Molecular patterns that are found in mammalian cells and are released as a result of cellular stress, cellular damage or non- physiological cell death (hyaluronate, HMGB1, ATP, S100 calcium-binding proteins and heat- shock proteins, etc.).

Molecular patterns that are found in pathogens but not in mammalian cells (terminally mannosylated and polymannosylated compounds, lipopolysaccharide, hypomethylated DNA, flagellin, double-stranded RNA)

Sense conserved molecules from bacterial, virus and parasites.

Sense bacteria products.

Binds-beta-glucans of the membrane of bacteria.

Binds to nucleic acids.

TLR- 1, 2, 4, 5, 6, 11 are

TLR- 3, 7, 8, 9 are

TLRs 3, 7 & 8 are derived from:

Th1 -> IL-2 -> Cell mediated immunity -> Cytokines that activates macrophages, phagocyte & kill. Drive proliferation and maturation of CTLs. (-) Th2 maturation.

Th2 -> IL-4 -> Humoral immunity -> Cytokines stimulate B cells to proliferate, mature and produce antibodies. Enhance differentiation and activation of eosinophils. (-) Th1/Th17. Anti-inflammatory.

Indicated in: Prophylaxis of organ rejection (kidney, liver & heart).

Rheumatoid arthritis

Plaque Psoriasis

Steroid/dependent Nephrotic syndrome

MAO: Binds to Cyclophilin -> (-) Calceneurin -> (-) NFAT activation -> Decrease IL-2 transcription -> Low T cells

Side effects:

1. Hepatotoxicity & Nephrotoxicity

2. Increase Bilirubin & ALP

3. Acute Renal failure & Tubular necrosis

4. Lymphomas and carcinomas

Indications:

1. Reduce risk of organ rejection (skin, heart, kidney & liver)

2. Psoriasis

3. Pyoderma gangrenous

4. Rheumatoid arthritis

5. Atopic dermatitis

6. Vitiligo

7. GVAD

MOA: Binds to FKB-12 -> (-) Calcineurin -> (-) NFAT activation -> No lymphocytes

(-) transcription of IL-3, IL-4, Il-5, GM-CSF and TNF-y

Indications:

1. Prophylaxis organ rejection (Renal, Liver & Cardiac) Given with Cyclosporine

2. 2nd line of treatment for Autoimmune hepatitis

3. Off-label uses Lupus-associated nephritis and dermatitis in children

MOA: Converted to MPA -> Uncompetitive inhibitor of IMPDH -> (-) Purine synthesis (guanosine) -> No lymphocyte proliferation

Indications:

1. Prophylaxis organ rejection of lung, heart, liver & renal

2. Chordomas

3. Lymphangioleiomyomatosis

4. Renal angiomyolipomas

5. GVHD

MOA: Binds to FKBP -> (-) mTOR -> (-) IL-2, IL-4, IL-15 -> (-) Antibody production

It's concentration is decrease by St.Johns wort.

Indications:

1. Rheumatoid arthritis

2. Prevents Renal transplant rejection

3. Crohns

4. Colitis

5. Sclerosis

6. Lupus nephritis

7. Pericarditis

8. Psoriasis

9. Uveitis

MOA: Purine analog -> (-) Nucleotide synthesis -> (-) mitosis -> No lymphocyte proliferation

Side effects:

1. Hepatotoxicity

2. Acute renal failure & necrosis

3. Carcinogenic

4. Marrow hypoplasia, bleeding, infection & death

MOA: Folic acid antagonist -> (-) Folic acid reductase ( DHFR)-> (-) nucleotide synthesis

Treatment of severe psoriasis and rheumatoid arthritis

In neoplastic diseases like gestational choriocarcinoma, chorioadenoma, and hydatidiform mole

Most severe side effect: Fatty liver disease, Fibrosis & Cirrhosis.