Innate Immunity - week 2 Flashcards
What are the main functions of the immune system?
Protects against infectious agents.
Detects and kills cancer cells.
Has the ability to distinguish, neutralise and destroy the non-self toxins or foreign bodies.
What are the issues that defence against foreign proteins can cause?
It may fight against the workings of gene therapies and transplants.
Outline the 4 main steps after infection
- Pathogens where to the epithelium
- Local infection, penetration of epithelium
- Local infection of tissues
- Adaptive immunity
What barriers are present against a pathogen adhering to the epithelium of a blood vessel ?
Normal skin flora, local chemical factors such as the natural pH of the skin and the oils being produced etc.
Phagocytes - especially in the lungs.
What happens to to prevent penetration of pathogens into the blood vessels?
Wound healing.
Induced antimicrobial proteins and peptides.
Complement system.
Phagocytes.
Macrophages and dendritic cells also often engulf and remove pathogens.
What is present to prevent local infections of the tissues?
Complement system.
Cytokines.
Chemokine.
Activation of macrophages.
Dendritic cells migrate to lymph nodes to initiate adaptive immunity.
Blood clotting to prevent spread of infection.
How do dendritic cells initiate adaptive immunity?
They migrate to the lymph nodes.
What is present as part of the adaptive immune system?
Infection cleared by specific antibodies.
T-cell dependent macrophages are activated.
Cytotoxic T-cells produced.
How quickly can the non-specific immune system destroy pathogens?
Very quickly
How effectively can the non-specific immune system destroy pathogens and why ?
Not very effective because it just destroys everything. Not specific.
Name some of the physical and chemical barriers that are part of the non-specific immunity
- Keratinisation in the skin.
- Mucus formation on the mucosal epithelium and cilia clearance in the respiratory tract.
- Production of various antimicrobial factors such as lysozyme, lactic and fatty acids.
- Microbial antagonism. by mutualistic and commensal microorganisms.
- Cytotoxicity by complement
- Phagocytosis and Netosis
What are mutualistic pathogens?
Microorganisms that benefit the host and the host benefits them.
What are commensal bacteria?
Organisms that use food supplied by the host.
How does cytotoxicity by complement act as a chemical barrier in the non-specific immune system ?
Kills any cells that may have got past other features of the innate immune system or any harmful cells which may have entered the blood stream.
What protein can be used as a good measure of inflammation?
C-reactive protein
What is usually the first antibody produced in a non-specific immune response?
IgM
Are memory cells part of the innate immune system?
No
What is the response to an infectious agent if there is a normal level of antigen present?
Protective immunity
What is the response to an infectious agent if there is a deficient level of antigen present?
Recurrent infection
What is the response to an innocuous substance if there is a normal level of antigen present?
Allergy
What is the response to an innocuous substance if there is a normal level of antigen present?
No response
What is the response to a grafted organ if there is a normal level of antigen present?
Rejection
What is the response to a grafted organ if there is a deficient level of antigen present?
Acceptance
What is the response to a self organ if there is a normal level of antigen present?
Autoimmunity
What is the response to a self organ if there is a deficient level of antigen present?
Self tolerance
What is the response to a tumour if there is a normal level of antigen present?
Tumour immunity
What is the response to a tumour if there is a deficient level of antigen present?
Cancer
When are immune responses likely to be harmful?
When you don’t have a great enough response - deficient immune response.
What are the mechanical defences that are part of the immune system on the skin?
Longitudinal flow of air or fluid.
What are the chemical defences that are part of the immune system on the skin?
Fatty acids
Beta defensins
Lamellar bodies
Cathelicidin
What are the mechanical defences that are part of the immune system in the gut?
Longitudinal flow of air or fluid.
What are the chemical defences that are part of the immune system in the gut?
Low pH
Enzymes
alpha defensives
Cathelicidin
What are the mechanical defences that are part of the immune system in the lungs?
Movement of mucus by cilia
What are the chemical defences that are part of the immune system in the lungs?
Pulmonary surfactant
alpha defensins
Cathelicidin
What is the main function of catherlicidin?
Wound healing
What are the mechanical defences that are part of the immune system in Eyes, nose and oral cavity?
Tears (lysozyme)
Nasal cilia
What are the chemical defences that are part of the immune system in Eyes, nose and oral cavity?
Enzymes in tears and saliva
Histatins
Beta defensins
Define antigen
A substance triggering the immune effector responses ad memory to this antigen.
What are the 2 categories of antigen?
Complete
Incomplete
What are incomplete antigens?
They cannot promos antibody formation by themselves but can do so when conjugated to a protein.
What are haptens?
Small compounds that penetrate the skin and generate modified self proteins as immunogenic antigens.
What are incomplete antigen often called?
Haptens
What are the antigen characteristics?
Antigenicity
Specificity
Immunogenicity
What does the innate immune system respond to ?
Molecular patterns on the cellular surface.
Is the innate immune system specific?
No
How fast is the innate immune system?
Immediate
What does the innate immune system use to recognise molecular patterns on the cellular surface?
Pattern Recognition Receptors
What are Pattern Recognition Receptors trainer to recognise as part of the innate immune system?
Pathogen associated molecular patterns
Where are pattern recognition receptors found ?
On the cell surface or intracellular soluble molecules
Define molecular patterns
Low-molecular weight substances evoking the reaction of the innate immune system.
What are the different types of molecular patterns?
Pathogen-associated
Allergen-associated
Damage associatd
Tumour associated
Name the different types of patter recognition receptors found on the cellular surface
Scavenger receptors
Lectin receptors
Toll-like receptors
How do scavenger pattern recognition receptors work?
They recognise cell debris that neutrophils and macrophages have left over.
What do lectin pattern recognition receptors recognise?
Bacterial carbohydrates
What do toll-like pattern recognition receptors recognise?
Pathogen associated molecular patterns
What are the triggers for both innate and adaptive immunity?
Innate - patterns
Adaptive - antigens
How quickly do both the innate and adaptive immune systems developed?
Innate - Rapid
Adaptive - slow
What is the fate of the pathogen in terms of innate and adaptive immunity?
Innate - immune containment.
Adaptive - Immune clearance.
What are the different memories for both innate and adaptive immunity?
Innate - No formation of monoclonal memory after a primary infection.
Adaptive - Formation of long-term monoclonal memory after a primary infection.
What are the crucial cells in both innate and adaptive immunity?
Innate - Phagocytes, NK cells, mast cells
Adaptive - T cells and B cells
What are the effector events in both innate and adaptive immunity ?
Innate - ‘Acute phase recognition’, complement activation, phagocytosis, NETosis, pyropoptosis, simple inflammation, apoptosis.
Adaptive - Antigen neutralisation by antibodies, immune inflammation, induced apoptosis in target cells.
What are the selection theories in both innate and adaptive immunity?
Innate = pattern recognition theory.
Adaptive = clonal selection theory.
How does immunopathology work in both the innate and adaptive immune response?
Innate - Immunodeficiency and auto inflammatory disorders.
Adaptive - Immmuodeficiecy, autoimmune diseases, allergic disorders.
What are pattern recognition receptors?
Molecules expressed by cells of the innate system, which capable of sensing “patterns” triggering the reactions of the innate immune system.
What are the 5 types of pattern recognition receptors?
- Toll-like receptors
- C-type lectin receptors
- NOD-like receptor
- RIG-1 like receptors
- AIM-2 like receptors
Where are toll-like receptors found?
The membranes of macrophages, neutrophils, dendritic cells, lymphocytes, epithelial cells, platelets, splenocytes, atheoscletotic plaques and some endosomal cells.
How do TLRs become activated?
Ligands bind to them
Once ligands have bound to TLRs what do they do?
They transduce signals that eventually lead to the activation of inflammasome and proptosis.
What is pyroptosis?
Highly inflammatory form of programmed cell death.
What type of molecular patterns do toll-like receptors recognise?
Pathogen associated and damage associated molecular patterns.
Where are C-type lectin receptors found?
Bound to the cell membranes
What are C-type lectin receptors mainly involved in?
Fungal recognition and endocytosis
Why are C-type lectin receptors compatible to toll-like receptors?
They recognise both patterns and antigens and can therefore bridge the innate and adaptive immunity.
Why can toll-like receptors link the innate and adaptive immunity?
Because they recognise antigens.
What are the main roles of C-type lectin receptors?
They are anti fungal, antitumoural and antimycobacterial.
Where are NOD-like receptors found?
Cytosol
What does NOD mean in terms of nod-like receptors?
Nucleotide-binding oligomerisation domain
What do NOD1 receptors recognise?
Peptidoglycan of gram -ve bacteria
What do NOD2 receptors recognise?
Intracellular muramyl dipeptide on both gram -ve and gram +ve
What receptor type tase part in the formation of an inflammasome?
NOD-like
What factors do NOD-like receptors activate?
Caspace-1 or inflammasome
Pro-inflammatory cytokines
What do NOD-like receptors do?
Aid proptosis and help start the inflammatory process
What are granulomas?
A collection of macrophages
Where are RIG-1-like receptors found?
In the cytoplasm
What do RIG-1-like receptors consist of?
RNA helices domain anda. caspase activation and recruitment domain.
What does activation of RLRs lead to?
Type I interferon production.
Cytokine production by infected cells.
What do RIG-1-like receptors recognise?
Viral RNA
What are interferons?
Proteins that are made and released by host cells in response to the presence of pathogens. They allow communication between cels to trigger a greater immune response.
Where are AIM-2-like receptors found?
Cytoplasm and nucleus
What does the activation of AIM-2-like receptors led to?
Formation of AIM-2 inflammasome and production of pro-inflammatory cytokines and type I interferons.
What are the 4 categories of pattern recognition receptors?
Host cell receptors
Extracellular
Intracellular
Secreted
Where are Pathogen repetitive pathogen associated molecules not found?
In eukaryotic cells
Why are pattern recognition receptors so important?
They induce inflammation
What can be the issues with inflammation caused by pattern recognition receptors?
This inflammation may lead to tissue damage and promote an excess o pro-inflammatory cytokines to be produced and cause toxic shock syndrome.
What is a phagocytic burst?
A respiratori burst required for primal killing of bacteria and fungi.
What is an inflammasome?
A multi protein intracellular complex that detects pathogenic microorganisms and sterile stressors and that activates the highly pro-inflammatory cytokines interleukin-1b and IL-18.
Inflammasomes also induce pyroptosis.
What is NETosis?
The killing of extracellular pathogens to minimise damage to host cells.
How does NETosis work?
Neutrophils are activated and release chromatin plus granule protein. Granule protein then destroy microbes extracellularly. NETs concentrate proteins which prevent diffusion into host cells and therefore traps microbes.
What branch of the immune system is complement part of?
Innate
What are the main functions of the complement system?
- Attraction of phagocytes to a site of inflammation by chemotaxis.
- Opsonisation using C3b
- Phagocyte activation
- Triggering of mast cells to release inflammatory mediators.
- Membrane attach complex against bacteria and enveloped virus.
What is opsonisation?
Microorganisms are coated with host-produced proteins and lipids, facilitating the binding to specific receptor molecules present on the phagocyte.
What occurs in the opsonisation phase of the complement system?
- Opsonisation of pathogens for phagocytosis
- Opsonisation of immune complexes for uptake by phagocytes
- Activation of phagocytes to destroy material they have taken up
What occurs in the inflammation phase of the complement system?
- Attraction of phagocytes to the site of inflammation via chemotaxis.
- Triggering mast cells to release their inflammatory mediators.
What happens in the lysis phase of the complement system?
*Membrane attack complex causes osmotic rupture of cells which have been recognised as foreign.
What are the 3 stages of the complement system?
- Opsonisation
- Inflammation
- Lysis
How many possible pathways can the complement system have?
3
What are the 3 complement pathways?
Classical
Lectin
Alternative
What always happens at the start of each complement cascade?
Clevage of C3 into C3a and C3b.
Which of the C3a or C3b pathways is biggest?
C3b
What repeat domains are present on most pattern recognition receptors?
Leucine-rich domains.
What are Leucine-rich domains that are found on pattern recognition receptors?
Repeating 20-30 amino acid stretches that are unusually rich in the hydrophobic amino acid Leucine. These tandem repeats then fold together to form a leucine-rich repeat domain
Is Leucine hydrophilic or hydrophobic ?
Hydrophobic
What is meant by the ‘anticipatory’ property of the adaptive immune system?
Increased resistance against future infections with the same pathogen.
Which branch is the phylogenically oldest component of the human immune system?
Innate immune system
How do barrier and white blood cells differentiate between different infectious cell types?
They use pattern recognition receptors.
Why are different types of pattern recognition receptors in different locations?
So that all possible locations where pathogens could exist or replicate are monitored.
Where are Kupffer cells found ?
In the liver
What is the function of Kupffer cells?
They perform Phagocytic functions to remove protein complexes, small particles, senescent red blood cells and cell debris from the blood flow through pattern recognition receptors.
What is the main role of the liver as part of the innate immune system?
Delivers immune signals and danger signals and antigens to the effector immune organs.
What are the effector immune organs?
Lymph nodes, thymus and spleen
What evokes danger signals in the liver?
Pathogens or damage
Describe the blood flow in the liver
Slow
How is the immunotolerance of the liver beneficial?
This is helpful in the case of a liver transplant as it prevents chronic inflammation and/or adaptive immune responses which cold lead to liver fibrosis or liver cirrhosis. The new transplant won’t be rejected.
Why are liver transplants very unlikely to be rejected?
The liver is immunotolerant systemically and in itself.
What are the immune cells of the liver?
Neutrophils, Monocytes and Macrophages
What are the functions of neutrophils as part of the innate immune system in the liver?
They are the first cell to be recruited to the site of injury and produce reactive oxygen species.
They help with tissue repair and phagotysation of bacteria and damaged cells.
Produce repair remodelling tissue.
How are circulating Neutrophils recruited to the liver?
By chemotaxis through interactions between cell adhesion molecules expressed on Neutrophils.
What is a senescent cell?
One which has aged and is no longer capable of dividing but is still alive and metabolically active.
What is liver cirrhosis?
Scarring of the liver caused by long-term liver damage.
What is the immune system?
A system that has evolved to protect the body against a huge range of potentially damaging smaller organisms.
Define pathogen.
Any smaller organism that has the potential to damage our bodies.
What antimicrobial chemical property does the GI tract have?
It is highly acidic
Why is salmonella resistant to the antimicrobial properties of the GI tract?
Salmonella has an outside coating which makes it resistant to the acidic conditions.
What are the pathogens that can invade the body?
Bacteria
Viruses
Fungi
Parasites
What property makes the stomach highly protective against ingested microbes?
The stomach is very alkaline.
How do lysosomes affect bacterial cells?
They attack bacterial cell walls, causing the cells to burst.
In what fluids are lysozyme found?
Tears, blood, sweat and nasal secretions.
By what cells are interferons produced?
Cells that are infected by a virus.
How do interferons work as part of the immune system?
They interfere with the product of new virus proteins, both in infected and normal cells.
What are the main cells of the innate immune system?
Neutrophils
Macrophages
Lymphocytes
How do macrophages work as part of the immune system?
They engulf and digest pathogens and debris.
What cell types do lymphocytes act upon?
Virally infected and tumour cells.
What are the main defence mechanisms of the innate immune system?
Phagocytosis
Cytotoxicity
Inflammation
What cells carry out phagocytosis ?
Macrophages, Neutrophils and dendritic cells.
What is an acute inflammatory response?
A response to infection or injure after a cut, bite or entry by bacteria.
How does the redness and swelling of inflammation occur?
Blood vessels are dilated and becoming leaky.
Why do the blood vessels dilate and become leaky during inflammation?
To allow lots of protective chemicals and cells of the immune system to flood to the affected area.
Briefly outline the process of phagocytosis.
- Chemotaxis and adherence of microbes to phagocyte.
- Ingestion of microbe by phagocyte.
- Formation of phagosome.
- Digestion of ingested microbe by enzymes.
- Formation of residual body containing indigestible material.
- Discharge of waste materials.
How do Leukocytes recognise microbes?
They have pattern recognition receptors that identify generalise proteins (PAMPs) on bacterial surfaces.
What are Epitopes?
Clusters of molecules on the surfaces of antigens.
How are epitopes part of the immune system?
They identify that the cell is ‘non-self’ and is legitimate target for an immune response.
What type of MHC do CD8+ cells recognise?
Class I
What are the main functions of CD8+ cells?
Recognise MHC I cells.
Kill infected and cancerous cells.
What type of cells display they internal endogenous antigens on MHC I?
All nucleated CD8+ cells
What type of MHC do CD4+ cells recognise?
MHC class II
What type of cells display they internal exogenous antigens on MHC II?
CD4+ T cells
On what type of cells are endogenous antigens presented?
CD8+ T cells
On what type of cells are exogenous antigens presented?
CD4+ T cells
By what methods does complement combat bacteria?
Opsonin
Membrane attack complex
Chemotactic molecules
By what methods do antibodies combat bacteria?
Opsonin Activate complement Clump bacteria together Interfere with adhesion molecules Neutralise toxins
What is complement?
A system of plasma proteins that can be activated directly by pathogens or by pathogen-bound antibodies, leading to a cascade of reactions that occur on the surface of pathogens and generate activate components with various effector functions.
What can activate complement ?
Directly by pathogens or indirectly by pathogen-bound antibodies.
What cells are used in the immune response against viruses?
Phagocytes, antimicrobial peptides, natural killer cells, complement, cytotoxic T cells, interferons, Tc cells and antibodies.
What is the main function of interferons in the immune system?
They inhibit viral replication by inhibition protein synthesis and inducing an anti-viral state.
They also activate natural killer cells.
What are the issues that may cause an immunodeficient disorder?
- Genetic defects (primary immune deficiency).
- A disease or medication that impairs the immune system. (secondary immune deficiency).
- An overactive immune response leading to hypersensitivity or anaphylactic shock.
- Immune response attacking its own body cells - autoimmune response.
What is primary immune deficiency?
A genetic defect that leads to the absence or dysfunction of some cells or components of the immune system. This then results in servers, persistent and recurrent infections.
What is secondary or acquiredimmune deficiency?
A disease or medication that impairs the immune system
What time of immunodeficiency causes HIV, AIDS and malnutrition?
Secondary/ acquired
Which cells of the immune system does HIV infect?
CD4+ T-cell receptors
When is a person with HIV diagnosed with AIDS?
When the T cell count drops below 200 cells per microliter.
If T cell count of a person with AIDS drops below 50 cells, what is their life expectancy?
12-18 months.
What antibodies mediate a type I hypersensitivity reaction?
IgE
How does the IgE antibody mediated response work with type I hypersensitivity reaction?
If an allergen cross links the receptors of IgE on a second exposure, degranulation of mast cells occurs, leading to the release of inflammatory mediators such as histamine. Histamine dilates and increases permeability of blood vessels, increases mucus secretions and contortions of the bronchi.
What does histamine do when causing an immune reaction?
Dilates and increases permeability of blood vessels, increases mucus secretions and contractions of the brooch.
Name some scenarios that are a type I hypersensitivity reaction
Hay fever Reactions to animal stings Reaction to penicillin injectons Food allergies Eczema
What causes an anaphylactic shock?
A type I hypersensitivity reaction which causes a massive drop in blood pressure.
What causes a type II hypersensitivity response?
IgG and IgM mediated cytotoxic response.
Outline how a type II hypersensitivity reaction occurs
Antibodies are directed against cell surface antigens which mediate destruction via complement activation.
What is the mediator for type III hypersensitivity ?
Immune complexes
Outline how a type III hypersensitivity reaction occurs
Large quantities of antigen are combines with antibody and they produce an immune complex which can cause local inflammation and damage when deposited in the tissues.
If a type III hypersensitivity reaction occurs in the blood vessels what occurs?
Vasculitis - inflammation of the blood vessels.
If a type III hypersensitivity reaction occurs in the joints what occurs?
Reactive arthritis
If a type III hypersensitivity reaction occurs in the kidneys what occurs?
Glomerulonephritis
What is Glomerulonephritis?
Damage to the filters in the kidneys caused by the immune system attacking healthy body tissue.
How long does the onset of a type IV hypersensitivity reaction take?
Days, weeks or months
Why is a type IV hypersensitivity reaction cell mediated?
It is caused by sensitised T cells which activate macrophages and releases inflammatory cytokines leading to tissue damage.
What is Schistosomiasis?
Ova lodged in the liver induced granulomatous reaction leading to hyperplasia and granulomas in the liver and spleen after chronic infection.
What people are prone to TB?
Children with rare genetic defects affecting cytokines or their cellular receptors.
What is autoimmunity?
Tissue injuries caused by the body’s own immune response.
What mediates autoimmunity?
Either cell or antibody mediated
What is Guillan Barre Syndrome?
Rapid onset of muscle weakness following in infection where the immune system mistakenly attacks peripheral nerves.
What is rheumatic fever?
An autoimmune response that attacks the heart valves after streptococcal infection.
Which branch of the immune system are Eosinophils in?
Innate
Which branch of the immune system are Neutrophils in?
Innate
Which branch of the immune system are Basophils in?
Innate
Which branch of the immune system are Dendritic cells in?
Innate
Which branch of the immune system are B cells in?
Adaptive
Which branch of the immune system are T cells in?
Adaptive
Which branch of the immune system are Macrophages in?
Innate
