Immunology Flashcards
What do living organisms consist of
Plants animals micro-organisms (bacteria, fungi, algae and protozoa)
Name two pathogenic eukaryotes
fungi and protozoa
Name a pathogenic prokaryote
bacteria
What are viruses?
non-living/ small obligate parasites
Name three differences between prokaryotes and eukaryotes
eukaryotes are much more compartmental so have specific organelles that perform specific functions they also have linear chromosomes and histone proteins compared to the singular circular chromosome in prokaryotes etc etc etc
Name the 6 properties of the prokaryotic cell
plasma membrane, cell wall, nucleoid, ribosomes, cytoplasm and capsule/flagellar or pili
Name the different properties of a eukaryotic cell
cell membrane, nucleus, centriole, nucleus, ribosomes, ER, cytosol, mitochondria, golgi, cytoskeleton, secretory vesicle/lysosomes etc etc
Name three different barriers to infection in the body
skin, mucus and commensal bacteria
How does skin provide a barrier to infection
Physical barrier of tightly packed keratinised (makes it waterproof) multiple-layered epithelium, has low pH, secrete lysozymes, antimicrobial peptides and hydrophobic oils to prevent the survival of pathogens
How does Mucus provide a barrier to infection
cilia (traps and expels via coughing etc) secretory IgA, physical barrier (thick consistency), lactoferrin starves the bacteria of iron
Name 3 types of mucus membranes
respiratory, gastrointestinal and urogenital
What are commensal bacteria
Bacteria that are present in the microbiota that do not cause harm and are often involved in miantaining health of the individual
What is innate immunity
the first line of defence which is non-specific
What is adaptive immunity
specific more tailored in response to foreign non-self particles
Give examples of cells involved in the innate immune response
neutrophils, macrophages, mast cells and NK cells
What cells are involved in the adaptive (acquired) immune response
T and B lymphocytes and DCs (bridge between innate and adaptive)
What are the functions of a macrophage
they’re anti-inflammatory; phagocytosis, degradation of pathogens in the lysozyme vacuole, antigen presentation and wound healing/tissue response
What is the role of mast cell
involved in allergy + parasitic infections , secretes histamine, pro inflammatory
NK cell roles
Destruction of virally infected cells as well as cancer cells
What are PAMPs
pathogen-associated molecular patterns, molecules expressed on non human cells
Give examples of of PAMPs
LPS, viral dsRNA, beta glycans from fungi and bacterial cell walls
What are PRRs
Pattern recognition receptors, are present on immune cells and recognise pathogens and pathogenic material
what is pinocytosis
ingestion of fluid from surroundings
what is receptor mediation endocytosis
when the membrane-bound receptors are internalised into the cell - important for adaptive immunity later on
Describe the steps of Phagocytosis
PRR engages with PAMP and signals relased into cell, rearranges the cytoskeleton to “cup” around the pathogen and internalise it into a phagosome which fuses with a cytosolic lysozyme (acidic pH) allowing it to breakdown the pathogen, debris is released into extracellular fluid and the cytokine TNalpha is released
What is phagocytosis
specific endocytosis which internalises solid matter such as apoptotic cells as well as microbial pathogens
Give examples of opsonins
C3b, IgG, IgM and CRP
What is opsonisation
the coating of pathogens by soluble factors (opsonins) to enhance phagocytosis
Upon recognition of a pathogen what do mast cells do?
Release pre-existing histamine in the cell as well as gene expression for the production of prostaglandins and leukotrienes
What is acute inflammation
response to cellular injury or infection
Under homeostasis neutrophils are found circulating in the blood
true
How do neutrophils leave the circulation and migrate to the tissue of interest?
neutrophils circulating will express LFA-1 and weakly bind to selectins and then stable adhesion to ICAM-1 on endothelial cells and cells move through the tissue via chemotaxis and activated by TNFa and PAMPs
Endothelial cells express adhesion molecules during inflammation to slow down WBCs
true
Name three ways neutrophils can kill pathogens
NETs, phagocytosis and degranulation
what do interferons do during an anti-viral response
cause neighbouring cells to reduce protein production/RNA synthesis, induce programmed cell death and activate NK cellsl,
What is oxygen dependent killing in neutrophils
assembly of NADPH oxidase complex recruits the ROS and released into the granules to degrade pathogen
What is oxygen-independent killing of neutrophils
granules fuse with the phagosome and reduce pH and induce bacterial killing
What is the function of lactoferrin
competes with bacteria to bind to iron
what are lysosomes
granules that degrade the cell wall of gram -ve bacteria
What cytokines are good for viral responses
IFNa and b
What are NETs
a form of neutrophil suicide that helps immobilise pathogens
What process by neutrophils immobilises the pathogen preventing it from spreading as well as making it available for oppsonisation
NETs
What is your pus made out of
neutrophils
NK cells recognise self-peptides using MHC II, true or false?
False, it is via MHC I
Once activated NK cells produce what
perforin which creates pores in the recipient cell causing apoptosis
How do NK cells recognise self-peptides
through the inhibitory receptor which upon activated prevents any of the killing mechanisms in the cell
Where are acute-phase proteins made?
liver
What are examples of acute-phase proteins?
CRP and C3 and MBL (complement proteins)
What is the function of CRP
functions as an opsonin to enhance phagocytosis by other immune cells
What is the diagnostic importance of CRPs
their levels in the blood can indicate the severity of inflammation/illness
What is the MBL pathway does the activation of C3b and C3a occur in the MBL pathway
A MBL binds to the mannose found on bacteria recruiting C3 covertase to covert the inactive C3 to the active forms C3a and C3b
What complement protein is the prerequisite for the membrane attack complex
C5b
What complement protein induces the cleavage of C5 to C5a and C5b
C3b
What is the function of C3a and C5a
amplification of acute inflammation - changes in local vasculature (vasodilation and expression of adhesion molecules), activation of mast cells
What complement protein is a powerful opsonin?
C3b
What cell is known as the bridge between the innate and adaptive immune response?
dendritic cell
What is the function of B cells?
antibody production and responsible for the humoral immune response key in defending against extracellular pathogens
What is the function of T cells?
defence against intracellular pathogens
What are CD4+ T cells?
helper T cells that help coordinate/regulate the immune response
What are CD8+ T cells?
cytotoxic T cells that induce cell killing of virally infected cells
What is it meant by specific recognition of B and T cells
they only express one antigenic receptor that binds to one specific antigenic epitope
What is the molecular structure of an antibody
A heavy chain and a light chain are held together by disulphide bonds, each chain containing a variable region and a constant region
What region determines the specificity in antibodies?
variable region
What consists of the antigen binding site on a B cell?
variable regions of a the heavy and light chains
What receptor is made up of a heterodimer of alpha and beta chains
TCR
CD8+ T cells recognise MHC II molecules, true or false?
false, they recognsie MHC I
What MHC Class do CD4+ T cells recognise?
MHC II
What cells express MHC II
professional antigen-presenting cells such as DCs, macrophages and B cells
What class of MHC is expressed on all nucleated cells?
MHC I
Where are B and T cells originated
bone marrow
T cells complete their maturation in the thymus, true or false?
true, they develop in the bone marrow and then travel to the thymus to complete development
What are primary lymphoid tissues
bone marrow and thymus
What are the spleen, lymph nodes and peyer’s patch known as?
secondary lymphoid tissues
What are T and B cells doing if they don’t meet their specific antigen
circulating through blood and lymph between tissues and lymphoid organs
How do B cells encounter antigens?
stromal cells of the B cell zones bind to opsonins and hold them for weeks for circulating B cells to hopefully arrive and encounter their specific antigen
How do T cells encounter antigen?
dendritic cells internalise pathogens inside and then present the antigens on their MHC I or II, TNFa increases costimulatory expression on these cells and they travel to the lymph node presenting these antigens to their antigen-specific T cells
What Ig is secreted by short-lived plasma cells
low affinity IgM
What is affinity maturation?
the rearrangement of the variable region of the antibody to become more specific
What is class switching
By rearrangement or changing of the constant chain of the antibody
Which is the most versatile antibody in terms of its functions?
IgG
What are the two weaker costimulatory methods for B cells?
non protein antigens - BCR and antigen and PRR and PAMP
repeating antigenic epitopes of BCR and antigen (polysaccharide/fatty acid etc)
What is the most optimum costimulatory method for B cells?
B cells use Ab to bind to opsonin and the MHC II binds to the TFhelper cell as the costimulatory interaction which causes proliferation and class switching/affinity maturation
germinal centre tends to be the derived area where lymphomas and leukaemia arise relating to the mutations that occur in this area, true or false
true
What antibody is present as a pentameric structure and involved in agglutination and complement activation
IgM
What is agglutination?
cross-linking of multiple antigens by the antibodies creating larger lumps
What is the importance of agglutination?
Prevents the spread of viruses and increases the efficacy of phagocytosis
Which antibody forms the C1 complex
IgM
What are the six functions of IgG
agglutination
complement activation
foetal immune protection
neutralisation
opsonisation
NK cell activation
What antibody can be transported across the placenta?
IgG
Which antibodies are involved in Neutralisation?
secretory IgA and IgG
What is neutralisation?
binding to the pathogen thereby;
blocking attachment to the cell
blocking endocytosis
blocking uncoating and releasing RNA into the cell
What is opsonisation?
IgG binds to the pathogen and phagocytes express fc receptors that binds to the constant region of the IgG; therefore enhances phagocytosis
Which is the second most abundant antibody in the blood?
IgA
Which antibody is present as a dimeric form in secretions such as breast milk and mucus?
IgA
Which antibody is involved in allergic response?
IgE
What cells express fc receptors for IgE?
mast cells and basophils
Which is the effector region of the antibody
heavy chain constant region
which is the recognition region/antigen binding site of the antibody?
variable region on both the heavy and light chains
Name a type of specialised DC
Langerhans cells
What indicates the maturation of dendritic cells?
expression of costimulatory molecules
DCs only present on MHC II, true or false?
False, They present on both as they are nucleated cells but are also antigen-presenting cells
what cytokine do activated CD4+ cells produce
IL-2
What is the function of IL-2
promote proliferation and clonal expansion of T cells
What is the function of Th1 cells?
release of proinflammatory cytokines to enhance macrophage-mediated killing
What is the fucntion of Tfh cells?
stimulate clonal expansion of B cells upon recognition of its specific antigen
- these B cells differentiate into long-lived plasma cells (high affinity antibodies) and memory B cells
What does the IFNg secretion by a Th1 cell to macrophage cause?
induce gene expression of the NADPH oxidase complex to enhance oxygen-dependent killing
What is the function of CD8+ T cells?
induce apoptosis in target cells expressing foreign molecules on MHC I
How do CD8+ T cells induce the killing of an infected cell?
bind to the peptide presented on MHC class I and release perforin and granzymes to induce apoptosis
what is the role of perforin
polymerises to form a pore in the membrane of a cell
What are granzymes
serine proteases that activate apoptosis once in the cytoplasm of the target cell
Define immunisation
the process by which an individual develops immunity to a disease
Define vaccination
the deliberate administration of antigenic material to produce immunity to a disease
What cell is important for resolution of an immune response?
macrophages
How are macrophages important in a an active process of immune resolution?
anti-inflammatory cytokines such as IL-10, tissue repair by releasing growth factors that help with wound repair by creating more cells
What is herd immunity
the goal to vaccinate everyone in the population that can be and is healthy enough to in order to protect those who are unable to receive the vaccine
Name the four classifications by Gel and Coombs of hypersensitivity
Type I: Immediate hypersensitivity (allergy)
Type II: Direct cell effects (cellular effects)
Type III: Immune complex-mediated
Type IV: Delayed type hypersensitivity
What’s the difference between allergy and sensitivity?
allergies have circulating IgE for the specific antigen, sensitivities do not
What type of T cell is involved in allergy?
Th2 cells
what cytokines are secreted by Th2 cells?
IL-4, IL-5 and IL-13
What happens upon reexposure to the allergen?
mast cells or basophils containing IgE bound to their fc receptors causing degranulation of histamine
increased mucus production
vasodilation
increasing pain
proinflammatory cytokines and leukotriene secretion
What are type II hypersensitivity reactions mediated by?
IgG and IgM with opsonisation, complement activation and fc mediated activation of other immune cells such as NK cells
What is a type III hypersensitivity reaction?
soluble immune complexes lodge in the capillaries between endothelial cells and basal membrane, promoting vasodilation and inflammation leading to tissue death and haemorrhage
What are type IV hypersensitivity reactions?
Th1 cell releases cytokines that activate macrophages
What are examples of hypersensitivity type IV reactions?
dermatitis and tubercular lesions/graft rejection
what types of hypersensitivity are considered autoimmunity?
II, III and IV
What is the rearrangement of the variable regions of BCRs called
VDJ recombination
What is central tolerance?
T and B cells are exposed to self-antigens in the thymus and bone marrow and if reactive to sell they will get eliminated
What is the role of Treg cells
CD4+ T cells that suppress the activity of self reactive T and B cells - dampen the immune response
What are the suppressive cytokines released by Treg cells
IL-10 and TGFb
What is the defect in IPEX syndrome?
mutation in FOXP3 causing a defect in Tregs resulting in a failure of peripheral tolerance
What are the three types of HLA genes in MHC class I
HLA-A HLA-B and HLA-C
What are the three types of HLA in MHC II
HLA-DR, HLA-DQ and HLA-DP (these come from separate alpha and beta proteins)
Why do certain HLA genes increase your susceptibility to autoimmune diseases
Because it results in you having MHC or receptors that will bind and respond to self-peptides
What is graves disease?
an autoimmune disease characterised by the overproduction of the T3 and T4 throid hormones causing hyperthyroidism
What are four main environmental influences that can trigger autoimmunity?
infections
cigarette smoking
hormone levels
tissue damage - chronic inflammation for eg
What mechanisms are used to influence an autoimmune disease?
molecular mimicry
alterations to self antigens
antigen sequestration
bacterial superantigens
What is the term used when there are shared antigen epitopes causing antibodies to bind to proteins expressed on self organs
molecular mimicry
Give an example where molecular mimicry is used in a disease
acute rheumatic fever where antibodies directed to destroy streptococcal (M5) cell walls can also cross-react in the heart tissue and bind to cardiac tissue proteins causing tissue damage
What is antigenic sequestration
antigens that reside in hidden areas and do not come in contact with the immune system unless sometimes in injury or trauma
What is meant by bacterial superantigens
toxins that can trigger an excessive reaction of the immune system (massive cytokine release and activation of T cells) - this is the case in toxic shock
What are examples of autoimmune disease driven by type II hypersensitivity
autoimmune hemolytic anaemia
graves disease
myasthenia gravis
guillen barre syndrome
goodpastures syndrome
SLE is caused by type IV hypersensitivity, true or false
false, it is caused by type III because of the presence of complement activation
Name type III hypersensitivities
SLE
Rheumatoid arthritis
glomerylonephritis
What is SLE
Systemic lupus erythematosus - here triggers such as excess UV radiation causing apoptosis of cells and the clearance by phagocytes is lacking causing an increased presence of self antigens resulting in increased T and B cell responses causing inflammation
Examples of Type IV autoimmunities
multiple sclerosis
rheumatoid arthritis
diabetes mellitus
autoimmune myocarditis
Autoimmune diseases can only be classified in one type of hypersensitivity, true or false?
false, they can involve a combination of these types of hypersensitivities
What cells are present in the crypts?
goblet cells (mucus secreting) and intestinal stem cells
