7. Immunology & Blood Flashcards
Prostacyclin - role in what
what is syhtn by paltetets and what dose it induce
What other factors mediate platelet aggregation
x4
Prostacyclin is thought to have a role in inhibiting platelet aggregation.
TBX A2 is synthesised by platelets and its effects are to induce vasoconstriction and procoagulant.
Other factors mediating platelet aggregation include contact with the subendothelium, thrombin, fibrin, exposed collagen, etc.
CD4 lymphocytes are what
What are the subtypes
what doo they release
what hla do they react with
what about cd8
Are they IEL
Delayed hypersensitivty reactions
CD4 lymphocytes are T helper cells and there are two subtypes:
Th1 which release interleukin-2 (IL2) and interferon gamma Th2 which release interleukin-4 and interleukin-10 (IL4 and IL10). CD4 lymphocytes react with HLA class II antigens, whereas cytotoxic T cells (CD8) react with HLA class I antigens.
Intraepithelial lymphocytes (IELs) are distinct from peripheral blood lymphocytes. Technically they are not T cells because only a few possess CD4 and some do not even have CD3.
The Th1 subgroup of CD4 lymphocytes is involved in delayed hypersensitivity reactions and they mature in the thymus, which explains the ‘T’ in T helper cells.
Can igG cross placenta
What pathway are 5 lipoxygeanse
PG from what path
Degran mast cell from what Ig
where are mast cell found
what type of condition is herid angio oedmea
deficiency of what
All four sub-classes of IgG are able to cross the normal placenta.
Leukotrienes are products of the 5-lipoxygenase pathway.
Prostaglandins are the products of the cyclo-oxygenase pathway, which is the other arm of arachidonic acid metabolism.
Degranulation of mast cells is caused by crosslinking of IgE (not IgM).
Mast cells are the tissue equivalent of basophils and are found in the lungs, skin and gastrointestinal tract. They are the principal mediators of immediate hypersensitivity reactions.
Hereditary angio-oedema is an autosomal dominant condition associated with a quantitative or qualitative deficiency of C1 esterase inhibitor.
DIC
what is it
how does it happen
what cuases
how is it diagnosed
Disseminated intravascular coagulation (DIC) is the most common cause of a coagulopathy during pregnancy and is caused by activation of the coagulation cascade by circulating thromboplastic material, with secondary activation of the fibrinolytic system.
Its occurrence in a pregnant patient is usually as a result of an underlying obstetric disorder such as:
Abruptio placentae Eclampsia Intrauterine foetal death (IUFD) Amniotic fluid embolism Placental retention, or Sepsis. Diagnosis of DIC syndrome rests on the demonstration of reduced levels of fibrinogen and platelets, prolongation of the thrombin, prothrombin and partial thromboplastin times, and the presence of fibrin/fibrinogen degradation products (FDP) in the serum. FDP are non-specific and may not be raised in severe DIC.
DIC is a late sign of pre-eclampsia. Mild DIC may occur without a drop in platelet numbers.
Thrombocytopaenia may also be a feature of HELLP syndrome, sepsis or leukaemia that occurs during pregnancy.
T cells -
how do they recognise foreign
how long do they last
what do they secrete when activated
T cells have characteristic surface glycoproteins and their own form of receptors.
Helper T cells recognise foreign antigens in association with HLA class II antigens on presenting cells.
Survival of T cells varies from several weeks to the lifetime of an individual, such as the T cells in thymus.
They secrete IL-2 when activated.
B lymphoctyes -
express what on surface
do they recognise native
B-lymphocytes express immunoglobulins on their surface and secrete immunoglobulins (not T cells).
B cells recognise native antigens, and T cells recognise processed antigens. Both components must be brought together and matched in order to trigger an immune response. B cells and T cells may, however, recognise different parts of the same antigen.
Fc segment ig
formed from what
define what
Isotype determine what:
Fc (fragment crystalline) is formed from constant domains of heavy chains, which define isotope of antibody (for example, IgG, IgA).
The isotypes determine the properties of antibodies, for example,
Activation of complement
Ability to cross the placenta
Half life of the immunoglobulin molecule and
Binding of mast cells and basophils.
FAB (
FAB (fragment antigen binding) are highly variable regions, which determine the affinity/specificity of antibody for antigen
Anti A and B
what type of Ig
Cold or hot
Rhesus is what type of antibody
what type Ig
Cold or hot
What type of Ig are capable of transplacental passage
Anti-A and anti-B are naturally occurring antibodies and are usually IgM. They react optimally at cold temperatures (4°C) and, although reactive at body temperature, they are called cold antibodies.
Immune antibodies like the rhesus antibody, anti-D are commonly IgG. They react optimally at 37°C and are called warm antibodies.
Only IgG antibodies are capable of transplacental passage to the fetus.
5 types of allergy
Type I - Allergy (immediate) ig
Atopy
Anaphylaxis
Asthma - IgE mediated.
Type II - Cytotoxic, antibody dependent
Autoimmune haemolytic anaemia
Thrombocytopenia - IgM or IgG mediated.
complement
Type III - Immune complex
trig inflam site deposition
Serum sickness
SLE - IgG.
vasculitis / ai
Type IV - Delayed type hypersensitivity
Contact dermatitis
T cells.
Type V - Autoimmune
Graves’
Myasthesia - IgM or IgG.
What is the humoral response
Where are b produced & mature & what about T
WHere are they found
- how do they differentiatee
Activated B produce what
- respond to what
WHat is cell switiching
what are they comprised of
do they enter cells
B and T lymphocytes are part of the adaptive humoral or specific/adaptive immune response.
B lymphocytes (B cells) are produced and mature in the bone marrow while T lymphocytes migrate and mature in the thymus.
After maturation both are released and found in the circulation and peripheral lymphoid organs (for example, spleen, lymph nodes) where they differentiate further after contact with an antigen.
Activated B cells produce plasma cells which are responsible for producing large numbers of specific antibodies according to the lineage of that B cell. However “class switching” is a biological mechanism that changes a B cell’s abiltiy to produce immunoglobulin (antibodies) from one type to another, such as from the isotype IgM to the isotype IgG.
Antibodies (IgA, IgG, IgM, etc) comprise two heavy and two light chains.
Antibodies bind to circulating antigens but cannot enter cells.
Pyrexia repsonse stimulated by
what rises
yrexial responses may be stimulated by cytokines, for example, tumour necrosis factor (TNF), interleukins and prostaglandins.
C reactive protein (CRP) is increased in a febrile response but does not elicit the response.
Corticosteroids and IgE do not normally elicit febrile responses.
Rhesus antigens
What is the commenst in cacausion
Are rehsus natural
The rhesus system is coded by allelic genes at three closely linked loci.
In Caucasians the commonest rhesus genotype is CDe/cde and is found in approximately 32% of people (CDe/CDe is found in 17% of patients).
Rhesus antibodies rarely occur naturally and are usually the result of previous blood transfusion or pregnancy. Most commonly, hemolytic disease is triggered by the D antigen, although other Rh antigens, such as c, C, E, and e, responsible for most of the clinical problems associated with this system.
In the ABO system, the structure of the three antigens differs due to the addition of the following carbohydrate groups to the L-fucose of the H substance:
Blood group A antigens have an N-acetyl galactosamine
Blood group B antigens have a D-galactose
Blood group O antigens are unaltered.
Naturally occurring antibodies are found in the plasma of patients whose erythrocytes lack the corresponding antigens. Therefore,
Blood group O contains both anti-A and anti-B antibodies
Blood group A contains anti-B antibodies
Blood group B contains anti-A antibodies and
Blood group AB contains no antibodies.
Red cells may contain rhesus antigens for example:
A RhD positive (A+) A RhD negative (A-) B RhD positive (B+) B RhD negative (B-) O RhD positive (O+) O RhD negative (O-) AB RhD positive (AB+) AB RhD negative (AB-) About 85% of the UK population is RhD positive (36% of the population has O+, the most common type).
Whole blood storage
Whole blood is stored at 2-4 degrees centigrade for up to 35-days with preservative solutions [Acid citrate dextrose (ACD) and citrate phosphate dextrose(CPD)]
Storage is associated with a number of biochemical and haematological changes:
Decrease in pH Build up of lactic acid Decrease in glucose consumption Decrease in ATP level Low 2,3-DPG levels Reduced clotting factors:
The ABO blood group system is determined by the ABO gene, which is found on chromosome 9. The four ABO blood groups, A, B, AB and O, arise from inheriting one or more of the alternative forms of this gene (or alleles) namely A, B or O.
The A and B alleles are codominant so both A and B antigens will be expressed on the red cells whenever either allele is present. O alleles do not produce either A or B antigens, thus, are sometimes called ‘silent’ alleles.
Group O rhesus negative is the universal donor (O rhesus postive is the commonest blood type)
Group AB is the universal recipient
Acute phase involves what
Body temp
What happens proteins
What happens Cu Zn & Fe levels
The acute phase response involves a complex series of reactions with changes in metabolic, immunological and haematological functions.
There is an alteration in the set point temperature of the hypothalamus which results in a febrile response.
Plasma albumin levels decrease, C reactive protein increases and there is a neutrophil leucocytosis.
Copper is not sequestered by the liver and its levels actually increase, whereas iron and zinc concentrations decrease.
Prostaglandins -
differ hw from hormones
6 effects
Prostaglandins act as chemical messengers at the site where they are synthesised. They thus differ from hormones which can be transported in the blood and can act in distant sites in the body.
- Activation of the inflammatory response at the site of tissue injury, leading to pain, swelling, redness and increase in temperature.
- Haemostatic properties such as when there is blood
vessel damage (thromboxane stimulates vasoconstriction and activation of platelets). - Stimulate uterine contractions and thus are effective in inducing labour.
- Inhibit acid synthesis (including gastric acid) and increase secretion of protective mucus within the GI tract.
- Increase blood flow in kidneys.
- Constriction of bronchi, thus exacerbating bronchial asthma.
Abc on Ig
bound by what
Fc made up of what
- linked by what
What is major ab at mucosal surfaces
Which tpe can synthesise
What can bind worm antigen
The antigen binding sites on immunoglobulins are composed of the hypervariable regions of both heavy and light chains which together make the complementarity determining region (CDR) of the antibody.
The Fc is made up of two H chains, linked by disulphide bonds.
IgA (actually IgA2), constitutes the major antibody in secretions, and bathes mucosal surfaces. IgA1 is mainly confined to the serum.
Only B lymphocytes are capable of synthesising antibodies, as are plasma cells.
Worm antigens are constantly being released, and attach to specific IgE antibody that in turn has attached to mast cells by their receptor for IgE. Interactions with IgE results in mediator release by the mast cell, one effect of which is contraction of smooth muscle, which is intended to expel the parasite from the gut.
Mast cells - are they lipophilic?
where located
what do they contain in storage granules
release can be triggered by
Mast cells are basophilic cells (not lipophilic) in the connective and subcutaneous tissues, which are involved in inflammatory and immune responses.
They contain storage granules that contain lytic enzymes, for example, tryptase, and inflammatory mediators, for example, histamine, heparin, 5-HT, leukotrienes, platelet aggregating factor, leucocyte chemotactic factor and hyaluronidase.
Release of these mediators occurs during mast cell degranulation, which can be triggered by:
tissue injury drugs complement activation, and foreign antigenic material. An anaphylactic reaction occurs when a previously sensitised individual is re-exposed to the antigen. It is an IgE mediated immune response (not IgA).
Mastocytosis occurs when excess mast cells are present in the circulation or as tissue infiltrates.
Endotoxins
are what
how are they destreoye
what type of antibody response
elicit what kind of type of host response
activate what pathyway
is botox an endotoxin
Endotoxins:
Are lipopolysaccharides that form part of the outer cell wall of Gram-negative bacteria
Endotoxins are heat stable (boiling for 30 minutes does not destroy the endotoxin), but certain sterilants that are oxidisers (superoxide, peroxide and hypochlorite) help neutralize them
Are antigenic but the response is often directed against the lipopolysaccharide (LPS) component of the cell wall so this is not as effective as antibodies to exotoxins. They are only partially neutralised by specific antibodies. Future repeat infection may still take place.
Cause septicaemia and fever
Activate the alternative complement pathway, produce cytokines and activate the coagulation pathway
Clostridium botulinum produces a neurotoxic exotoxin
Platelets are what
do they have a nucles
can they activate substance
Whats their lifespan
form what species in body
How much % plt stored in sp
gp that bind whatleen
Platelets are membrane-encapsulated fragments of megakaryoctes cytoplasm
no nucles
Although platelets have no nucleus, they are metabolically active and are able to express membrane receptors and release stored substances when triggered. They contain dense granules containing adenosine diphosphate (ADP), adensine triphosphate (ATP), serotonin, calcium and magnesium ions.
However, because they have no nucleus they are unable to produce new proteins and therefore aspirin and other drugs affect function for the remainder of the platelet lifespan. Platelet lifespan is approximately 9-10 days in normal individuals.
Platelets are capable of producing nitric oxide, prostaglandins and thromboxane, but not the vasodilator prostacyclin.
In a normal person, 20% of the platelets are found in the spleen
express abo and hla class 1
gp1a - collagen
gpiib iia - vwf + fibronectio
