Immunology Flashcards
HIV 2
Specific to Portuguese and West Africans
Less progressive, less immunocompromised with less opportunistic infections
Less responsive to treatment
HIV testing
Before 12 weeks
- p24 Antigen < 10 days (rules in but not out)
- HIV RNA or pro-viral DNA
After 12 weeks
- HIV serology
- HIV PCR
Hypersensitivity Reactions
Type 1 - IgE mediated
Type 2 - IgG mediated cytotoxicity
Type 3 - Immune Complex Ab-Ag mediated cytotoxicity
Type 4 - T cell mediated excitotoxicity
CCR5 heterozygous individuals
CCR5 is a co-receptor for HIV binding (in early infection). A lack of co-receptor CCR5 causes a slower progression or relative protection against HIV infection
HLA B5701 in HIV
MHC molecule on CD4 which has higher affinity for CD8 killer cells & are more likely to be able to control there viral load/slower progression of disease. These patients cannot be treated with Abacavir (risk hypersensitivity)
HIV medications with highest risk metabolic syndrome
Protease inhibitors “NAVIR”
along with high bilirubin, renal stones and lipodystrophy
Abacavir
NRTI
Hypersensitivity reaction in patients with HLA B5701 & risk of cardiovascular events
HIV drugs causing Lipodystrophy
Protease inhibitors
Zidovudine (NRTI)
Hepatitis B serology
Hepatitis B treatment contraindicated in cirrhosis
Peg IFN - should only be used in mild - mod disease (not cirrhosis!)
Can cause psychiatric disturbances and transient cytopenia
Active against Hep D coinfection
contraindicated in pregnancy
Intracranial lesions in HIV
- Toxoplasmosis
- Progressive multifocal leukoencephalopathy (PML), JC virus
- Primary Lymphoma
- Tb
- Abscess
- Kaposis (HHV8)
Toxoplasmosis lifecycle and treatment
Cat as host for parasite -> cat faces containing Ova ingested by animals -> Undercooked animal meat ingested by Humans -> pass onto fetus
Rx with Pyrimithamine-Sulphadiazine, with folic acid-> inhibits dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines
CD4+ levels and Infections
< 200 PJP
< 100 Toxoplasmosis
< 50 Mycobacterim, CMV
IgM half life
7 days
T helper cells
Th1 - secretes IFN-gamma to activate macrophages, and induces B cells to produce opsonising IgG Ab’s which promote phagocytosis.
Th2 - secretes IL4, 5, 13 to up regulate IgE class-switching and activation of eosinophils (via IL5). Involved in Allergy and Parasite infections.
Th17 - secretes IL17 and IL22 to up regulate neutrophils and monocytes to target intracellular organisms, bacteria and fungi
TReg - Secretes IL10 and CTLA via FOXp3 transcription factor to suppresses IL2. Has an immunosuppressant role.
Hep B Immune phases
Immune Tolerance - HBeAg+, DNA ++, ALT normal
Immune Clearance - HBeAg+, DNA +, ALT high (treat)
Immune Control - HBeAg-, Anti-HBeAb +, DNA low, ALT normal
Immune Escape - HBeAg-, Anti-HBeAb +, DNA high, ALT high (treat)
Contrindication to PEG IFN in Hep B
- Cirrhosis or advanced Hep B (only used or mild-mod hep B)
- Pregnancy or lactation
- Neuropsychiatric disorders
Cryptococcus
CD4 count < 150
Yeast from bird dropping causing meningitis in HIV and immunocompromised patients
+ Cryptococcal Ag in serum and CSF
Treat with Amphotericin + Flucytosine for 2 weeks, then Fluconazole for 8 weeks
Toxoplasmosis
CD4 count < 50
Parasitic infection from Cats
Causes intracranial lesions with toxoplasmosis encephalitis
Toxoplasmosis Serology +
Rx with pyrimethamine-sulphadiazine (anti-parasitic)
Bactrim as prophylaxis CD4 < 100
Opportunistic infections in HIV
- Common bacterial infections, Tb CD4 > 200 (Isoniazid prophylaxis if positive skin or Q-Gold test)
- PJP < 200 (bactrim prophylaxis)
- Cryptococcus < 150 (Fluconazole prophylaxis)
- Toxoplasmosis < 100 (bactrim prophylaxis)
- CMV, MAC < 50 (Azithromycin prophylaxis)
CMV
HHV 5
CD4 count < 50
Ulcerative oesophagitis
Pneumonitis
Encephalitis with periventricular enhancement
Colitis
Hepatitis
Donar positive-Recipient negative in SOT
Donar negative - Recipient positive in BMT
“Owl Eyes” on blood film
Rx with Valganciclovir
Types of T helper cells
Th1 - release IFN-gamma to up regulate IgG production at B cells for opsonisation & NK cells to kill intracellular pathogens. Involved in MS pathogenesis
Th2 - release IL4, 5, 13 to induce class switching to IgE & increase eosinophils against Helminths
Th17 - release IL17 & 22 activates neutrophils against bacteria and fungi
Th reg - down regulate immune response via FOXp3 to secrete IL10, TGF-beta and CTLA 4
FOXp3 deficiency
T reg cells cannot secrete IL10 and CTLA to down regulate immune system, causing fatal autoimmune syndrome (immune dysfunction, polyendocrinopathy, enteropathy, dermatitis) which presents in first few months of life
Co-stimulation on APC & CD4 interaction
B7 on APC binds CD28 to cause CD4 proliferation
B7 on APC binds CTLA to cause CD4 inactivation
Coeliac immunological process
Gluten -> deaminated gliadin forms Ag on HLA DQ2 or 8 on CD4 Y cells -> differentiate into Th1 cells and increase production of Anti-deamidated Gliadin IgG, Anti-tissue transglutaminase IgA (Check total IgA levels to exclude false negatives) , Anti-endomysial Ab IgG
IPEX
Due to mutation in FOXp3 causing decreased turnover of Treg activity -
- Immune dysfunction with candida due to lack of IL17
- Polyendocrinopathy due to autoimmunity with lack of T cell inhibition in periphery
- Enteropathy
- X linked
Toll Like receptor for Gram negative bacteria
TLR 4 specific for Lipopolysacharide in gram negative cell walls
Hyper- IgE Syndrome
IgE > 2000 with eosinophilia
“Cold” Staph infections
Eczema-type rash
Severe respiratory infections
If autosomal dominant, can fail to lose baby teeth
Chronic Granulomatous Disease
- Phagocytes are unable to destroy bacteria, via respiratory burst, after ingestion
- Neutrophil oxidative burst testing showing no shift
- Treat with IFN-gamma which up regulates macrophages
Wiskott Aldrich Syndrome
“WATERS”
Wiskott Aldrich Syndrome
Thromboycytopenia
Eczema
Recurrent infections
Serum IgM reduced, High IgA and IgE
Severe combine immunodeficiency - Types
X-linked - gamma chain deficiency
Autosomal dominant - JAK 3 mutation
X-linked agammaglobulinaemia
Young males
Due to mutation in Brutons tyrosine kinase causing absence of mature CD19 B cells and decreased immunoglobulins
Asymptomatic until 6 months, when maternal IgG decreases
Lymphoid hypoplasia of tonsils
IL1
Released by macrophages, monocytes and dendritic cells in response to PAMPs causing an inflammatory response and fever
Cleavage to IL1 beta will cause hyperalgesia - blocked by colchicine and Anakinra (Rx Familial Mediterranean fever)
CD19, CD20, CD40
CD 19 on pro-B cells
CD 20 on mature B cells
CD 40 co-stimulation with MHC2 between T and B cells
Antibodies in compliment cascade
Classical via IgG and IgM
Alternative via IgA (A for alternative)
Types of hypersensitivity reactions
Type 1 - IgE mediated (asthma)
Type 2 - Cytotoxic - Antibody dependent (IgG) complement cascade (transfusion reaction, haemolytic anaemia)
Type 3 - Immune complex (SLE, GN, RA)
Type 4 - Th1, cell-mediated cytotoxic (contact dermatitis, granulomas)
Types of drug reactions
Immune-mediated
1. IgE mediated (immediate on second exposure I.e urticaria)
2. T cell mediated via Haptons (Delayed > 1hr i.e Steven Johnsons)
Non-immune mediated
1. Direct mast cell activation i.e. Contrast, Opioids
2. COX inhibition and up regulation of Leukotrienes i.e. Samters triad with Aspirin intolerance
Tryptase will be positive in any mast cell activation event I.e both IgE mediated & direct mass cell activation
Cytokines
IL1 - released by macrophages, monocytes and dendritic cells on PAMP binding to up regulate inflammation & fever
IL2 - Th cell turnover
IL6 & 8 - Acute inflammation to up regulate acute phase reactants (CRP, Mannose Binding Lectins)
IL4/5/13 - Released from Th2 for IgE class-switching
IFN- Gamma - Macrophage activation and IgG upregulation
IL 17 & 22 - Released from Th17 against fungal infections
TNF-alpha - acute inflammation (blocked by infliximab)
CTLA4
APC B7 binds CTLA -> deactivates T cells and downregulates immune system.
CTLA antagonists -> up regulates immune system
CTLA agonists -> down regulates immune system
CD 34
Is on stem cells only
MHC class expression
MHC 1 - on all nucleated cells (not on RBCs)
MHC 2 - only on antigen presenting cells
De Georges Syndrome
“CATCH 22”
Cardiac abnormalities - Tetrology of Fallot
Abnormal facies
Thymic aplasia
Cleft Pallate
Hypoparathyroidism with hypocalcaemia
Deletion 22q11.2 on Chromosome 22
Toll Like Receptor 4
Binds to lipopolysachrides on Gram Negative bacteria
Types of IgA
Differ in heavy chains
IgA1 - airways, serum and small intestine
IgA2 - Colon and small intestine
Mechanism of immune tolerance
- Clonal deletion at thymus
- Anergy
- T reg cells
Tryptase
- Helpful for all mast-cell mediated reactions i.e. IgE mediated and direct mast cell activation, but will not differentiate between IgE and Non-IgE mediated mast cell activation
- Peak 1-2 hours
- Requires serial measurement
- Less useful for food allergy
Late complement deficiencies
C5-9 predispose to meningococcal infection
B cell development
Stem cell
Pro-B cell
Pre-B cell - VDJ Heavy chain rearrangement
Immature B cell - VJ Light chain rearrangement
Naive B cell expressing IgM
Mature B cell expressing IgG
