Innate
- Barriers - skin, mucous
membranes, glands, hair, cilia, stomach acid.
- Cells - Leukocytes (blood/lymph/tissues) --> mast cell - vesicles; histamine
--> macrophage - phagocytosis
- Cytokines --> circulating paracrine/autocrine (IL/TNF)
- Inflammation - vasodilation, vascular permeability, chemokines,
phagocytosis, complement, tissue repair.
Acquired
- Lymphocytes - stem cells in the bone marrow are the source of T/B cells.
- T cells mature in the Thymus. B cells mature when activated by antigen
- B-lymphocyte receptors – IgA, IgD, IgE, IgM
- T-lymphocyte receptors – specific (1:1)
T Cell types
- Tc (cytotoxic) - express CD8, binds to MHC1 which destroys cells by binding to antigen.
- Th (helper) - express CD4, binds to MHC2 and causes production of cytokines.
- Tr (regulartory) - suppress immune response.
MHC (Major Histocompatability complex)
- proteins that present antigens on their surface for immune system to interact with.
- MHC1 - all nucleated cells
- MHC2 - antigen presenting cells (eg macrophage)
NK Cells
- Act like Tc. No activation needed.
- TNFα mediates apoptosis, bind to NK receptors on target cell.
Antobodies
- Produced by B cells
- 2 parts - variable (included in heavy chain, FAB)
- constant (can be crystallised, FC)
- Framework holds up 3 variable loops - CDRS
- Paratope = antibody binding site
- Epitope - Antigen
Isotypes
- Monomers - IgD, IgE, IgG
- Dimer - IgA
- Pentamer - IgM
Cytokines can signal a change in class, however once a change has occurred, it cannot change back.
Antibody Pathway
- 2nd meeting with antigen - T cell signals B cell (affinity maturation), somatic hypermutation
- T cell insoluble - binds MHC (peptides in centre)
- Activated B cells differentiate into plasma cells (Ab secretion) or memory cells
- Antobodies can activate complement classical cascade (attract it to FC)
- Antibodies activate effector cells by binding pathogens together.
Hypersensitivity
Type I
- Allergic
- Elevated serum IgE
- Degranulation of mast cells (IgE binds to antigen)
- Asthma, Atopic dermatitis, eczema, rhinitis, conjuctivitis, anaphylaxia, grass pollen, dust mites, food allergy, insect venom
- Skin prick test - intradermal injection, erythematous wheal of positive response. Not always accurate.
Type II
- Antibody mediated. IgG
- Targets antigen on cell surface
- Cell death - complement cytolysis
- immune adherence and phagocytosis
- direct cytotoxic
- Goodpasture's, Mysanthenia Gravis, Thrombocytopenia, Haemolytic Anaemia
Rhesus Haemolytic disease
- Mother +ve. Child -ve.
- When 1st child is born, sensitization occurs (foetal mother bleeding). Mother produces IgM
- 2nd pregnancy (child +ve), IgG is produced as IgM cannot cross placenta
- IgG crosses placenta and attacks foetal blood cells (complement)
- Child is anaemic. Screwed.
Type III
- Antibody/antigen complex mediated. IgG.
- Formation dependent on relative proportion of Ag/Ab, isotype of Ab, rate of complex formation
- Post Strep Glomerulonephritis (IgG complex deposition on basement membrane), serositis, iritis, vasculitis, EAA (extrinsic allergic alveolitis), serum sickness
- Enhanced by... Funtional impairment of complement (C3 loss), familial deficiency of components of classical pathway
- Heidelberger curve (be aware of this!) - precipitate formed when Ab/Ag volume is equal. Complexes remain soluble in excess.
Type IV
- Delayed T cell mediated
- Th cells (CD4 expressing) and macrophages accumulate to form a granuloma
- TB, Heaf test/mantoux reaction, Leprosy, Contact dermatitis (especially Nickel)
HIV
- HIV-1 and HIV-2 - retroviruses.
- Act by reverse transcription (RNA copied to DNA)
- Infects macrophages. When dendritic cells become infected they trap the virus and it gets transported to the lymph system --> infects T cells
- NO IMMUNITY - barrier to developing vaccine
Life cycle
- Attachement
- Entry (membrane fusion)
- Uncoating
- Reverse Transcript (error prone)
- Genome integration
- T cell activates trascription of viral RNA
- Splicing of mRNA + translation
- Assembly of new virus
- Budding
- HIV type B most common in Europe/USA
- Binds to cells expressing CD4 (binds by GP120)
CD4 Count>350
<350 <200 |
management decisionMonitor (3 monthly)
Treat Treat in all (AIDS) |
Normal CD4 Count is 400-1500 cells/mm3
Window period of 3 months where a positive will test negative.
Window period of 3 months where a positive will test negative.
Risk factors
- MSM
- Sex abroad (endemic countries)
- Multiple partners
- Blood/Blood products
- IVDU
- Sex workers
- Acute infection (seroconversion)
- Asymptomatic
- HIV related illness - oral candida, oral hairy leukoplakia, shingles, low platelets
- AIDS defining illness - kaposi's, toxoplasmosis, candidiasis (not oral), herpes simplex, recurrent salmonella
- Death
Screening
- Blood sample
- Antibodies in serum present in 99% of infected people 12 weeks post exposure
- HIV POCT (point of care testing) - finger prick, oral fluid, +ve convenience, lower sensitivity and specificity, false positive and negative results
Treatment
HAART - highly active anti-retroviral therapy