Basics Flashcards
Henoch schonlein purpura ( IgA vasculitis)
Immune mediated type III hypersensitivity reaction IgA immune complex deposition, activation of complement
1. Palpable purpura on thighs buttocks ankles
2. Arthritis or arthralgia
3. Abd pain or intussuseption
4. Renal disease
5. Leucocytoclastic vasculitis
Histopathologic finding: damaged small vessels with fibrinoid necrosis, peri vascular neutrophilic inflammation
Deposition of IgA and C3
Hereditary angioedema
C1 estrase inhibitor deficiency
C1 activated leads to consumption of C4
Decrease C4 level
C1 inhibitor also blocks kallikrein induce conversion of kininogen into bradykinin, results in increase Bradykinin activation cause vasodilation
ACEI are contraindicated in these pts bcoz ACE converts bradykinin into inactive products
Rx: supportive care, C1esterase inhibitor concentrate or kallikrein inhibitor
Sjogren syndrome
Dry eyes (keratoconjunctivitis sicca)
Dry mouth ( xerostomia)
Dry skin (xerosis)
Complications: Recurent dental infections
Corneal damage
Salivary glands hypertrophy
Non-Hodgkin lymphoma
Vaginal dryness causes dysparunia
Biopsy: lymphocytic infiltrate with germinal centers
Positive anti-Ro(SSA) and anti-la(SSB)
Inflammatory lymphadenopathy
Foreign antigens displayed by dendritic cells, processed by B cells displayed to naive T cells via MHC class II, naive T cells differentiate into helper T cells and activate B cells proliferation and secrete cytokines which causes pain and inflammation of lymph nodes and enlargement due to germinal centers.
Hyper IgM syndrome
X-linked recessive disorder
Deficient CD40L or CD40 interaction
Defective class switching in B cells
Dec IgG , IgA, IgE, Inc IgMMM
Recurrent sinopulmonary, GI and opportunistic infections
Interaction of CD40 and CD40L is required for APCs and B cells co stimulation due to this reason cell-mediated immunity is also deficient in this condition
Chronic Granulomatous Disease
Deficiency of NADPH oxidase
Unable to produce superoxide radical i.e oxidative burst to kill intracellular pathogen
Recurrent infection of catalase positive bacteria and fungi( bcoz catalase convert H2O2 into water)
Diffuse granuloma formation
Dx: NBT and DHR
Nitroblue tetrazolium test( no change in colour)
Dihydrorhodamine flow cytometry (no fluorescence)
E.g staph aureus, burkholderia, serratia, nocardia, aspergillus.
Serum Sickness
Type III hypersensitivity reaction deposition of immune complexes in tissues followed by activation of complement ( dec C3 level)
Histology: small vessel vascuilitis with fibrinoid necrosis and neutrophil infiltration
Serum sickness like reaction often occurs following drugs like penicillin, cefaclor, TMP-SMX. Other triggers are non-human immunoglobulin and chimeric monoclonal antibodies
Symptoms: fever, pruritic skin rash, arthralgia, sometimes lymphadenopathy and proteinuria after 7-14 days post exposure
SLE
Type II hypersensitivity mediated pancytopenia, autoantibodies against blood cell antigens
Symptoms:Pancytopenia, malar or discoid rash, photosensitivity, serositis, symmetric migratory arthritis, thromboembolic events due to vasculitis and antiphospholipid antibodies
Labs:positive ANA (sensitive but not specific), anti-DNA antibodies and anti-Smith ( specific but not sensitive)
Low complement level
Immune complex deposition
Elevated inflammatory markers ( ESR, CRP)
Severe combined immunodeficiency disease (SCID)
Low CD3+ T cells and hypogammaglobulinemia
Common findings: mucocutaneous candidiasis(thrush), chronic diarrhoea, severe bacterial viral fungal and opportunistic infection in infancy, failure to thrive
Thymic aplasia due to severe T cell deficiency
Rx: stem cell transplant
Retroviral gene therapy
Make sure not to confuse with DiGeorge
Congenital HIV infection also presents similar cause severe recurrent infection and failure to thrive
Candidal skin test is delayed type IV hypersensitivity assess cell mediated immunity via recruiting macrophages, CD4 and CD8 T-cells
Pneumococcal vaccines
Two types of vaccines
PPSV23 polysaccharide vaccine, generates humoral immunity which lasts for 05 years
PPSV23 is not immunogenic in children <2 years due to their immature humoral immunity
PCV13 conjugate vaccine contain protein and exhibit robust immune response through T cells, long lasting immunity due to memory B cells, strongly immunogenic recommended in children routine immunization where as PPSV23 is recommended for all adults age >65
Lupus Nephritis
Type III hypersensitivity immune complex deposition in mesengium sub endothelium, sub epithelial spaces results in diffuse proliferative glomerulonephritis
Asplenia
Splenic capillaries are open ended pour the whole blood into red pulp, there macrophges lining the pulp remove the dead and abnormal erythrocytes and any bacteria present in blood, will be displayed by macrophages to B and T cells in the white pulp.
Asplenic pts are prone to encapsulated bacterial infection and needs vaccination against strep pneumo, hemo influenza, neisseria.
Spleen is the most common injured organ in blunt abdominal trauma
Spleen is responsible for clearance of encapsulated bacteria
Type I hypersensitivity reaction
Pt predispose to allergy, on first encounter to allergen will cause Ab class switching from IgM to IgE which is specific to allergen bound to Fc receptors of basophils and mast cells, upon subsequent exposure IgE cross links and activate the release of inflammatory mediators like histamine, PGs and cause vasodilation results in wheal(central pallor) and flare(peripheral erythema) reaction.
In severe cases, cause anaphylactic shock
Monoclonal Antibodies
1) cytokine inhibitors: bind to free circulating cytokines or cytokine receptor e.g (infliximab and etanercept) bind TNF-a
IL-2 inhibitor (aldesleukin)
2) T cell costimulation inhibitor: e.g they block CD28 on cytotoxic T cells which binds to CD80/86 ligand (abatacept) block CD28
3) B-cell inhibition/depletion
Inhibit (belimumab) and deplet ( infliximab)
Rituximab block CD20
Anaphylaxis
Type I hypersensitivity
Trigger ( foods like nuts) medication like beta lactam antibiotic and insect sting
Cause by widespread mast cell and basophils degranulation that result in increase histamine and tryptase
Tryptase is specific to mast cell and can be used as clinical indicator for anaphylaxis
Lung Transplant Rejection
Hyperacute:within minutes to hrs due to preformed antibodies to donor ABO or HLA antigen, mechanism, neutorphilic infiltration with fibrinoid necrosis and ischemia (White Graft Rejection)
Acute: ( <6 months) due to cell mediated response to mismatched HLA antigens, mechanism: peri vascular and submucosal lymphocyte infiltrate
Chronic: within months to years due to mixed cell mediated and antibody response, mechanism, submucosal inflammation, granulation and scarring of small airways and BRONCHIOLITIS OBLILTERANS
1st generation antihistamine vs 2nd generation antihistamine:-
1st have side effects like anti muscarinic, anti-alpha adrenergic and anti- serotonergic and they are lipophilic cross BBB and cause sedation. They are avoided in elderly population
2nd are less side effects less lipophilic so more preferable in old population
T-regulatory cells
FOXP3 activates CD-4 T cells into regulatory T cells that inhibits immune system via:
IL-10:Decrease MHC-II expression, inhibits macrophages
TGF-beta: B-cell proliferation decrease and promotes T reg cells production
CTLA-4: binds CD-80/86 on APC and inhibits co-stimulation of T -cells
Mutation in FOXP3 results in “IPEX SYNDROME” marked by autoimmune enteritis, eczematous dermatitis and type 1 DM also increased immunoglobulin production and autoimmunity
Contact Dermatitis
Type IV hypersensitivity reaction (delayed)
Poison ivy,oak,sumac contain urshiol, a small allergenic substance when attached to protein( hapten) cause immune response
Symptoms: highly pruritic rash with papules vesicles bullae that may show excoriation.
2 phases of contact dermatitis
Sensitization phase: creation of hapten senstive T- cells takes 14 days, cutaneous dendritic cells take up the hapten and express on MHC- I and MHC-II travel to draining lymph node and activate CD- 4 or CD- 8 cells
Elicitation phase: 2 to 3 days following re-exposure to same antigen, hapten is taken up by skin cells and activate hapten sensitive T cells in dermis and epidermis results in inflammation.
In urshiol- induced contact dermatitis CD-8 T cells are main mediators
Leucocyte adhesion deficiency (LAD)
Results from absence of CD18 which lead to inability to synthesize beta-2 integrin, and affecting tight adhesion, crawling and transmigration
C/F : recurrent bacterial skin infection without pus formation , delayed separation of umbilical cord and poor wound healing
Three subtypes of this disease LAD type 1 mentioned above and LAD type 2 and 3
Wegner granulomatosis (granulomatosis with polyangitis)
C-ANCA positive (antibodies against neutrophils)
Features: necrotizing vasculitis of upper and lower respiratory tract causing nasal ulcerations, sinusitis, hemoptysis. Rapidly proliferating glomerulonephritis.
Immunosuppressants:-
1)Mycophenolate: inhibit conversion of IMP into GMP in purine de novo synthesis pathway via blocking IMPDH
It mainly affects lymphocytes bcoz they don’t have purine salvage pathway they mainly rely on de novo synthesis where as the other hematopoetic cell line have purine salvage pathway so they compensate
Its main side effects is lymphopenia and GI symptoms.
Red Man Syndrome
Cause by rapid infusion of vancomycin which directly activates the mast cell leading to the release of potent vasoactive mediators
It is not true IgE mediated allergic reaction, discontinuation and diphenhydramine will resolve the symptoms and later vancomycin can be continued at a slower rate
Glucocorticoids:-
Reduce inflammation and end organ damage in inflammatory disease
Dec macrophage and lymphocytes activation via decreasing transcription of pro-inflammatory cytokines( IL-1, INF-gamma)
Increase anti-inflammatory cytokines ( IL-10)
Impair migration of leucocytes towards site of inflammation
Reduce adhesion molecule expression on neutrophils and endothelial cells, also reduce chemokines which results in neutrophilia
Promote apoptosis of monocytes, lymphocytes and eosinophils.
Decrease production of prostaglandins and luekotrienes