Immunology- Introduction to Clinical Sciences Flashcards
What is immunology
Study of the immune system
and how it has evolved to protect us from pathogens/non-self
What is innate immunity
Instinctive, non-specific, does not depend on lymphocytes, present from birth
What is adaptive immunity?
Specific ‘Acquired/learned’ immunity, requires lymphocytes, antibodies
What are adaptive and innate immunity made up of
cells and soluble factors (humoral)
What is serum
plasma without fibrinogen and other clotting factors
What makes up blood?
Where are leukocytes made
Made in the bone marrow - Haematopioesis
Components of the immune system
Cells of the Immune system
Also:
Mast cell
Natural Killer Cell
Dendritic cells:
Kupffer- liver
Langerhans-skin
Soluble Factors called?
3 types:
Complement
Antibodies
Cytokines, Chemokines
Modes of action for complement (C’) factors
- Direct lysis
2.Attract more Leukocytes to the site of infection - Coat invading organism
How are complement factors only activated by?
They are activated only as part of the immune response – 3 activation pathways
What are complement factors?
Group of ~20 serum proteins secreted by the liver that need to be activated to be functional
What do antibodies bind to?
specifically to Antigens (Ag)
Are immunoglobulin soluble?
Yes
Where can you find immunoglobulins?
Cell Surface (on B cells)
5 distinct classes of immunoglobulins?
IgG
IgA
IgM
IgD
IgE
What do antibodies act as?
Adapter that links microbe to a phagocyte
What cells secrete cytokines?
Immune and non-immune cells
Types of cytokines?
Interferons (IFN)
Interleukins (IL)
Colony Stimulating Factors
Tumour Necrosis Factors (TNFa & b)
Chemokines
What do Interferons (IFN) do?
induce a state of antiviral resistance in uninfected cells IFNa & b - produced by virus-infected cells
IFNg - released by activated T cells
Role of interleukins (IL)
produced by many cells, over 30 types
It can be pro-inflammatory (e.g. IL1) or anti-inflammatory (e.g. IL-10)
Can cause cells to divide, differentiate and secrete factors
Role of Colony-Stimulating Factors
Involved in directing the division and differentiation of bone marrow stem cells – precursors of leukocytes
What are Colony-Stimulating Factors precursors of ?
Leukocytes
Role of Tumour Necrosis Factors (TNFa & b)
Mediate inflammation and cytotoxic reactions
What are Chemokines
Leukocyte chemoattractants
Defensive mechanisms?
Innate (non-specific)
Adaptive (specific)
Innate vs Adaptive Immunity
What does innate immunity integrate with
adaptive response
Innate Immunity is composed of …
Physical and chemical barriers
Phagocytic cells (neutrophils and macrophages)
Blood proteins (complement, acute phase)
Physical barriers (exterior defences)
Interior defences (Inflammatory Response)
Stop bleeding (coagulation)
Acute inflammation (leukocyte recruitment)
Kill pathogens, neutralise toxins, limit pathogen spread
Clear pathogens/dead cells (phagocytosis)
The proliferation of cells to repair damage
Remove blood clot – remodel the extracellular matrix
Re-establish normal structure/function of tissue
How are defence mechanisms/barriers breached?
Tissue damage (trauma) or infection
Define inflammation.
A series of reactions that brings cells and molecules of the immune system to sites of infection or damage
Hallmarks of inflammation
Increased blood supply
Increased vascular permeability
Increased leukocyte transendothelial migration ‘extravasation
Types of Inflammation
Acute Inflammation
Chronic Inflammation
What is an acute inflammation
Complete elimination of a pathogen followed by resolution of damage, the disappearance of leukocytes and full regeneration of tissue
What is chronic inflammation
Persistent, un-resolved inflammation
Sensing microbes in blood consist of?
Monocytes
Neutrophils
Sensing microbes in tissue consist of?
Macrophages
Dendritic cells
What is PRR, and where are they found
Pattern Recognition Receptors
on cells
What is PRR, and where are they found
Pathogen-Associated Molecular Patterns
Found on microbe
The function of complement factors?
Lyse microbes directly (MAC)
Chemotaxis (C3a and C5a)
Opsonisation
(C3b)
Stages of phagocytosis
- Binding
- Engulfment
- Phagosome Formation
- Lysosome fusion digestion
- Membrane disruption/fusion
Why do we need adaptive Immunity?
Microbes evade innate immunity (proteases, decoy proteins, etc)
Intracellular viruses and bacteria ‘hide’ from innate immunity
Need memory to specific antigen – ‘seen it before so faster response’
Types of adaptive immunity?
Cell-Mediated - T cells - intracellular microbes
Humoral (Ab) - B cells - extracellular microbes
What does cell-mediated immunity interlay between?
Antigen Presenting Cells
T cells
Name antigen-presenting cells
Macrophages
Dendritic Cell
B cells
What does cell-mediated immunity require?
Intimate cell-to-cell contact
Major Histocompatibility Complex (MHC)
Intrinsic/Endogenous (intracellular) antigens
Extrinsic/Exogenous (extracellular) antigens
Recognise Self or Non-Self
Why does cell-mediated immunity require intimate cell-to-cell contact
– to control Ab responses via contact with B cells
– to directly recognise and kill virally infected cells
What do T lymphocytes respond to?
presented antigens
What is a t-cell selection?
T cells that recognise self are killed in the foetal thymus as they mature
What does the T cell Receptor (TCR) recognise
foreign antigens in association with Major Histocompatibility Complex (MHC)
MHC & T cell table
What do antibodies do?
Neutralise toxin by binding to it
Increase opsonisation – phagocytosis
Activate complement
What do stem cells produce
precursors (immature leukocytes)
Where does T-cell precursor mature
Thymus
Where does B-cell precursor mature
Lymph node
What cells give rise to cells involved in adaptive immunity
Lymphoid progenitor cells
What cells give rise to cells involved in innate immunity
Myeloid progenitor cell
1st line of defence when a pathogen invades the body?
Innate immune system
What comprises the innate immune system
Physical barriers and chemical and biological barriers afterwards
What is the role of soluble proteins?
Opsonisation
Forming a membrane attack complex
Enhance inflammation
What is opsonisation
A process where the complement proteins coat the outer surface of the pathogen allowing the phagocytes (macrophage) to engulf the pathogen much more easily.
How can opsonisation occur?
This is because the macrophage contains special receptors for specific complement proteins
What is a membrane attack complex
A Group of complement proteins makes a hole in the pathogen, causing an in the flush of fluids, creating a disbalance in osmolarity causing the pathogen to lyse and be destroyed
What organ produces complement proteins?
Liver
How do complement proteins become activated
Circulate the bloodstream in an inactive form until they contact the pathogen. They then become activated
Name the three complement pathways
Classical pathway
Alternate pathway
Lectin pathway
What complement proteins are involved in the classical pathway
C1q
C1r
C1s
C4
C2
What complement proteins are involved in the alternate pathway
Factors:
D
B
C3
Properdin
What complement proteins are involved in the lectin pathway
Mol/Ficolin
C4
C2
MASP2
What is the purpose of the three complement factor pathways
In splitting C3 into C3a and C3b
Essentially C3 becomes activated via cleaving
What is the role of complement factor C3a
Enhance inflammation
What is the role of complement factor C3b
Opsonisation
Lysis of cell via membrane attack complex
How does the classical complement protein pathway start
Initiated when antibodies bind to the antigen of the pathogen
Complement proteins: C1q, C1R, C1s bind to the FC portion of the antibody-forming another complement protein complex called the C4b2a protein complex
What is another name for C4b2a protein complex
C3 convertase
Initiation of the lectin pathway
Complement proteins (Ficolin) bind to oligosaccharides of a pathogen
This makes the C4b2a protein complex
Similarities between lectin pathway and classical pathway
Both create the C4b2a protein complex
Purpose of C3b2a protein complex
The C4b2a protein complex splits the C3 into C3a and C3b
What does the alternate pathway do?
- C3b binds to the surface of the pathogen forming C3bBb
or
- C3b along with properin forms C3bBb protein complex
What is the purpose of the alternate complement protein pathway
Enhances the classical and lectin pathway or vice versa
Purpose of C3bBb protein complex
Splits C3 into C3a and C3b
Most important complement proteins
C3a
C5a
What do C3a do?
C3a and C5a stimulate mast cells in producing histamine
Role of histamine
Attract leukocytes
Enhance inflammation
Increase vascular permeability
What does C3b do?
C3b thioester bonds react with the pathogen surface - allowing opsonization.
C3b can bind to the C4b2a protein complex forming the C4b2a3b complex. c4b2a3b complex activates C3 and C5. This enhances inflammation and lyses pathogen via the formation of membrane attack complex
What does a naive T cell express
CD4 and CD8 co-receptor
What cells are present in the germinal centre of the lymph node?
B cells
Summary of Innate immune response
In case of inflammation due to invasion of the pathogen, more leukocytes are recruited in the infiltrated area to phagocytose and destroy the pathogen
Activated dendritic cells migrate to the lymph node to activate T-cell
What leukocyte cell will be recruited in case of inflammation and why?
Neutrophil because its fast acting
What do complement factors alow
Complement proteins will make it easier for leukocytes to destroy pathogens.
How are leukocytes recruited
Via chemical signals
Role of innate immune response
Halt the pathogen and wait for the pathogen to be recognised by the adaptive immune cells (B and T cells)
In case of inflammation due to invasion of the pathogen, more leukocytes are recruited in the infiltrated area.
How is this achieved?
In case of inflammation due to the pathogen invasion, PAMP receptors on the pathogen are recognised by mast cells stimulating histamine release and tissue macrophages to secrete cytokines attracting more leukocytes in the infiltrated area. This allows for leukocytes, primarily neutrophils and enters the infiltrated area.
It begins phagocytosing pathogens.
What protein stimulates phagocytosis?
Complement proteins
What do antigen-presenting cells activate?
Adaptive Immune Cells
What do macrophages and dendritic cells make to enhance immune response.
Cytokines
Main cytokines involved in innate immune response
CXCL8
IL6
IL-1B
IL-12
Role of CXCL8 cytokine?
Attract more leukocytes
Role of IL6 cytokine?
Activates lymphocytes.
Stimulate liver to make more proteins for immunity
Role of IL-1B cytokine?
Increases vascular permeability
Role of IL-12 cytokine?
Activates natural killer and differentiation of CD4 naive T cell into T helper 1 cell
Role of TNF-α cytokine?
Stimulates Inflammatory response
Role of activated macrophages in innate immune response
Secretes cytokines which do the following
Liver: Secretes fibrinogen and C reactive protein
Hypothalamus: fat and muscle to increase body temp
Bone marrow epithelial: attract more neutrophils
Dendritic cells: TNF-α stimulate the migration of dendritic cells to lymph node to initiate adaptive immunity
Why is the dendritic cell an important connection between the innate and adaptive immune systems?
TNF-α stimulates the migration of dendritic cells to lymph nodes to initiate adaptive immunity.
How can dendritic cells move to the lymph node?
Via a process called licensing
What happens to an infected macrophage?
Natural Killer cells will kill an infected macrophage via apoptosis
What cell is regarded as the ‘professional’ antigen-presenting cell
dendritic cell
What are Haematopoietic pluripotent stem cells (haemocytoblast)
the stem cell that every blood cell in the body originates from
Role of Neutrophils in immune response
Plays an important role in innate immunity (phagocytosis)
What are the 2 main intracellular granules of neutrophils
o Primary lysosomes – can kill microbes by secreting toxic substances
o Secondary granules
Role of monocytes in immune response
Plays an essential role in innate AND adaptive immunity (phagocytosis and Ag presentation)
Main role – remove anything foreign (microbes) or dead
What does monocyte differentiate into in the tissues
Macrophages
Role of macrophages in immune response
Play an important role in innate and adaptive immunity (phagocytosis and Ag presentation)
The main role – remove foreign (microbes) and self (dead/tumour cells)
Most often the first line of non-self recognition
Present Ag to T-cells
Role of eosinophil in immune response
Mainly associated with parasitic infections and allergic reactions
Activates neutrophils, induces histamine release from mast cells and provokes bronchospasm
Lifespan of eosinophil
8-12 days
What dyes to granules stain for eosinophil?
Acidic dyes
Role of basophil
Mainly involved in immunity to parasitic infections and allergic reactions
Binding of IgE to receptor causes de-granulation releasing histamine – main cause of allergic reactions
Lifespan of basophil?
2 days
What dyes to basophilic granules stain for?
Basic dyes
What cells are basophils very similar to?
Mast cells
Where are mast cells found
Only in tissues (precursor in blood)
Role of mast cells in immune response
Binding to IgE to receptor causes de-granulation releasing histamine – main cause of allergic reactions
Role of T cells
Play a major role in adaptive immunity
Recognise peptide Ag displayed presenting cells (APC)
Lifespan of T cells
hours-years
Where are T cells found?
blood, lymph nodes and spleen
4 main types of T cells
T helper 1 (CD4 – help immune response intracellular pathogens)
T helper 2 (CD4 – help produce antibodies extracellular pathogens)
Cytotoxic T cell (CD8 – can kill cells directly)
T regulator – regulate immune responses
What do B cells do?
Play a major role in adaptive immunity
Recognise Ag displayed by antigen-presenting cells (APC)
The lifespan of B cells
hours-years
Where do B cells mature
Bone marrow
What do B cells differentiate into?
plasma cells that make antibodies
Where are B cells found?
blood, lymph nodes and spleen
Where are natural killer cells found?
Spleen
Tissues
Role of Natural Killer Cells
They recognise and kill by apoptosis;
o Virus-infected cells
o Tumours cells
Account for 15% of lymphocytes
Role of IgG
Predominant in human serum, 70-75% of total Ig in serum
Crosses placenta
Role of IgA
Accounts for 15% of Ig in serum
Predominant Ig in mucous secretions such as saliva, milk and bronchiolar secretions
Role of IgM
Accounts for 10% of Ig in serum
Mainly found in blood (they’re big so they can’t cross the endothelium)
Mainly primary response, initial contact with Ag
Role of IgD
Accounts for 1% of Ig in serum
A transmembrane monomeric form is present on mature B cells
Role of IgE
Accounts for ~0.05% of Ig in serum
Basophils and mast cells express an IgE-specific receptor that has a high affinity for IgE – binding triggers the release of histamine
Associated with allergic response and defence against parasitic infections
Define epitope
the part of the antigen that binds to the antibody/ receptor binding site
Define affinity
measure of binding strength between an epitope and an antibody binding site. The higher the affinity the better
Define Antigen (Ag)
a molecule that reacts with preformed antibody and specific receptors on T and B cells.
Define Antibody.
the protein produced in response to an antigen. It can only bind with the antigen that induced its formation – i.e. specificity.
Define Cytokines?
proteins secreted by immune and non-immune cells. Substances produced by one cell influence the behaviour of another, thus effecting intercellular communication.
What are chemokines
Group of approx. 40 proteins that direct the movement of leukocytes from the bloodstream into the tissues or lymph organs by binding to specific receptors on cells.
They attract leukocytes to sites of infection/inflammation – like magnets.
Anatomical barriers
Skin – dermis and epidermis
Sebum (skin secretions)
Intact skin – prevents penetration, prevents growth
Mucous membranes – a physical barrier
Saliva
Tears – lysozyme in tears and other secretions
Low pH and commensals of the vagina
Mucous secretions
Mucous–entrapment
Cilia – beating removes microbes
Commensal colonies – attachment, nutrients
Physiological barrier
Temperature – chickens have high body temperatures and are Anthrax resistant
Fever response inhibits micro-organism growth
pH
Gastric acidity – neonate stomach is less acidic than an adult, so susceptible to infection
What happens when a naive t cell recognises a self-antigen
The naive T cell will be destroyed before it matures because we don’t want a T cell attacking our own body
How does a CD8 T cell become activated
When an infected antigen-presenting cell, such as a phagocyte, presents a foreign antigen on MHC class 1 to the naive CD8 T cell.
The activated CD8 T cell then becomes a cytotoxic T cell.
What do cytotoxic cells do?
Destroy infected cells with the same specific antigen as was presented by the infected phagocyte
How does a CD4 T cell become activated
When a non-infected antigen-presenting cell, such as a phagocyte presents a foreign antigen on an MHC class 2 to the naive CD4 T cell
The activated CD4 T cell becomes a T-helper cell
What is the purpose of a T helper cell
Enhance the immune response by activating B cells, macrophages, natural killer cells and other phagocytes
How does a naive B cell become activated
Naive B cells can recognise a specific antigen of a pathogen, causing the naive B cell to engulf the pathogen, process and present foreign antigen on MHC class 2 to the activated T helper cell
Relationship between T-helper cell and B cell
The activated T-helper cell can activate B cell to proliferate, and differentiate into either a memory B cell or a plasma cell
What do plasma cells secrete
specific antibodies towards that antigen memory B cells for the memory of that specific antigen, so the next infection can be resolved quickly
Role of antibodies
Neutralise a pathogen: antibodies prevent bacterial adhesion
Opsonisation: antibodies promote phagocytosis
Complement activation: antibodies activate complement -> opsonisation causes lysis of pathogen
How do B and T cells recognise specific antigens
B -cells have specific antibodies on the surface of their cell membrane that only binds to a specific antigen
What gives antibodies diversity to bind to different antigens
Antibody consists of:
Variable region on the N terminal
Constant agent on the C terminal
The constant agent determines what class of antibody this is
The variable region can be composed of diff types of amino acid sequences giving it its uniqueness
When does adaptive immunity take place?
Microbes evade innate immunity
Intracellular viruses and bacteria hide from innate immunity
Types of adaptive immunity
Cell-mediated – T cells – intracellular microbes
Humoral (Ab) – B cells – extracellular microbes
What does the Major histocompatibility complex (MHC) display
Peptide from self OR non-self proteins (e.g. degraded microbial proteins) on the cell surface – invasion alert
Different types of MHC
MHC I – glycoproteins on all nucleated cells
MHC II – glycoproteins only on APC
MHC III – code for secreted proteins
Intrinsic (intracellular) & MHC
class I (all cells) – Tc (CD8) – kill infected cell with intracellular pathogen
Extrinsic (extracellular) & MHC
class II (APC only) – Th (CD4) – help B cell make Ab to extracellular pathogen
What does cell-mediated immunity interlay between
-Antigen-presenting cells (APC)
Macrophages
Dendritic cells
B cells
-T cells
What is required for cell-mediated immunity
- Requires intimate cell-to-cell contact
Control Ab responses via contact with B cells
Directly recognise and kill virally infected cells. - Major histocompatibility complex (MHC)
- Intrinsic (endogenous) antigens
- Extrinsic (exogenous) antigens
- Recognise self or non-self
What do T cells only respond to?
to intracellular presented antigens
When do B cells become activated
upon binding with an antigen
Where does the clonal expansion of B cells take place
go to the lymph nodes where clonal expansion takes place with the cells differentiating into plasma cells
What do plasma cells secrete
Ab (usually IgM), which later turns into IgG
What happens with clonal expansion with B cells
B cells divide – clonal expansion and differentiate into plasma cells and memory B cells.
What leads to a secondary response?
Re-stimulation of memory B cells
What does a T cell receptor contain, and what does this allow?
Can bind to a specific epitope of an antigen as it has both a variable and constant region
How does a T cell become activated
Infected phagocyte presents epitope of antigen to naive T cell on either MHC I or MHC II.
What does hypersensitivity refer to?
abnormal reactions of the immune system against certain antigens
Causative factors for hypersensitivity
Self-reactivity of immune cells
Effectors/Regulators’ Imbalance
What occurs in Type 1 hypersensitivity
Previous exposure to the antigen results in the production of antibody IgE
IgE molecules bind to the receptors on the surface of mast cells and basophils
Upon re-exposure to the same antigen, it causes mast cell degranulation and the release of pharmacologically active substances such as histamine
What is required for a type 1 hypersensitivity allergic reaction to take place?
Prior exposure to the antigen
Signs of type 1 hypersensitivity allergic reaction?
Immediate response:
Smooth muscle spasms and inflammation
Examples of type 1 hypersensitivity allergic reaction
Anaphylaxis
Allergies:
-food
-drugs
-pollen
Allergic bronchial asthma
How does a Type II hypersensitivity allergic reaction take place?
Previously formed IgG or IgM antibodies bind to the surface of a particular cell type.
Antibody marking marks the cell for destruction, with cytotoxic cells killing cells by complement system or phagocytosis
Examples of Type II hypersensitivity allergic reaction?
Autoimmune diseases (immune thrombocytopenia, autoimmune neutropenia, myasthenia gravis)
How does a Type III hypersensitivity allergic reaction take place?
Mediated by IgG or IgM
The antibodies bind to free-floating antigens forming antibody-antigen complexes.
The complement system is activated, and inflammation causes damage to the affected tissue
Examples of Type III hypersensitivity allergic reaction
Serum sickness
Arthus reaction
What is a Type IV hypersensitivity allergic reaction
Delayed (after a day) reaction mediated by T cells
How does a Type IV hypersensitivity allergic reaction happen
Pre-sensitised T cells are produced during the previous contact with the antigen.
Upon exposure to the same antigen, T helper cells release inflammatory cytokines while T killers induce cytotoxic reactions
Examples of Type IV hypersensitivity allergic reaction
Contact dermatitis
TB skin test
Name the three different vaccines used.
whole killed
toxoids
live attenuated
Define Passive immunity
Passive immunity is short-term immunity which results from the introduction of antibodies from another person or animal
Advantages of Passive Immunity
- Gives immediate protection
- Effective in immunocompromised patients
Disadvantages of Passive Immunity
- Short-lived
- Possible transfer of pathogens
Define vaccines
antigenic substance prepared from the causative agent of a disease
What is active immunisation
- Non-living vaccines (whole killed and toxoids)
- Live attenuated vaccines
What are non-living vaccines, and how does it work?
Whole killed vaccines
These vaccines do not cause infection, but the antigens contained in them induce an immune response which protects against infection.
Limitations to non-living vaccines
- The organisms must be grown to high titre in vitro
- Whole pathogens often cause excessive reactogenicity
- usually need at least two vaccinations
What are toxoids vaccines?
Non-living vaccines can also be cell-free toxoids (inactivated toxins).
What are Live attenuated vaccines
The organisms replicate within the host, and induce an immune response which is protective against the wild-type organism
Advantages of Live attenuated vaccines
- Lower doses are required, so the scale of in vitro growth needed is lower
- Immune response more closely mimics that following real infection
- Route of administration may be more favourable
- Fewer doses may be required
Limitations to live attenuated vaccines
- Often impossible to balance attenuation and immunogenicity
- Reversion to virulence
- Transmissibility
- Live vaccines may not be so attenuated in immunocompromised
Which pathogens lack vaccines?
- HIV
- Malaria
- Herpes simplex virus
Why do some pathogens lack vaccines
- Pathogen is too hard to grow
- Killed pathogen not protective
- Impossible to obtain attenuated and suitably immunogenic strain
Novel approaches to vaccines?
- Recombinant proteins
- Synthetic peptides
- Live attenuated vectors
- DNA vaccines
Stages of vaccination
- Engage the innate immune system
- Danger signals that activate the immune system triggers such as molecular fingerprints of infection – PAMPs (pathogen-associated molecular patterns)
- Engage TLR receptors
- Activate specialist APC
- Engage the adaptive immune system
a. Generate memory T and B cells
b. Activate T cell help
What does PAMP stand for?
Pathogen Associated Molecular Pattern
Where is PAMP found?
On pathogens such as viruses and bacteria.
Not normally found inside the body
Examples of PAMP
Lipopolysaccharides (LPS)
Lipoproteins
Peptidoglycans
What organisms can you find PAMP?
Pathogenic and non-pathogenic organisms
What are PAMP essential for?
The survival of all pathogens
What is the receptor for PAMP referred to as?
PRR (Pattern Recognition Receptor)
Where can PRRs be found?
- Secreted and circulating PRRs
- Cell-associated PRRs (more traditional receptors)
What do PRRs trigger?
Innate Immune Response and inflammatory response
What is the role of PRRs
Optimise the pathogen
Activate the complement protein
Phagocytise the pathogen
Activate the inflammatory mediators
Secrete: Interferons, cytokines, pro-inflammatory cytokines
Induce apoptosis
What is Secreted and circulating PRRs
- Antimicrobial peptides secreted in lining fluids from epithelia
- Lectins and collectins (carbohydrate-containing proteins that bind carbohydrates or lipids in microbe walls
What does secreted and circulating PRRs do?
Activate complement
Improve phagocytosis
What are the main family of Cell associated PRRs
Toll-Like Receptors (TLR)
What do Cell-associated PRRs recognise
broad range of molecular patterns
What does the recognition of microbes and viruses depend on
seeing ancient, conserved features of them
Role of pattern recognition
pathogen responses
homeostasis
damage recognition
Why do families of receptors in pattern recognition exist?
to detect these in fluids, cell surfaces and compartments, and intracellularly
Pattern recognition and homeostasis
- Blood neutrophil numbers may be dependent upon TLR4 signalling, independent of LPS (lipopolysaccharide) in homeostasis
- Induction of endotoxin tolerance in the new born gut
- Maturation of the normal immune system
What are TLRs adapted to recognise
range of endogenous damage molecules, which may share characteristics of hydrophobicity
What does TLR signalling by cellular damage products activate
immunity to initiate tissue repair and perhaps enhance local antimicrobial signalling
What is PRRs involvement with disease
- Recognition of host molecules in autoimmune disease
- Failure to recognise pathogens or increased inflammatory responses
What is the recognition of molecular patterns key to
survival and successful establishment of commensal microbiome
Pattern recognition receptors are highly conserved systems of …
immunity, evolved to recognise unchanging patterns
What TLR form dimer when peptidoglycan, lipoproteins, zymosan e.t.c are detected
TLR 1 & TLR 2
TLR 2 & TLR 6
What does TLR 4 recognise
Lipopolysaccharides of Gram +
What does TLR 5 recognise
Flagella
What TLRs are found within endosomes?
TLR 3,6,7,9
How is TLR 3 activated
Once it comes into contact with double-stranded RNA (virus)
How are TLR 7 & 8 activated?
Once it comes into contact with single-stranded RNA viruses
How is TLR 9 activated
Once it comes into contact with the CPG DNA of bacteria or fungi
What happens once TLRs become activated?
Initiate a cascade of events -> leading to the activation of certain transcription factors. These transcription factors then become translated to do the following:
-Make proteins for cell signalling
-Make interferons
-Make proinflammatory cytokines
The immune system is non-specific, meaning it doesn’t differentiate between pathogens
Innate
The innate immune system responds (faster/slower) ________ than the adaptive immune system.
Faster
Immunologic memory is a feature of the (adaptive/innate) immune system.
Adaptive
Clonal deletion is when most of the clonally expanded cells of the immune system die off after the infection is over.
Adaptive
The ________ develop into cells of the innate immune system like neutrophils, eosinophils, basophils, mast cells, dendritic cells, macrophages, and monocytes.
myeloid progenitor cells
of the innate immune system destroy pathogens using cytoplasmic granules or oxidative burst.
Neutrophils
Monocytes migrate into tissues and differentiate into
____ which remain in tissues and aren’t found in the blood
Macrophages
cells destroy pathogens and break up its proteins into short amino acid chains to present to T-helper cells.
Dendritic cells
cells are large lymphocytes that target cells infected with viruses and cancer cells.
Natural Killer
Antibodies are produced by lymphocytes.
B
CD8 T cells only kill the body’s own cells that present antigens on ____- molecule on the cells surface.
MHC type I
Cytokines promote (3 processes) of immune cells.
activation, proliferation, and differentiation
___ is a cytokine secreted by CD4+ T helper cells that promotes the proliferation of all lymphocytes.
IL-2
IL-1beta, IL-6, and TNF-alpha are cytokines that travel to the liver and promote the production of proteins like C-reactive protein and complement proteins.
Acute phase
______ are cytokines numbered in the order they were identified.
Interleukins
are cytokines in charge of activating endothelial cells, increasing vascular permeability, and helping to induce fever
Interferons
______- is an inhibitory cytokine that helps CD4+ T cells develop into a regulatory cell that can slow down or stop the overall immune response.
TGF-beta
What are the major cell type of the immune system
Phagocytes
How does opsonisation occur
via the binding of soluble proteins to microbial surfaces so that they can be recognized later by phagocytes.
What is damage-associated molecular patterns.
The components of dying cells that are recognized by pattern recognition receptors on phagocytes
What prtoein is expressed on cell types that transmit the signal to inhibit phagocytosis.
CD47
What are TLR
family of pattern recognition receptors that have dimers of chains with extracellular leucine-rich domains that bind to microbes.
they interact with extracellular ligands on the microbes’ plasma membrane.
Type I interferons are typically produced by (virus/bacteria) ____-infected cells.
virus
Three of the major proinflammatory cytokines released in response to pattern recognition receptor activation are
interleukin-1, interleukin-6, and tumor necrosis factor-α.
What chemokine serves as a chemoattractant for neutrophils in the early stages of infection.
IL-8
What does complement refer to?
collection of serum proteins that connects the innate and adaptive immune systems.
What enzyme component cleaves the complement components C3 and C5 respectively.
C3 and C5 convertases
What is a T cell ?
type of lymphocyte involved in paracortex hyperplasia of a lymph node.
What is the most abundant lymphocyte in a normal person.
T cell
What is the T cell that MHC 1 binds to?
CD8+ T cell
What is the T cell that MHC 2 binds to?
CD4+ T cell
What is a CD4+ T cell?
type of T cell that functions to produce cytokines that activate other cells of the immune system.
What is a CD8+ T cell?
type of T cell that functions to kill virus-infected cells directly
What are TH1 cells?
class of lymphocytes that proliferate during a type IV hypersensitivity reaction.
What is a regulatory T cell?
type of T cell that functions to maintain specific immune tolerance through the suppression of CD4+ and CD8+ T cell effector function.
How to Regulatory T cells differentiate from other T cells
Through cytokine activity TGF beta are involved in the down-regulation of effector T cells.
What induces the differentiation of T cells to TH1 cells
Interleukin-12, released from macrophages
two immunoglobulin isotypes expressed on the surface of mature, naive B cells
IgM and IgD
We B naive MD’s
Which type of inflammation is characterized by the presence of lymphocytes and plasma cells in tissue?
Chronic
Remember, acute = neutrophils
Which immune cell is associated with a clock-face distribution of chromatin?
Plasma cells
What cell surface marker is associated with helper T cell
CD4
The first immunoglobulin made in response to an infection is
IgM
There are 5 major types of heavy chains which encode the classes of immunoglobulins.
IgM, IgD, IgG, IgA, and IgE
GAMED
Whihc antibody is the most numerous antibodies in the serum and their main role is to serve as opsonins
IgG
___ antibodies can be found in large quantities in breast milk.
IgA
What do IgD antibodies do?
found on mature B-cells and serve as a signal that they are ready to leave the bone marrow.
The only class of antibody that does not need T-cells to be produced is
IgM
___ antibodies form the antigen receptors on B-cells
IgM
What do vaccines induce?
active long-term immunity
What are adjuvants
The substances that are added to vaccines to enhance the response
What vaccines have the advantage of inducing both humoral and cell-mediated immunity
Live
What is immunisation?
The process of evoking a long-lived immune response against a particular pathogen
Vaccination (does/does not) ____ ensure immunity
does not
What is a vaccine
form of a pathogen that is intentionally introduced to an individual without causing disease.
Maternal IgG crossing the placenta is known as (passive/active) _______ immunity.
passive
What is antiserum
substance consisting of preformed antibodies that is injected into a patient to confer passive immunity.
Toxin or venom exposure warrants the use of (active/passive) ______ immunization.
passive
Does passive immunisation activate the host’s own immune system
No
What are two ways that confer active immunity
vaccine and natural infection
Define herd immunity
The phenomenon known as herd immunity protects individuals who were not adequately protected from a vaccine in the past.
What is the prime target location for vaccines
Mucosal surface
Are Inactivated vaccines are more/less safe than live attenuated vaccines.
More
What vaccine means that there is a lack of pathogenicity
attenuated vaccine
How can Attenuated live vaccines be generated
by growing a pathogenic bacterium or virus in abnormal culture conditions for a long period.
Inactivated vaccines elicit a (weaker/stronger) immune response than live attenuated vaccines.
weaker
Attenuated live vaccines typically require
one immunization(s)
Adjuvants have improved
humoral immunity
What is alum
adjuvant used in human vaccines that enhances the TH2 responses more than TH1.
What do DNA vaccines utilise
plasmid DNA that encode for particular antigenic proteins
Inactivated vaccines are (more/less) effective at inducing cell-mediated immunity because they do not replicate in the host.
Less
