CBG Lecture 25&26: Immunology Flashcards
why study immunology
control infectious disease autoimmuno disease treatment cancer treatment transplantation veterinary immunology digestive diseases sometimes related to immune system eg. Crohns
what type of infections are ranked number 1 on infectious disease killers
respiratory infections
give an example of a digestive disease related to immune system
Crohns
what are the major categories of human infection
virus
fungi
parasites
bacteria
what are the major viral diseases
HIv-aids
Poliovirus-polio
rubeola-measles
what are the major fungal diseases
tinea corporis - ringworm
candida albicans - candidiosis (thrush)
what are the major parasitic diseases
plasmodium - malaria
leishmania - leishmaniasis
what are the major bacterial diseases
myobacterium tuberculosis - TB
pertussis - whooping cough
vibrio cholerae-cholera
borrelia burgdoferei - lime
what is the purpose of the IS
to dead with harmful pathogens and internal threats like cancer
what is the nature of the threat of harmful pathogens
- bacteria and viruses grow exponentially - we dont
- microbes evolve rapidly, therefore IS must adapt - hard wiring specificity is not enough
- IS has to kill off foreign pathogens without destroying “self”
what are general/broad difficulties IS has to face when fighting infections
- bacterial and viruses grow exponentially-we dont
- viruses and bacteria can evolve rapidly
- IS needs to make sure it doesnt destroy self
outline key properties of innate IS
- fixed response
- rapid response -4hrs
- limited number of specificities
- constant during response
outline key properties of adaptive IS
- variable response
- slower response - 4 days
- numerous highly selective specificities
- improve during response
when does the adaptive immmune response begin
when a pathogen is ingested by an immature dendritic cell in the infected tissue
name some cells involved in innate immunity
phagocytes
complement
NK cells
name some cells involved in adaptive immunity
B lymphocytes - antibodies
T lymphocytes
effector T cells
what constitutes the serum component of blood
cell free liquid minus the clotting factor
what does serum include
electrolytes ABs hormones drugs microorgs
what does plasma include
vell free liquid with clotting factors in solkn
includes EDTA
all of serum
what is EDTA
a good anticoagulant
if you centrifuge blood what do you get
55% plasma
buffy coat - leukocytes+platelets
what makes up 55% blood
plasma
what makes up buffy coat
leukocytes and platelets
what makes up 4% blood
erythrocytes
what is a stem cell called
hematopoietic
what are hematopoeitic cells
blood cells that give rise to all the other blood cells and are derived from mesoderm. They are located in the red bone marrow, which is contained in the core of most bones.
what are two main types of lymphocytes
B lymphocytes - B cells
and T lymphocytes - T cells
where are B and T cells produced
B - bone marrow
T - thymus
what other lymphocytes are produced
memory cells
what do natural killer cells do
kill cells infected with certain viruses - theyre both innate and adaptive
involved in tumour surveillance
what is a plasma cell
a fully differentiated B cell which secretes Abs
what are memory cells critical for
vaccination and repeated response/exposure to infectoin
name a major human disease that has been eradicated
small pox
what cell response do most vaccines generate
B cell response - but to be super effective want a cytotoxic T cell response
for a vaccine to be super effective, what type cell response would you ideally want to be generated
a cytotoxic T cell response
what is another word for a monocyte
macrophage
whats the difference between monocyte and macrophages
monocytes are young macrophages in blood
monocytes have kidney shaped nucleus, macrophages have round shaped nucleus
what are macrophages involved in
phagocytosis and killing of microogs- activation of T cells and initiation IS
what are the largest cells in the blood
monocytes/macrophages
why are there tssue specific macrophages
due to antigen presentation
describe the shape of a monocyte nucleus
kidney shape
why is a neutrophil a granulocyte
because it contains cytoplasmic granules
outline features of a neutrophil
granulocyte with cytoplasmic granules polymorphonuclear undergoes phagocytosis short life span - hours important at clearing bacterial infections innate immunity
are neutophils involved in adaptive or innate immunity
innate
describe the nucleus of a neutrophil
polymorphonuclear and multilobular
what cells has a multilobular nucleus
neutrophil
what is complement
a group of serum proteins that activates inflammation, destroys cells and participates in opsonisation
is complement innate or adaptive
innate
what pathways can activate complement
classical or alternative pathway
what does complement do
produce a cascade of reactions
what is the membrane attack complex
forms a hole in cell membrane causing cell to lyse
what are mast cells associated with
allergies
what does antigen processing depend on
whether they originate within or outside the host cell
how are antigens that are produced within the cell processed
fragments of foreign proteins are antigens
antigens transported to RER
antigens combine with MHC Class 1, then transported to Golgi, then plasma membrane
cell becomes APC and stimulates destruction by CD8+ T cells - self antigens arent recognised by T cells and dont stimulate cell destruction
give sequence of events for processing antigens produced within cell
proteins broken into fragments -> rough ER -> MHC Class 1 -> golgi -> plasma membrane
give sequence of events for processing antigens originating from outside cell
proteins broken into fragments within vesicle -> fuse with golgi containing MHC2 -> complex transported to PM
how are antigens originating outside cell processed (eg. bacteria/viruses)
ingested by phagocytosis by macrophages, undergo endoctosis
foreign fragments broken down in a vesicle
vesicle containing the foreign fragments fuses with vesicles from Golgi containing MCHclass2
MHC Class2/antigen complex is transported to the plasma membrane
the displayed MHC2/antigen complex can stimulate other immune system cells to respond to antigen
outline immunologival memory case study
Faroe Islanders 0> N.Atlantic
measles epidemic 0> infected entire pop
reintroduced later, almost all inhabitants infected except those who has survived previous infection and retained immunological memory
what is the immune system made of
physical barriers
cells
souluble effector protesins: ABs, complement
cytokines - ocmmunication
name some communication signals in IS
cytokines
name some intrinsic epithelial barriers to infection
chemical:acids/lsozyme/antibac peptides
normal flora - in gut
what is innate IS mediated/initiated by
phagocytes
NK cells
soluble proteins
what are phagocytes
cells specialised in phagocytosis
name some phagocytes
macrophages
neutrophils
outline process of phagocytosis
capture
engulfment
and break down of bacterial pathogen
where do macrophages reside
can be tissue resident or recruited to sites of inflammation
what do macrophages do - what are they important for
engulf and kill viruses and bacteria
important for antigen presentation to T cells
what are neutrophils attracted by
chemokines which are activated by microphages
what are phagocytes’ recognition of pathogens based upon
pattern recognition using germline encoded receptors or proteins
name some receptors that macrophages express
express receptors for microbial constituents
LPS receptor - commonly found in bacterial cell wall
TLR-4 and TLR-2 : toll light receptor - recognise pathogen motifs in all cells in IT , recognises dsRNA therefore recognises virus
what induces the synthesis of inflammatory cytokines
bacterial components binding to signaling receptors of macrophages
what is TLR-4 / TLR-2
toll light receptor - found on macrophages recognise dsRNA (non self - humans dont have dsRNA)
how do neutrophils respond to inflammatory stimuli
highly motile - migrate out of blood into tissues in large numbers
what is the most common leukocyte in blood
neutrophils (80%(
outline nucleus of neutrophils
distinctive lobed nucleus and intracellular granules
what is lifespan of neutrophils
short life span c.24hrs
what is a major constituent of pus
dead neutrophils
what is the inflammatory response
accumulation of fluid and cells at infection site - swell, red, heat pain
outline main roles of complement
opsonisation - complement proteins coat outser surface of pathogens so phagocytes can engulf and recognise them easier
membrane attack complex-grp of ocmplement proteins punch hole in pathogen - lysis
enhance inflammation
what three outcomes of complement activation
- opsonization
- membrane attack Complex
- enhance inflammation
state how infection triggers an inflammatory response
bacteria trigger macrophages to release cytokines and chemokines
vasodilation and increased vascular permeability:heat, red,swelling
inflammatory cells migrate to tissue rekeasing inflammatory mediators that cause pain
what causes pain in inflammatory response
inflammatory mediators
i
in inflammatory response, what causes redness and swelling
vasodilation and increased vascular permeability
what three pathway types of complement activation
classical - antigen:antibody complexes
MB lectin pathway:lectin bind to pathogen surface
alternative pathway - pathogen surfaces
what is the first line of defence against infection called
innate immunity
what is recognition of pathogens in innate immunity based on
pattern recognition using germ line encoded receptors or proteins
why is innate immunity non adaptive and not inclusive of memory cells
because pattern recognition is based on receptors that are coded for in germ line cells therefore non adaptive
also theyre evolnarily early- viruses have now evolved
what is adaptive immunity
specific to a particular antigen and detected by specific receptors on T and B cells
why is adaptive immunity called adaptive
response improves with time and results in memory = protection against reinfection with the same pathogen
why is adaptive immunity described as evolnarily late
only present in vertebrates
what are the main cells involved in adaptive immunity
T and B lymphocytes
what is humoral immunity
immunity due to production of antibodies due to B cells - humoral immunity
what can B cells differentiate into
plasma cells
memory cells
antibodies
what do B cells require to be fully functional
activation by T cells
what can b cells release
ABs but also cytokines
what is a BCR
b cell receptor - a membrane bound immunoglobin
what is a TCR
a T cell receptor
how does a t cell recognise a foreign antigen
as a peptide on an MHC molecule presented by an APC - antigen presenting cell
what are types of T cells
helper CD4+
cytotoxic CD8+
regulatory
where are T and B cell responses initiated
in seocnary lymphoid organs - lymph nodes and spleen
what are the secondary lymphoid organs
lymph nodes and spleen
what is antibody/humoral mediated adaptive immunity
directed agains extracellular microorgs and toxins
B lymphocytes differentiate into plasma cells which produce ABs
what is cell mediated adaptive immunity
directed against intracellular microorgs
T lymphocytes differentiate into effector cells following antigen presentation by APCs and activating B cells
define antigen
molecule which stimulates production of and binds specifically to an antibody
outline structure of antigens
primarily peptides, short strings aas but carbs, nucleic acids and lipids also potential antigens
what are the molecules recognised by the immune response claled
antigens
what are epitopes
sites within antigens to which antigen receptors bind
what are sites within antigens to which antigen receptors binds
epitopes
what area of antigens are individual antibodies made against
epitopes/antigenic determinants
what are antigenic determinants
epitopes
what is the difference between AB and T cell antigen binding
AB bind antigen directly
T cell requires antigen/MHC complex
where does adaptive IR occur
lymph node and spleen
outline structure of ABS
2 heavy chains
2 light chains
exist as monomers, dimers or pentamers of basic structure
contains variable and constant regions
what is variable region of AB
antigen receptor
what region defines structure of AB
constant region
what are isotypes of ABs
IgA-@mucosal surfaces, large hinge region IgM IgG-DEFAULT ISOTYPE IgD -defaul IgE -parasites
what is default AB isotype
IgG
what is AB
secreted form of IG made m y plasma cells
what are different isotypes determined by
strcutural differences in constant regions fo heavy chains
following exposure to antigen, what happens to B lymphoctes
differentiate into plasma and memory cells
what do plasma cells produces
ABs of all immunoglobin classes
what is clonal selection
activation of antibody producing cells
outline clonal selection
biding of specific antigen results in proliferation of a clonal popn of cell
antigen determines clonal proliferation
what are T and B cell responses
clonal
discuss T and b cell receptor diversity
T and B cells have receptors specific for only 1 antigen and each cell is unique
what are effector cells aka
memory cells
discuss T cells and cell mediated immunity
T cells respond to antigens on surface of APCs - APCs ingest and process antigens then display fragments on their surface in association with MHC
which MHC/antigen complex does CD4+ bind to
MHC Class 2
which MHC/antigen complex does CD8+ bind to
MHC Class 1
what do T cells which encounter antigens do
differentiate into effector cells
what does antigen determine
clonal proliferaiton
name some APCs
macrophages
dendritic cells
