CD8+ T-cells (Cytotoxic T cells)
Recognise antigen only in association with HLA Class I molecules (found on all nucleated cells; present endogenous antigens such as those found in cells infected by viruses or intracellular bacteria.)
Comprise about 25% of peripheral T-cells
Responsible for cytotoxic killing of target cells

In February 2016 the Society of Critical Care Medicine published a JAMA article reformatting the definitions of sepsis in an attempt to overcome the shortcomings of the old definitions.
The main changes are a new definition of sepsis, the replacement of the SIRS criteria with the quick Sepsis-related Organ Failure Assessment (qSOFA), and the complete removal of “severe sepsis” as an entity.
The new definition of sepsis is that it is “life-threatening organ dysfunction caused by a dysregulated host response to infection.”
Septic shock is “a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are profound enough to increase mortality.”
In essence this means that septic shock is sepsis plus the following, despite adequate fluid resuscitation:
Vasopressors required to maintain a MAP > 65 mmHg
Serum lactate > 2 mmol/l
The qSOFA score is a bedside prompt designed to identify patients with suspected infection who are at greater risk for a poor outcome outside of the intensive care unit. It uses the following three criteria:
Hypotension (SBP < 100 mmHg)
Tachypnoea (RR > 22)
Altered mental status (GCS < 15)
The presence of 2 or more of the qSOFA criteria near the onset of infection is associated with greater risk of death or a prolonged intensive care unit stay.

All the Haemophilia’s have an X-linked recessive inheritance pattern, so they only manifest in male patients. Diseases with a mitochondrial inheritance pattern include MELAS syndrome, Leigh syndrome, LHON and MERRF syndrome. Autosomal dominant disorders include Huntingdon disease and Marfan syndrome. X-linked dominant diseases include Fragile X syndrome. Autosomal recessive diseases include cystic fibrosis and sickle cell disease.

Classic signs:
Rubor (redness)
Calor (heat)
Dolour (pain)
Tumour (swelling)
Functio laesa (loss of function)
These classic signs are produced by a rapid vascular response and cellular events. The main function of these events is to bring elements of the immune system to the site of injury and prevent further tissue damage.

In infants and young children, lymphocytosis often occurs in response to infections that would normally produce a neutrophil reaction in adults.
Lymphocytosis occurs in:
1. Viral infections (e.g. infectious mononucleosis, HIV, rubella, mumps, viral hepatitis, cytomegalovirus, herpes simplex or zoster)
2. Bacterial infections (e.g. pertussis, tuberculosis, toxoplasmosis, syphilis)
3. Chronic lymphoid leukaemias
4. Acute lymphoblastic leukaemias
5. Non-Hodgkin lymphoma
6. Thyrotoxicosis

Haemostasis is your body’s defence against an injury that causes bleeding. It stops bleeding in three main steps:

1) Primary haemostasis – formation of a weak platelet plug
– The primary reaction of the body is to cause local vasoconstriction at the site of injury and decrease blood flow to the affected area
– the release of cytokines and inflammatory markers lead to adhesion of platelets and aggregation at the site of injury forming a platelet plug
– the injured vessel wall has exposed subendothelial collagen that releases von Willebrand factor

Any damage to the vessel wall causes the release of the Von Willebrand factor, which is necessary for platelet adhesion. Tissue Thromboplastin is also released, which activates the coagulation pathway, a component of secondary haemostasis. The coagulation cascade ultimately results in the conversion of fibrinogen to fibrin.

2) Secondary haemostasis
3) Fibrinolysis

Fibrin (factor Ia) is a long, thin protein with branches produced at the end of the coagulation cascade when fibrinogen (factor I) is converted to fibrin, which stabilizes the blood clot.

Neutropenia is defined as a total neutrophil count of < 2.0 x 109/l.
It can be caused by:
Viral infections
Collagen disease e.g. SLE and RA
Chemotherapy and radiotherapy
Hypersplenism
Marrow infiltration
Vitamin and folate deficiency
Drug reactions
Drugs that cause neutropenia include flecainide, phenytoin, carbimazole, indomethacin and co-trimoxazole.

Immunodeficiency is present in all patients with chronic lymphocytic leukaemia (CLL), though it is often mild and not clinically significant. Infections are the leading cause of death in 25-50 percent of CLL patients, with respiratory tract, skin, and urinary tract infections being the most common.

Hypogammaglobulinemia is the most common cause of immunodeficiency in CLL patients, accounting for about 85 percent of all cases.

Blood transfusion can be a life-saving treatment with significant clinical benefits, but it also comes with a number of risks and potential complications, including:
Immunological side effects
Errors in administration (episodes of ‘wrong blood’)
Viruses and Infections (bacterial, viral, possibly prion)
Immunodilution

A culture of better safety procedures as well as steps to reduce the use of transfusion has emerged as a result of growing awareness of avoidable risk and improved reporting systems. Transfusion errors, on the other hand, continue to occur, and some serious adverse reactions go unreported.

Transfusion-associated graft-vs-host disease (TA-GVHD) is a rare blood transfusion complication that causes fever, rash, and diarrhoea 1-4 weeks after the transfusion. Pancytopenia and liver function abnormalities are common laboratory findings.

TA-GVHD, unlike GVHD following allogeneic marrow transplantation, causes profound marrow aplasia with a mortality rate of >90%. Survival is uncommon, with death occurring within 1-3 weeks of the onset of symptoms.

Because of immunodeficiency, severe immunosuppression, or shared HLA antigens, viable T lymphocytes in blood components are transfused, engraft, and react against the recipient’s tissues, and the recipient is unable to reject the donor lymphocytes.
The following is a list of the most common transfusion reactions and complications:

1) Reaction to a febrile transfusion
The temperature rises by one degree from the baseline. Chills and malaise are also possible symptoms.
The most common response (1 in 8 transfusions).
Cytokines from leukocytes in transfused red cell or platelet components are usually to blame.
Only supportive. The use of paracetamol is beneficial.

2) Acute haemolytic reaction is a type of haemolytic reaction that occurs when the
Fever, chills, pain at the transfusion site, nausea, vomiting, and dark urine are all symptoms of a transfusion reaction.
Early on, many people report a sense of ‘impending doom.’
The most serious reaction. ABO incompatibility is frequently caused by a clerical error.
STOP THE TRANSFUSION OF INFORMATION. IV fluids should be given. It’s possible that diuretics will be required.

3) Haemolytic reaction that is delayed
It usually happens 4 to 8 days after a blood transfusion.
Fever, anaemia, jaundice, and haemoglobinuria are all symptoms that the patient has.
Positive Coombs test for direct antiglobulin.
Because of the low titre antibody, it is difficult to detect in a cross-match, and it is unable to cause lysis at the time of transfusion.
The majority of delayed haemolytic reactions are harmless and do not require treatment.
Anaemia and renal function should be monitored and treated as needed.

4) Reaction to allergens
Foreign plasma proteins are usually to blame, but anti-IgA could also be to blame.
Urticaria, pruritus, and hives are typical allergic reactions. It’s possible that it’s linked to laryngeal oedema or bronchospasm.
Anaphylaxis is a rare occurrence.
Antihistamines can be used to treat allergic reactions symptomatically. It is not necessary to stop transfusions.
If the patient develops anaphylaxis, the transfusion should be stopped and the patient should be given adrenaline and treated according to the ALS protocol.

5) TRALI (Transfusion Related Acute Lung Injury)
Within 6 hours of transfusion, there was a sudden onset of non-cardiogenic pulmonary oedema.
It’s linked to the presence of antibodies to recipient leukocyte antigens in the donor blood.
The most common cause of death from transfusion reactions is this.
STOP THE TRANSFUSION OF INFORMATION. Oxygen should be given to the patient. Around 75% of patients will require aggressive respiratory support.
The use of diuretics should be avoided.

6) TACO (Transfusion Associated Circulatory Overload)
Acute or worsening respiratory distress within 6 hours of a large blood transfusion. Fluid overload and pulmonary and peripheral oedema can be seen. Rapid blood pressure rises are common. BNP is usually 1.5 times higher than it was before the transfusion. It is most common in the elderly and those who have chronic anaemia.

Blood transfusions should be given slowly, over the course of 3-4 hours.

Natural killer (NK) cells are cytotoxic CD8 positive cells that lack the T-cell receptor. They are large cells with cytoplasmic granules. NK cells are designed to kill target cells that have a low level of expression of HLA class I molecules, such as may occur during viral infection or on a malignant cell. NK cells do this by displaying several receptors for HLA molecules on their surface. When HLA is expressed on the target cell these deliver an inhibitory signal into the NK cell. When HLA molecules are absent on the target cell this inhibitory signal is lost and the NK cell can then kill its target. In addition, NK cells display antibody-dependent cell-mediated cytotoxicity. In this, antibody binds to antigen on the surface of the target cell and then NK cells bind to the Fc portion of the bound antibody and kill the target cell.