Immunology Flashcards
What do sebaceous glands produce that has antibacterial effects?
Hydrophobic oils – repels water and microorganisms
Lysozyme – destroys the structural integrity of the bacterial cell wall
Ammonia and defensins – anti-bacterial properties
How do NK cells determine whether to lyse cells or not?
They have inhibitory receptors which recognise self HLA and they have activating receptors that recognise heparan sulphate proteoglycans
The balance of these signals determines the response
They kill ‘altered self’ cells (e.g. malignancy or virus-infected cells)
What does a dendritic cell do after phagocytosis?
Upregulate expression of HLA molecules
Express co-stimulatory molecules
Migrate via lymphatics to lymph nodes
Which receptor is involved in the migration of dendritic cells to lymph nodes?
CCR7
For each of the following subsets of CD4+ T cell, list their polarising factors and effector factors.
a. Th1
b. Th2
c. Th17
d. Follicular T cell
e. Treg
a. Th1 Polarising IL-12 IFN-gamma Effector IL-2 IL-10 IFN-gamma TNF-alpha b. Th2 Polarising IL-4 IL-6 Effector IL-4 IL-5 IL-10 IL-13 c. Th17 Polarising IL-6 TGF-beta Effector IL-17 IL-21 IL-22 d. Follicular T cell Polarising IL-6 IL-1 TNF-alpha Effector IL-2 IL-10 IL-21 e. Treg Polarising TGF-beta Effector IL-10 Foxp3 CD25
Outline the mannose binding lectin pathway of complement activation.
Activated by the direct binding of MBL to microbial cell surface carbohydrates
This directly stimulates the classical pathway involving C4 and C2 (but NOT C1)
NOTE: this is NOT dependent on the adaptive immune response
What are the effects of complement fragments that are released during complement activation?
Increase vascular permeability Opsonisation of immune complexes Opsonisation of pathogens Activation of phagocytes Promotes mast cell/basophil degranulation Punches holes in bacterial membranes
What are the ligands for the CCR7 receptors on dendritic cells?
CCL19
CCL21
This interaction is important in directing dendritic cells towards lymph nodes
Give three examples of failure of neutrophil production and outline their mechanism.
Reticular dysgenesis
Autosomal recessive severe SCID with no production of lymphoid or myeloid cells
Caused by failure of stem cells to differentiate along lymphoid or myeloid lineage
Kostmann syndrome
Autosomal recessive congenital neutropaenia (mutation in HAX-1)
Cyclic neutropaenia
Autosomal dominant episodic neutropaenia due to mutation in neutrophil elastase (ELA-2)
Occurs every 4-6 weeks
Describe the pathophysiology of leucocyte adhesion deficiency.
Caused by deficiency of CD18
CD18 normally combined with CD11a to produce LFA-1
LFA-1 normally binds to ICAM-1 on endothelial cells to mediate neutrophil adhesions and transmigration
A lack of CD18 means a lack of LFA-1, so neutrophils cannot enter tissues
During an infection, neutrophils will be mobilised from the bone marrow (HIGH neutrophils in the blood) but they will not be able to cross into the site of infection (NO pus formation)
Outline the pathophysiology of chronic granulomatous disease.
Absent respiratory burst (deficiency of components of NADPH oxidase leads to inability to generate oxygen free radicals)
Excessive inflammation (persistent neutrophils and macrophage accumulation with failure to degrade antigens)
Granuloma formation
Lymphadenopathy and hepatosplenomegaly
Can be treated with IFN-gamma
Describe the cytokine cycle between macrophages and T cells.
Macrophages produce IL12 which stimulates T cells, which then produce IFN-gamma
IFN-gamma acts back on the macrophages and stimulates the production of TNF-alpha and free radicals
Deficiencies in IL12, IL12R, IFN-gamma or IFN-gamma receptor can cause immunodeficiency (inability to form granulomas - mycobacterial)
Name and describe the colour changes of two tests used to investigate chronic granulomatous disease.
Nitroblue Tetrazolium (NBT) – yellow to blue
Dihydrorhodamine (DHR) – fluorescent
NOTE: both of these tests are looking at the ability of neutrophils to produce hydrogen peroxide and oxidative stress
What is the main clinical consequence of complement deficiency?
Increased susceptibility to infection by encapsulated bacteria
NOTE: Properidin (P) deficiency will also lead to increased risk of meningococcal infection
Outline the clinical phenotype of complement deficiency.
SLE (if early components involved (e.g. C2)
Usually have severe skin disease
Increased risk of infection (common pathway deficiency)
What are nephritic factors?
Autoantibodies that are directed against components of the complement pathway
They stabilise C3 convertases (break down C3) resulting in C3 activation and consumption
What disease is associated with the presence of nephritic factors?
Membranoproliferative glomerulonephritis
It may also be associated with partial lipodystrophy
NOTE: it can cause a ‘tram track’ appearance on microscopy (immune complex and complement proteins deposit in the subendothelium
Outline the management of complement deficiencies.
Vaccination (especially against encapsulated organisms)
Prophylactic antibiotics
Treat infection aggressively
Screen family members
What is basophilic stippling?
Basophilic appearance of red blood cells caused by the presence of aggregated ribosomal material
In which conditions might you see target cells (codocytes)?
Iron deficiency Thalassemia Hyposplenism Liver disease NOTE: target cells have a high SA: V ratio
What are Howell-Jolly bodies? Which condition are they associated with?
Nuclear remnants present within red blood cells
Present in hyposplenism
Which deficiencies are typically seen in Coeliac disease?
Iron B12 Folate Fat Calcium
Which HLA alleles are particularly common in patients with coeliac disease?
HLA-DQ2 (80%) – DQA10501 and DQB102 alleles
HLA-DQ8
Describe the T cell response to gluten in coeliac disease.
Peptides from gluten (gliadin) are deamidated by tissue transglutaminase
Deamidated gliadin is taken up by antigen-presenting cells and presented via HLA molecules to CD4+ T cells
CD4+ T cell activation results in secretion of IFN-gamma and may increase IL-15 secretion
These cytokines promote activation of intra-epithelial lymphocytes (gamma-delta T cells)
The intraepithelial lymphocytes will kill epithelial cells via the NKG2D receptor (normally recognises the stress protein MICA)
NOTE: anti-gliadin antibodies are the most persistent
List some other causes of high intraepithelial lymphocytes.
Dermatitis herpetiformis Giardiasis Cows’ milk protein sensitivity IgA deficiency Tropical sprue Post-infective malabsorption Drugs (NSAIDs) Lymphoma
How often should a DEXA scan be performed in coeliac patients?
Every 3-5 years
Name a defect in stem cells that causes SCID and name the gene that is mutated.
Reticular dysgenesis – adenylate kinase 2 (AK2)
NOTE: this is a mitochondrial energy metabolism enzyme
Which mutation is responsible for X-linked SCID?
Mutation in common gamma chain on Xq13.1
This is a component of many cytokine receptors (in particular, IL2) leading to an inability to respond to cytokines, causing arrest in T and NK cell development and the production of immature B cells
Describe the typical cell counts you would expect to see in X-linked SCID.
Very low T cells
Very low NK cells
Normal or increased B cells
Low immunoglobulin
Describe the typical cell counts you would expect to see in ADA deficiency.
Very low T cells
Very low B cells
Very low NK cells
In which group of syndromes does the thymus gland fail to develop properly?
22q11.2 deletion syndromes (e.g. Di George syndrome)
This is characterised by failure of development of the pharyngeal pouch
What are the immunological consequences of an underdeveloped thymus gland?
Normal B cell count
Low T cell count
Homeostatic proliferation with age (T cell numbers increase with age)
Immune function is mildly impaired and tends to improve with age
Which defect leads to bare lymphocyte syndrome type 2?
Defects in the regulatory proteins involved in expression of class II genes:
• Regulatory factor X
• Class II transactivator
List some investigations that may be used for suspected T cell deficiencies.
Total white cell count and differentials
Lymphocyte subsets
Immunoglobulins
Functional tests of T cell activation and proliferation
HIV test
Describe the typical levels of CD4, CD8, B cells, IgM and IgG that you would expect to see in the following diseases:
a. SCID
b. Di George
c. BLS Type 2
a. SCID CD4 low CD8 low B cells normal/low IgM normal/low IgG low b. Di George CD4 low CD8 low B cells normal IgM normal IgG normal/low c. BLS Type 2 CD4 low CD8 normal B cells normal IgM normal IgG low
Outline the pathophysiology of Bruton’s X-linked hypogammaglobulinaemia.
Prevents the maturation of B cells at that point at which they emerge from the bone marrow
Caused by an abnormal B cell tyrosine kinase (BTK) gene
This results in the absence of mature B cells and, hence, an absence of antibodies
Outline the pathophysiology of X-linked hyper IgM syndrome.
Blocks the maturation of IgM B cells through germinal centres into B cells that produce other classes of immunoglobulin (i.e. prevents germinal centre reactions)
Caused by a mutation in the CD40 ligand gene
This is technically a T cell problem, however, it means that CD4+ T helper cells cannot provide help to B cells so they cannot undergo germinal centre reactions
NOTE: CD40 ligand is encoded on Xq26
What is common variable immunodeficiency and what are the main features?
A group of disorders caused by some form of failure of differentiation of B lymphocytes
Defined by:
• Marked reduction in IgG, IgA and IgE
• Poor/absent response to immunisation
• Absence of other defined immunodeficiency
List some investigations that may be used for suspected B cell deficiencies.
Total white cell count and differential
Lymphocyte subsets
Serum immunoglobulins and protein electrophoresis
Functional tests of B cell function (e.g. measure IgG antibody against a specific pathogen (e.g. S. pneumoniae), if this is low, vaccinate using a killed vaccine and check levels again in 6-8 weeks)
NOTE: IgG production is a surrogate marker for CD4+ T helper cell function
Which protein is upregulated in autoinflammatory diseases caused by a gain-of-function mutation in NLRP3? Name 3 diseases that are caused by this mutation.
Cryopyrin (NALP3)
Muckle Wells syndrome
Familial cold autoinflammatory syndrome
Chronic infantile neurological cutaneous articular syndrome
All of these are autosomal dominant
NOTE other examples of monogenic autoinflammatory conditions: TNF receptor associated periodic syndrome (TNF receptor mutation), Hyper IgD with periodic fever syndrome (mevalonate kinase mutation)
Which gene mutation causes Familial Mediterranean Fever and which protein does this gene encode?
MEFV gene
Encodes pyrin-marenostrin which is a negative regulator of the inflammatory pathway
Describe how the inflammasome complex functions.
The pathway is activated by toxins, pathogens and urate crystals
These act via cryopyrin and ASC (apoptosis-associated speck-like protein) to activate procaspin 1
Activation of procaspin 1 results in the production of NFB, IL1 and apoptosis
Pyrin-maronestrin is a negative regulator of this pathway
NOTE: pyrin-marenostrin is found in neutrophils
What is the inheritance pattern of Familial Mediterranean Fever?
Autosomal recessive
Outline the clinical presentation of Familial Mediterranean Fever.
Periodic fevers lasting 48-96 hours associated with • Abdominal pain (peritonitis) • Chest pain (pleurisy, pericarditis) • Arthritis • Rash
It can lead to AA amyloidosis
Outline the treatment of Familial Mediterranean Fever.
Colchicine 500 µg BD (binds to tubulin and disrupt neutrophil migration and chemokine secretion)
2nd line: blocking cytokines
• Anakinra – IL1 receptor blocker
• Etanercept – TNF-alpha blocker
Which autoimmune conditions tend to occur in APECED?
Hypoparathyroidism (COMMON) Addison’s disease (COMMON) Hypothyroidism Diabetes mellitus Vitiligo
APECED: autoimmune polyendocrinopathy candidasis ectodermal dystrophy (aka polyglandular autoimmune syndrome type 1)
Why are patients with APECED prone to Candida infections?
They produce antibodies against IL17 and IL22
What does IPEX stand for?
Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome
Caused by mutation in FoxP3 (Forkhead Box P3)
Which mutations cause ALPS?
Mutations in the FAS pathway leading to defects in apoptosis of lymphocytes
This leads to a failure of lymphocyte tolerance (as autoreactive lymphocytes don’t die by apoptosis) and failure of lymphocyte homeostasis (you keep producing lymphocytes)
Describe the clinical phenotype of ALPS.
High lymphocyte count
Large spleen and lymph nodes
Autoimmune disease (usually cytopaenias)
Lymphoma
What is the best known chromosomal region that is implicated in Crohn’s disease?
IBD1 on chromosome 16 (NOD2/CARD15 gene)
NOTE: NOD2 is found in the cytoplasm of myeloid cells and is a microbial sensor, mutation is also seen in Blau syndrome
NOD2 = nucleotide-binding oligomerization domain-containing protein CARD15 = caspase-activating recruitment domain
List the autoimmune diseases associated with the following HLA polymorphisms:
a. DR3
b. DR3/4
c. DR4
d. DR15
a. DR3 Graves’ disease SLE b. DR3/4 Type 1 diabetes mellitus c. DR4 Rheumatoid arthritis d. DR15 Goodpasture’s syndrome
Name and state the function of 2 genes that are involved in T cell activation and are often mutated in polygenic autoimmune disease.
PTPN22 – suppresses T cell activation
CTLA4 – regulates T cell function (expressed by T cells)
PTPN = protein tyrosine phosphate non-receptor 22 CTLA = cytotoxic T lymphocyte-associated protein 4
Name the autoantigen in the following diseases:
a. Goodpasture’s disease
b. Pemphigus vulgaris
a. Goodpasture’s disease
Alpha-3 subunit of non-collagenous domain of collagen IV
b. Pemphigus vulgaris
Epidermal cadherin
Describe the difference between immune responses mediated by Th1 and Th2 cells.
NOTE: both are types of CD4 cell
Pathogens that have conserved structures (PAMPs) such as bacteria are recognised by Th1 and Th17 cells Multicellular organisms (e.g. helminths) and allergens don’t have conserved structured but they release mediators that damage epithelial cells. Disturbance of epithelial cells is recognised by the Th2 cells
List some elective investigations for allergic disease.
Skin prick and intradermal tests Specific IgE measurement Component resolved diagnostics Basophil activation test Challenge test
What is component resolved diagnostics?
A blood test to detect IgE to single protein components (useful for peanut and hazelnut allergy)
IgE sensitisation to heat and proteolytic labile proteins = minor symptoms
IgE sensitisation to heat and protolytic stable protein = major symptoms
List some indications for allergy component testing.
Detect primary sensitisation
Confirm cross-reactivity
Define risk of serious reaction for stable allergens
What is a basophil activation test?
Measurement of basophil response to allergen IgE cross-linking
Activated basophils show increased expression of CD63, CD203 and CD300
This is increasingly used in food and drug allergy
List some mechanisms of anaphylaxis.
IgE – mast cells and basophils – histamine and PAF (triggered by food, venom, ticks, penicillin)
IgG – macrophages and neutrophils – histamine and PAF (triggered by blood product transfusions)
Complement – mast cells and macrophages – histamine and PAF (triggered by lipid excipients, liposomes, dialysis membranes)
Pharmacological – mast cells – histamine and leukotrienes (triggered by NSAIDs)
List some IgE-mediated food allergy syndromes.
Anaphylaxis (e.g. peanut)
Food-associated exercise-induced anaphylaxis (ingestion of food leads to anaphylaxis if the individual exercises within 4-6 hours of ingestion (e.g. wheat, shellfish))
Delayed food-induced anaphylaxis to beef/pork/lamb (symptoms occur 3-6 hours after ingestion, induced by tick bites)
Oral allergy syndrome (limited to oral cavity with swelling and itching, occurs after pollen allergy is established, caused by cross-reaction of IgE antibody to pollen with stone fruits (e.g. apples), vegetables and nuts)
Which chromosome is HLA encoded on?
Chromosome 6
Describe the basic structure of HLA Class I and Class II.
Class I: have three alpha domains and a beta-2 microglobulin domain, has one transmembrane domain
Class II: has two alpha and two beta domains, had two transmembrane domains
Which HLA alleles are most immunogenic?
A, B and DR
What are the typical histological features of T-cell mediated rejection?
Lymphocytic interstitial infiltration
Ruptured tubular basement membrane
Tubulitis (inflammatory cells within the tubular epithelium)
Name and describe three assays for anti-HLA antibodies before transplants.
Cytotoxic Assays (CDC): tests whether patient serum kills donor lymphocytes in the presence of complement Flow Cytometry (FACS): tests whether patient serum binds donor lymphocytes irrespective of complement Solid Phase Assays (Luminex): beads containing all the possible HLA epitopes are mixed with the patient’s serum. This determines which HLA types the patient has antibodies against. Having many antibodies against different HLA epitopes suggests that the patient is highly sensitised.
Name two drugs that target TCR.
Anti-CD3 antibody (OKT3 - also known as muromonab-CD3)
Anti-thymocyte globulin
Used for transplant rejection
Name an anti-CD52 antibody and state its effect.
Alemtuzumab (campath) – causes lysis of T cells
Used for solid organ transplantation, multiple sclerosis and NHL, CLL, MS
Side-effects: ITP, Graves disease
Name an anti-CD25 antibody and state its effect.
Daclizumab – targets cytokine signalling
How to BAFF inhibitors work?
Target cytokines (BAFF) that promote B cell activation and growth
Name a proteasome inhibitor and describe how it works.
Bortezomib
Blocks the production of antibodies by plasma cells
Name a complement inhibitor.
Eculizumab
Outline the components of modern transplant immunosuppression regimes.
Induction agent (e.g. OKT3, anti-CD52, anti-CD25)
Baseline immunosuppression (e.g. calcineurin inhibitor, mycofenolate mofetil, azathioprine, steroids)
Treatment of acute rejection
• Cellular: steroids, OKT3
• Antibody-Mediated: IVIG, plasma exchange, anti-CD20
Which antibodies have a protective role in HIV infection?
Anti-gp120
Anti-gp41 (Nt)
Non-neutralising anti-p24 gag IgG (CD4+ cells recognise these antigens when presented on MHC class II)
NOTE: HIV remains infectious even when coated with antibodies
What are the screening and confirmatory tests for HIV?
Screening: HIV antibody ELISA
Confirmatory: HIV antibody Western blot
Describe how haemagglutinin inhibition assays work.
If you put normal red blood cells in a petri dish, they will clump at the bottom forming a red spot
If you add influenza virus, the HA makes red cells stick together and causes a diffuse coloration across the well
If you add the serum of someone who has a lot of antibodies against HA, it will inhibit the haemagglutination effects of HA so the red cells remain as a discrete red spot
The higher the dilution of serum at which the red cells remain as a little dot, the more antibodies are present in the serum
NOTE: sialic acid receptors on RBCs bind to HA leading to haemagglutination
What is a live attenuated virus vaccine? List some examples.
The organism is alive but modified to limit its pathogenesis
Examples: MMR, typhoid, BCG, yellow fever, polio (Sabin)
List some examples of the following types of vaccine:
a. Toxoids
b. Component/Subunit
a. Toxoids Diphtheria Tetanus b. Component/Subunit Hep B (HBsAg) HPV (capsid) Influenza (HA)
Describe how conjugate vaccines work.
Polysaccharide and protein carrier
Polysaccharide induces a T-cell independent B cell response (transient)
Addition of the protein carrier promoted T cell immunity which enhances B cell/antibody responses
List some examples of conjugate vaccines.
Haemophilus influenzae type B
Meningococcus
Pneumococcus
List some indications for IVIG.
Primary antibody defect • X-linked agammaglobulinaemia • X-linked hyper IgM syndrome • Common variable immunodeficiency Secondary antibody defect • CLL • Multiple myeloma • After bone marrow transplantation
List four types of T cell adoptive cell transfer.
Virus-specific T cells
Tumour infiltrating T cells (TIL)
T cell receptor T cells (TCR)
Chimeric antigen receptor T cells (CAR T Cell Therapy)
Using an example, describe how virus-specific T cells are used.
Used for EBV in patients who are immunosuppressed to prevent the development of lymphoproliferative disease
Blood is taken from the patient or from a donor
Peripheral blood mononuclear cells are isolated and stimulated with EBV peptides
This creates an expansion of EBV-specific T cells which are then reinfused into the patient
NOTE: tumour infiltration T cell therapy follows the same principle but uses tumour antigens
Describe how TCR and CAR T cell therapy works.
T cells are taken from the patient and vectors are used to insert gene fragments that encode receptors
In TCR therapy, the gene will encode a specific TCR (e.g. against tumour antigen)
In CAR therapy, the receptors are chimeric (containing both B and T cell components)
Describe a use of CAR T cell therapy.
Used to target CD19 (present on B cells)
Receptors on the CAR cell have an immunoglobulin variable domain and is joined to a TCR
This means that it recognises CD19 through an immunoglobulin domain but signals through the TCR pathway
NOTE: this is used in ALL and NHL
What is ipilimumab and how does it work?
CTLA4 and CD28 are both expressed by T cells and they recognise antigens (CD80 and CD86) on APCs
Signalling through CD28 results in a stimulatory response
Signalling through CTLA4 results in an inhibitory response
Ipilimumab is a monoclonal antibody that blocks CTLA4 thereby removing this inhibitory response
It is used in advanced melanoma
Explain the use of antibodies against PD-1 in treating cancer.
PD-1 and PD-2 ligands are present on APCs and interact via PD-1 receptors on T cells to cause an inhibitory response
They can also be expressed by some tumour cells
Pembrolizumab and nivolumab are antibodies that are specific to PD-1, thereby blocking this effect
This is also used in advanced melanoma
List some examples of the therapeutic use of recombinant cytokines.
Interferon alpha – used as an adjunct in the treatment of Hep B, Hep C, Kaposi sarcoma, CML and multiple myeloma
Interferon beta – Behcet’s disease, relapsing MS
Interferon gamma – chronic granulomatous disease
Describe the effects of steroids on:
a. Prostaglandins
b. Phagocytes
c. Lymphocyte Function
a. Prostaglandins
Inhibits phospholipase A2
Phospholipase A2 is responsible for the conversion of phospholipids into arachidonic acid (which will then be converted to eicosanoids by COX)
Inhibiting phospholipase A2 leads to a reduction in arachidonic acid and prostaglandin formation and, hence, a reduction in inflammation
b. Phagocytes
Decrease traffic of phagocytes to inflamed tissue (reduces the expression of adhesion molecules on the endothelium)
This leads to a transient increase in neutrophil count
Decreased phagocytosis
Decreases proteolytic enzymes
c. Lymphocyte Function
Lymphopaenia (sequestration in lymphoid tissue)
Blocks cytokine gene expression
Decreased antibody production
Promotes apoptosis
List some examples of anti-proliferative agents.
Cyclophosphamide
Mycophenolate
Azathioprine
Methotrexate
What is the mechanism of action of cyclophosphamide?
Alkylates the guanine base of DNA which damages the DNA and prevents replication
Affects B cells more than T cells
List some side-effects of cyclophosphamide.
Toxic to proliferating cells – bone marrow suppression, sterility (mainly males), hair loss
Haemorrhagic cystitis – due to toxic metabolic (acrolein) in the urine
Malignancy – bladder cancer, haematological malignancy, non-melanoma skin cancer
Teratogenic
Infection (e.g. PCP)
Outline the mechanism of action of azathioprine.
Metabolised by the liver to 6-mercaptopurine
Blocks de novo purine synthesis (e.g. adenine and guanine)
Prevents DNA replication
Preferentially inhibits T cell activation and proliferation
Which precaution must you take before starting a patient on azathioprine?
Check TPMT activity – 1 in 300 individuals have a TPMT polymorphism which means that they are unable to metabolise azathioprine leading to bone marrow suppression
Outline the mechanism of action of mycophenolate mofetil.
Blocks de novo nucleotide synthesis
Prevents replication of DNA
Affects T cell proliferation more than B cells
Non-competitive inhibitor of IMPDH (inosine-5-monophosphate dehydrogenase)
List some side-effects of mycophenolate mofetil.
Bone marrow suppression
Teratogenic
Infection (particularly HSV reactivation and PML (JC virus))
Describe the mechanism of action of calcineurin inhibitors.
Normally, TCR engagement leads to increased cytoplasmic calcium which binds to calmodulin leading to the activation of calcineurin
Calcineurin then activates NFATc resulting in the upregulation of IL2
Calcineurin inhibitors block this pathway, thereby blocking IL2 production
What are the main side-effects of calcineurin inhibitors?
Hypertension and nephrotoxicity
Diabetes
Neurotoxic
Gingival hypertrophy (ciclosporin)
Give an example of a JAK inhibitor. State which disease it is used to treat.
Tofacitinib (JAK1 and JAK2 inhibitor)
Rheumatoid arthritis
Give an example of a PDE4 inhibitor. State which disease it is used to treat.
Apremilast
Psoriasis
Describe the mechanism of action of PDE4 inhibitors.
PDE4 is important in the metabolism of cAMP
PDE4 inhibitors result in increased levels of cAMP which activates PKA and prevents the activation of transcription factors
This leads to a decrease in cytokine production
Effective in psoriasis and psoriatic arthritis
For each of the following monoclonal antibodies, state the antigen that they are targeting:
a. Basiliximab
b. Abatacept
c. Rituximab
d. Natalizumab
e. Tocilizumab
a. Basiliximab Anti-CD25 b. Abatacept CTLA4-Ig c. Rituximab Anti-CD20 d. Natalizumab Anti-4 integrin e. Tocilizumab Anti-IL6 receptor
List some side-effects of anti-thymocyte globulin.
Infusion reactions
Leukopaenia
Infection
Malignancy
Describe the mechanism of action and the use of basiliximab.
Targets IL2 receptor alpha chain (aka CD25)
This part of the receptor is specific for IL2 receptors
Results in inhibition of T cell proliferation
Uses: allograft rejection
Describe the mechanism of action of abatacept.
It is made from the fusion of CTLA4 and IgG Fc
APCs bind to CTLA4 (inhibitory) and CD28 via CD80 and CD86 receptors
Abatacept binds to CD80 and CD86 receptors and prevents engagement with T cells thereby reducing T cell activation
It is effective in rheumatoid arthritis
List some indications for rituximab.
Lymphoma
Rheumatoid arthritis
SLE
NOTE: it is given as two IV doses every 6-12 months
Describe the mechanism of action of natalizumab.
Antibody against alpha-4 integrin
Alpha-4 integrin is expressed with beta-1 or beta-7
This complex binds to VCAM1 or MadCAM1 to mediate rolling and arrest of leukocytes
Blocking this integrin inhibits leukocyte migration
Uses: multiple sclerosis, Crohn’s disease
Describe the mechanism of action of tocilizumab.
Antibody against IL6 receptor
Results in reduced activation of macrophages, T cells, B cells and neutrophils
