Roger Booth Flashcards
What is the disease called when you don’t have T cells?
Severe combined immunodeficiency (SCID)
Recurrent infections with extracellular bacteria indicate what type of immundeficiency?
IgM and IgG, complement or pgagocytosis
Recurrent infections with intracellular bacteria indicate what type of immundeficiency?
T cells and macrophages
Recurrent infections with viruses indicate what type of immundeficiency?
T cell, IgG, IgA, IFN
Recurrent infections with paracites indicate what type of immundeficiency?
IgE, eosinophils, mast cells, T cells
When will congenital immunodeficiencies be recognised in new borns?
After 4 months when the transferred immunity from the mother decreases.
What do Th1, Th2 and Th17 cells do?
Th1 - IgG and IgM, cytotoxic T cells, acute viral and bacterial infections.
Th2 - IgG and IgE, mucisal immunity, chronic infections, especially paracites
Th17 - mucosal immunity and promote inflammatory response
What is the outcome from the modern environment relative to the primitive environment?
Less expose to antigens means less ability to control pathogens -> less Treg stimulation and more inflammation -? allergies and hypersensitivities
How does the immune system interact with the autonomic nervous system?
Nerves of the ANS can innervate the secondary lymphoid organs which can control lymphocyte activation and downstream responses.
Hormones of the endocrine system also can interfere with T cells, B cells and APCs
Cytokines of the immune cell also influences the nervous system.
What cytokines can influence the nervous system and what do they do?
IL-1, IL-6 and TNF -
Fever, - IL-1
Sleep wake cycles -
Promote illness behaviors
IL-1 acts on the vagus nerve branches, can be secreted by astrocytes and glial cells
IL-1 has neurotransmitter activity.
What do sympathetic nerves do in the lymph node?
The sympathetic NS branches into the paracortical region where T cells are and release norepinephrine that communicates with T cells
What are the most common bacteria that contaminate devices and what features allow them to do that?
Staphylococcis epidermis
Staphylococcus aureus
Escherichia Coli
Adhesive proteins (MSCRAMMS) Polysaccharide intercellular adhesion (PIA)
What factors favor bacterial adhesion to devices?
Duration that it’s in.
What the device is made of
How often the device is used
Surface of the device (smooth or irregular)
What is myasthenia gravis?
An autoimmune condition where antibodies bind to and remove acetylcholine recpetors from postsynaptic receptors. Causes ptosis and diplopia
What receptors promote phagocytosis?
PAMP receptors - weak but common
Fc region of antibodies
C3b of complement
What are specific PAMPS?
Danger signals
Cell wall components - - LPS and peptidoglycans
Bacterial metabolic products
Heat shock proteins - released by stressed cells
What are acute phase proteins?
Stimulated by inflammation - in the blood
Released in the acute phase
Involved in complement and activation the adaptive immune response
Come from liver
Promote resolution and repair of lesions
Limit tissue injury
What does complement do?
Vascular permeability
Opsonisation - C3b
MAC formation
Chemotaxis - C5a
What are the MHC I and II subtypes and structures?
MHC I: HLA-DP, DQ and DR
MHC II - HLA-A, B and C
MHC I: alpha and beta subunits
MHC II: Alpha subunit and B2 microblobulin
What happens to people who have deficiences in TAP proteins?
Low HLA-A, B and C expression. Can’t generate CD8 T cell responses. Few CD8 T cells
- have poor immunity against viruses. Recurent URTIs
What are the different selectins?
For slowing immune cells in the blood.
L-selecting - lymphocytes
P-selectin - platelets
E-selectin - leukocytes ( induced by IL-1 and TNF-alpha
What are the receptors involved in lymphocyte activation?
I-CAM-3 on the APC to LFA-1
TCR to MHC
CD4 0r CD8 to MHC
Checkpoint molecules
CD40L on CD4 T cells and CD40 on B cells
What are the function of IFN-alpha, beta and gamma?
They inhibit vital infections - interfere with viral replication.
Virus infected cells release IFNs which stimulate non-infected cells to cause them to change which prevents them from being infected
IFNs also stimulate natural killer cells to kill virus infected cells
What are the different classes of cytokines and what do they do?
1 .Innate cytokines - wound healing and immune stimulating
- Adaptive cytokines - lymphocyte stimulation
- Chemokines - recruit
- CFU - stimulate cell development
What are the regions of an antibody?
Conserved region and variable region. Light and heavy chains
CH2 - complement -binding region
CH3 - Fc region
How do you treat a B cell deficiency in an infant (no antibodies)
Transfer serum
Bone marrow transplant
What to Abs do?
Neutralisation: preventing attachment and entry of bacteria and toxins, immobilising bacterial flagella
Agglutination - clumping to assist phagocytosis (IgM) - depends of ratio of antigen to antibody
Opsonisation - Fc region
Activating complement - C5b -> MAC. C3a - > vascular permeability and chemotaxis (C5a too). C3b -> opsonisation. C5a ->
ADCC - NK cells and K lymphocytes
What are the classical and alternative pathways for complement activation?
Classical: antigen-antibody complexes
Alternative pathway - pathogen surfaces
Different proteins - both cleave C3
What are the differences between the antibodies?
IgM - pentimer, initial ab produced. Confined to circulation (too large) - 10% of AB pool. Good at agglutination and complement activation. Important defence against blood-borne infections such as bacteria.
IgG -small can gets out of the blood easy (extra vascular space). 70% of ABs. Good at neutrilisation, complement activation, and at enhancing phagocytosis, effective against viruses, also bacteria. Cross placenta.
IgA- Dimer. 15% of blood antibodies. Produced by mucosal immune system into seromucus to protect those surgaces, particularly in the gut and lungs.
IgD: small amounts - surface molecules on B cells (is a receptor)
IgE - small amounts - Binds to mast cells - paracytic and allergies
How can CD8 T cells induce apoptosis and necrosis separately?
Apoptosis - production of TNF-alpha, and IFN-gamma
Necrosis - perforin and granzyme
What antibodies does a mature B cell express?
IgM and IgD
How is a antibody variable region created?
There are multiple Vh, Dh, Jh exons that recombine to create the variable region. Also a constant region.
Recombination is independent of antigen.
which happens once a cells has committed to become a B cell. Transcribed into RNA for VDJ and C.
Light chain is only V, J and C.
This recombination creates wide variation.
One way process. One Vh and Vl region per receptor. All constant regions are present initially.Mew is the first constant region which codes for the IgM antibody.
Convert from IgM to IgG by cutting out the constant regions. Retain V, D, J
How does tolerance of B cell receptors occur?
Central tolerance.
Once variable region is developed. The cells is presented with self antigens that if the b cell binds it with high affinity it will be deleted.
Also peripheral tolerance - no costimulation
How are T cell receptors created?
alpha and beta chains
Valpha, J alpha and C alpha
Vbeta, D beta, J beta and C beta (mixed in order). Random rearrangement.
Flow of differentiation is from the cortex to the medulla of the thymus.
How is T cell tolerance conducted.
alpha beta receptor developed.
Expresses both CD4 and CD8
Positive selection - can it recodnise MHC I or MHC II. Does Cd4 or CD8 bind. No recondition = death. (positive = keep; selection = binding)
Down regulate either CD4 or CD8 depending on what binds.
Negative selection: tested against some self peptides. Strong binding = remove. (negative = remove; selection = binding).
CD3 then expressed and T cell is exported.
Peripheral tolerance.
What type of pathogen are antibodies most effective against?
Bacteria
What happens in mucosal immuntiy?
Pathogen gets through the serum IgA that is in the mucosal tissues and then to the mast cells with the IgG expression. This triggers the release of granules that vasodilation and recruitment, complement products etc.
What are the function of NK cells?
They have Fcreceptor binding of antibodies that allow them to do ADCC.
They have killeractivator and killer inhibitor receptors.
Activity enhanced by IL-2 and IFN-y. Are an early response, prior to T cell response.
What is the order of immune response to a virus?
Virus: infected cells release IFN that reduces spread (also stimulate NK cells).
If down regulation of HLA then NK killing
Then CD8 T cells
Antibodies to prevent reinfection
What are the functions of proinflammatory cytokines?
Induce acute phase proteins
Fever and behavioural changes
Tissue repair
Acivate T and B cells
What is the function of IFNs?
Induce transient anti-viral state
Activate NK cells
Upregulate MHC expression
What sort of vaccine uses T cells?
Protein antigens generate T cell dependent antibodies
Polysaccharide antigens - T cell independent antibodies
Live vaccines - antibodies and CD8 T cells
What are the different types of antibodies?
Live attenuated vaccines - good memory development
Inactivated vaccines - a) whole pathogen b) protein-based vaccines - toxoids Polysaccharide based vaccines - cell wall from bacteria Conjugate vaccines
Who is at risk with live attenuated vaccines?
Immunocompromised people - this places babies at risk because you don’t know if they will be immunocompromised until the mothers antibodies have gone
What are the type of inactivated vaccines?
Killed whole pathogen
Component vaccine (subunit) - subunits or toxoids
What are some component antigen vaccines?
Diptheria, tentus, hep B, pertussis, polio, haemophilus influenzae type B
What is tetanus?
Clostridium tetani - an anaerobic spore forming gram-positive bacillis, penicillin-sensitive.
Spores everywhere -
symptoms 10 days after exposure - muscle rigidity - arching back, lock jaw
Who is most at risk of tenanus?
Infants - neonatal tetanus - entry via the umbilicus of an unvaccinated mother.
Mortality (>90%)
Give all mothers of child bearing age the vaccine 3 doses.
What are the disadvantages of passive immunity?
No long term protection
Risk of transmission disease
Expensive and poor access
Serum sickness
What are the features of bordetella pertussis?
Gram negative bacilli
Highly contagious - sneeze or cough
Catarrhal phase - runny nose, conjunctival, malase (1-2 weeks)
Bad cough (1-10 weeks)
What is the treatment for bordetella pertussis?
Erythromycin (macrolide)
May shorten illness - decrease infectivity
Was a whole cell killed vaccine but now component vaccine vaccine containing a number of virulence factors - many don’t get 3rd dose. Old people resivour for disease.
What is polio?
A disease caused from poliovirus that destroys lower motor neurons resulting in paralysis
Was a live attenuated oral vaccine -intestinal immunity
Now component vaccine -
What type of vaccine is the tetnus vaccine?
Vaccine against the tetanus toxoid.
What are the four hypersensitivity reactions?
Type I: IgE-mediated mast cell response
Type 2: IgG mediated cell cytotoxicity (ADCC) of coated cell, and complement induction
Type 3: IgG immune complex formation resulting in complement
Type 4: delayed type hypersensitivity - activation of CD4 T cells -> macrophage activation
Type I hypersensitivity?
Mast cells have Fc episolon receptors that bind IgE. When stimuilated they release granules containing chemoattractants, vasodilators, complement and platelet activation, smooth muscle contraction, mucus secretion
Rhinitis - house dust mite
pollens
animal dander
Insect stings
Food allergies
Drugs
What are the common sites for allergies to occur?
Respiratory tract: Sinusitis Conjunctivitis Asthma Rhinitis
Skin
Urticaria
Angioedema
Food allergy
Gut
Multiple organs
Type II hypersensitivity?
An antibody binds to a cell surface antigen and activates K lymphocytes or complement. Frustrated phagocytosis
Haemolytic disease of the newborn
Type III hypersensitivity?
Soluble antigens: dependent of ratio.
Localise in capillaries - complement mediated damage -> kidneys, skin
Immune complex-induced vasculitis and nephritis
Type IV:
Delayed type hypersensitivity
CD4 T cell activation
Contact sensitivity.
Antigen uptake - CD4 activation - recruit more cells - macrophage activation
Nickle ions - bind to a hapten (carrier protein)
What is the organ specific hypersensitivity and the systemic?
Type II and type III
What is an example of a type III hypersensitivity disease?
Sytstemic lupus erythematosis
Rheumatoid arthritis
What are the treatments of autoimmune diseases?
Replacement - insulin
Suppression -
