Immunology Flashcards
What are the primary lymphoid organs (2)
bone marrow and thymus
What happens in the primary lymphoid organs
Lymphocytes develop and mature
What are the secondary lymphoid organs (2)
spleen and lymph nodes
What happens in secondary lymphoid organs
mature lymphocytes encounter antigens, become activated, and initiate immune response
What are the cells involved in the innate immune system (8)
neutrophil
Basophil
Eosinophil
Monocyte
Dendritic cell
Nk cell
Mast cell
Macrophage
What cells are involved in the adaptive immune response (3)
B cell, T cell, plasma cells
What are the anatomical and physiological barriers (5)
skin
Sebaceous glands
Commensalism bacteria
Mucus
Coughing + sneezing
What does it mean if the immune response is humoral
It involves antibodies
How do innate immune cells recognise pathogens
Via pattern recognition receptors which bind to pathogen associated molecular patterns
Where are selectins found
on endothelial cells
What do selectins do
facilitate rolling of immune cells which then adhere to the vessel walls
How do immune cells arrive at the site of the infection
They are drawn by chemotatic signals
How do innate immune cells recognise pathogens
Via their pattern recognition receptors which intersect with the pathogen associated moleculular patterns
What modes of ingestion may occur in the innate immune response (3)
Pinocytosis
Phagocytosis
Receptor-mediated endocytosis
Describe pinocytosis
Ingestion of the fluid surrounding cells
What does of ingestion are used in the innate immune system (3)
pinocytosis, receptor mediated endocytosis, and phagocytosis
Describe phagocytosis (6)
PRRs bind to PAMPs, signalling the formation of the phagocytic cup
The cup extend around the target and forms a phagosome
The phagosome fuses with lysosomes (phagolysosome), this leads to killing of pathogens and degradation of contents
Debris are related into extracellular fluid
Pathogen derived peptides are expressed on cell surface receptors (MHC II)
Pro-inflammatory mediators are released
What is pinocytosis
Ingestion of fluid surrounding cells
What is endocytosis
molecules bound to membrane receptors are internalised
Which method of ingestion is important for the generation of adaptive immunity
endocytosis
What facilitates these modes of ingestion
opsonisation - coating of pathogens by soluble factors
What do mast cells release (2)
pre-formed pro-inflammatory mediators (degranulation)
New pro-inflammatory mediators
What does inflammation promote (3)
vascular changes
Recruitment and activation of neutrophils
Production of chemical signals to attract neutrophils
What are the steps of transendothelial migration (5)
migration to endothelium near affected tissue
Binding to adhesion molecules on endothelial cells
Migration across endothelium
Migration within tissue (due to chemotaxis)
Activation by PAMPs and TNFα
What are the physiological sings of acute inflammation (4)
redness
Heat
Swelling
Pain
Why is redness and heat observed in acute inflammation
Dilation of blood vessels increases blood flow, cell accumulation, and cell metabolism
Why is swelling a sing of acute inflammation
there is increased permeability of post-capillary venues which means that fluid accumulates in extravascular spaces
What methods of killing exist (2)
oxygen dependent
Oxygen independent
Describe degranulation (2)
release of antibacterial proteins from neutrophil granules into extracellular milieu, causing killing of pathogens and tissue damage
NETS (2)
A method of killing pathogens, neutrophil extracellular traps
How can neutrophils kills pathogens (3)
phagocytosis
Degranulation
NETS
What do virally infected cells produce and release
interferons (a type of cytokines)
What do interferons do (3)
signal to uninfected to destroy RNA
Signal neighbouring infect cells to undergo apoptosis
Activates immune cells
What adhesion molecule do neutrophils bind to priori to migrating across endothelium (2)
selectins, IcAM-1
What does the acute phase response involve (2)
changes in plasma concentration of certain proteins in response to inflammation
Production of acute phase proteins
What are examples of acute phase proteins (3)
c3
MBL
C reactive protein (CRP)
What does CRP do
Acts as an opsonin
What are the three pathways for activating the complement system
classical
Alternative
Lectin
Describe the classical pathway
IgM and IgG cause a conformational change in C1, thus activating the cascade
What lectin pathway for activating the complement system
mannose binding lectin binding to carbohydrates
Mimics c1 binding to immune complexes
What is the alternative pathway for activating the complement pathway
Spontaneous hydrolysis of c3 and its binding to bacterial cell walls
What happens in the complement pathway (6)
c3 convertase activation
C3 is broken down into C3a and c3b by c3 convertase
C5 convertase activation
C5a binds to c6, c7, and c8 to form the c5 convertase complex
C5 convertase complex inserts onto cell membrane
C9 binds to the complex, forming the membrane attack complex
How do the innate and adaptive immune systems communicate with each other
dendritic cells
What activated dendritic cells
pro-inflammatory mediators
Which immune response are B cells involved in
humoral immune response
Which immune response are T cells involved in
cellular immune response
What are the functions of C3a and C5a (2)
inflammatory mediators
Recruit phagocytes
Examples of complement inhibitors (5)
C1, Factor I, Factor H, C4 binding protein, CD59
What are the protein components of the adaptive immune system (2)
Cytokines
Antibodies
which is the most abundant antibody
IgG
Describe the regions found on antibodies
Heavy chains - have variable regions
Light chains - have constant regions
Which antibody is the first to be produced in an immune response
IgM
What else may antibodies be known as
immunoglobulins
Where are mature, quiescent, antigen-specific B and T cells found
constantly circulating between the blood, secondary lymphoid tissues, and lymphatic vessels
What type of antibody is IgA
Secretory
where is IgA secreted (3)
mucus, saliva, and tears
How do the innate and adaptive immune systems communicate
Dendritic cells
What activates dendritic cells
pro-inflammatory mediators
which immune response are B cells involved in
humoral
Which immune response are T cells involved in
cellular
Where are mature, quiescent, antigen-specific B and T cells found
circulating between the blood, secondary lymphoid tissues, and lymphatic vessels
which is the most abundant antibody type
IgG
Which antibody type is the first to be produced in a response
IgM
What else may antibodies be known as
immunoglobulins
What are the regions on antibodies
heavy chains - have variable regions
Light chains - have constant regions
What two functions can antibodies have
recognition - binding to the antigen
Effector - heavy chain region interacts with effector molecules
what does IgA do
tags the pathogen for destruction
What does IgD do (2)
acts as a B cell receptor
Stimulates release of IgM
What does IgE do
binds to mast cells and basophils
What does IgG do (6)
binds to phagocytes
Crosses placenta
Complement system activation
Nk activation
Agglutination
Neutralisation
What does IgM do (4)
acts as a B cell receptor
Secretory
Agglutination
Complement system activation
What is agglutination
when an antibody cross-links with multiple antigens, forming columns of antigens
A process that increases efficacy of pathogen elimination
What are the routes a B cell can be taken to be activated (2)
An antigen binding to the receptor then a PRR binding to a PAMP
Or multiple antigens and receptors engage, dismissing the need for a PRR
once activated, what happens to B cells
they clonally proliferate and differentiate into two types of effector cells
What are the types of effector cells that B cells can differentiate into, and what do these cells (2) do
Plasma cells (produce and secrete antigen-specific antibodies)
Memory B cells (long-life, circulate the body)
What antigens can T cell recognise
those presented to their receptors by MHC molecules
What types of T cells are they + what do these do (2)
cd4+ - regulates immune system and secretes Il-2
Cd8+ - kills infected cells
Which class of MHC presents to cd4+
MHC II, only expressed on professional antigen presenting cells
Which class of MHC presents to cd8+ cells
MHC I, expressed on every nucleic cell
What does MHC stand for
major histocompatibility complex
What are dendritic cells capable of doing (2)
Recognising and internalising pathogens/antigens
What compound stimulates immature dendritic cells, and what is the effect
TNFα
Increased expression of co-stimulators molecules
After dendritic cells have internalised and digested pathogens, what happens
They display pathogen-derived peptides on their surface in complex with MHC I/MHC II molecules
What do cd4+ cells secrete
Il-2
What does Il-2 do
stimulates cells to divide and differentiate
What can naive cd4+ cells differentiate into
cd4+ effector cells
What are the different types of cd4+ effector cells (5)
TH1
TH2
TH17
TFH
Regulatory T cells
What do TH1 cells do
enter affected tissue
Boost killing function of macrophages by switching on expression of NADPH oxidase genes
What does activation of NADPH oxidase genes allow
the macrophage’s lysosome to contain reactive oxygen species
What are TFH Cells (2)
Pro-inflammatory
Secrete pro-inflammatory cytokines
How is the immune response resolved (3)
macrophages switch from being pro-inflammatory to being anti-inflammatory
Macrophages secrete anti-inflammatory cytokines
Tissue repair occurs
What long-lived adaptive immune cells can be present after the immune response is resolved (4)
memory cd4+ cells
Memory cd8+ cells
Memory B cells
Long-lived plasma cells
Which antibody is more effective: IgG or IgM
IgG
What is immunisation
the process by which an individual develops immunity to a disease (deliberate or natural)
Vaccination
deliberate administration of antigenic material to acquire immunity to a certain disease
Active immunity (2)
protection by the individual’s own immune system
Permanent
Passive immunity
Protection transferred from another person/animal
Temporary
Examples of passive immunity (3)
placental antibody transfer
Antibodies in breast milk/colostrum
Venom antidotes
What is a hypersensitive reaction
an exaggeration of normal immune mechanisms that results in bystander damage to self
What is type one hypersensitivity
immediate
What is type two hypersensitivity
direct cell effects
What is type three hypersensitivity
immune complex mediated
what is type four hypersensitivity
Delayed
What stages are involved in hypersensitivity reactions (2)
sensitisation
Pathological
What happens during the sensitisation stage
Naive cd4+ cells are activated, converting to cd4+ TH0 cells
The receptors of mast cells and basophils combine with IgE antibodies
IgE antibodies are stabilised once bound
What is the pathological stage of hypersensitivity (5)
allergen binds to IgE coated mast cell/basophil
Degranulation occurs
Vasoactive mediators are released
Expression of pro-inflammatory cytokines and Leukotrienes is increased
Eosinophils are recruited and activated
What are the features of a type one hypersensitivity reaction (4)
immediate
More than one organ system involved
Presentation is influenced by site of contact
Threshold for reactions can be influenced by cofactors
What co-factors can alter the threshold for type one hypersensitivity reactions (3)
alcohol, exercise, and infection
What can be used to manage IgE mediated allergic reactions (6)
avoiding allergen
Anti-inflammatory agents
Adrenaline
Blocking mast cell activation
Biologics
Preventing effects of mast cell activation
How do biologics work
neutralise TH2 cytokines
What are type two hypersensitivity reactions mediated by (2)
IgM or IgG antibodies
What happens in a type 3 hypersensitivity reaction (4)
immune complex formed
complex passes between endothelial cells of blood vessels
Complex becomes trapped on basement membrane
Causing inflammation
How can an immune complex be formed
binding of multiple antigens to antibodies
What drives type four hypersensitivity reactions
cd4+ cells
What are the features of type four hypersensitivity reactions (3)
high numbers of macrophages at affected area
Symptoms take 24-48 hrs to manifest
Granulomas can form
Autoimmunity
immune response against self-antigens
What can high levels of auto-antibodies/aut0-reactive T cells cause (2)
Chronic inflammation
Tissue/organ damage
What are the components of T cell receptors
Alpha and beta chains
What allows each developing b cell to generate antibodies with a unique variable region
random selection and recombination of V, D, and J gene segments within Ig heavy and light chain genes
What tolerance mechanisms exist (2)
Central tolerance
Peripheral tolerance
Describe central tolerance
Deletion of self-reactive lymphocytes in primary lymphoid tissue during early stages of development
Describe peripheral tolerance
suppression of self-reactive lymphocyte activity in peripheral tissues by regulatory T cells
How do regulatory T cells suppress self-reactive T cells
producing anti-inflammatory cytokines
What causes autoimmunity
a breakdown of immune tolerance to self antigens
What factors can trigger autoimmunity (4)
smoking
Infections
Hormone levels
Tissue damage
Describe superantigens
bacterial toxins which non-specifically activate all lymphocytes (including those that are auto-reactive)
What are the possible responses to infection (3)
resolution
Latent infection
Chronic infection
What does latent infection mean
the pathogen is controlled, but infection may occur again
What does chronic infection mean
the immune response is defective
The pathogen is not cleared/controlled
What are the four signs of immunodeficiency
Serious infections
Persistent infections
Unusual infections
Recurrent infections
What are the two classes of immunodeficiency disorders
primary and secondary
What are the types of primary immunodeficiency disorders (3)
Antibody deficiency disease
T cell mediated disease
Combined immunodeficiencies
What are the B cell defects associated with antibody deficiency diseases (2)
reduced peripheral B cell numbers
Serum Ig levels absent/reduced
What are the features of antibody deficiency diseases (3)
increases susceptibility to extracellular pathogens
Growth/developmental delay
Increased incidence of autoimmune disease + malignant tumours
What is the pathogenesis of antibody deficiency diseases (2)
development of B cells is blocked
CD4+ TFH cell development is blocked
What is the defect associated with T cell mediated immunodeficiencies
reduced peripheral blood T cell numbers
What are the features of T cell mediated immunodeficiencies (3)
increased susceptibility to intracellular pathogens
Delayed growth/development
Increased incidence of malignant tumours
What is the pathogenesis of T cell mediated immunodeficiency (3)
Thymus development problems
Blocked T cell development
Associated Ig deficiencies
Which part of the immune system involves the gastrointestinal epithelial barrier
Innate
What can the gi epithelial barrier secrete (3)
cytokines
Antimicrobial peptides
MUC proteins
What is found at the base of a crypt
Lg5+ stem cells
What happens at the tip (of the crypt???)
cell shedding
What controls epithelial barrier growth dynamics
Signalling molecules
Where are immune cells found in the GI tract
lamina propria
What structures are found on the intestinal mucosa (2)
Peyer’s patches
Villi
What are the components of a Peyer’s patch (4)
Immune cells
Lymphoid tissue
Thinner mucus layer
Specialised phagocytic cells (M cells)
What do villi contain (3)
Lgr5+ stem cells
Loose connective tissue network (laminate propria)
What can M cells do
transport material across the epithelial barrier via transcytosis
How are antigens sampled (2)
By dendritic cells
Which extend dendrites between epithelial cells
What happens once dendritic cells have sampled antigens (2)
antigens are broken down and used for presentation to lymphocytes
what do dendrites with antigens do (2)
Go to T cell zone of a Peyer’s patch
Convert T cells to regulatory T cells
What do the newly formed regulatory T cells do now (3)
Go to lamina propria of villi
Via lymphatics
Then secrete Il-10
Il-10 function (2)
suppressing immune cell activity
Preventing unnecessary inflammation
what is the function of MUC proteins (3)
Forming a scaffold
Which entangled mucus produced by goblet cells
Forming a mucus layer that gives protection
What effect do microbes have on the epithelial barrier (2)
stimulate secretion of cytokines
Help regulate permeability
What effect does the epithelial barrier have on microbes (2)
determines which microbes reside in the lumen
Provides mucin (a microbial energy source)
Which cytokine promotes epithelial barrier repair
Il-22
Function of integrin (3)
directs T cells to the gut
Interacts with a complementary protein on endothelial cells
Thus slowing the cell down and causing it to move through blood vessel to tissue and be anchored
What does anchoring of T cells in the epithelial barrier mean
increased efficacy for longer
When are TH2 cells important
parasitic infections
What cell balance maintains gut health
T helper cells to T reg cells
Once anchored in the epithelium, what are T cells known as
intraepithelial lymphocytes
Which antibody is particularly important in the GI immune system
IgA
What is the definition of the microbiome
The genetic material associated with all microorganisms colonising the body
What is the most common mediator of sepsis
endotoxin released by gram negative bacteria
