week 3 Flashcards
give me three examples of innate immune response?
patter recognition receptor, cellular ( phagocytes, NK cells) physical and chemical barriers/ mechanism
give me 2 examples of adaptive immune response?
humoral and cellular
what is pattern recognition receptor? give examples?
Inclusive term for antigen recognition receptor in innate system
Each immune cell carries identical receptor of a given type
Examples are
Toll-like receptors (TLR’s), NOD-like receptoes (NLR’s), RigI-like receptors (RLR’s) C-type lectins (CLR’s), scavenger receptors
what do cytokines do?
they are chemicals that tell the immune system what to do
what are the two groups of pattern recognition receptors?
Cell surface (transmembrane) and intracellular receptors – TLRs, NLRs, RLR’s and CLR’s Fluid-phase soluble molecules
What is the first cytokine you produe in response of infection?
IL-1 –> fever like symptomes but allows the rest of the immune system to engage
What are the two fluid phase recognition molecules?
Mannan-binding Lectin
Surfactant Protein A & D
What is the process and function of fluid phase recognition
Recognition of microbial complex carbohydrates
Bind via Carbohydrate-Recognition Domains (CRDs) –> sugars or combination of sugars and protein on the surface of the bacteria
Role in neutralisation of pathogen
Role in recruitment of adaptive response
how is the classical pathway activated?
antigen antibody interaction
how is the MB-lectin pathway activated?
the mannose binding lectin binds to the lectin on the surface of the pathogen
how is the alternative pathway activated?
on the pathogen surface
what do TNF and IL-6 instruct?
they tell what the immune system should do such as T cells
what do macrophages do?
bind and kill bacteria –> APC –> produce and bind to inflammatory cytokines
what are the role of Plasmacytoid dendritic cells (DCs)?
Produce large amounts of interferon- (IFN-) which has antitumor and antiviral activity, and are found in T cell zones of lymphoid organs; they circulate in blood.
what is the role of Myeloid dendritic cells?
produce IL-12 and IL-10 and are located in T cell zones of lymphoid organs, circulate the blood and present in the interstices of the lung, heart, and kidney.
what do eosinophils do?
kills invading parasites
what do Neutrophils do?
Phagocytose and kill bacteria, produce antimicrobial peptides
what do Mast cells and basophils?
Release TNF-, IL-6, IFN- in response to a variety of bacterial PAMPs (pathogen associated molecular pattern)
what is the contribution of epithelial cells to the immune system
produce antimicrobial peptides–> tissue specific epithelial produce mediators of the local innate immunity
what is clonal expansion?
the Proliferation of chromosomes in response to a infection –> the one with the corrrect receptor will carry on ploriferating
what are the name of the two regions of the receptor on B and T cells
FC region that is variable region and FAB region –> constat region
give example of Antigen presenting cells
macrophages, B cells and dendrites
what cells are MHC class 1 found on? What are the 3 HLA’s found on class 1
Found on all cells
Classes –> HLA-A , HLA-B, HLA-C
what cells are MHC class 2 found on?
What are the 3 HLA’s found on class 2
On antigen presenting cells such as dendritic cells, macrophages, some endothelial cells, thymic epithelial cells, and B cells.
Classes–> HLA-DP, HLA,DQ and HLA-DR
which T cell type does MHC class 1 present too?
They present the antigen peptides to cytotoxic T cell
what T cell does MHC class 2 present peptides too?
They present the antigen peptides to T helper cells
what is suppressor T lymphocytes?
help to dappen down immune response
what are Helper T cells?
secrete growth factors (cytokines) which control immune response: Help B lymphocytes and T lymphocytes (Helper T cells are target of HIV)
what are the types of invactivation of a antigen by a antibody?
What do they lead onto?
neutrilization –> blocks viral binding sites –> coats bacteria
agglutination of microbes
precipitation of dissolved antigens
These 3 enhance phagocytosis
activation of the complement system which leads to cell lysis
What is the outcome when dendritic cells activate Th1 CD4+ T cells
Induce CD8 cytotoxic T cells which kill microbe infected cells
B cell and IgG antibody which opsonise microbes for Phagocytosis
macrophage activation –> kills opsonized microbes
Inhibit the TH2 pathway
What is the outcome when dendritic cells activate Th2 CD4+ T cells
Eosinophill–> Kill parasite
mast cells basophils
B cells that produce IGM
IGG IGA and IGE
Inhibition of TH1 response
which cytokines are directly involved in allergic reactions?
IL-4 and 5
which cytokine is inovled in autoimmunity?
IL-17
what does immunosuppression mean?
a natural or artificial process which turns off the immune system either fully or partially. –> accidently or purposly
what can be the potential result of immunosuppression?
Immunodeficiency: the lack of effecient immune system that is susceptible to infection if the immune system is too switched off
what are the uses of immunosuppression?
transplant rejection
autoimmune disease
Lymphoproliferative diseases –> cancer of the immune system
what is the possible outcome if PRR doesn’t work early in life?
you are susceptible to pneumococcus early in life –~> no inflammatory response because the PRR is not working can lead to the development of meningitis but if you survive then adaptive immune system will kick in
what is a common problem when you lack the complement pathway?
If you don’t have complement pathway will get recurrent meningococcal
what does Hypersensitivity mean?
Undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system (directed against innocuous antigens) in a pre-sensitized (immune) host.
what are the 4 types of hypersensitivity?
I - IgE MEDIATED REACTION
II - CYTOTOXIC REACTION
III - IMMUNE COMPLEX REACTION
IV - CELL MEDIATED REACTION (DTH)
give clinical features and common causes of type 1 hypersensivity?
Give example of allergic reactions
fast onset (15-30 min)
wheel and flare
can have a secondary reponse later on
common causes –> pollen, Bee venom and animal dander
Examples are: Hay fever Allergic asthma, RHINITIS, DERMATITIS, FOOD ALLERGY
which antibody is involved in type 1 hypersensitivity and what is the consequence of a severe attack?
IgE antibody
ANAPHYLAXIS
what are the outcome to the body of type 1 hypersensitivity?
release of histamine
get Bronchospasm in smooth muscles
hypertension as blood vessel dilate and become leeky
mucous glands are affected –> coughing and production of mucous to try and get rid of the parasite
how is immunoglobin E produced?
Produced by plasma cells from class-switched B cells under the control of IL-4 and CD40L - CD40 interaction
What are the serum level of IgE and how well does it bind?
Low serum levels but high affinity to basophils and mast cells and forms stable binding over longer period.
What occurs in the early phase reaction of type 1 hypersensitivty?
high-affinity IgE receptor at high density on the mast cell –> cross linkage occurs by allergn promotion which activated mast cells. This lead sto degranulation which release pre formed mediators and synthesis of lipid mediators.
what are the pre mediators that are released during degranulation in type 1 hypersenisitivity?
Histamine –> stimulation of irritant nerve receptors, smooth muscle contraction and increase in vascular permeability
kallikrein –> activates bradykinin which has similar affects to histamine
TRYPTASE –> role unclear
What cells are involved in late phase reaction of type 1 hypersensitivty?
Basophils –> similar to mast cells but work over longer period
Eosinophils –> contain granules of cytotoxic properties, attarcted to sight of infection by chemokines. Cause the release of granule content and damage to the tissue –> main cause of damage in allergic reaction
T cells are invovled both initial and late phase of the type 1. The active T cells produce cytokines that act as the driven activity for the main source of pathogensis in allergic reaction
what is type 2 hypersensitivity?
antibody mediate cytotoxic response
what happens in type 2 hypersensitivity?
Binding of the antibody to target antigen on the surface membrane causes:
activation of the complement cascade leading to cell lysis.
Aggregation of Fc portions of immunoglobulin/C3b with binding to FcRs/C3bR resulting in opsonisation, phagocytosis & destruction
which antibody is the main antibody for the type 2 hypersensivity reaction?
IgM is the most effective as has 5 bits ( pentavelent)
but also complement binding IgG1 and 3 but need multiple binding sites
what cells does type 2 hypersensivity occur in?
haematopoietic cells
Give 4 examples of type 2 hypersnesitivity
ABO incompatability
Autoimmune haemolytic anaemias
Affecting neutrophils
Affecting platelets
what drug can cause all 4 types of hypersensitivity?
Penicillin
what occurs in type 3 hypersensitivity?
What antibody mediates this reaction
- IgG + Ag = AgAb complex this his deposits in parts of the body, if they accumulate in large enough quantities you get activation of the complement system
- FcR in complex bind C1q
- Complement activation leads to generation of activated complement fragments
4a. C5a - attractant for neutrophils
4b. C3b - Opsonin - Attempted phagocytosis of complexes - release of enzymes, oxygen radicals
- Consequence is tissue damage
IgG mediated reaction
what is type 4 hypersensitivity?
T cell mediated –> CD4 cells –> MHC class 2.
What is granulomas?
What type of T cells are present and what do macrophages release?
Focal collections of inflammatory cells in tissues
Contain:
Macrophages
Epitheliod cells ( phagocytes that have engulfed foreign material)
Lymphocytes
Giant cells
T cells are TH1 type –> release IL-2 and IFN gamma
Macrophages release IL-12 critical in the initiation of the response
Give example of mycobacterial infectious diseases that cause granulomas reactions
Tuberculosis
Atypical mycobacteria
Leprosy
Tuberculoid - Th1 - Protective
Lepromatous Th2 - Non-protective
what is Osteomyelitis?
chronic condition of abcess in the bone marrow cavity. It is a bacterial infection most commonly involving Staphylococcus species. Comonly associated with complication of compound fractures
what does Vascular endothelial growth factor (VEGF) do?
it is a vascular cell growth factor for endothelial cells–> increase vascular permeability and mitogenic for endothelial cells
what Type of granulocyte takes part in allergic response?
EOSINOPHIL
Cytokines recruit what cell type into sites of chronic inflammation?
lymphocytes
what are giant cells associated with at sight of infection?
granulomas which is the formation of granuloma tissue in response to infection.
what are langerhan cells?
Dendritic cells found in the skin epithelium
what are the major components of the innate immune system?
Pattern recognition receptor Antimicrobial peptides Complement components Cytokines Cells
What is the common theme of recognition of PRR?
Recognition of:
Pathogen associated molecular patten
Or
Danger associated molecular pattern
TNF is released from what cells 2, has what targets and thus what effects 4?
Released from Macrophages and T lymphocytes Targets and effects Endothelia - increased coagulation and inflammation Hepatocytes - increased acute phase proteins Neutrophils - increased activation Hypothalamus- increased fever
IL6 is released from what cells 3, has what targets and what effects 2
Released from Macrophages and T lymphocytes and endothelia Targets and effects Hepatocytes - increased acute phase proteins B lymphocytes - increased proliferation
what is the function of C3b in the complement pathway?
Opsonisation and removal of immune complexes
What is the function of C3a and C5a in the complement pathway?
Phagocyte recruitment
What makes lymphocytes unique and what occurs when there is a infection?
They each have a unique antigen receptor.
When there is a infection each lymphocyte rapidly replicates and the one that is specific to that infection will carry on proliferating
What is the primary lymphoid organs?
Lymphocytes development and selection
B cells –> bone marrow
T cells –> thymus
What is the secondary lymphoid organs?
Immune response
Spleen
Lymph nodes
Mucosal surface
When are most of the T cells produced in your body and in what state are they?
Most of T cell are produced early in life so important you get exposure
They are niave until they encounter a antigen and then produce a immune response
The range of antigen variability is estimated at what?
10 to power of 9
What is VDJ recombonitation?
Recomboniation of different genes allow the creation of more B and T cells that are possible with just the normal number of genes.
Increase the variability of immune response
What is the mechanism of antigen presenting cells?
The antigen is internalised The antigen is brocken down to peptides THe peptide interacts with the newly synthesised class 2 molecule which will inturn be expressed on the surface If it is foreign then this will activate T helper cells which in turn will produce cytokines to activate T killer cells, B cells etc
When to T cells interact with antigens?
They interact with antigens when they are associated with MHC proteins
What structure within cell will break down a bacteria?
Proteasome
what type of immunity is B cells involved in?
They produce antibodies and are involved in humoral immunity
What type of immunity are T killer cells involved in?
They are able to kill pathogens and are involved in cellular immunity
What infections are patients with defeciency in PRR prone to?
Pneumoccocus and HSV
What infection are patients with defeciency in macrophages and neutrophils prone to?
CGD, Staphylcoccus and Aspergillus
What infection are patients with defeciency in complement proteins prone to?
meningococus
What infection are patients with defeciency in B cells prone to?
Reccurent sino-pulmonary infection
What infection are patients with defeciency in cytokines prone to?
Mycobacterium
What infection are patients with defeciency in effector T cells prone to?
SCID and opportunistic infections
How does sensitisation and the early phase reaction of a Type I hypersensitivity reaction work?
1) Exposed to an allergen 2) B cell has a receptor that recognises this allergen and presents allergen to CD4 cells 3) CD4 cells release IL 4 causing IgE Ab to be produced by plasma cells aswell as the formation of some memory cells 4) The IgE Ab binds to the IgE Fc receptor on the mast cell - cross linking the FcR1 (IgE receptor) The above process is sensitisation 5) On re-exposure to the same allergen, it binds to the IgE receptors on the now-sensitised mast cell inducing degranulation of pre-formed mediators and synthesis of lipid mediators leading to allergic response
Degrenulation of mast cells in type 1 hypersensitivity acts on what structures?
1) Smooth muscle 2) Blood vessels 3) Mucous glands 4) Platelets 5) Sensory nerve endings 6) Eosinophils
What is released by mast cell in the primary phase reaction?
Degranulation occurs and histamine and protease is released
In the second phase/late response what is released by mast cell?
The arachanoid acid too:
Leukotrines: B4,C4 and D4
Postaglandin:D2
what are the lipid mediators produced in the initial response of type 1?
Arachanoid acid derivatives
Via 5 lypoxgenase –> Leukotrines : LA4-LD4
Via Cyclo-oxygenase–> Prostaglandin: D2,E2,F2
What disease is caused by immune complex depostion from type 3 reaction on the blood vessel walls?
Vasculitis
What disease is caused because of immune complex depostion from type 3 reaction on the renal glomeruli?
Nephritis
What disease is caused because of immune complex depostion from type 3 reaction on the joint space?
Arthritis
What disease is caused because of immune complex depostion from type 3 reaction on the perivascular area?
Arthus reaction
What disease is caused because of immune complex depostion from type 3 reaction on the capillary/bronchi intergace
Farmers lungs
Inactivation is seen as the 5th hypersensitive reaction.
Give me 3 examples?
Direct e.g. to Intrinsic factor - B12 deficiency
Indirect : binding to e.g. hormone results in clearance of AgAb complex
Receptor blockade: e.g. To AChR in Myasthenia Gravis
How does the tuberculin skin reaction work?
T cell mediated CD4 cells ( mhs class 2)
Small amount of mycobacterium tuberculosis is injected intradermally (Mantoux test)
In individuals with no immunity there is no effect
In individuals with previous exposure as a result of TB infection of BCG vaccine you get a local inflammatory response as T cells have already been sensitized
Langerhan’s cells present Ag to T cells which produce cytokines
Get infiltration of lymphocytes and macrophages around the small blood vessels and the activated macrophages cause tissue damage
How does contact dermatitis work?
T cell-mediated cytotoxicity
CD8+ T cells (MHC Class I)
Small amounts of Ag (eg. nickel or poison ivy) bind to covalently to tissue or skin proteins - the sensitising agent is known as a hapten and the protein as a carrier
The hapten-carrier complex is presented as an Ag by Langerhan’s cells in conjunction with MHC II to CD4+ cells
Induction of T cells normally occurs after months of exposure to an Ag
Re-exposure to that Ag triggers the elicitation phase where effector T cells migrate to the epidermis to meet the Langerhans cells presenting the complex and release cytokines leading to skin inflammation
What are diseases with unknown aetiology that cause granulomats reactions?
Sarcoidosis
Wegener’s Granulomatosis
Crohn’s disease
What are langerhan cells?
They are dendrite cells on your skin and mucosa
