Immunology Flashcards
What key feature must the immune system have?
Ability to discriminate between self and non-self.
List 6 features of innate immunity.
1) non-specific
2) instinctive (from birth)
3) rapid response (hours)
4) no memory - resistance doesn’t improve
5) limited-range of antigen recognition - can be evaded
6) neutrophils, macrophages, natural killer cells
List 6 features of adaptive immunity.
1) specific
2) acquired
3) slow response (days-weeks)
4) memory - resistance improves
5) wide-range of antigen recognition
6) T lymphocytes and B lymphocytes
What is the lifespan of a neutrophil?
6 hours - 12 days.
List 2 functions of neutrophils.
1) phagocytosis - innate immunity
2) granule secretion - innate immunity
What is the lifespan of monocytes?
Months.
List 2 functions of monocytes.
1) phagocytosis (pathogens or damaged/necrosed)- innate immunity
2) antigen presentation - adaptive immunity
List 4 types of receptors found on monocytes.
1) antibody Fc receptors
2) complement receptors
3) toll-like receptors (TLR)
4) mannose receptors
What is the relationship between monocytes and macrophages?
Monocytes differentiate into macrophages in tissues.
What is the lifespan of a macrophage?
Months - years.
List 2 functions of macrophages.
1) phagocytosis (pathogens or damaged/necrosed) - innate immunity
2) antigen presentation - adaptive immunity
List 4 receptors found on macrophages.
1) antibody Fc receptors
2) complement receptors
3) toll-like receptors (TLR)
4) mannose receptors
What molecule is found in monocyte and macrophage lysosomes that help phagocytosis?
Peroxide, oxygen molecule with an extra electron pair.
What is the lifespan of an eosinophil?
8-12 days.
What is the function of eosinophils?
Immunity to parasitic infections and allergic reactions.
What is MBP?
Major basic protein. Protein secreted from eosinophil granules.
List 4 functions of MBP.
1) activate neutrophils
2) induce histamine release from mast cells
3) induce bronchospasm (in allergy)
4) potent toxin for helminth worms
What is the lifespan of basophils?
2 days.
What is the difference between basophils and mast cells?
Basophils circulate in the blood whilst mast cells are fixed in tissue.
What is the function of basophils and mast cells?
Immunity to parasitic infections and (the main cause of) allergic reactions.
What do basophils and mast cells express a lot of?
High affinity IgE receptors.
What happens when IgE bind to basophils or mast cells?
De-granulation, releasing histamine, causing an allergic reaction.
What is the lifespan of T lymphocytes?
Hours - years.
List the 5 types of T lymphocyte.
1) helper T 1
2) helper T 2
3) cytotoxic T
4) natural killer T
5) T reg
What is the basic function of helper T 1 lymphocytes?
Help cell-mediated response against intracellular pathogens.
What is the basic function of helper T 2 lymphocytes?
Help humoral response against extracellular pathogens.
What is the basic function of cytotoxic T lymphocytes?
Kill cells via apoptosis.
What is the basic function of T reg lymphocytes?
Regulate and dampen immune responses.
What is the lifespan of B lymphocytes?
Hours - years.
Describe the function of B lymphocytes. (4)
1) express a specific antibody on membrane surface
2) recognise antigens presented by antigen presenting cells via specific antibody
3) differentiate into plasma cell
4) secrete antibodies
What is the basic function of natural killer lymphocytes?
Kill virus-infected or tumour cells via apoptosis.
List 2 functions of dendritic cells?
1) antigen presenting cells (APC) - activate T lymphocytes
2) secrete cytokines - promote B lymphocytes activation and differentiation
Where are dendritic cells found? (5)
Tissues that have contact with the outside environment, e.g.
1) skin
2) nose
3) lungs
4) stomach
5) intestines
What is the complement system?
Complex series of interacting plasma proteins that enhance the immune response.
Where are complement proteins formed?
Liver.
How many complement proteins are there?
Over 30.
Give a basic description of the complement system. (3)
1) exist as inactive precursors
2) once activated, behave as an enzyme to cleave the next complement in the series
3) each precursor is cleaved into an minor fragment (a) and a major fragment (b)
What is the general function of ‘a’ fragments?
Enhance inflammation.
What are the 2 functions / active sites of ‘b’ fragments?
1) bind to cell membranes
2) enzymatic cleavage of the next complement precursor
List 3 functions of the complement system when activated by contacting a foreign antigen.
1) lyse microbes - MAC
2) opsonisation
3) increase inflammation
List 3 ways complement system increases inflammation.
1) increase vascular permeability
2) stimulate chemotaxis
3) stimulate mast cells to secrete histamine (a fragments, esp. C3a and C5a)
What is the critical step in activation of the complement system?
Cleavage of C3 by C3 convertase.
List 3 routes to cleave C3.
1) classical (antibody dependant) - C4bC2a
2) alternative (antibody independent) - C3bBb
3) lectin (antibody independent) - C4bC2a
Describe how opsonisation helps phagocytosis. (4)
1) C3b bind to pathogen surface via thioester bond - coating pathogen surface (opsonisation)
2) C5a binds to macrophage C5a receptor - recruitment
3) C3b (on pathogen) bind to macrophage CR1 receptor
4) macrophage phagocytoses pathogen more easily
What is the function of MAC?
Membrane attack complex, lyse bacteria.
Describe the formation of the membrane attack complex (MAC). (3)
1) C3b binds to C3 convertase forming C3/C5 convertase
2) C3/C5 convertase can cleave C3 or C5
3) C5b initiates the formation of MAC
Define immunoglobulins.
Soluble glycoproteins secreted by plasma cells.
Define epitope.
Part of the antigen that binds to the immunoglobulin binding site.
Define affinity.
Measure of binding strength between epitope and immunoglobulin binding site.
What is the function of immunoglobulin Fab regions?
Antigen recognition. Bind to specific antigens.
What is the function of immunoglobulin Fc regions?
Antigen elimination. Bind to Fc receptors on phagocytes and natural killer cells.
How many types of heavy chain are there?
5.
How many types of light chain are there?
2.
List the 5 classes of immunoglobulins.
1) IgA
2) IgD
3) IgE
4) IgG
5) IgM
What percentage of immunoglobulins do each class make up?
1) IgG - 70-75%
2) IgA - 15%
3) IgM - 10%
4) IgD - 1%
5) IgE - 0.05%
Which immunoglobulin class is predominantly found in mucous secretions?
IgA. E.g. saliva, colostrum, milk and bronchiolar secretions.
Which immunoglobulin class is a pentamer of IgG?
IgM, i.e. has 10 antigen binding sites
What is the function of IgD?
B-cell antigen receptors (i.e. on naive B cells).
Which immunoglobulin class provides immune protection to the neonate and why?
IgG, as it is the only immunoglobulin that can pass through the placenta.
List 7 functions of immunoglobulins.
1) neutralise toxins by binding to them (IgG and IgA)
2) immobilise motile microbes (IgM)
3) activate complement system (IgG and IgM)
4) enhance phagocytosis (IgG and IgA)
5) release inflammatory mediators (IgE)
6) enhance killing of infected cells (IgG)
7) increase opsonisation (all)
Define cytokines.
Soluble proteins secreted by immune cells that signal between cells.
List 5 types of cytokines.
1) chemokines
2) interleukins
3) interferons
4) colony stimulating factors (CSF)
5) tumour necrosis factors (TNF)
List 3 common features of cytokines.
1) short half-lives
2) rapid degradation
3) affect multiple organs
Define chemokines.
Cytokines that induce chemotaxis of leukocytes.
From where to where do chemokines stimulate movement of immune cells?
From blood stream to infected/inflamed tissue or lymph nodes.
How many types of chemokine are there?
Over 40.
List the 4 main chemokines.
1) CXCL - neutrophils (+lymphocytes)
2) CCL - monocytes, lymphocytes, basophils and eosinophils
3) CX3CL - T and NK lymphocytes
4) XCL - T lymphocytes
Describe the function of interferons. (2)
1) induce antiviral resistance in uninfected cells
2) limit spread of viral infection
List the 3 types of interferon and where there produced.
1) IFN α - virus infected cells
2) IFN β - virus infected cells
3) IFN γ - T helper 1 cells
What is the function of colony stimulating factors?
Direct division and differentiation of bone marrow stem cells.
What is the function of tumour necrosis factors?
Mediate inflammation and cytotoxic reactions.
Define interleukins.
Cytokines that act between immune cells.
How many types of interleukins are there?
Over 30. Some pro-inflammatory (IL1) and some anti-inflammatory (IL-10).
List 3 things interleukins cause cells to do.
1) divide
2) differentiate
3) secrete factors
List 5 barriers in innate immunity.
1) skin (dermis + epidermis)
2) mucous secretions (e.g. saliva , sebum or tears)
3) cilia
4) pyrexia
5) gastric acidity
Define pattern associated molecular patterns (PAMPs).
General molecular features common to many types of pathogen.
What is the classical PAMP?
Lipopolysaccharide (LPS).
What are pattern recognition receptors (PRRs)?
Proteins that recognise and bind to PAMPs.
What are the 2 forms of PRRs?
1) secreted/circulating
2) cell-associated (more traditional)
What is the general function of most PRRs?
Drive cytokine production in antigen-presenting cells to increase the likelihood of T cell activation.
List 5 examples of secreted/circulating PRRs.
1) defensins
2) cathelicidin
3) lectins
4) collectins
5) pentraxins
What is the function of defensins and cathelicidin.
Disrupt bacterial membranes.
List 2 cells that secrete defensins and cathelicidin.
1) phagocytes
2) epithelia
What is the function of pentraxins, lectins and collectins.
Activate complement system.
List 3 cell-associated PRRs.
1) toll-like receptors (TLRs)
2) nod-like receptors (NLRs)
3) rig-like helicase receptors (RLRs)
List 3 cells TLRs are found on.
1) neutrophils
2) macrophages
3) dendritic cells
List 3 things recognised by TLRs.
1) PAMPs (e.g. LPS, nucleic acids and flagellum proteins)
2) endogenous damage molecules
3) host molecules in unfamiliar contexts
How many TLRs are there?
Around 10. TLR4 is the archetypal TLR.
List 2 functions of TLRs.
1) secretion of inflammatory mediators (e.g. IL1, IL2, TNFα)
2) initiate tissue repair —> in response to damage
List 2 things detected by NLRs.
1) intracellular microbial pathogens
2) peptidoglycan (and breakdown products, e.g. muramyl dipeptide (MDP))
What is peptidoglycan?
A glycoproteins that forms the outer membrane of bacteria.
List the 3 most common NLRs.
1) NOD1
2) NOD2 (widespread expression)
3) NLPR3
List 2 functions of NLRs.
1) activate inflammatory signalling
2) activate antiviral signalling
List the 2 most common RLRs.
1) RIG-I
2) MDA5
What do RLRs detect?
Intracellular double stranded viral DNA and RNA.
What do RLRs couple with effectively and why?
Interferon production. To enable the antiviral response.
List the 2 killing pathways used by macrophages and neutrophils.
1) oxygen dependent
2) oxygen independent
List the 2 oxygen dependent reactive oxygen intermediates.
1) hydroxyl free radical
2) nitric oxide
List 4 O2 independent methods of killing pathogens.
1) enzymes
2) lysozymes
3) pH
4) TNF
List 2 reasons why adaptive immunity is necessary.
1) microbes evade innate immunity
2) need memory to specific antigens —> faster and stronger response
List 2 cell groups of cell-mediated immunity.
1) antigen-presenting cells (APCs): dendritic cells, macrophages and B cells
2) T cells
What are major histocompatibility complexes (MHC complexes)?
Cell surface glycoproteins that present antigenic peptides to T cell receptors (TCRs).
What are MHC complexes also known as?
Human leukocyte antigen molecules (HLA molecules).
Why do MHC complexes exist?
Safety mechanism that prevents the immune system from activating too easily.
T cell antigen-specific receptor will only bind to an antigen if it is presented with an MHC complex.
What is the function of MHC I?
Present antigens of intracellular pathogens (viruses).
Where are MHC I found?
Surface of all cells (except RBCs).
Describe the MHC I and cytotoxic T cell relationship.
Cytotoxic T cells require antigens presented via MHC I before it can kill the infected cell.
What is the function of MHC II?
Present antigens of extracellular pathogens.
Where are MHC II found?
Surface of APCs.
Describe the MHC II and helper T cell relationship.
Helper T cells require antigens presented by MHC II before they induce B cell activation.
List 4 functions of helper 1 T cells.
1) produce IL2, IFNγ, TNFβ
2) induce B cells differentiation
3) activate macrophages
4) activate cytotoxic T cells
List 4 functions of helper 2 T cells.
1) produce IL4, IL5, IL6, IL10, IL13
2) induce B cells differentiation (IL4, IL5, IL10)
3) induce IgE and IgG antibodies release (via B cells)
4) activate basophils and mast cells (via IgE)
List 4 functions of cytotoxic T cells.
1) induce lysis
2) induce apoptosis
3) release pro-inflammatory mediators
4) release macrophage activating cytokines
How do cytotoxic T cells induce lysis?
Release perforin and granulysin from secretory granules which form pores in infected cell cell membranes, killing infected cells.
Describe clonal selection.
Lymphocytes that recognise self are killed. B cells are killed in the bone marrow and T cells are killed in the thymus.
Describe B cell activation. (9)
1) naive B cell surface IgD antibody binds to antigen presented by APCs
2) naive B cell presents antigen via MHC II
3) IL1 released by APC activates B cell
4) naive helper 2 T cell is presented the same antigen by another APC
5) helper 2 T cell activates
6) B cell presents antigen to helper 2 T cell (TCR binds to MHC II)
7) helper 2 T cell releases IL4, IL5, IL10, IL13
8) B cell is induced to divide via clonal expansion
9) B cell differentiates into plasma cells and memory cells
Define allergy.
Abnormal response to harmless foreign antigens, e.g. a drug.
Define atopy.
Inherited tendency to develop allergies.
List 3 examples of atopy.
1) hay fever
2) eczema
3) asthma
Define intolerance.
Inability to properly metabolise or absorb a drug.
List 3 skin clinical conditions related to allergy.
1) eczema
2) itching
3) reddening
List 2 airway clinical conditions related to allergy.
1) bronchoconstriction
2) excessive mucus production
List 3 gastrointestinal clinical conditions related to allergy.
1) abdominal bloating
2) vomiting
3) diarrhoea
List 7 allergic diseases.
1) anaphylaxis
2) allergic asthma
3) allergic rhinitis
4) allergic conjunctivitis
5) atopic dermatitis
6) food allergy
7) oral allergy syndrome
List 6 low affinity IgE receptor expressing cells.
1) B lymphocytes
2) T lymphocytes
3) neutrophils
4) monocytes
5) platelets
6) eosinophils
List 3 functions of low affinity IgE receptor expressing cells.
1) regulate IgE synthesis
2) trigger monocyte cytokine release
3) antigen presentation
List 3 high affinity IgE receptor expressing cells.
1) mast cells
2) basophils
3) eosinophils
What cells are the main effector of IgE mediated immunity? (1)
Mast cells.
List 5 substances found in mast cell granules.
1) histamine —> increased vascular permeability and diameter and bronchoconstriction
2) cytokines —> eosinophil attraction and activation
3) proteases
4) prostaglandin D2 —> smooth muscle contraction
5) platelet activating factor —> increases platelet aggregation, vascular permeability and neutrophil degranulation
List 8 allergens.
1) latex
2) venoms
3) foods
4) drugs
5) pollens
6) dust mite faeces
7) animal fur
8) nickel
List 4 features that make an allergen.
1) particulate delivery of antigens
2) prior sensitisation
weak PAMPs —> weak innate immune response, NO adaptive immune response
3) nasal/skin delivery
4) low doses
How long does anaphylaxis take to occur?
Minutes (IV) —> hours (GI)
Define anaphylaxis.
An extreme and severe allergic reaction.
List 3 types of features of anaphylaxis.
1) skin
2) respiratory
3) cardivascular
List 4 skin features of anaphylaxis.
1) itching
2) reddening
3) rash
4) oedema
List 3 respiratory features of anaphylaxis.
1) wheeze
2) laryngeal obstruction
3) cyanosis
List 2 cardiovascular features of anaphylaxis.
1) tachycardia
2) hypotension
What is the Gell and Coombs classification?
Classification of hypersensitivity reactions.
What is a type 1 hypersensitivity reaction?
IgE mediated.
Describe a type 1 hypersensitivity reaction. (6)
1) exposure to antigen
2) IgE formed after exposure
3) IgE attaches to mast cells —> expressed as cell surface receptors
4) re-exposure to antigen
5) mast cell degranulation
6) inflammation
List 4 examples of type 1 hypersensitivity reactions.
1) acute anaphylaxis
2) hay fever
3) eczema
4) asthma
What is a type 2 hypersensitivity reaction?
IgG/IgM mediated.
Cell-surface-associated antigens.
Describe type 2 hypersensitivity reactions. (5)
1) exposure to antigen
2) IgG/IgM formed after exposure
3) re-exposure to antigen
4) IgG/IgM bind to antigen
5) inflammation
Give an example of type 2 hypersensitivity reactions.
Haemolytic disease of foetus. RhD-ve mother, RhD+ve baby.
What is a type 3 hypersensitivity reaction?
Immune complex mediated. (IgG).
Describe a type 3 hypersensitivity reaction. (5)
1) IgG binds to soluble antigen
2) antigen-antibody complex forms
3) complement system is activated
4) small blood vessels become damaged
5) inflammation
List 4 examples of type 3 hypersensitivity reactions.
1) farmers lung
2) malt-workers lung
3) mushroom-workers lung
4) pigeon fanciers lung
What is a type 4 hypersensitivity reaction?
Helper T cell mediated.
Describe a type 4 hypersensitivity reaction. (5)
1) exposure to antigen
2) excessive helper T cell cytokine secretion
3) cytokines activate macrophages
4) macrophage secrete pro-inflammatory mediators
5) inflammation
List 3 type 4 hypersensitivity reactions.
1) TB
2) sarcoidosis
3) contact dermatitis from poison ivy
Which type of hypersensitivity reaction is immediate?
Type 1.
Which type of hypersensitivity reaction is delayed?
Type 4.
List 4 features of non-immune anaphylaxis.
1) due to direct mast cell degranulation
2) no prior exposure to antigen
3) clinically identical
4) previously known as anaphylactoid reactions.
List 3 risk factors for hypersensitivity.
1) female
2) immunosuppression
3) HLA group
List 4 clinical criteria for allergy to a drug.
1) unrelated reaction to pharmacological properties of drug
2) no linear relation to dose —> tiny dose can cause severe reaction
3) reaction disappears on cessation
4) reaction reappears on re-exposure
What is the concept of immunisation and vaccines?
Manipulate immune system to generate a persistent protective response against pathogens.
Define passive immunisation.
Transfer of preformed antibodies.
List 2 examples of natural passive immunity.
1) maternal antibodies across placenta to foetus
2) maternal antibodies via breast milk to baby
Define artificial passive immunity.
Treatment with human IgG against specific pathogens or toxins.
List 5 instances when artificial passive immunisation would be used.
1) agammaglobulinaemias (B cell defects)
2) immunocompromised
3) no time for active immunisation
4) acute danger of infection
5) anti-toxins or anti-venins
List 3 conditions passive immunity is used prophylactically (to prevent disease).
1) hepatitis
2) measles
3) rabies
List 3 conditions passive immunity is used for anti-toxins.
1) botulism
2) tetanus
3) diphtheria
List 3 conditions passive immunity is used for anti-venins.
1) snake
2) insect
3) jellyfish
Define adjuvants (in context of vaccines).
Substances added to a vaccine to stimulate the immune system.
What is the drawback of passive immunisation?
No immunological memory, therefore no long term protection.
List 5 antigen choices for vaccine design.
1) whole organism (live attenuated or killed inactive)
2) subunit (toxoid, antigenic extract, recombinant protein)
3) peptides
4) DNA
5) engineered virus
List 4 properties of the ideal vaccine.
1) safe
2) generate T and B cell memory
3) stable and easy to transport
4) not require repeated boosts
List 4 ways adrenaline combats anaphylaxis.
1) acts on α1-adrenoreceptors —> vasoconstriction (increased peripheral vascular resistance, BP and coronary perfusion)
2) acts on β1-adrenoreceptors —> positive ionotropic and chronographic effects on heart
3) acts on β2-adrenoreceptors —> bronchodilation
4) reduces further release of inflammatory mediators from mast cells and basophils
List 6 treatment strategies for allergic reactions.
1) avoid allergen
2) allergen desensitisation
3) inhibit IgE production
4) inhibit IgE interaction with receptor
5) inhibit mast cell activation
6) inhibit mast cell products
What influxes into the lungs during asthma?
Eosinophils.
