Immunology and Infection 2 Flashcards
Why is immune regulation required and if it fails what are the three outcomes
Avoid excessive lymphocyte activation and tissue damage during protective response against infections
prevent reactions against self antigens (tolerance)
1) autoimmunity
2) Allergy
3) Hypercytokinemia and Sepsis
What is the definition of autoimmunity and give examples of diseases that come from this
immune response against self antigen
immune mediated inflammatory diseases can be systemic or organ specific
Rheumtoid arthritis, Irritable Bowel Disease, Multiple Sclerosis, Lupus
can target self antigens or microbial antigens (crohns disease)
Explain the underlying causes of autoimmune diseases
Failure of control mechanisms as well as causative factors such as susceptibility genes and environmental influences
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What is allergy
Harmful immune response to non infectious antigen that causes tissue damage
mediated by IgE and mast cells or T cells (type IV)
What is hypercytokinemia and Sepsis
too much immune response, positive feedback as causes more damage and bigger response
triggered by pathogens entering iron compartment (sepsis) or failure to regulate to correct level (hpercytokinemia)
What are the three phases of cell mediated immunity
INDUCTION- dendritic cell collects infected material and displays on MHCII, moves into lymph nose and presents to T-cells , T cell that matches is activated and clonal expands
EFFECTOR- the effector T cells then return to the site of infection and kill antigen
MEMORY- Effector pool contracts to memory pool shutting down immune response - this is SELF LIMITATION as removed the antigen source and can shut down
What signals are required to stimulate a T cell
antigen recognition
co stimulation
cytokine release
What are the outcomes of an immune response
Resolution- no tissue damage, back to normal, macrophages phagocytose the debris
Repair- heal with scar tissue and regenerate through fibroblasts and collagen synthesis
chronic inflammation- active inflammation attempts to repair damage
What is tolerance and what two types of tolerance is there
unresponsiveness to an antigen once lymphocytes have been exposed to it
before T or B cell enter circulation- central tolerance - destroys self reactive T or B cells
before can enter circulation, need to be deleted here before cause a response as self-reactive ones are made from generation of immune repertoire
destroy any self reactive T or B cells which do enter the circulation - peripheral tolerance
Describe B and T cell selection
B cell- if immature B cells in bone marrow encounter antigen in a form which can crosslink their IgM then it triggers apoptosis
T CELL- in thymus need to select ones that can bind to self MHS, don’t want it to bind too strongly (negative selection as dangerous), if binds weakly but doesn’t trigger immune response then positive selection
How do T cells meet antigen in the thymus
The transcription fact AIRE (autoimmune regulator) it allows the thymus expression of genes that are expressed in peripheral tissues.
problems with this causes multi organ immunity
What happens after a B cell meets antigen
B cell receptor is a surface bound antibody
After antigen exposure, naive B cells are activated by T cells and become perifollicular B cells which can become
1) antibody production by becoming a plasma cell
2) Memory by becoming a Memory B cell
3) Affinity maturation- it recognises antigen and changes shape to bind
What is it called when B cells can change specificity after leaving the bone marrow
Somatic hyper mutation - normally improves antibody quality but can alter outcome if meets self antigen during infection
What are the mechanisms of peripheral tolerance
Anergy- naive T cell sees MHC without appropriate costimulatory protein so becomes anergia, less likely to be stimulated. sees antigen but no stimulation
Ignorance- concentration of antigen too low of a concentration won’t trigger T receptor, places like eye brain (immunologically privileged sites) and compartmentalised places. no antigen and no co stimulation
Antigen Induced Cell Death (AICD)- Activated T cell to express the death ligand Fas ligand (CD95 ligand, FasL) . antigen + FasL
Regulation- T cells exposed to the cytokine TGF-beta can differentiate into “induced” T regulatory cells (Tregs) in the peripheral tissues.
“Induced” T regulatory cells have similar effector functions as natural T regulatory cells, but they are produced in the periphery rather than in the thymus. They block activation, or inhibit effector function of T cells and other cels
What is the phenotype of Treg cells and their mechanisms of action
CD4, high IL2 receptor, FoxP3 transcription factor
Secrete immunosuppressive cytokines TGFbeta, IL-10,IL-35, inactivation dendritic cells or responding lymphocytes
Mutation in FoxP3 results in what
mutation in FoxP3 transcription factor leads to severe IPEX syndrome, because FoxP3 turns T cells into Tregs so if it leads to improper development of Tregs then autoimmune disorders
What does IL-10 do
LIMITS IMMUNE RESPONSE pleiotropic- multi functional acts on many cells to block proinflammatory cytokine synthesis like TNF, IL-6, IL-8, IFNgamma down regulates macrophage function mimics virals making similar proteins
stops severe inflammation and decreases risk of autoimmune disorders by limiting response
What are the types of Tregs
Natural Tregs (nTregs)- develop in thymus recognise self antigen during T cell regulation and reside in peripheral tissues to prevent reactions against cells Indicible Tregs (iTregs) develop from mature CD4 T cells that are exposed to antigen in periphery
Difference between cytokine and chemokine
Cytokines programme immune response, can be inflammatory or antiinflammatory depending on the responses needs. IFNgamma, IL-2, IL-10. T cells make cytokines to activate B cells to switch Ig class and make different antibodies
chemokine drive movement around body
What are the main types of CD4 T helper cells and how do they work
TH1 cells used when pathogens are taken in by macrophages, broken down and presented
TH2 cells used when its receptor mediated endocytosis
they produce cytokines which will cross regulate to shut down other t helper cells response and produce more of the cytokine needed
Difference between T and B cell antigen stimulation, co stimulation and cytokine
T cells are activated by detecting MHC. Co stimulates by expressing CD40L to activate B cells and CD28 to be activated itself. IL-21 nd other cytokines activates response in T cell
B cells are activated by soluble antigen.Co stimulated by expressing CD40 to be activated by T cells and expressed B7 to be activate T cells
Describe Type 1 hypersensitivity reactions
‘immediate’
re exposure to an antigen called an allergen
asthma, allergic rhinitis, atopic dermatitis
People with allergies make IgE in response to common mutlivalent environmental antigens (allergens) instead of only making it in response to parasitic infections and venoms.
can use skin prick tests - wheal and flare
After IgE is made, TH2 CD4 cells and B cell helper follicular CD4 T cells which produce IL-4 and IL13 switch B cells to make antigen specific IgE. IgE rapidly binds to mast cells and basophils via the FcER1 receptor so isn’t found in circulation.
When allergen meets cell bound IgE there is rapid cross linking and degranulation so more TH2 differentiation and recruitment of other cells. Histamines released from degranulation cause capillaries to dilate and leak
How does anaphylactic shock occur
Instead f antigen meeting IgM lymphocyte and it switching to produce IgG, TH2 CD4 cells are activated to make IgE. IgE binds on mast cells and basophils via the FcER1 receptor to cause degranulations and release fo histamines.
Histamine dilates blood vessels, increases blood flow to surface and movement of fluid out blood stream (oedema)
constriction of airways, contract of smooth muscle
urticaria- red rash
effect depends on where allergen enters so if inhaled, mucosal mast cells, if in nasal passages then oedema in epithelial lining of nose which is allergic rhinitis aka hay fever
if allergen ingested then intestinal mucosal mast cells cause vomiting and diarrhoea
food ,insect bites, medication
What can be used to treat anaphylaxis shock
Adrenaline should be given as the dilation of blood vessels causes oedema and rashes but also blood pressure drops which can lead to shock. can cause breathing difficulties from lung constriction or cramps/ nausea from intestine
Antihistamines can be given and anti inflammatory corticosteroids
oxygen, bronchodilators
may feel faint from blood pressure drop so monitor to check for recovery
Describe Type II Hypersensitivity
antibody mediated cytotoxic hypersensitivity
IgG or IgM antibody destroys cells by binding to SURFACE BOUND antigens
mismatched blood transfusion, haemolytic disease of newborn, graves disease
can be exposure to foreign antigen or self antigen.
self antigen results in disease through these mechanisms:
anti receptor activity- blocking or activating its function - FUNCTIONAL LOSS
antibody dependent cell- mediated cytotoxicity ADCC- antibody antigen complexes bound to Fc receptors of IgM or IgG cause lysis - CELLULAR DESTRUCTION
activation of complement cascade- antibody recognised by complement, forms MAC membrane and cell death due to loss of osmotic integrity. results in inflammation, opsonisation, recruitment and activation of immune cells- DAMAGE TO TISSUES
Describe Type III Hypersensitivity
immune complex driven disease
immune complex and non cell bound antibody and antigen complexes which the immune system normally clear. I not cleared are deposited in blood vessel walls and tissue which causes inflammation and tissue damage, fever, rashes, joint pain.
rheumatoid arthritis, lupus, multiple sclerosis
in lupus develop IgGs against DNA so immune complexes are persistent
can also be from forming antigens like anti-serum for snake bites will help but can’t use again
Describe Type IV Hypersensitivity
Delayed type, T cell mediated
need sensitisation where antigen presented to naive T cell by antigen presenting cells to make a memory cell
on second exposure as memory T cells are slower than antigen there’s an inflammation response 2-3 days later (infiltration of monocytes and lymphocytes) e.g contact dermatitis (with poison ivy)
drives TH1 response, reexposure memory cells make cytokines activate macrophages = swelling and oedema
Tuberculin skin test measures previous exposure
What is S.aureus and what are the two groups of S.aureus causing diseases
gram positive bacterium that lives harmlessly in most, an opportunistic pathogen
LOCALISED pyogenic (pus producing) diseases causes tissue destruction due to hydrolytic enzymes and cytotoxins
diseases mediated by toxins that function as super antigens, SYSTEMIC
Properties of S.aureus and its immune evasion mechanisms
grow aerobically and anaerobically at many temperatures and even high salt concentrations
polysaccharide capsule to stop phagocytosis
cell surface proteins (protein A and clumping factor protein) so bacteria can bind to host tissues
Catalase that protects staphylococci from peroxides that neutrophils and macrophages produce
Coagulase converts fibrinogen to insoluble fibrin to form clots and protect S aureus from phagocytosis
hydrolytic enzymes: lipases, nuelases, hylauronidasem to cause tissue destruction
cytotoxins (alpha beta gamma leukocidin) that lyse erythrocytes neutrophils, macrophages and other host cells
toxins:
1) enterotoxins - heat stable and acid resistant toxins responsible for food poisoning
2) exfoliative toxins A and B on the superficial layer of skin to peel off (scalded skin syndrome)
3) toxic shock syndrome toxin is a heat and protease resistant toxin
What is the cause of S.aureus infections
infections in community and hospital, easily spread person to prison through direct contact or exposure to contaminated bed linens, clothing and other surfaces
antibiotic resistant strains are in hospital and community
List some S.aureus pyrogenic and toxin-mediated diseases
PYOGENIC: (usually end in tis)
Impetigo: skin infection pus filled on reddened ertythramatous tissue
Wound infections: pus at site of trauma
Pneumonia: abscess in lung
Septic arthritis: swollen reddened infected joint
TOXIN-MEDIATED:
food poisoning: food contaminated with heat stable enterotoxin is rated causes severe vomiting, diarrhoea and stomach cramps after 2-4 hours
Scalded skin syndrome: bacteria in a localised infection produces a toxin that spreads in circulation so skin blisters and peels off- young children only
toxic shock syndrome- bacteria in a localised infection produce a toxin that affects other organs causes fever, hypotension and a rash.
What is the treatment, prevention and control of S.aureus
Infections managed by incision and drainage
antibiotics for systemic infections
trimethoprim-sulphametoxazole, clindamycin, or doxycycline as oral therapy
treat symptoms of food poisoning and identify course
cleanse wounds and wash hands, cover exposed sin
What are the innate immune cells
Neutrophils, `Eosinophils, Basophils, Dendritic Cells, Macrophages
What are neutrophils and what do they do
Most abundant leukocyte, recruited to infection site, detect microbes and kill them, ‘simple’ immune cells
neutrophils must be balanced to prevent infection and inflammation damage
Neutrophils adhere to the endothelial cells roll and transmigrate across, chemotaxis causes them towards complement components and bacterial proteins, there they meet pathogen and are activated so they can perform effector functions. They phagocytose antimicrobial molecules, degranulate to target antimicrobial molecules, they also undergo opsonisation which is where antibodies bind to surface of bacteria by recognising antigens , results in deposition of complement and neutrophils and others phagocytes can detect, causes inflammation
