immunology Flashcards
Categorise different types of white blood cell..
myeloid
- neutrophils - most abundant
- macrophages / monocytes
- basophils
- eosinophils
lymphoid
- NK cells
- lymphocytes
(monocytes also differentiate into dendritic cells)
which cells are granulocytes?
basophils
eosinophils
neutrophils
appear granular under microscope
can you name any tissue specialised macrophages?
Kupfer cells
microglial cells
alveolar macrophages
what is the difference between the innate and adaptive immunity?
Innate immunity
- fast acting
- present from birth
- non specific
- includes protective barriers, immune cells (neutrophils, macrophages, mast cells, eosinophils etc), complement system and acute phase response
adaptive immunity
- slower to develop
- relies on previous exposure and history
- very specific to antigen / infection
- memory exists
- includes T and B lymphocytes
Describe the components of the innate immune system
1st line defences
- skin
- mucus membranes - macrophages, goblet cells, cilia, IgA.
- stomach acid
- tears
- lysozyme in saliva and teers
- coughing/ sneezing
cellular responses
- macrophages and neutrophils mostly
complement system
acute phase response proteins
what are acute phase proteins?
name some acute phase response proteins..
group of proteins produced by the liver in response to inflammation / infection
The acute phase response is a response by the liver to produce such proteins but also downregulate others over to aid inflammatory process.
CRP acts as an opsonin and activates complement and macrophages
fibrinogen to help wound healing
ferritin reduces iron available for bacteria.
what is a cytokine?
small protein molecule involved in signalling immune response and inflammation.
often released by immune cells and act on other components to activate / proliferate them.
major ones IL1, TNFa, IL6, IFNg
e.g. IL1 induces fever
IL6 & TNFa can stimulate acute phase response
their roles are a lot more complex than this
what role does the arachidonic pathway have in inflammation?
tissue injury causes injury to phospholipid membrane which promotes phospholipase A2. Increases production of arachidonic acid and thus prostaglandins and leukotrienes
leukotrienes acts to increase permeability/ vasodilation, chemotaxis, bronchospasm
prostaglandins - pain , vascular permeability, chemotaxis
i.e. both promote inflammation and regulate immune response.
what is the role of the complement system?
25 plasma proteins produced by the liver and circulate in blood stream
when activated, biochemical cascade causes activation and amplification and production of membrane attack complex
can be activated in 3 ways =
classical pathway = C3 convertase activated by Ag-Ab complex
alternative pathway = C3 convertase activated via microbial surface
lectin pathway = activated by mannin binding protein which is bound to bacterial carbohydrates
once activated
C3 convertase cleaves C3 to C3a andC3b
this results in positive feedback and other complement activation.
overall roles
- inflammation - cause mast cell degran
- opsoniation - C3b coats microbes
- membrane attack complex - C5-C9 - produces holes in bacterial wall and cell lysis
- chemotaxis
what is inflammation?
The immediate non specific response to injury to promote destruction of harmful substances and healing
consists of 4 cardinal features
- rubor - redness - from vasodilation
- calor - heat - as above
- dolor - pain - prostaglandins and other mediators have receptors on nerve ending. protects from further damage
- tumour - swelling - increased permeability and migration of cells (chemotaxis)
describe the process involved in inflammation…
- tissue damage stimulates process e.g. arachidonic pathway or cytokines
- hyperaemia - vasodilation and increased permeability.
- exudation - fluid, complement, cytokines leak out into tissue - swelling and pain
- emigration - white cells migrate via chemotaxis.
many mediators involved and very complex interactions.
e.g. histamine and leukotrienes increase capillary permeability and chemotaxis
prostaglandins also do this + cause pain.
what is SIRS response?
systemic inflammatory response syndrome
life threatening condition related to deregulated host response to inflammation/infection.
characterised by
temp >38/<36
tachycardia >90
Tachypnoea >20 or PaCO2 <4.3
WCC >12 or <4
describe the immune response to exogenous pathogens..
exogenous pathogens first come into contact with barriers
if they pass these barriers they are next exposed to phagocytes (e.g. macrophages)
phagocytosis occurs and pathogen is destroyed via ROS and hydrolytic enzymes
fragments of this pathogen are combined with MHC class II and presented on the surface of the cell.
the cells move to lymph nodes where T cells reside and the specific TCR that is complementary to the antigen/MHC II complex is selected and activated. This will be a T helper cell (as it is exogenous)
This results in clonal expansion
meanwhile B cells also phagocytose and present on MHC II
when B cells and T cells with complementary MHC II and TCR meet it results in activation of B cell to plasma cell. Also relies on co-receptor activation.
plasma cells can now secrete antibodies to help clear exogenous pathogen
what cells are antigen presenting cells?
macrophages
dendritic cells
monocytes
can you describe the process of phagocytosis?
foreign material detected via its antigen
binds surface receptors of phagocytes
triggers endo cytosis
the pathogen is endocytosed into a vesivle
this is now called a phagosome.
the phagosome combines with a lysosome and is exposed to ROS
causes breakdown of material inside
what are MHC molecules?
Major histocompatibility complex
group of glycoproteins texpressed on cell surface in combination with self antigen.
thus acts as markers for recognition by immune system.
MHC I present on all cells - for presenting self antigen and protecting from immune destruction
MHC II present on immune cells and for presenting exogenous antigen
how are virally infected cells detected and cleared by immunity?
virally infected cells will express MHC class I
however they will expose viral peptides on these.
MHC Class I + viral peptide is presented to T cells and promotes production of CD8 cytotoxic T cells
Type 1 T helper cells will also be activated which promote the CD8 cells.
cytotoxic T cells put holes in infected cells via perforins
can you explain the roles of the different lymphocytes in adaptive immunity..
can be categorised into B and T cells
T cells have further category of CD8 cytotoxic and CD4 helper T cells.
CD4 helper T cells can be further divided into
Th1 = help CD8 for intracellular infections e.g. viruses
Th2 = help B cells for exogenous pathogens e.g. bacteria.
what is the thymus gland?
gland present in the upper anterior portion of the chest behind the sternum
larger during child hood whilst T cell maturation occurring
atrophies in adulthood
what is an antigen?
An antigen is any substance that can be recognized by the immune system and trigger an immune response.
can be protein, glycoprotein, lipisaccharide etc
can be endogenous or exogenous or may be self antigen triggering autoimmunity.
what is a B and T cell receptor?
integral membrane proteins that have a constant region that is integrated in the phospholipid bilayer and a variable region which is specific for a certain type of antigen.
collectively all the T and B cells are able to detect a vast range of antigens.
The antibody is a soluble version of a BCR
what are the different forms of immunological memory?
active or passive
passive = lasts few days to months. from acquiring antibodies e.g. baby across placenta/ breast milk.
active = immunity produced by activation of adaptive immune system and formation of memory B and T cells which can produce antibodies on repeated exposure to the same pathogen. long lived.
can you draw and describe the structure of an antibody
peptide molecules consisting of 2 light chains and 2 heavy chains joined by disulphide bonds.
they come together to form a constant region and variable region for contact with various antigen.
the heavy chain determines the class of Ab e.g. IgA, M etc
what are the functions of antibodies
antibodies have variable region capable of recognising and binding antigen
opsonisation - constant portion binds leukocytes and helps them to phagocytose
neutralisation - stops bacteria dividing and making toxins
agglutination - clumps bacteria together, makes phagocytosis more efficient
activate classical complement pathway
what different types of antibody do you know?
IgA - mostly in body fluids and mucosal areas e.g. saliva, tears, gut, respiratory. helps as first line defence preventing colonisation.
IgM - exist as a monomer - star shaped 5 together - found in blood stream helps to remove bacteria and activate complement
IgG - provides most Ab based immunity. most abundant antibodies.circulates blood waiting to coat microbes. can cross placenta
IgE - binds pathogen, stimulates mast cell degranulation. invovled in allergy
IgD - less defined function
what are the 4 main classes of hypersensitivity?
type 1 - IgE mediated. Causes mast cell degranulation, inflammation & bronchoconstriction. immediate response and is the mechanism of allergy and anaphylaxis
type 2 - antibody mediated (IgG/M) e.g. antibodies which bind self antigen and trigger tissue destruction e.g. by complement activation, phagocytosis, cytotoxicity. E.g. myasthenia gravis, rheumatic fever. this occurs within minutes to hours
type 3 - immune complex mediated (IgG/M) - antigen-Ab complexes circulate and deposit in tissues causing inflammation e.g. RA, SLE. This takes hours.
type 4 - T cell mediated. E.g. T1DM, TB. this is delayed and can take over 1 month.
(More recently group 5 has been created for antibodies against receptors. this would take myasthenia gravis out of class 2. also Graves would be in class 5).
can you describe the mechanism behind anaphylaxis..
sensitising event:
- exposure to antigen - triggers immune response, B cells activated, IgE produced specific to that antigen.
- these IgE bind surface of mast cells and basophils
next exposure
- antigen binds IgE
- triggers mast cell degranulation
- histamine and other mediators released
- histamine causes vasodilation and bronchospasm.
can you tell me about immunodeficiency …
immunodeficiency encompasses a collection of diseases whereby there is an impairment of the immune system.
This can be further categorised into specific forms of deficiency or whether the deficiency is primary or secondary.
primary immunodeficiency = genetic disorders that result in impaired immunity e.g. Severe combined immunodeficiency disease (SCID) where there is both T and B cell dysfunctions. DiGeoge is another primary immunodeficiency disorder with defects in T cell function. Others can be as specific as antibody deficiencies.
secondary immunodeficiency are those acquired. with the major one being HIV. others may be from prolonged steroid use or due to leukaemia
how is the immune system affected by anaesthesia?
can be divided into physical and chemical factors
physical:
disruption of physiochemical barriers - cannulas, incision of surgery, ET tubes bipass mucocilary escalator
hypothermia - depresses immunity
chemical:
exposure to allergens e.g. anaphylaxis risk
stress response to surgery releases cortisol - depresses immunity
volatiles and opioids have also been shown to impair immune dysfunction
on the other hand TIVA has shown to be better in cancer patients and reduces reoccurance.
what specific roles does skin have in innate immunity?
physical barrier
chemical barrier - slightly acidic due to sweat, antimicrobial peptides
commensal microbes - inhibit growth of others through competition
langerhan cells - specialised dendritic cells.
