IAH Flashcards
Name an autoimmune disease affecting
a) Kidneys
b) IgE on basement membrane
c) Thyroid
d) B cells
e) Salivary glands
a) Goodpastures syndrome
b) Bullous pemphigoid
c) Graves disease
d) SLE, MS
e) Sjogren’s
What type of disease is Bruton’s X-linked agammaglobulinemia?
Immunodeficiency
What causes Bruton’s?
Defect in B cell receptor signalling so B cell deficiency resulting in decreased Ig
How does Bruton’s affect Ig levels?
B cell deficiency so low Ig
Why is Bruton’s more common in boys?
Girls have 2 copies of the X chromosome so can be a carrier, boys only have one X chromosome from the mother so if the mother is a carrier the boy will have it
What surface molecule is expressed on T helper cells only?
CD4
What surface molecule is expressed on all T cells?
CD3
What microorganism causes Karposi’s sarcoma, pneumonia and B cell lymphoma?
Characteristic of AIDS
HIV1 (HIV2 but less severe)
What bacteria causes pneumonia in AIDS?
P. Jirovecci
How do commensal bacteria help prevent infections?
Prevent pathogen from gaining an ecological foothold
Stimulate colonic epithelial cells to from a balanced state = physiological inflammation
Compete with pathogens for nutrients, attachment sites and living space
Secrete bactericidal products e.g. FA from propionibacterium and lactic acid from lactobacilli
What bacteria causes infection at burns?
P. aeruginosa
What makes burns susceptible to infection?
Opportunistic infection
Moist surface
Vascular damage
Lots of nutrients like haem
Function of CD4 on actual membrane?
Binds antigen presented on MHC II
If activated by BCR it an activate B cell differentiation
Co-stimulatory factor - activates CD8 cells
Describe structure of granuloma
Central area of infected macrophages surrounded by outer layer of CD4 TH1 cells
What cytokine is secreted by lymphocytes in the granuloma, what is the effect?
Th1 cells secrete IL-2 to promote T cell proliferation and IFN gamma to activate macrophages
What causes granulomas to form?
Mycobacterium resisting bactericidal attempts of macrophages
Function of CD8 Tc cells
Control infection by directly killing infected cells
How do Tc cells cause cell death?
Release of cytotoxins to induce apoptosis
Interaction of FasL and Fas on target - apoptosis
What cells form from the myeloid and lymphoid lineage?
WBC
Myeloid = granulocytes (neutrophils, basophils, eosinophils, monocyte, mast cell)
Lymphoid = B cell, T cell, NK cell, ILC
Acute rejection
Type IV (T cell mediated) hypersensitivity reaction Alloreactions in transplant rejection (recipients T cells attack the transplant alloantigen (HLA) or graft vs host disease (when T cells transplanted they react to host alloantgien (HLA))
Hyperacute rejection
Type II hypersensitivity caused by ABO or HLA mismatch
Pre-existing antibodies bind to graft = endothelial damage
What can increase the risk of hyper acute rejection?
Pre-existing anti-HLA antibodies e.g. pregnancy, multiple blood transfusion, past transplantation
How is hyper acute rejection circumvented?
Serological testing and antigen cross matching
Chronic rejection
Type III hypersensitivity reaction (immune complexes)
Donor-specific alloantibodies bind HLA not he surface on the graft, recruit inflammatory cells
Arteriosclerosis, fibrosis, hypo perfusion, loss of function
Other than HIV what causes karposis Sarcoma
HHV8
Use of monoclonal antibodies?
Target specific antigens
target cancer molecules
target host immune response to boost performance
identify size and location of tumour
Function of CD3 receptor on T cells?
Generates signal to activate signal transduction pathways once the binding has occurred
Function of CD28 receptor on T cells?
On surface of T cells interact with co-stimulatory molecules
What activates TLR4?
Where is it found?
LPS
Membrane bound
What activates TLR3?
Where is it found?
Ds viral RNA
Endoplasm
Function of
a) Th1
b) Th2
c) Treg
d) Th17
e) TFH
a) Activation of macrophage
b) Mast cell activation
c) Suppression of immune system
d) Re-enforcement of inflammation
e) activate B cells in lymph
How are CD8 cells activated?
Presentation of antigen on MHC class I molecule, CD3 then sends signal for signal transduction = release of cytotoxic release
What type of cell is MHC class I presented on?
Virally infected cells
Function of
a) IL1 and TNF
b) IL6
c) IL12
d) IL8
e) IL17
a) pro-inflammatory
b) Lymphocyte activation and increased Ig production
c) NK and T cell differentiation
d) chemokine release (neutrophil migration)
e) Th17 activation
Length of phases in HIV graph
a) symptomatic phase
b) non-symptomatic phase
a) 4-8 weeks (flu-like symptoms)
b) 2-12 years (reduction in CD4 equal to production of CD4 = fluctuations of virus in plasma
What disease results in the inability to class switch the Ig molecules, and what is the aetiology of this disease?
Common variable immune deficiency
Limited to IgA
What cells produce AMPs?
Paneth cells Neutrophils (alpha defensins) Epithelial cells (beta defensins)
How do AMPs kill pathogens?
Ampipathetic properties = insert into membrane and disrupt pore formation = lysis
Name a virus that lays dormant in B cells? Which disease does this cause?
Epstein-Barr virus
In immunosuppressed individuals EBV can re-activate and cause B cell lymphoma
How does herpes simplex evade the immune response?
Virally encoded Fc receptor blocks effector functions of antibodies bound to virally infected cells Virally encoded complement receptor blocks effector functions of complement Blocks MHC class I presentation = no activation of Tc cells
How does p. gingivalis and mycobacterium tuberculosis evade the immune response
P. gingivalis = releases proteases that digest antibodies
Mycobacterium = phagocytosed but highly resistant to proteolysis/lysosome fusion = no MHC II presentation
Cause of cell necrosis in Granuloma formation?
Centre of granuloma cut off from blood supply, cells die through anoxia and excessive macrophage lytic enzymes = necrosis
2 disease caused by mycobacterium?
TB and leprosy
What tissue does HSV first infect?
Which tissue does it become latent in? Why?
Treatment?
Epithelial
Neurones (trigeminal ganglia) - very few MHC class I (so there isn’t an immune response within- = evade immune system
Aciclovir
Structure and function of Peyers patch?
Within the SI
M cell on surface which samples antigens
Antigens activate DC cells which present antigen to cells within the germinal centre of lymph nodes
Function of germinal centre of lymph node?
generate new cells - B and T cell activation
Mast cell
a) function
b) contents
c) activation
a) degranulation releases inflammatory mediators (histamine)
b) granules containing histamine
c) Cross linking of IgE (by antigen binding) causes degranulation
Identification of monocyte?
Function?
% of cells made up of monocytes
Large cell, kidney bean nucleus
Pre-cursor for macrophage. Circulates in the blood
2-10%
Candida albicans identification
Budding/hyphae form
Function of B cell antigen transport?
Present to T cells
Affinity mature
How do B cells change during life?
Somatic recombination
V region recombinase
Junctional diversity
Function of neutrophil?
Professional phagocyte
Release pro-inflammatory cytokines
Release AMP, ROS, NO
Function of MAC?
Form pits in membrane = lysis
Function of fibroblasts in inflammation?
Formation of scar tissue
Type I hypersensitivity?
Immediate
IgE mediated = Mast cells release pro-inflammatory cytokines
3 causes of haemolytic anaemia (type II reaction)
Penicillin hypersensitivity
Autoimmune haemolytic anaemia
Blood group incompatibility
Example of type II autoimmune reaction?
Pemphigus vulgaris
Autoimmune haemolytic anaemia
Example of type III autoimmune reaction?
Rheumatoid arthiritis
Example of type IV autoimmune reaction?
T1DM (autoantigens = beta cell antigen)
Chron’s (autoantigen = antigens of microbial microbiota)
Atopy
Allergy with genetic predisposition (e.g. hay fever)
Example of type I hypersensitivity?
Anaphylactic shock
Eczama
Asthma
Type III reaction
Formation of immune complex that invade tissues and causes inflammation and destruction
Pus?
Dead/dying neutrophils
Polymorphism?
Example?
Genetic variation = different forms within the population
MHC
Which receptor has holotypes associated with autoimmune disease?
TCR
If they don’t have central tolerance
Hypermutation effect
Mutations in B cells to produce Ig with higher affinty
SCID?
Causes?
Severe combined immunodeficiency
Defects in T cell development = no T cells, antibodies, memory
Caused by mutations in genes for cytokine signalling e.g. Il2 receptor
HHV8
Consequence
Herpes simplex virus 8
Highly prevalent in HIV patient = enlargement of lymph nodes
What Ig component recognises LPS?
Constant region (Fc)
What Ig component is most polymorphic?
Antigen binding site
What cell surface molecule recognises LPS?
TLR4
What is rearranged after a primary immune response?
Random recombination of gene segments to produce diversity in the antigen binding sites
Consequence of excessive tissue exudates
Neutrophils
Chronic inflammation and tissue destruction
What cells secrete performs?
NK
Most abundant WBC in healthy peripheral tissue?
Neutrophil
What WBC is low in chemotherapy patients?
Neutrophil
What is the consequence of S. pyogenes infection?
Strep throat = sore throat
What component of the immune response is mostly involved in S. pyogenes infection?
IgA
What is the general consequence of pyogenic bacterial?
Production of pus
How do streptococci evade the immune system?
Polysaccharide capsule
What cell surface receptor helps distinguish between active and naive T cells?
IL2 receptors
Cytokine associated with
a) TH1
b) TFH
c) Treg
d) Th17
a) IFN gamma
b) IL4
c) IL-10
d) IL-17
Example of
a) type IV hypersensitivity
b) type III
c) type II
d) type I
a) Chronic asthma
b) serum sickness
c) blood group incompatibility
d) allergic rhinitis (hay fever)
Anatomical structure tonsils protect?
Larynx and back of throat
What cell synthesise IgA in the mouth and where are they located?
Plasma cells
Salivary glands
Where are the antigens that stimulate the production of IgA taken up in the body and where have they likely originated?
In the gut (M cells of peyer’s patch)
Antigens probably come form mother
Difference between classical and alternative pathway
classic = C-reactive protein or antibody presentation Alternative = pathogen surface causes activation
Clinical consequence of complement deficiency?
More infections from extracellular bacteria like staphylococcus or pyogenic bacteria
2 cytokines that induce vascular changes associated with inflammation and their target?
IL1 and TNF
Endothelial cells of BV
3 social and/or demographic factors influencing the pattern of infectious disease?
Availability and infrastructure to healthcare Travel availability Poverty Porous borders Insolation/heirachy
Genetic basis fro antigenic shift and drift and how the outbreaks differ?
Drift = point mutation (gradual) = seasonal variation and limited epidemics Shift = recombination between strains = widespread infection (pandemics), jump between species = no immune response
Other than herpes simplex name another disease caused by re-actiavtion of latent herpes virus and name the virus responsible.
What 2 locations of the body are the lesions commonly manifested?
Herpes Zoster = shingles
Skin of torso and head and neck
How does T. palladium evade antibody recognition?
Coated in fibronectin
Function of staphylococcal enterotoxins on T cells?
Superantigens = bind MHC and TCR independent of antigen specificity = polyclonal T cell response = excessive release of cytokines = toxic shock syndrome = apoptosis
Aetiology of primary immunodeficiencies>
Genetic mutation
Clinical consequence of B cells deficiency?
Increase infections from extracellular bacteria e.g. S/ pneumonia
Causes fo secondary immunodeficiency?
Immune senecence (age and nutrition) Trauma (burns, surgery) Drugs (immunosuppressants) Tumours (CLL) Infection (HIV)
Why is it difficult to gauge true extent of HIV infection?
Many asymptotic carriers that don’t know they are HIV +
3 properties that compromise host immune response giants HIV?
High mutation rate, genetic variability, latency
Mode of anti-viral nucleoside analogues?
Interfere with viral transcription from viral RNA to viral cDNA
Other than nucleoside analogue, 2 other anti-HIV drugs?
Reverse transcription inhibitors and protease inhibitors
HAART?
Advantages?
Disadvantages?
highly active antiretroviral therapy
Combination of anti-viral drugs = good when some viruses have resistance to some drugs
Lifelong treatment (need gets rid of viral load), expensive, serious side effects
What elements of immune response mediate autoimmune disease?
Autoantibodies and autoimmune T cells
2 autoimmune disease involving CNS
MS
Myasthenia gravis
3 autoimmune disease of endocrine system
Graves
T1DM
Addisons
Autoimmune disease effecting exocrine gland
Sjogrens
3 lines of evidence that autoimmune disease have heritable element
Association with HLA genotype
Run in families
Different susceptibility of mice with different genetics
High concordance in twin studies
Why are autoimmune disease often characterised by deficiency disorder to compromised function?
Often involve tissue destruction
3 autoimmune disease with oral manifestations?
Sjogrens, SLE, pemphigus vulgaris
Why are autoimmune diseases unequally distributed between sexes?
Endocrine effect
Imprinting
Allergen encountered through
a) inhalation
b) injection
c) ingested
d) contacted
a) pollen
b) drugs
c) food
d) plants/synthetics
Immune mediators of
a) Type I hypersensitivity
b) Type II
c) Type III
d) Type IV
a) IgE
b) IgG
c) IgG
d) T cells
Red patch often associated with wheal and flare?
Erythema
2 cells involved in type I hypersensitivity?
Mast cell
Plasma cell
Another name for atopic dermatitis?
Eczema
Management of type I hypersensitivity?
Anti-histamines
Avoidance
Desensitisation
Properties of Ig produced by memory B cells?
Class switched and high affinity to antigen
Properties of good vaccine preventing viruses entering cells of vaccinated individuals?
Induce neutralising antibodies
Properties of good vaccine helping responses against intra-cellular pathogens in vaccinated individuals?
Induce protective T cells
3 Practical difficulties with vaccinations by injection?
Needs a professional
Expensive
Equipment disposal problems
Reasons many populations remain unvaccinated?
Need for refrigeration
Need for skilled workers
3 manufacturing processes for antigen element of vaccine?
Killed
Live attenuated
Recombinated
Purified
What is the challenge in developing vaccines against encapsulated bacteria?
By themselves they only provide and inadequate thymus independent immune response so a conjugated capsular vaccine is need to provide an environment for T cell differentiation
What 2 vaccines administered by mucosal route?
Polia and influenza
Why are adjuvants needed?
Purified antigens don’t elicit an innate immune response, adjuvants promote a better immune response
Possible consequence of endocrine function of developing child of mother with Graves?
Hyperthyroidism as autoantibodies are passively transferred through placenta. Stimulate TSH receptor = more thyroid hormones release
Why does London have a higher incidence of certain infectious disease than other parts of the country?
Varied and dynamic population
Variable disease exposure
Variable immunity
Factors that may compromise the effectiveness of vaccination programmes?
Reduced uptake (fear, apathy)
Expense
Mutation of live attenuated viruses
Shift in herd immunity
Other than organ transplantation, identify 4 further tissues commonly transplanted?
Cornea, blood, bone marrow, heart valves
Organ least likely to be rejected as a result of imperfect tissue matching?
Liver
Allotransplantation
Xenotransplatation
Autotransplatation
Between same species
Between different species
Within individual
Universal donor and universal recipient, why?
O = donor = no ABO antigens so cannot be recognised as non-self AB = no A or B antibodies so will not mount an immune response
Visible symptom of graft vs host disease?
Skin rash
3 features of rejected organ?
Swollen
Hameorrhage
Necrosis
Whta function of T cells do immunosuppressants target?
Cytokine secretion
