autoimmunity and immunodeficiency

RHEUMATOID ARTHRITIS FACTS + RISK FACTORS + MORPHOLOGY (5)

• chronic systemic autoimmune disorder, f>M middle aged

• genetic predisposition (drb1, ptpn22) and environmental factors like smoking

• gross morphology : destructive proliferative synovitis with oedema and hyperplastic synovium

• Microscopically, synovial cell hyperplasia w fingerlike projection

• pannus formation also happening with fibroblast proliferation

RA sx

• Genetal sx : malaise, weakness, fatigue

• inflammation of joint, tendons and bursae : swelling, pain, tender and warm

• Joint stiffness : worse in morning for >30 minutes which eases with activity, symmetrical small joints (MCP &PIP)

• ulnar deviation, boutonnière deformity, volar subluxation and swan neck deformity w long term

• extraarticular manifestations : necrotising vasculitis, infection, cvd

Pathogenesis and molecules released (6)

• genetic predisposition + environmental factors

• citrullination. of host proteins by PAD enzymes

• activate T and B cells → inflammation

• In synovium inflammatory molecules invades and destroys bones by osteoclast causing cartilage degradation

• fibroblast at synovium also sctivated to form pannus

• release Autoantibodies (anti ccp, ra), cytokines (tnf a, il-1,il-6)

RA dx & treatment

dx : sx & lab/radiological rsults

tx : NSAIDS, GLUCOCORTICOIDS FOR SHORT TERM, DMARDS TO SLOW PROGRESSION (MTX, INFLIXIMAB, ADALIMUMAB, RITUXIMAB, ABATACEP)

What is seronegative arthropathies and name (4)

group,of disease characterised by lack of RF, involvement of sacroiliac joings and ssoc w hla-b27

which are:-

ankylosing spondylitis

reactive arthritis / reiter’s syndrome

enteropathic arthritis

psoriatic arthritis

Anjylosing spondilitis NDS

N : serinegative chronic synovitis, assoc w articular cartilage and bony alkylosis, M>F

D : scholar test

S: pain in lower back which improves with activity, fusion of vertebraw, asymmetric w systemic diseases like uveitis,aortitis

Reactive arthtritis

N : Reiter syndrome, men 20-40

d: triad of arthritis, conjuctivitis, non gonoccoccal urethritis / cervitis

s :episodes have wax and wave over several weeks

Enteropathic arthritis types

• axial arthtritis : sacroiliatis, spomdylitis, morning stiffness esp after sitting/standing

• peripheral arthtritis : acute, self limiting, asymmetrical affecting large joints

psoriatic arthtrities SX

psoriasis, dip joints, asymmetric, pencil in cup

osteoarthtritis dx sx risk

• dx by xray:-

  L oss kf joint space

  O steophyte

  S ubchondrsal sclerosis

  S ubchondral cyst

  sx : pain that worsens with activity, joint effusiin, asymmetric

osteoarthtritis pathogenesis (5)

• constant chondrocyte injury and proliferation

• chindrocyte proliferation

• granular st articular system

• loose bodies and cystic spines formed

• bone remodelling

non immune mediated immune disease other than osteoarthritis (3)

• gout : monosodium urate crystal deposition (needle shaped urate crystal,-vely birefringent under polarised light)

• pseudogout : calcification of fibrous and hyaline cartilage that is +ve birefringent rhomboid crystals

• septic arthritis : infection of joint causing monoarthtrities (from s aureus, n gonorrhea, gnb)

SLE risk factors and dx

chronic systemic autoimmune, F>M

dx :check if have 3>

• A rthtritis

• R enal disease

• A NA

• S erositis

• H aematollgical disorder

• P hotosensitivity

• O ral ulcers

• I mmunological disorder (Anti -dsDna, Anti-Sm)

• N eurological disorder

• M alar rash

• D iscpid rash

For renal manifestations : check creatinine protein/haematuria, kidney biopsy

SLE pathogenesis

Type ii and iii hypersensitivity

• genetic predisposition + environmental factors

• cell injury → apoptosis which release nuclear antigen

• failure to clear apoptopic cells, exposing nuclear antigens

• failure of self tolerance, activates T and B cells

• autoantibodies and immune complex formed

• deposit in tissue to activate complement and inflammation

Lupus manifestation (2)

• skin (80%) : malar/discoid rash, photosensitivity, oral ulcer

• lupus nephritis (30-50%) : tubulitis, arteriosclerosis by deposition of immune complex in glomeruli, 6 classes (minimal mesangeal, mesangial proliferative, focal,diffuse, membranous, advanced sclerosing)

sjorgen syndrome types and dx

2 types : primary/sicca and secondary

dx :-

• labroratory findings (anaemia, ctp, leukopaenia)

• serology (polyclonal hypergammaglobulinaemia amd autoantibodies like anti ss-a, anti ss-b)

• ehe test (tear breakup test)

• lip biopsy

sjorgen syndrome pathogeneis and sx

• viral infectiin of salivary glands

• cell death releasing autoantibodies

• cd4+ cells lose self tolerance causing inflammation, tissue damage and fibrosis

• sx : no tears, so saliva, systemic manifestations

Systemic sclerosis what and pathogenesis and tx

chronic inflammation os small vessel which cause interstitial finrosis of skin and organs

pathogenesis

• vasculopathy (endothelial damage causing ischsdmus

• immune dysfunction ( t/B cell activated inappropriately → inflammation)

• activate fibroblast

No Tx

Classification of systemic sclerosis and dx

-Limited cutaneous systemic sclerosis, anti centromere Ab

C alcinosis

R aynaud

E sophageal dismotility

S clerodactyly

T alangiectasia

• diffuse cutaneous, widespread and involves anti topoisomerase 1 Ab

Dermato myositis what and pathogenesis

inflammation of skeletal muscle and skin

5b-9cmas deposition in capillaries

release of autoantibodies (Anti Mi2 and anti Jo-1 antibodies)

Dermatomyositis sx

• in muscle : progressive and systemic muscle weakness, fine motor movement, dysphagia, dyspnea, myalgia

• in skin : heliotrope rash, upper eyelid, gettrons papule

what is giant cell arteritis and beurger disease takayasu arterities (sx, defining characteristics)

• giant cell arthtritis : granulomatous arterities, cause fever,headache, pain from high esr and crb w multinucleated giant cells in elastic lamina

• takayasu arteritis : granulomatous vasculitis (airtic arch syndrome) causing malaise, fever. same histological features as gca

• beurger disease : clots in vessels in fingers and toes causinh ulcer, gangrene. histologically looks like segmental thrombosing vasculitis

Polyarteritis nodosa and kawasaki (and sx and features)

polyarteritis nodosa : systemic necrotising vasculitis of arteries (smallto med). abd pain, bleeding, fever with segmental transmural infection w fibrinoid necrosis (+immune cells)

kawasaki disease : self limiting vasculitis of coronary arteries. sx is crash and burn

C onjuctivitis

R ash

A denopathy

S trawberry tongue

H ands and feet

Burn (fever)

Small vessel vasculitides (2)

• Anca +ve (microscopic polyangitis, granulomatous with polyangitis, churg straus

• An ANCA negative henoch schonlein purpura (igA antibody

X linked agammaglobulinaemia NDST

N : X linked mutation in BTK causing defect in b cell maturation

D : nephelometry, cytometry

S : RECURRENT INFECTION, MENINGITIS, SEPSIS

T : IVIG AND ANTIBIOTICS

SCID NDST

N : DEFECTS IN T OR B CELL DUE TO COMMON Y CHAIN OR JAK 3 KINASE

D: TREC, BEAD ARRAY, CYTOMETRY

S : RECURRENT AND OPPORTUNISTIC INFECTIONS

T : ISOLATION IN POSITIVE PRESSURE, ABX, GENE THERAPY

Complement deficiency types, sx, tx

2 types (genetic liike c2 deficiency /acquired like sle and glomerulonephritis)

sx : recurrent pyogenic infection, susceptibility to neisserial infection

tx : prophylactic antibiotics

chronic granulomatous disease nst

n: mutation of nadph components causing failure of respiratory burst in phagocytic cells

s : catalase +ve infection, bon caesiating granulomata

t : prophylaxis

neutrophil disorders nds

• n : abnormal neutrophil no/function(movement/adhesion/phagocytosis/respiratory burstkilling)

• d: fbc,wcc,immunoglobulin, complement

• s : skin infection, abcesses, oral ulceration

Myasthenia gravis nds

n : weakness due to anti achr, anti musk

d : ct thorax for thymus

s : muscle weakness, orbitalmeye weakness

pemphigus vulgaris ndst

n : autoantibodies pemphigus vulgaris, pemphigus foliacuss, paraneoplasmic pemphigus dp

d : immunofluoresence for igg deposition

S : oral ulceration, widespread flaccid bullae

T : high dose steroid/ immunosuppression

Autoantibody assoc diseases (4)

• autoimmune liver disease : anti mitochondria antibody

• autoimmune gi disease : anti tissue transglutamate

• endocrine autoimmune : anti tsh, anti islet cell

• pernicious anaemia : anti gastric parietal cell, anti intrinsic factor

type 1 hypersensitivity from what and phases

type i from IgE from miges, animal dander release degranulated mast cell release histamine

Phases:

• sensitisation ;initial no sx, th2 produce IgE that bind to mast cell

• exposure and eaely : degranulatiom causing more histamine → vasodilation, vascular oermeabilitu, bronchiconstriction

• late phase : leukostrine and cytokine attract other immune cell. environment allow more th2 cell development. chronic inflammation, tissue injury and remodellling occur

how todx allergy (6)

• component testing : molecular dx

• skin prick test : put different extract onto skin

• mast cell tryptass investigation : test tryptase conc after exposure

• DBDAC : give increase dose of allergen but also placebo to test

• isac allergy test, mad alex test

• multiples screening

Anaphylaxis ndst

N : severe allergic rxn

D: history of food/drug

S : hypotn, bronchospasm, laryngeal oedema

t : adrenaline, antihistamine , education

Allergy sx (3)

• atopic dermatitis : chronic pruritic inflammatory

• allergic rhinitis : inflamed nasal airway

• urticaria and angioedema : rash and sweelinh

hereditary angioedema what and tx

• c1 inhibitor due to gene deletion or protein malfunction

• tx by complent replacement

Allergy medication (3)

• normal : anti histamine, steroids, desensitisation

• anti ige : omalkzumab

• anti il 5 : mepolizumab

types of grafting (3)

• cells : rbc, stem cells, islet cells

• tissue : autograph, syngraft, allograft, xenograft

• solid organ : kidney, heart, lover

Major histocompatibility complex classes and recognition

2 classes

• mhc class 1 : on nucleated cells as internal peptides which are recognised as cd8+ tcells

• mhc class 2 : on apc as external peptide which recognise cd 4+

recognition 2 ways

• direct presentation : recipient T cells recognise mhc class i and ii from donor apc

• indirect presentation : foreign mhc class ii processed by recipient apc then presented to recipient t cell

types of allograft rejection

• hyperacute rejection : minutes to hours due to presence of anti donor antibodies due to previous transplant/transfusion

• accelerated acute : days, due to memory b/t cell after past exposure

• acute rejection : days to weeks due to cellular and humoral response (type iv)

• chronic rejection : months to years due to cell mediated or viral infection (type iv)

graft vs host disease what type tx

immunologically competent t cell transplanted to immunocompromise, 2 types

• acute gvhd

• chronic gvhd ; th,ic injury, dysregulation of th17 cells causing fibrosis

tx by immunosuppression or remove classical t cells when donating