferons (beta and alpha). NK cells recognise this and destroy cells.
two functions of mast cells
- degranulation: released of pro-inflammatory substances
2. gene expression: production of inflammatory mediators
how can macrophage activation be enhanced?
pro-inflammatory mediators such as interferon-gamma
chemicals released in localised acute inflammation?
nitric oxide, prostaglandins, leukotrienes, histamines, TNF-alpha (cytokines)
define chemokines
promote directional movement of cells
what do pro-inflammatory mediators do?
enter the blood and are transported to the bone marrow where they stimulate the the production of neutrophils
define trans endothelial migration
movement of neutrophils from the blood to tissues through the blood vessel wall
what do pro-inflammatory mediators change in vasculature
- tight junctions lost (increased permeability)
- dilation of venues
- expression of specific adhesion molecules (VCAMs and ICAMs)
describe the process of transendothelial migration
- white cell (neutrophil) migration in venules
- binding of neutrophils to adhesion molecules on endothelial cells (adhesion binding is promoted by histamine and TNF-alpha)
- diapedesis
- chemotaxis
- pathogens express PAMPs
define diapedesis
migration of neutrophils across the epithelium
define chemotaxis
movement of neutrophils within a tissue
three killing mechanisms of neutrophils
- phagocytosis
- degranulation
- NETs
describe neutrophils in phagocytosis
chemokine attract neutrophils and bind via PRRs. they can kill via phagolysosome or ROS
describe neutrophil granulation
release of anti-bacterial proteins that kill pathogens
describe NETs (neutrophil extracellular traps)
activated neutrophils release intracellular structures to the extracellular environment
define the acute phase response
changes in plasma concentrations of specific proteins
define the function of the C reactive protein
primes bacteria for destruction by the complement system
define the complement system
family of proteins that circulate in the blood and enter infected tissues when needed.
how do the proteins in the complement system enter the tissues?
pro-inflammatory mediators increase vascular permeability and leakiness
three pathways of the complement system
- mannose-binding lectin activation pathway
- alternative pathway
- classic pathway
what does C3b promote?
- opsonisation and therefore phagocytosis
2. C5
what does C5b promote
MAC (membrane attack complex)
what does C5a and C3a stimulate?
acute inflammation
explain the mannose-binding pathway
mannose is only present on pathogens
two types of lymphocytes
B cells
T cells
describe the structure of an antibody
2 light and 2 heavy polypeptide chains with two binding sites.
how do B cells recognise antigens?
membrane-bound antibodies
how do T and B cells enter the lymph nodes?
trans endothelial migration
where in the lymph node do B cells go?
lymphoid follicle
two cells that B cells differentiate into?
- plasma cells (secrete antibodies)
2. memory cells
two signals B cells require to become fully activated
- antigen
2. ‘helper’ signals from T cells
two ways antibodies kill the pathogen
- recognition function
2. effector function: clearance mechanisms (complement system and Fc receptors)
describe the antibody IgM
serves as a B antigen receptor
involved in agglutination and complement system activation
which is the first antibody to be secreted
IgM (low affinity, short lived)
higher affinity antibodies
IgG, IgA and IgE
which antibodies is agglutination mediated by?
mediated by IgM and IgG
describe the classic complement pathway
- activated by Fc regions of antibodies initiated by IgM and IgG
- conformational change in Fc regions which exposes sites for C1
- C1 activates C3
describe IgG
- most abundant
- secondary immune response (memory)
- transported across the placenta
define neutralisation
blocks sites that pathogens use to enter cells. It is mediated by IgG and IgA
describe IgA
present in serum, breast milk
describe IgD
role largely unknown but does activate B cells
IgE
allergic response
two types of T cells involved in intracellular pathogen defence are?
- CD4+ T cells
2. CD8+ T cells
which type of antigens do T cells respond to?
peptide antigens when MHC molecules are present
which area on T cells is specific to the peptide antigen?
hypervariable region by the alpha and beta TCR
two classes of MHC molecules
- class 1 MHC
2. class 2 MHC
describe class 1 MHC
expressed on all nucleated cells and present antigens for CD8+ cells
describe class 2 MHC
expressed only on antigen-presenting cells (dendrites, macrophages, B cells) and present antigens for CD4+ cells.
which cells do CD4+ T cells activate?
- TH0 cells: CD4 causes these to proliferate
- TH1 cells: TH0 can differentiate into these. they exit the lymph node and enter inflamed tissue
- TFH cells: expresses MHC
which cells do CD8+ differentiate into?
cytotoxic T lymphocytes
describe the role of cytotoxic T cells
migrate out of lymph nodes into infected sites. they bind to infected cells and programme apoptosis.
name the protein lytic granules in cytotoxic T cells
- perforin(membrane holes)
- granzymes (apoptosis)
- granulysin (apoptosis)
describe the role of dendritic cells in acquired immunity
- phagocytes release debris of the pathogen
- dendrites phagocytose this material
- TNF-alpha increases expression of co-stimulatory molecules
- dendritic cells digest proteins and display with MHC proteins
which growth factor do CD4+ T cells secrete?
interleukin 2
define interleukins
glycoproteins that are produced by leukocytes to regulate the immune system
describe the functions of IgM
agglutination and the complement system
which is the first antibody to be produced in the adaptive immune response?
IgM
which is the most abundant antibody?
IgG
which two antibodies mediate agglutination
IgG and IgM
functions of IgG
- memory cells
- agglutination
- complement system
- foetal protection
- neutralisation
- opsonisation (Fc receptors)
- NK cells
which antibody is transported across the placenta into the foetal blood circulation?
IgG
functions of sIgA
neutralisation and transported into breast milk
functions of IgD
B cell antigen receptor
functions of IgE
allergic response
which growth factor causes proliferation of TH0 cells?
IL-2
function of TH0 cells
stimulate proliferation of CD4+ and CD8+
which cell can TH0 cells differentiate into?
TH1
function of TH1
leave the lymph node and enter sites of infection/ inflammation. Here they secrete TNF-gamma which enhances macrophages to stimulate ROS
function of TFH
stimulate B cells to cline and proliferate into plasma cells that produce high affinity antibodies and memory cells
describe the Germinal centre reaction
secretion of high affinity antibodies