Immune responses Flashcards
Actue-phase reactants are mainly produced by
liver
APR are induced by
IL-6
Opsonin that fixes complement and facilitates phagocytosis
C-reactive protein
Function of ferritin
Binds and sequesters iron to inhibit microbial iron scavenging
APR that correlates with ESR
Fibrinogen
APR that dicreases iron absorption by degrading ferroportin and iron release from macrophages
Hepcidin
Acute phase reactants: upregulated
C reactive protein Ferritin Fibrinogen Hepcidin Serum Amyloid A Procalcitonin
Prolonged elevation can lead to amyloidosis
Serum amiloyd A
Acute phase reactants: downregulated
Albumin
Transferrin
System of hepatically synthesized plasma proteins that play a role in innate immunity and inflammation
Complement
Membrane attack complex defends against
Gram - bacteria
Pathways of complement activation
- Classic pathway: IgG or IgM mediated
- Alternative pathway: microbe surface molecules
- Lectin pathway: mannose or other sugars on microbe surface
C3b function
Opsonization: C3B Binds Bacteria
C3a, C4a, C5a function
Anaphylaxis: A
C5a function
Neutrophil chemotaxis
C5bC9 function
Cytolisis by membrane attack complex
Opsonins
C3b: binds bacteria
IgG
Opsonin function
Greek: prepare for eating=enhance fagocytosis
Secondary function of C3b
Clearing immune complexes
Inhibitors of complement, preventing complement activation on self cells
DAF: decay accelerating factor: CD55
C1 esterase inhibitor
C3 deficiency
- Increases risk of severe recurrent pyogenic sinus and respiratory tract infections
- Susceptibility to type III hypersensitivity reactions
C5-C9 deficiencies
Susceptibility to recurrent Neisseria bacteriemia
C1 esterase inhibitor deficiency
Hereditary angioedema due to unregulated activation of kallikrein that increases bradykinin
Low C4 levels
ACE inhibitors are contraindicated (bradykinin causes dry cough)
CD55 (DAF) deficiency
Complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria
Hereditary angioedema
C1 esterase inhibitor deficiency
Inerleukines: hot t-bone steak
Il1: fever IL2: stimulates T cells IL3: stimulates bone marrow IL4: Stimulates IgE production IL5: Stimulates IgA production IL6: Stimulates akute-phase protein production
Major chemotactic factor for neutrophils
IL-8
IL-12 functions
Induces differentiation of T cells into Th1 cells
Activates NK cells
Tumor necrosis factor alpha function
Activates endothelium
WBC recruiment
Vascular leak
Causes cachexia in malignancy
Tumor necrosis factor alpha
Maintains granulomas in Tuberculosis
Tumor necrosis factor alpha
Cytokines secreted by macrophages
1, 6,8,12,TNFalpha
IL that funcitions like GM-CSF
IL.3
Secreted by T cells in response to antigen/IL-12 from macrophages; stimulates them to phagocyte pathogens; Inhibits differentiation of Th2 cells
Interferon gamma
Attenuate immune response
TGF beta
IL-10
Enhances class switching to IgE and IgG
IL-4 (Th2)
Enhances class switching to IgA Stimulates eosinphils
IL-5
Increases MCH expression and antigen presentation by all cells
Interferon gamma
Respiratory (oxidative burst)
Activation of phagocyte NADPH oxidase complex which utilizes 02 releasing ROS
Deficiency of NADPH oxidase
Chronic granulomatous disease
Patients with NADPH oxidase are at risk of
Infection by catalase positive species:
- S.aureus
- Aspergillus
Protein in P aeruginosa that generates ROS to kill competing microbes
Pyocyanin
Part of innate host defense against RNA and DNA viruses, synthesed by virus infected cells that act locally on uninfected cells
Interferon alpha and beta
Binds do B7 of APC
CD28 in T cells
Cytotoxic T cells coreceptors for HIV
CXCR4
CCR5
Co receptor for EBV in B cells
CD21: you can drink beer at the bar when you are 21
Marker for NK
CD56
Hematopoietic stem cells, cell surface marker
CD34
State during which a cell cannot become activated by exposure to its antigen
Anergy
T and B cells become anergic when
Exposed to their antigen without costimulatory signal
Bacteria that can produce superantigens
S pyogenes
S aureus
Superantigens effect
Cross-link te beta region of the T cell receptor to the MHC class II on APCs: activate Cd4+: massive release of cytokines
Antigenic variation examples
- Bacteria: salmonella, Borrelia recurrentis (relapsing fever), N gonorrhoeae (pilus protein)
- Viruses: inflenza, HIV, HCV
- Parasites: trypanosomes
Receiving preformed antibodies is a form of
Passive immunity
Treatment in non-vaccinated After exposure to:
Tetanus toxin, Botulinum toxin , HBV, Varicella, Rabies virus, diphteria
Preformed antibodies (passive)
Duration of passive immunity
Short span of antibodies: 3 weeks
Vaccines are a for of ____ immunity
Active: humoral (B cells) or cellular (T cells)
Types of vaccine
- Live attenuated vaccine
2. Inactive or killed vaccine
Live attenuated vaccines that can be given to HIV patients who have a CD4 account >200/mm3
MMR: triple vírica
Varicella
Examples of Live attenuated vaccine
BCG: Bacilo Calmette-Guerin: tbc Measles Mups Polio: Sabin Rotavirus Rubella Varicella Yellow fever
Live attenuated vaccine induce a
Cellular and humoral response
Inactivated or killed vaccine induce a
Humoral response
Examples of inactivated vaccines
Rabies Influenza Polio: Salk Hepatitis A RIP always
Hypersensitivity types
ACID Type I: Anaphylactic and Atopic:. antigen-IgE Type II: Citotoxic: antibody mediated Type III: Immune complex Type IV: Delayed, cell mediated
Hypersensitivity antibody mediated types
I, II, III
Free antigen cross links IgE on presintized mast cells and basophils
Hypersensitivity type I
Antibodies bind to cell surface antigens
Hypersensitivity type II
Hypersensibility type I tests
Skin test
Blood test: ELISA
Hypersensibility type II tests
Direct Coombs test
Indirect Coombs test
Direct coombs test detects
Antibodies Directly attached to RBC
Indirect Coombs test detects
Presence of unbound Antibodies in the serum
Type II hypersensibility reactions
- Cellular destruction
- Inflamation
- Cellular dysfunction
Examples of type II Hs cellular destruction
Hemolytic disease of the newborn
Immune thrombocytopenic purpura
Transfusion reactions
Autoinmune-hemolytic anemia
Examples of type II Hs cellular inflamation
Goodpasture syndrome: Ab anti-GBM
Rheumatic fever
Hyperacute transplant rejection
Examples of type II Hs cellular disfunction
Myasthenia gravis
Graves disease
Immune complex antigen-antibody (IgG) are responsable for hypersensitivity reaction type
III
Hypersensitivity reaction type III
Immune complex antigen antibody activates complemente which attrack netrophils that release lysosomal enzymes
Examples of hypersensitivity reaction type III
SLE
Polyarteritis nodosa
Postestreptococcal glomerulonepfritis
Serum sickness
hypersensitivity reaction type III
Antibodies to foreign proteins (drugs) are produced
Fever, urticaria, arthalgia, proteinuria, lymphadenopathy
Arthus reaction
hypersensitivity reaction type III
Intradermal injection of antigen into presensitized individual leads to immune complex formation in the skin
Edema, necrosis, complement activation
hypersensitivity reaction type IV mecanisms
Direct cell cytotoxicity CD8+
Delayed type hypersensitivity: CD4+
Examples of hypersensitivity reaction type IV
Type 1 DM: CD8 Contact dermatitis Graf versus hostage PPD and patch tests 4Ts: transplant rejections, T cells, TB skin tests, touching (contact dermatitis)
Blood transfusion reactions
- Allergic/anaphylactic reaction
- Febrile nonhemolytic transfusion reaction
- Acute hemolytic transfusion reaction
- Transfusion-related acute lung injury
Transfusion to IgA deficient individuals
Blood products without IgA
Allergic anaphylactic reaction to blood transfusion
Type 1 hypersensitivity
Febrile nonhemolytic transfusion reaction
Type 2 hypersensitivity reaction
Acute hemolytic transfusion reaction
Type 2 hypersensitivity reaction
Donor anti-leukocyte antibodies against recipient neutrophils and pulmonary endothelial cells
Transfusion related acute lung injury
Autoantibody implicated in Miastenia gravis
Anti Ach Receptor
Autoantibody implicated in Goodpasture syndrome
Anti glomerular basement membrane
Autoantibody implicated in antiphospholipid syndrome
Anti beta2 glycoprotein
Autoantibodies implicated in SLE and antiphospholipid syndrome
Anticardiolipin
Lupus anticoagulant
Autoantibody implicated in CREST syndrome
Anticentromere
Autoantibody implicated in penfigus vulgaris
Anti-desmoglein (desmosome)
Autoantibody implicated in DM1
Anti-glutamic acid decarboxylase
Islet cell cytoplasmic antibodies
Autoantibody implicated in polymiositis and dermatomyositis
Antisynthetase: anti Jo1
Anti SRP
Antihelicase: anti mi 2
Autoantibody implicated in Hashimoto thyroiditis
Antimicrosomal
Antithyroglobulin
Anti thyroid peroxidase
Autoantibody implicated in 1º biliary cirrosis
Antimitochondrial: AMA
Autoantibody implicated in Pernicious anemia
Antiparietal cell
Anti intrinsic factor
Autoantibody implicated in 1º membranous nephropathy
AntiPLA2 Rc
Autoantibody implicated in Slcerodermia
Anti-Scl-70 (Dna topoisomerase I)
Disease in which autoantibody Anti-smooth muscle has an active role
Autoimmune hepatitis type I
Autoantibody implicated in Sjögren syndrome
Anti-SSA
Anti-SSB
Sjögren syndrome: SS
Autoantibody implicated in Graves disease
Anti TSH receptor
Autoantibody implicated in Lambert Eaton myasthenic syndrome
Anti presynaptic voltage gated CALCIUM channel
Autoantibody implicated in Celiac disease
IgA anti endomysial
IgA anti-tissue transglutaminase
If IgA deficient individual: IgG
p-ANCA diseases
- Churg-strauss
- Microscopic polyangiitis
- Ulcerative colitis
c-ANCA diseases
Wegner granulomatosis
Autoantibody implicated in reumathoid arthitis
Reumatoid factor: IgM vs IgG Fc region
Anti-CCP
Autoantibody implicated in SLE
ANA
Anti dsDNA
Anti Smith
Autoantibody implicated in drug-induced lupus
Anti-histone
Autoantibody implicated in mixed connective tissue disease: SLE, sclerodermia, polymyositis
Anti-U1 RNP
B cell immunodeficiencies
Bruton (X-linked) agammaglobulinemia
Selective IgA deficiency
Common variable immunodeficiency
X linked (Bruton) agammaglobulinemia: deffect
Deffect in BTK : B cell tyrosine kinase
No B cell maturation
X linked recessive: higher prevalence in boys
Recurrent bacterial and enteroviral infections after 6 months from birth
X linked (Bruton) agammaglobulinemia: No more maternal IgG is left
Absent B cells in peripheral blood
Low Ig of all isotypes
Absent/scanty lymph nodes and tonsils
Life vaccines contraindicated
X linked (Bruton) agammaglobulinemia
Most common 1ary immunodeficiency
Selective IgA deficiency
Presentation of Selective Ig A deficiency
- Majority are asymptomatic
- Airway and GI infections
- Atopy
- Anaphylaxis to IgA containing products: blood
Selective Ig A deficiency has increased susceptibility to
Giardiasis
Defect in B cell differentiation
Common variable immunodeficiency
Low count of plasma cells and immunoglobulins
Common variable immunodeficiency
Increased risk of autoimmune disease, bronchiectasis, lymphoma and sinopulmonary infections
Common variable immunodeficiency
T cell immunodeficiencies
- Thymic aplasia: DiGeorge syndrome
- IL-12 receptor deficiency
- Autosomal dominant hyper-IgE syndrome: Job syndrome
- Chronic mucocutaneous candidiasis
22q11 deletion
DiGeorge syndrome: Di=22
DiGeorge syndrome
Failure to develop 3rd and 4th pharyngeal pouches: absent thymus and parathyroids
DiGeorge findings
T disease: Tetany: hipocalcemia T cell deficiency: recurrent infections ConoTruncal abnormalities: Tetralogy of Fallot, truncus arteriosus Chromosome Twenty Two Thymic aplasia Hypertelorism
IL-12 Rc deficiency: consequence and inheritance
Low Th1 response
Autosomal recessive
Autosomal dominant hyperIgE syndrome: Job syndrome: deficiency
Deficiency of Th17 cells due to STAT3 mutation: impared recruiment of neurophils
isolated Low IFN gamma (immunodeficiency)
IL12 receptor deficiency
Coarse Facies Cold staphlococcal abscesses Retained primary teeth High IgE Dermatologic problems Bone fractures from minor trauma
Autosomal dominant hyperIgE syndrome: Job syndrome: deficiency
High IgE
Low IFN gamma
High Eosinophils
Immunodeficiency
Autosomal dominant hyperIgE syndrome: Job syndrome: deficiency
Absent in vitro T cell proliferation in response to Candida agents
Chronic mucocutaneous candidiasis
B and T cell immunodeficiencies
- Severe combined immunodeficiency
- Ataxia telangiectasia
- Hyper IgM syndrome
- Wiskott-Aldrich syndrome
Severe combined immunodeficiency defect
Deffective IL-2R gamma chain (X linked, most common)
Deffective adenosine deaminase (AR)
Treatment of Severe combined immunodeficiency
Avoid live vacines
Antimicrobial prophylaxis and IVIg
Bone marrow transplant curative with no concern for rejection
Absence of thymic shadow in CXR, germinal centers (lymph node biopsy) and T cells (flow citometry)
Severe combined immunodeficiency
low T cell receptor excision circles (TRECs)
Severe combined immunodeficiency
Failure to thrive, chronic diarrea and thrush
Recurrent viral, bacterial, fungal and protozoal infections
Severe combined immunodeficiency
Deffect in ataxia telangiectasia
ATM gene: failure to repair DNA double strand breaks: cell cycle arrest
ataxia telangiectasia triad
- Ataxia
- Angiomas: telangiectasia
- Ig A deficiency
high AFP in immunodeficiency
ataxia telangiectasia
High risk of lymphoma and leukemia in immunodeficiency
ataxia telangiectasia
Defective CD40L on Th cells
HyperIgM syndrome: class switching deffect
HyperIgM syndrome inheritance
X linked recessive
Wiskott Aldrich syndrome: defect
WASp gene: leucocites and platelets unable to reorganise actin cytoskeleton: deffective antigen presentation
Wiskot Aldrich syndrome presentation
WATER Wiskott aldrich Thrombocytopenia Eczema Recurrent pyogenic infections
Wiskott Aldrich syndrome inheritance
Xlinked recessive
X linked recessive immunodefficiencies
Xlinked Bruton Agammaglobulinemia
Severe combined immunodeficiency IL-2R gamma chain
Hyper IgM syndrome
Wiskott Aldrich syndrome
Phagocyte disfunction diseases
- Leukocyte adhesion deficiency type 1
- Chédiak.-Higashi syndrome
- Chronic granulomatous disease
Defect in Leukocyte adhesion deficiency
LFA 1 integrin (CD18)
Findings in Leukocyte adhesion deficiency
high neutrophils
Absence of neutrophils at infection sytes (impaired migration and chemotaxis)
Delayed separation of umbilical cord
Leukocyte adhesion deficiency
Chédiak-Higashi syndrome defect
LYST: lysosomal trafficking regulator gene: microtubule disfunction in phagosome-lysosome fusion
Partial albinism
Chédiak-Higashi: melanosoma
Giant granules in granulocytes and platelets
Pancytopenia
Coagulation defects
Chédiak-Higashi
Chronic granulomatous disease defect
Defect of NADPH oxidase: less reactive oxigen species and less respiratory burst in neutrophils
Nitroblue tetrazolium dye reduction test fails to turn blue
Chronic granulomatous disease
Abdnormal dihydrodamine test: less green fluorescence
Chronic granulomatous disease
Bacterial infections in B cell immunodeficiency
Encapsulated: Some Killers Have Pretty Nice Capsules
- Streptococcus pneumoniae, Group B streptococcus, Salmonella
- Klebsiella pneumoniae
- Haemophillus influenzae type B
- Pseudomonas aeruginosa
- Neisseria meningitidis
- Criptoccoccus neoformans
Bacterial infections in T cell immunodeficiency
Sepsis
Bacterial infections in patents with low granulocytes
- Staphylococcus
- Burkholderia cepacia
- Pseudomonas aeruginosa
- Serratia
- Nocardia
Bacterial infections in complement deficiency
- Early complement deficiencies: Encapsulated
2. C5-C9 deficiency: Neisseria
B cell deficiencies tend to produce recurrent _____ infections
Bacterial
T cell deficiencies tend to produce recurrent ___ and ____ infections
Viral
Fungal
Syngenic graft (isograft)
From twin or clone)
Allograft
From nonidentical individual of the same species
Xenograft
From different species
Types of transplant rejection
- Hyperacute: type II HS
- Acute: type IV HS (cellular/humoral)
- Chronic: type IV and II HS
- Graft vs host disease: tupe IV
Pathogenesis of hyperacute transplant rejection
Pre existing recipient antibodies react to donor antigen (type II hypersensitivity reaction), activate complement
Features of hyperacute Transplant rejection
Widespread thrombosis of graft vessels: ischeima/necrosis
Graft must be removed
Types of acute transplant rejection
Type IV hypersensitivity reaction:
- Cellular: T cells CD8+ against donor MHC
- Humoral: B cells: similar to hyperacute, except antibodies develop after transplant
Features of acute transplant rejection
- Vasculitis of graft vessels with dense intersticial lympocytic infiltrate
- Prevent or reverse with immunosupressants
Pathogenesis of chronic transplant rejection
CD4+ T cells respond to recipient APCs presenting donor peptides, including allogenic MHC
Features of chronic transplant rejection
Recipient T cells react and secrete cytokines: proliferation of VSM, parenchymal atrophy and intersticial fibrosis
Atteriosclerosis
Organ-specific examples of Chronic transplant rejection
- Lung: bronchiolitis obliterans
- Heart: accelerated atheriosclerosis
- Kidney: Chronic graft nephropathy
- Liver: Vanishing bile duct syndrome
Grafted immunnocompetent T cells proliferate in the immunocompromised host and reject host cells with foreign proteins
Graft vs host disease
In what situation is graft vs host disease considered beneficial?
Bone marrow transplant for leukemia
Graft vs host disease is more frequent in ____ and ____ transplants
Bone marrow
Liver
(more lymphocytes)