Requires adaptive immunity which will take around 72 hours

Involves degranulation of mast cells and Ab IgE

Involves antibody binding to antigen, activating complement system and NK cells (ADCC)

Involves immune complex activate complement system and neutrophils

Involves antigen presentation to T cells Th1 and Th17

"Atopic" means people that can develop allergic reaction

🌪 Why is this reaction so fast? 🌪

• IgE is predominantly localised in tissues
• Mast cells are present in all connective tissue can detect allergens really quickly
• Positive feedback activation, Plasma cells produce IgE to bind to mast cells, mast cells then bind to B cells via CD40L (to CD40) and IL4 to stimulate them to produce more IgE

Tryptase is a diagnostic marker ⚠ for such a hypersensitivity reaction

Other diagnostic markers includes total IgE more than 100 IU/ml

Abnormal physiological response

• Graves disease ⚠ When antibody bind to TSH receptor and results in a release in thyroid hormones
• Myasthenia gravis ⚠ When antibody binds to Ach receptor and inhibit neurotransmitter receptor
• Haemolytic disease of the newborn ⚠ Anti-Rh antibodies from mother during second pregnancy, Enlarged spleen and liver, elevated bilirubin and facial haemorrhaging
• Systemic Lupus Erythematosus (SLE) ⚠
• Arthus reaction ⚠ local hypersensitivity reaction triggered by immune complexes

Examples of type IV:

• Contact dermatitis ⚠ (Bind to self protein and taken up by Langerhan cells)
• Chronic asthma ⚠
• Tuberculin reaction ⚠ (Th1 cells recognise antigens)

Contact-sensitising agent: small molecule that penetrates skin and bind to self-proteins, making it look like foreign

Autoimmune Regulator (AIRE) ⚠
Expresses antigens that are specific to tissues outside of thymus, allow negative selection of TCRs that are normally not expressed in they thymus

1. CTLA4 only produced after activation, CD28 produced even before activation by costimulation
2. CTLA4 higher affinity to B7
3. CTLA4 inhibit production of IL2 but CD28 increases

IL2 important for T cell proliferation and differentiation

Loss of immune response with tissue damage or physiological dysfunction due to autoimmunity

Common diseases ⚠

• Graves thyroiditis
• Rheumatoid athritis
• SLE
• Thyroiditis/hypothyroidism

Type 1 DM by cytotoxic cells ⚠
CTL destroys pancreatic beta cells by granzyme B and FasL-Fas pathway

SLE ⚠

• Butterfly rash on face
• Urine dipstick
• Proteinuria
• Worsens with sun exposure
• Anti-DNA antibodies present
• Lighting up of DNA in immunofluorescent light
• Deposits of Immune complexes at dermal-epidermal junction
• Renal biopsy light microscopic changes
  
  

More common in women, can be triggered by sunlight, oestrogen, infection, linked to some HLA genes

Mechanism Loss of immune tolerance, lead to formation of immune complexes, lead to activation of complement and phagocytes and tissue damage

🌪 How does NK cells kill? 🌪

NK cells kill many tumour cells, especially those with reduced MHC I expression

NK cells activated by: NK cell-activating receptors like MIC-A, MIC-B and ULB

NK cells deactivated by: KIR or by lectin-like CD94-NKG2

Normally cells have MHC I which is recognised by killer cell immunoglobulin-like receptors (KIR), without MHC I, cannot produce negative signals

Etc PDL-1 & PD1 and CTL4 & B7 between APC and T cell

Function of TGF-Beta ⚠
Suppresses CTL, DC, M1, NK, B induce M2 and Treg

Function of M2 and MDSC ⚠
M2: promotes metastasis and invasion
MDSC: recruited from bone marrow, accumulate in lymphoid suppress anti-tumour response

CD28 on T cells (to dendritic)
CD40 on B cells or any APC (to CD40L on T cells)
CD16 on NK cells
CTL4 on T cells (to dendritic cells)
CD6 on T cells (binds to BiTE)

Problem is that it takes 4-6 weeks or tumour samples not available and it requires specialised facility

Problem is that need to be genetically matched

Provenge vaccine for prostate cancer

Organ retrieval and transplantation across injury will lead to release of DAMPs, activate innate then adaptive

Question: So is it right to say that transplant has both MHCI and MHCII?

Manifestation of immune deficiency

• Reactivation of latent infections
• Infection with atypical organism
• Persistent infection
• Unusually widespread infection
• Cancer

NOTE: Patients with this condition may produce IgE against IgA in transfused blood because they view it as foreign

Most common cause: cytotoxic drug, radiation, leukemias, infection, drug reaction thus common in patient receiving onco treatment

Treatment: infuse with antibodies or BONE MARROW TRANSPLANTATION

Such cells are present in the bone marrow

They are multipotent can turn into any cell

Indicator of successful transplant: Rise in absolute neutrophil count after 2 weeks ⚠

Sequence of recovery:

• Neutrophil count (prone to bacteria)
• CTL count (prone to virus)
• B cell count (prone to encapsulated bacteria)

Risk of CMV disease in HSCT
Highest in those where donor is (+) and recipient is (-), otherwise may have reactivation

100 days to differentiate if it is acute or chronic GvHD

The donor derived T cells have never been negatively selected

How does the donor T cell receive secondary signals?
Via endogenous signals released by host tissue damage by under lying disease such as ATP

Form complexes and directing inhibit calcineurin, remain phosphorylated and inhibit NFAT pathway

Bind to Immunophilin FK-binding protein 12 (chaperone protein)

Inhibit IL-2 receptor cascade, bind to immunophilin block mTOR, no cell cycle protein produce, arrest at g1 phase

Normal pathway: JAK-STAT or JAK-PI3K--> mTOR --> proteins

⚠ combine sirolimus and cyclosporine has good effect but have renal impairment

Converted to 6-thioguanin and insert into DNA

Normally used as a triple therapy to decrease side effects: Calcineurin inhibtior + steroid + azathioprine

Subsequently will die down due to T cell depletion

Just remember the target receptor for the drugs for each condition ⚠

1. IL-2 receptor - transplantation
2. IL-5 - Severe asthma
3. TNF-alpha RA
4. IL-4 receptor Severe eczema