principles immunology Flashcards
what are 3 barriers to infection
skin
mucous
commensal bacteria
how does the skin protect against infection
physical barrier tightly packed, highly keratinised undergo constant renewal and replacement low pH and low oxygen sebaceous glands - secrete hydrophobic oils, lysozyme, defensins, ammonia
how does mucous protect against infection
traps invading organisms
contains secretory IgA, enzymes such as lysozyme, defensins, antimicrobial peptides which directly kill pathogens, lactoferrin which starves bacteria of iron
cilia remove mucous
how does commensal bacteria protect against infection
compete with pathogens for scarce resources
what can the use of broad spectrum antibiotics cause
oral
IV
oral - oral/vaginal candidiasis
IV - c diff
what does the adaptive immune response involve and what is it
B cells
antibodies
T cells
dendritic cells
slow response, responsible for immunological memory
Neutrophils, monocytes, macrophages and dendritic cells are all…
phagocytes
phagocytes are an important source of …
cytokines
B cells, T cells and NK cells are all …
lymphocytes
eosinophils, mast cells and basophils are all …
granular cells - release chemicals for acute inflammation
give 2 factors associated with humoral immunity
antibodies
complement proteins
where do mast cells reside and what do they do
reside in tissues and protect mucosal surfaces
where are basophils and eosinophils located
circulate in blood and are recruited to sites of infection
what do basophils, eosinophils and mast cells do upon activation
release histamine, heparin, tryptase and pro-inflammatory cytokines
what are basophils, eosinophils and mast cells involved in primarily
defence against large anti-body coated pathogens that can’t be phagocytosed e.g. parasitic worms
if a cell is multinucleate it is a …
neutrophil
where are neutrophils found
circulate freely in blood and are rapidly recruited to inflamed and infected tissue
what are 3 mechanisms by which neutrophils attack pathogens
phagocytosis
degranulation - release of antimicrobial peptides and degradative proteases
generate extracellular traps
what do active neutrophils release
TNF (pro-inflammatory cytokine)
neutrophils are numerous and short lived
true/false
true
neutrophils make use of PAMP recognition and activation
true
true
what makes up pus
dead and dying neutrophils + tissue cells + microbial debris
what cells are precursors of macrophages
monocytes
where are macrophages found
reside in tissues
what do macrophages do when active
ingest and kill extracellular pathogens
what do macrophages do when neutral
clear debris from tissue cells
give 3 other functions of macrophages
inflammation
tissue repair and wound healing
antigen presentation
how are macrophages attracted to apoptotic cells
apoptotic cells release an ‘eat-me’ signal
what are the 4 stages of phagocytosis
apoptotic cell
1) formation of a phagocytic cup around cell
2) pinches off forming a phagosome
3) fusion with lysozyme forms a phagolysosyme - degradation of contents
4) debris released into ECF
what is released along with cellular debris from a phagocyte
anti-inflammatory mediators e.g. IL10
what are the 5 stages of phagocytosis of a pathogen
1) phagocytic cup around pathogen
2) pro inflammatory stimuli released e.g. LPS, INF-Y
3) this enhances macrophage activation and the production of toxic NOS and RNS
4) pinches off forming phagosome
5) antigen presentation –> activated macrophage
give 3 infections which evade phagosomal killing
salmonella
staph aureus
mycobacteria
where are dendritic cells found
immature cells in peripheral tissues / tissues with contact to external environment
what do dendritic cells do when they come into contact with a pathogen
mature and migrate to secondary lymphoid tissues
stimulate adaptive immune response through antigen presentation
how do dendritic cells become activated
phagocytose, process and present antigen on surface to T cells
what do NK cells release
pro-inflammatory mediators e.g. IFN-Y
what kind of cells are NK cells
large granular lymphocytes
what do NK cells kill
tumour and virally infected cells - don’t express MHC class 1 which is present in normal cells to inhibit NK action
can also kill antibody-bound dresses
what do B cells do
produce antibodies (humeral immune response) which coat pathogens to help phagocytosis
what are the 2 types of T cells
helper T cells
cytotoxic T cells
what do helper T cells release
CD4+
most people need HELP for T4
what do cytotoxic T cells release
CD8+
what do helper T cells do
activate other immune cells - receptor:ligand interactions
produce cytokines that help phagocytes kill ingested bacteria
what do cytotoxic T cells do
kill virally infected body cells
what is primary lymphoid tissue
site of leukocyte development
red Bone marrow and Thymus
(B for B cells) (T for T cells)
what is the function of lymph nodes
positioned regularly along lymph vessels - trap pathogens and antigens in lymph
how does lymph move
valves and muscle movement
what is secondary lymphoid tissue
sites where adaptive immune response is initiated (lymph nodes - tissue infections, tonsils, spleen-blood borne infections)
what are cytokines
produced in response to infection, inflammation and tissue damage
they co-ordinate the immune system by modulating cell behaviour
indirect communication
what are 4 examples of cytokines
interferons
TNF
chemokines
interleukins
what kind of cells produce and release interferons and what is their function
virally infected cells
signals neighbouring cells to destroy RNA and reduce protein synthesis and to undergo apoptosis
activates immune cells e.g. NK cells
what is the function of IL2 and what is the source
T cell proliferation
Th1 cells
what is the function of IL10 and what is the source
anti-inflammatory - inhibits Th1 cytokine production
Th2 cells
what are some s/s of acute inflammation
redness heat swelling pain loss of function fever
what does the innate immune response involve and what is it
mast cells NK cells phagocytes complement neutrophils macrophages
rapid, general response responsible for acute inflammation and killing of pathogen
what are the 3 phases of the innate immune response
recognition phase (PRRs:PAMPs)
activation phase
effector phase
PAMPs are specific to certain pathogens
true/false
false
there is a limited number of PAMPs which are common to many different pathogens
what are the 2 forms of communication in the immune system and give an example of each
1) direct - receptor:ligand
MHC:TCR
PAMP:PRR
2)indirect - production and secretion of cytokines
ILs, interferons, TNF
what drives the acute phase response
cytokines
what organ produces acute phase proteins in response to pro-inflammatory cytokines (IL1, IL6, TNF)
liver
what are 3 examples of acute phase proteins
CRP
complement proteins (C3, C4, mannose-binding lectin)
Serum amyloid A
what is the complement system
family of proteins produced in the liver that circulate in blood and enter inflamed and infected tissues where they become activated
what are the 3 pathways of complement system activation
classical
mannose binding lectin
alternative
when triggered specific complement proteins can enzymatically activate other complement proteins in cascade
true/false
true
what is the complement equation
C3 —> C3b + C3a
what do C3b + C3a do
activation of downstream complement proteins
what does the activation of downstream complement proteins cause
pathogen killing (MAC)
pathogen opsonisation
leukocyte recruitment and inflammation (chemotaxis)
removal of immune complexes
how is the mannose-binding lectin pathway stimulated
mannose expression unique to certain microorganisms (not expressed on human cells)
how is the alternative pathway stimulated
spontaneous breakdown of C3
C3b is stabilised on bacterium but degraded on human cells
how are C5a and C5a formed
C3b causes C5 —> C5a and C5b
what complement proteins are involved in leukocyte recruitment and inflammation
what do they do?
C3a and C5a
act directly on BVs to increase permeability and therefore increase leakage from blood
activate mast cells/basophils which release pro inflammatory mediators e.g. histamine and chemokines
how is the MAC formed
C5b binds to surface of pathogen
C6 7 8 and 9 assemble with C5b forming MAC
how does the MAC work
inserts into target cell walls - osmotic cell lysis of pathogen
what is pathogen opsonisation
coating of pathogen by humoral factors (opsonins) to facilitate phagocytosis
phagocytes express receptors for opsonins on cell surface
what are 4 examples of opsonins
C3b
CRP
IgG
IgM
complement proteins have a short half life
true/false
true
only cleaved complement proteins are active
true/false
true
what traps opsonised cells in B cell zones
stromal cells
how do T cells recognise a pathogen
T cell antigen receptor
- membrane bound protein heterodimer
- has alpha and beta chain
how do B cells recognise a pathogen
B cell antigen receptor
- membrane bound antibody (IgM or IgD)
- has a light and heavy chain and disulphide bridges
how do lymphocytes find the pathogen
secondary lymphoid tissue
lymphocytes require 2 signals to be activated
true/false
true
how are T cells activated
MHC/HLA proteins display peptide antigens to T cells
what class of MHC/HLA present peptide antigens to cytotoxic T cells (CD8+)
class I expressed on all nucleated cells
what class of MHC/HLA present peptide antigens to helper T cells (CD4+)
class II expressed only on dendritic cells, macrophages, B cells
do B cells need dendritic cells to recognise antigens
no - do not need antigen to be presented by MHC
what is the name for the immunoglobulins that are produced by B cells in response to an antigen that bind specifically to a single epitope
antibodies
what do antibodies provide defence against
extracellular pathogens - bacteria, viruses, toxins
how do the 5 types of antibody differ
different Ig heavy chain constant region
how are the 2 heavy and the 2 light polypeptide chains held together
disulphide bonds
what is the most abundant Ig
IgG
G for global
how does IgG cross the placenta
active transport
what is the 1st Ig produced during an immune response
IgM
IMmediately
what Ig is produced in the allergic response
IgE
what Ig is the 2nd most abundant and found in mucosal secretions
IgA
what form is IgA in secretions
dimer
what form is IgA in the blood
monomer
what Ig can form a pentamer
IgM
too big to pass to foetal circulation
M has 5 points on it
what region of the Ig is responsible for recognition function
variable region
what region of the Ig is responsible for effector function
constant region
where does IgE bind
Fc receptor
give 5 functions of antibodies
agglutination - immune complex formation - aids phagocytosis (IgM and IgG)
opsonins (IgG)
stimulate NK cells (antibody dependent cell mediated cytotoxicity - ADCC) - IgG
trigger allergic reactions
undergo class switching ( switch heavy chain segment) - induced by specific cytokines
what can B cells differentiate into
plasma cells - effector B cells which produce antibodies
Memory B cells - immunological memory
what is the Germinal centre reaction
B cell proliferation
antibody heavy chain switching
generation of high affinity antibodies
differentiation into plasma cells and memory B cells
how do naive B and T cells enter lymph nodes from high endothelial venules
transendothelial migration
- after several days if they don’t encounter specific antigen they return to blood via the efferent lymphatics
what is a major source of IL2
helper T cells
what immune cells mediate acute and chronic organ rejection
helper T cells and cytotoxic T cells
what immune cells mediate hyperacute organ rejection
B cells
what is the most common WBC
neutrophils
what is the main immune cell against protozoan and helminth infections
eosinophil
also IgE
E
what shape nucleus do monocytes have
kidney
what cell is a source of IL1 and TNF alpha
macrophage
Basophils and Mast cells express what receptors on their surface
IgE receptors (Fc)
what cells release histamine during an allergic reaction
mast cells
what kind of molecule is IgG
monomer
what is the most commonly produced Ig
IgA
but conc. lower than IgG which is most common
what Ig mediates hypersensitivity reactions
IgE
what is the least abundant Ig
IgE
what does HIV use to enter a cell
CD4
what is the co-receptor for MHC class II
CD4
what is the co-receptor for MHC class I
CD8
what is the function of TNF alpha/IL1
induces fever, neutrophil chemotaxis
what is the function of INF gamma
activates macrophages
what is a source of INF gamma
Th1 cells
