Pathology
Immune Responses
Regarding the major histocompatibility complex (MHC) molecules, which of the following statements is CORRECT:
Answer:
The major histocompatibility complex (MHC) is a set of genes that code for cell surface proteins essential for the acquired immune system to recognise foreign molecules. The human MHC is also called the human leucocyte antigen (HLA) complex. Class I and class II major histocompatibility complex (MHC) molecules are glycoproteins expressed on the cell surface and consist of cytoplasmic transmembrane and extracellular portions. T-cells have T-cell receptors (TCR) which recognise antigen only when it is presented in association with 'self' HLA molecules. Class I MHC molecules are found on all nucleated cells and present endogenous antigens, such as those found in cells infected by viruses or intracellular bacteria, to cytotoxic CD8+ T cells (cell-mediated immunity). Class II MHC molecules are found on antigen presenting cells (APCs) and present exogenous antigens, that may have been phagocytosed or endocytosed into intracellular vesicles, to Helper CD4+ T cells (humoral immunity).Immune Response
Pathology / Immune Responses
Last Updated: 29th August 2024
The white blood cells (leucocytes) may be divided into two broad groups: the phagocytes and the lymphocytes. Phagocytes comprise the cells of the innate immune system, which can act very quickly after an infection, whereas lymphocytes mediate the adaptive immune response, which can develop immunological memory. Phagocytes can themselves be divided into granulocytes (neutrophils, eosinophils and basophils) and monocytes. The function of phagocytes and lymphocytes in protecting the body against infection is closely connected with two soluble protein systems of the body, immunoglobulins and complement.
Haemopoiesis. (Image by Mikael Häggström and A. Rad [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0/)])
Innate Immune Response
Tissue damage and invasion of phagocytes activates mast cells and resident phagocytes, primarily macrophages and dendritic cells, which release inflammatory mediators, cytokines and cytotoxic agents. Inflammatory mediators cause vasodilation (heat and redness), stimulate nociceptors, (pain), and increase endothelial permeability, leading to extravasation of protein and fluids and thus oedema (swelling).
Cytokines (e.g. interleukin-8, IL-8) attract many more phagocytes, chiefly neutrophils (chemotaxis); these leave the blood by squeezing between endothelial cells. Phagocytes ingest microorganisms, and in the case of macrophages also damaged cells and debris. Pathogens can be detected because they express pathogen-associated molecular patterns (PAMPs) not found in mammals. PAMPs are recognised by phagocyte pattern recognition receptors (PRRs). Injured, infected or cancerous cells express PAMP-like molecules recognised by natural killer cells, which kill the cells and activate macrophages to remove the debris. In major infections, cytokines such as IL-1 cause fever; high temperatures may assist the immune response.
Complement is an important non-cellular mechanism comprised of a cascade of plasma proteins. On activation it coats and opsonises pathogens for phagocytosis, kills by membrane rupture, recruits phagocytes and induces inflammation. It is activated by some surface molecules and by antibodies that have 'tagged' a pathogen as foreign.
Adaptive Immune Response
The adaptive response takes ~5 days to become effective, and peaks after 1-2 weeks. It involves a cell-mediated response involving T-cells and a humoral response involving B-cells and antibodies.
Cell-Mediated Immunity:
Cell-mediated immunity is directed towards antigen within cells, which are made visible by class I major histocompatibility complex (MHC I). MHC I is found on the surface of cells and displays antigen to cytotoxic T cells, which proliferate on recognising the antigen and destroy the infected cell.
Humoral Immunity:
Humoral immunity is particularly effective against extracellular pathogens, as it involves secretion of antibodies into extracellular fluid. When an antigen binds to its matching receptor on naive B-cells, the latter activate and undergo clonal expansion. These differentiate into plasma cells which secrete antibody in massive amounts. T helper cells substantially enhance the response if the antigen is a protein. Memory cells which persist for years are also produced during clonal expansion. These respond much more rapidly and powerfully to subsequent exposures to the same pathogen and provide long-term immunity.
T helper cells only recognise protein antigens when they are presented to them by class II major histocompatibility complex (MHC II) on antigen presenting cells (APCs), which include dendritic cells, macrophages and activated B-cells. If they recognise the antigen, the cell proliferates and releases cytokines which strongly potentiate B-cell proliferation and performance. They also release cytokines that regulate the activity of other immune cells.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
