immunology diseases

all diseases from every topic/week

diGeorge Syndrome/congenital athymia

• complete lack of thymus from birth, very rare → impaired T cell development, ↓ CD4+ T cells

• profound immunodeficiency

• deletion of chromosome 22q11.2 on TBX1 gene

• implications: delayed-type hypersensitivity

diGeorge Syndrome clinical presentation

• abseny CD3+ T cells

• ↓ T cell count (esp CD4+)

• normal B cell count, impaired function

• normal NK cells

complement deficiency

• PID

• deficiencies in C1, C2, C4

• SLE

• frequent infections

severe combined immunodeficiency (SCID)

• group of genetic disorders, impairment of B and T cell mediated immunity

• T cell deficiency

• failure to thrive, onset in first few months of life

• persistent, severe infections

• low CD3+ T cells

• low immunoglobulin levels

• haematopoietic stem cell transplant

Omenn Syndrome

• RAG1/RAG2 genes affect VDJ recombination

• the developed T cells are self-reactive/pro-inflammatory

• SCID variant

• hypomorphic mutations in lymphocyte developmenet genes

Omenn Syndrome clinical presentation

• chronic diarrhoea

• failure to thrive

• ↑ IgE levels

• recurrent, severe infections

• low/absent B cells

Wiskott-Aldrich Syndrome

• X-linked recessive mutation in the WAS gene encoding for WASP protein

• WASP= essential for actin cytoskeleton remodelling for immune cell signalling, phagocytosis and migration

• thrombocytopenia

• combined defect in T and B cells → recurrent infections

• abnormal AB production from B cells, reduced function of T cells

hereditary ataxia-telangiectasia

• autosomal recessive disorder caused by mutations in ATM gene

• ATM= gene crucial for cell cycle control and VDJ recombination for T and B cell development

hereditary ataxia-telangiectasia clinical presentation

• ↓ IgA, ↓ IgG, ↓ T cells

• recurrent sinopulmonary infections

• high lymphoma and leukaemia risk

• impaired class switching

• slurred speech, oculomotor apraxia

• telangiectasia (small dilated blood vessel, purpura, web-like patterns) appear after age 5

graft-vs-host disease

• T cells from donor recognise recipient of transplant tissues as foreign

• T cell mediated attack on skin, liver

• type IV hypersensitivity

• rash, jaundice, diarrhoea

• cytokine storm promotes inflammation

selective IgA deficiency

• most common PID

• ↓ IgA with normal IgG and IgM levels

• normal B cell count but failure to class switch to IgA

• recurrent sinopulmonary infection, increased autoimmune risk,

Bruton’s X-linked agammaglobulinaemia

• mutation in BTK gene on X chromosome

• blocks B cell development at pre-B cell stage in bone marrow

• ↓ or absent mature B cells, normal T cells

• ↓ or absent immunoglobulins (all classes)

• after 6 months of age (when maternal IgG wanes)

• recurrent bacterial/sinopulmonary infections

common variable immunodeficiency (CVD)

• impaired B cell differentiation and function, defective AB production

• unknown exact genetic cause

• low immunoglob levels

• presents in late childhood/adulthood

• recurrent infections

• very low IgG

• absent AB response to vaccines

systemic inflammatory response syndrome (SIRS)

• exaggerated systemic inflammatory response

• triggered by either infectious or non infectious: sepsis, trauma, burns, major surgery, autoimmune

• activation of innate immune system

• pro-inflammatory cytokines such as TNF-alpha, IL-1, IL-6

• activation of complement system

• cytokine storm

autoimmune haemolytic anaemia

• autoABs against RBC surface antigens

• premature destruction of RBCs

• warm AIHA (ABs active at body temps) → extravascular haemolysis

• cold AIHa (IgM ABs active at cold temps) → IgM activates complement

• autoAB production is loss of self tolerance

AIHA clinical presentation

• anaemia symptoms

• jaundice

• splenomegaly

• positive Coombs

Goodpasture’s Syndrome/anti-glomerular basement membrane disease

• autoimmune disease caused by autoABs directed against alpha 3 chain of type IV collage in:

  • GBM of kidneys

  • alveolar basement membrane of lungs

• autoABs cause complement activation and inflammation to basement membranes

Goodpasture’s clinical presentation

• kidney and lung symptoms

• common in young men/smokers

• haematuria/proteinuria

• IgG deposits along GBM

systemic lupus erythematosus

• chronic autoimmune disease → loss of self tolerance

• autoABs target nuclear/cytoplasma antigens on dsDNA

• immune complex formation/tissue deposition → complement activation

• both innate and adaptive involvement

SLE clinical presentation

• ↓ C3, C4

• abnormal B and T cell activation

• ↑ type I interferon

• butterfly/malar rash, photosensitivity

• arthritis

• positive ANA

serum sickness

• type III hypersensitivity

• immune complex formation between foreign proteins and host ABs

• deposit in tissues, activate complement and trigger inflammation

• IgG/IgM ABs produced

• antigen-AB complexes form and circulate

Grave’s disease

• autoimmune, hyperthyroidism

• autoABs that stimulate thyroid-stimulating hormone receptor and bind to it and ↑ thyroid hormones T3 and T4

• results in hyperthyroidism and gland enlargement

• type II/ V hypersensitivity (AB mediated cytotoxicity that stimulates rather than destroys)

Grave’s clinical presentation

• weight loss, diarrhoea, low TSH

myasthenia gravis

• chronic autoimmune neuromuscular disease caused by autoABs that impair Ach signalling at neuromuscular junction, leading to muscle weakness

• autoABs against Ach receptor

• fluctuating skeletal muscle weakness

• complement activated

• type II hypersensitivity

myasthenia gravis clinical presentation

• muscle weakness

• facial/bulbar swelling

• thymic abnormalities

• ocular muscles affected

allergic contact dermatitis

• type IV hypersensitivity

• skin contact with small reactive chemicals/haptens

• T cell mediated immune response → localised inflammation

• itching, thickened skin, 24 hours after contact

• involves memory T cells, Th1 and CD8+ cytotoxic T cells

autoimmune myocarditis

• loss of self tolerance

• autoantigens presencted by APCs → CD4+ Th cell activation

• leads to cytotoxic CD8+ T cell infiltration

• cytokine-mediated damage

• occurs in settings of systemic autoimmune diseases like SLE

• type IV hypersensitivity

• chest pain, fatigue

type 1 diabetes mellitus

• immune mediated destruction of beta cells in pancreatic islets

• insulin deficiency

• loss of self tolerance, failed central and peripheral tolerance

• CD8+ cytotoxic T cells are primary effectors (kill beta cells) and CD4+ Th cells amplify immune response with cytokine production

• B cells produce autoABs

• type IV hypersensitivity

• presents in childhood or adolescence

Hashimoto’s thyroiditis

• organ specific immune disorder where immune system targets thyroid gland → chronic inflammation

• loss of self tolerance, CD8+ cytotoxic T cells kill thyroid cells

• CD4+ Th1 cells release IFN-gamma, further tissue damage

• autoABs, TPO ABs

• type IV hypersensitivity, with components of type II hypersensitivity

• fatigue, weight gain, dry skin, strong HLA and family clustering

• ↑ TSH, ↓ T3/T4

multiple sclerosis

• autoimmune, demyelinating disease of CNS

• type IV hypersensitvity

• loss of tolerance: CD4+ T cells become autoreactive to CNS myelin, CD8+ T cells induce axonal injury

• TH1 crosses BBB and releases pro-inflammatory cytokines

• ↑ VCAM-1 = more immune cell entry

• type IV hypersensitivity

• ↑ B cells, macrophages

• vision loss, limb weakness

rheumatoid arthritis

• chronic autoimmune disease targeting synovial joints → inflamamtion, joint destruction

• loss of tolerance and initiation: CD4+ and Th1 cells activate macrophages, B cells (autoABs)

• rheumatoid factor: IgM against Fc portion of IgG

• immune complexes deposit in joints → complement→ further inflammation

• type III hypersensitivity

• fatigue weight loss, fever, stiffness, ↑ CRP, +ve RF

IBD/Crohns/ulcerative colitis

both: dysregulated immune responses to intestinal microbiota

Crohn’s: altered Th cell reponses and cytokine profiles (Th1 and Th17)

• ↑ TNF-α, IL-17, IFN-γ

• whole GI tract

UC: dominated by Th2-like cytokines

• inflammation of colon

• eosinophils and NK cells

immune thrombocytopenia purpura

• autoimmune disorder where immune system targets and destroys platelets → thrombocytopenia

• IgG autoABs are generated against plt surface glycoproteins

• type II hypersensitivity

• triggered by vaccines, viral infections

• purpura, petechiae, bruising

Sjogren’s Syndrome

• autoimmune disease that targets exocrine glands, esp salivary/lacrimal glands → dey eyes

• type IV hypersensitivity

• CD4+ T cell mediated gland destruction

• B cells hyperactivity → AB production

• lymphoma high risk

severe congenital neutropenia

• rare primary immunodeficiency due to neutropenia

• profound innate immunity deficiency

• neonatal/infancy onset, skin infections, sepsis, failure to thrive

• Ig, lymphocytes and monocytes= normal

chronic granulomatous disease (CGD)

• rare PID in NADPH complex in phagocytes → impaired respiratory burst

• mutation in X linked CYBB mutation

• neutrophils and macrophages can phagocytose microbes but can’t generate ROS, therefore impaired intracellular killing

• body compensated by forming granulomas to contain persistent infections

• recurrent pyogenic infections, infancy/early childhood, granulomatous inflammation

leukocyte adhesion deficiency (LAD)

• innate immune defect, PID

• defective leukocyte adhesion and migration

• caused by mutations affective leukocyte adhesion molecules

• neutrophils can’t exit bloodstream to reach infection sites

• delayed umbilical cord separation, recurrent bacterial skin/mucosal infections, poor wound healing

SID-HIV

SID-chronic kidney disease

SID-asplenia/hyposplenism

graft-vs-leukaemia effect

cytokine release syndrome

• excessive cytokine storm due to overactivation of immune system

immune effector cell-associated neurotoxicity syndrome

influenza

Chediak-Higashi Syndrome

• autosomal recessive PID

• defective fusion of lysosome with phagosome in phagocytes

• mutation in LYST gene

• innate immune defect (impaired phagocytosis)

• uncontrolled T cell activation

• defective type IV hypersensitivity

• neutropenia, giant granules in lymphocytes, partial albinism, recurrent bacterial infections