IMMUNOLOGY- Immune Responses Flashcards
Which are acute phase reactants?
Factors whose serum concetration change significantly in response to inflammation
When and where is produced the acute phase reaction?
Produced by the lieer in both acute and chronic inflammatory states
Who induces acute phase reactions?
IL-6, IL-1, TNF α and IFN γ
How are acute phase reactants classified?
Positive
Negative
Which is the upregulated and which is the downregulated in Acute phase phase reactants?
Positive (Upregulated)
Negative (Downregulated)
In Acute phase phase reactants which are positive regulators?
Serum Amyloid A C reactive protein Ferritin Fibrinogen Hepcidin
C reactive protein
Opsonin
Which is the function of Opsonin?
Fixes complement and facilitates complement
What is teh clinical meaning of C- reactive protein?
Sign of ongoing inflammation
Which is the relationship between ferritin and microbials?
ferritin binds ans sequesters iron to inhibit microbial iron scavenging
What is Fibrinogen?
Coagulation factor
What does Fibrinogen promotes?
Endothelial repair
Which lab correlates with Fibrinogen?
Erythrocyte sedimentation rate (ESR)
This is the function of Hepcidin
Prevents release of iron bound by ferritin
Which disease does Hepcidin prevents?
Anemia of chronic disease
These are Negative (Downregulators) or Acute phase reactants
Albumin
Transferrin
What is the effect of Albumin reduction?
Conserves amino acids for positive reactants
What is the effect of Transferrin?
Internalized by macrophages to sequester iron
What is the main purpose of the Complement?
System of interacting plasma proteins that play a role in innate immunity and inflamation
This is a mechanism of defense used in complement that uses the membrane?
Membrane Attack Complex (MAC)
From which bacterias does Membrane Atack complex (MAC) protects?
Against Gram negative bacteria
Which are the pathways to activate Complement?
Classic pathway
Alternative pathway
Lectine pathway
Who mediates classic pathway of complement?
IgG or IgM
Who stimulates the activation of alternative pathway of Complement?
Microbe surface molecules
Who stimulates Lectin pathway of complement?
Mannose or other sugars on microbe surface
What does C3b manages?
Opsonization
These complements carried anaphylaxis process
C3a, C4a and C5a
This complement manages Neutrophil chemotaxis
C5a
What is the purpose of C5b-9?
Cytolysis by membrane atack complex (MAC)
Which complement binds bacterias?
C3b
Who are the primary opsonins in bacterial defense?
C3b and IgG
Which other function does C3b has?
Helps clear immune complexes
Whoare inhibitors of Complement?
Decay accelerating factor and C1 esterase inhibitor help prevent complement activation on self cells (eg RBC)
Which are Decay accelerating factors?
DAF, aka CD55
These are complement disorders
C1 esterase inhibitor deficiency
C3 deficiency
C5- C9 deficiencies
DAF (GPI anchored enzyme) deficiency
What does C1 esterase inhibitor deficiency clinically cause?
Hereditary angioedema
Which medicines are contraindicated in C1 esterase inhibitor deficiency?
ACE inhibitors
Which diseases are increased in C3 deficiency?
Increase risk of Severe, recurrent pyogenic sinus and respiratory tract infections
Increases Susceptibility to type III hypersensitivity reactions
From which bacteria is increased the susceptibility in C5- C9 deficiencies?
recurrent Neisseria bacterimia
What does DAF (GPI anchored enzyme) deficiency cause?
Complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria
How is consider IL-1?
An endogenous pyrogen
This is another name for IL-1
Osteoclast activating factor
These are the clinical manifestations of IL-1
Causes fever
Acute inflamation
Which is the mechanism of action of IL-1?
Activates endothelium to express adhesion molecules; induces chemokine secretion to recruit leukocytes
How is classified IL-6?
An endogenous pyrogen
Who else can secrete IL-6?
Th2 cells and macrophages
What is the effect of IL-6?
Causes fever and stimulates production of acute phase proteins
Major chemotactic factor for neutrophils
IL-8
This IL Induces differentiation of T cells into Th1 Cells
IL-12
Which other effect does IL-12 has?
Activates NK cells
Who secretes IL-12?
B cells and macrophages
Which cytokines are secreted by macrophages?
IL-1 IL-6 IL-8 IL-12 TNF α
Who mediates septic schock and activates endohtelium?
TNF α
What is the effect of TNF α?
Causes leukocyte recruitment, vascular leak
Which are the main effect of the first 6 IL?
IL-1 FEVER IL-2 stimulates T cells IL-3 stimulates bone marrow IL-4 stimulates IgE production IL-5 stimulates IgA production IL-6 stimulates acute phase protein production
These IL are secreted by all T cells
IL-2
IL-3
Which is the effect of IL-2
Stimulates growth of helper , cytotoxic and regulatory T cells
Supports the growth and differentiation of bone marrow stem cells
IL-3
Functions like GM-CSF
IL-3
Who secretes interferon γ?
Th1 cells
Which properties does Interferon γ has?
Antiviral and antitumoral properties
What cells are activated by Interferon γ?
NK to kill virus infected cells
Which other effect does Interferon γ has?
Increases MHC expression and antigen presentation in all cells
Which IL are produced by Th2 cells?
IL-4
IL-5
IL-6
What effect does IL-4 has on Th2 cells?
Induces differentiation into Th2 cells
Promotes growth of B cells. Enhances class switching to IgE and IgG
IL-4
Which are the effects of IL-5?
Promotes differentiation of B cells
Enhances class switching to IgA
Stimulates the growtlh and differentiation of eosonophils
This IL modulates inflamatory response
IL-10
What does IL-10 do?
Inhibits action of activated T cells and Th1
Who else secretes IL-1?
Th2 cells and regulatory T cells
Who else has similar actions as IL-10 by inhibiting inflamation?
TNF β
Which is the importance of Interferon α and β?
A part of innate host defence against both RNA and DNA viruses
What are the interferons?
Are glycoproteins synthesized by viral infected cekks that act locally on uninfected cells “priming them” from viral defense
Once the Virus infects primed cells, what does Viral dsRNA activates?
RNAase L
Protein kinase
Which is the effect of RNAase L?
Degradation of viral/ host mRNA
What does Protein kinase inhibits?
Inhibition of viral/host protein synthesis
What are the results of Interferon α and β?
Essentially results in apoptosis, thereby interrupting viral amplification
Which cells possess MHC I?
All cells except mature RBCs
Which are the cell surface proteins that T cells have?
TCR
CD3
CD28
This is the importance of TCR
Binds antigen -MHC complex
In which process is CD3 associated?
Associated with TCR fpr signal transduction
What is the effect of CD28?
Binds B7 to APC
These are the cell surface proteins on Helper T cells
CD4 and CD40 ligand
Which is the cell surface protein on Cytotoxic T cells?
CD8
Name all cell surface proteins for B cells
Ig (binds antigen)
CD19, CD20, CD21, CD40
MHC II, B7
This is the receptor for EBV
CD21
For Macrophages these are the cell surface proteins
CD14, CD40
MHC II, B7
Fc and C3b receptors
Cell surface proteins on NK cells
CD16
CD56
What is the effect of CD16?
Binds Fc of IgG
Unique marker for NK
CD56
What is anergy?
Self reactive T cells become nonreactive without constimulatory molecule
Can B cells become anergic?
B cells also become anergic, but tolerance is less complete than in T cells
Who can produce Superantigens?
S. pyogenes
S. aureus
Which are the habilities of superantigen?
Cross link the β region of the T cell receptor to the MHC class II on APCs
What are the effects of superantigen on T cells?
Can activate any T cell, leading to massive release of cytokines
Who can produce Endotoxins/ lipopolysaccharide?
Gram negative bacteria
Which cells are stimulated by Endotoxins/ lipopolysaccharide?
Macrophages
How can Endotoxins/ lipopolysaccharide stimulate macrophages?
Directly stimulates macrophages by binding to endotoxin receptor CD14, Th cells are not involved
Which bacterias show Antigen variation?
Salmonella (2 flagellar variants) Borrelia (relapsing fever) Neisseria gonorrhea (pilus protein)
Which is the classic virus that shows Antigen variation?
Influenza virus (major = shift, minor= drift)
This parasite has antigenic variation
Trypanosomes (programmed rearrangement)
How does passive acquisition of immunity happens?
Receiving preformed antibodies
How is the onset of acquiring passive immunity?
Rapid
How long does Passive immunity last?
Short span of antibodies (half life= 3 weeks)
Which are examples of Passive immunity?
IgA in breast milk
Maternal IgG crossing placenta
Antitoxin
Humanized monoclonal antibody
After which microorganism exposure are given preformed antibodies?
Tetanus toxin
Botulinum toxin
HBV
Rabies virus
How is active immunity acquired?
Exposure to foreign antigens
This is the onset of Active immunity
Slow
How long does Active immunity last?
Long lasting protection (memory)
Which are examples of Active immunity?
Natural infection
Vaccines
Toxoid
When is recommended the combined passive and active immunization?
For Hepatitis B or Rabies exposure
Which is the reason of vaccination?
Vaccines are used to induce an active immune response (humoral and/ or cellular) to specific pathogens
How are vaccines classified?
Live attenuated vaccine
Inactive or killed vaccine
What is a live attenuated vaccine?
Microorganism loses its pathogenicity but retains capacity for transient growth within inoculated host
Which kind of response does live attenuated vaccine induces?
Mainly induces a cellular response
Which is the advantage of administering live attenuated vaccines?
Induces strong, often lifelong immunity
Which disadvange do live attenuated vaccines have?
May revert to virulent form
When is contraindicated the use of live attenuated vaccines?
In pregnancy and immune deficiency
These are examples of live attenuated vaccines
Measles Mumps Rubella Polio (Sabin) Influenza (intranasal) Varicella Yellow fever
Which are the characterisitics of Inactivated or killed vaccines?
Pathogen is inactivated by heat or chemicals; maintaining epitope structure on surface antigen is important for immune response
Which immunity is induced with Inactivated or killed vaccines?
Humoral immunity induced
This is an advantage of Inactivated or killed vaccines
Stable and safer than live vaccines
This is a disadvantage of Inactivated or killed vaccines
Weaker immune response; booster shots usually required
Which are examples of Inactivated or killed vaccines?
Cholera Heàtitis A Polio (Salk) Influenza (injection) Rabies
How many types of Hypersensitivity exist?
I, II, III, IV
How else is Hypernsensitivity type I is known?
Anaphylactic and atopic
Which is the mechanism of action of Hypernsensitivity type I?
Free antigen cross links IgE on presensitized mast cells and basophilsm triggering immediate release of vasoactive aminesthat act at postcapillary venules (eg. histamine)
Why does the reaction develops rapidly in Hypernsensitivity type I?
Because of preformed antibody
Whho manages the delayed reaction in Hypernsensitivity type I?
Due to production of arachidonic acid metabolites (leukotrienes)
Which Hypernsensitivity types are mediated by antibodies?
Types I, II, III
Which test helps in Hypernsensitivity type I?
Skin test for specific IgE
This is the alternative name for Hypernsensitivity type II
Cytotoxic (antibody mediated)
How does Hypernsensitivity type II works?
IgM, IgG bind to fixed antigen on enemy cell, leading to cellular destruction
Which the three mechanism of Hypernsensitivity type II?
Opsonization leading to phagocytosis or complement activation
Complement mediated lysis
Antibody dependent cell mediated citotoxicity, ussually due to NK cells or macrophages
In Hypernsensitivity type II, who lead to Membrane attack complex?
Antibody and complement
Which lab test helps for Hypernsensitivity type II?
Direct and Indirect Coombs
What does Direct Coombs detects?
Detects antibodies thathave adhered to patients RBCs
Which is an example of Direct Coombs?
Test an Rh + infant of an Rh - mother
This is what indirect coombs detects
Detects antibodies that can adhere to other RBCs
Give an example of Indirect coombs
Test an Rh - woman for Rh + antibodies
This Immunity type is also known as Immune complex
Hypernsensitivity type III
What happens in Immune complex immunity?
Antigen- antibody (IgG) complex activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes
Which diseases are Immune complex immunity related?
Serum sickness
Arthus reaction
What happens in Serum sickness?
An immune complex disease in which antibodies to the foreign proteins are produced
How much times does it takes for antibodies to be produced in Serum sickness?
5 days
How is damage produced in Serum sickness?
Immune complexes form and are deposited in membranes, where they fixed complement (leading to tissue damage)
Who is more common Serum sickness or Arthus reaction?
Serum sickness
What is Arthus reaction?
A local subacute antibody mediated hypersensitivity (type III) reaction
This an example of how to cause Arthus reaction
Intradermal onjection of antigen induces antibodies, which form antigen-antibody complexes in the skin
Which are the clinical manifestations of Arthus reaction?
Edema, necrosism and activation of complement
What causes most cases of Serum sickness?
By drugs acting as haptens
When do you suspect Serum sickness?
Fever, urticaria, arhtralgias, proteinuria, lymphadenopathy 5-10 days after antigen exposure
What causes Arthus reaction?
Antigen- antibody complexes
Which test can be used for Arthus reaction?
Immunofluorescent staining
Delayed type of Immunity
Hypersensitivity Type IV
Who mediates delayed type of immunity?
T cell mediated
How does Hypersensitivity Type IV works?
Sensitized T lymphocytes encounter antigen and then release lymphokines
Which is the final result of Hypersensitivity Type IV?
Macrophage activation; no antibody involved
Can Hypersensitivity Type IV be transferable by serum?
Cell mediated; therefore it is not transferable by serum
Which test are used for Delayed immunity?
Patch test, PPD
Which is the mnemonic for Hypersensitivity types?
ACID Anaphylactic and Atopic (Type I) Cytotoxic (Type II) Immune complex (Type III) Delayed (cell mediated, Type IV)
Which are examples Hypersensitivity type I disorders?
Anaphylaxis
Allergic and Atopic disorders
Bee sting, some food/drug allergies, are examples of this Hypersensitivity disorder
Hypersensitivity type I- anphylaxis
These are allergic and atopic disorders
Rhinitis Hay fever Rczema Hives Asthma
Which are the presentation of Hypersensitivity type I disorders?
Immediate
Anaphylctic
Atopic
Name examples of Hypersensitivity type II disorders
Autoimmune hemolytic anemia Pernicious anemia Idiopathic thrombocytopenic purpura Erytroblastosis Fetalis Acute hemolytic transfussion reactions Rheumatic fever Goodpasture syndrome Bullous pemphigoid Pemphigus vulgaris
Which are the characteristics of Hypersensitivity type II disorders?
Disease tends to be specific to tissue or site where antigen is found
Give examples of Hypersensitivity type III disorders
SLE Polyartheritis nodosa Poststreptococcal glomerulonephritis Serum sickness Arthus reaction (swelling and inflammation following tetanus vaccine)
Which possible presentations can Hypersensitivity type III disorders have?
Can be associated with vasculitis and systemic manifestations
These are Hypersensitivity type IV disorders
Multiple sclerosis Guillian Barre syndrome Graft versus host disease PPD (test for M. tuberculosis) Contact dermatitis (poison ivy, nockel allergy)
What is a characteristic of Hypersensitivity type IV disorders?
Response is delayed and does not involve antibodies
Which are the possible blood transfusion reaction?
Allergic reaction
Anaphylactic reaction
Febrile nonhemolytic transfusion reaction
Acute hemolytic transfusion reaction
Which is the pathogenisis of Allergic reaction to Blood transfusion?
Type I hypersensitivity reaction against plasma proteins in transfused blood
In case of allergic reaction to blood transfusion which could be the clinical presentations?
Urticaria, pruritusm wheezing, fever
How do you treat Allergic reaction to Blood transfusion?
With antihistamines
What is anaphylactic reaction to blood transfusion?
Severe allergic reaction
What happens in anaphylactic reaction to blood transfusion? and what is the solution?
IgA deficient individuals must receive blood products that lack IgA
Which is the clinical presentation of anaphylactic reaction to blood transfusion?
Dyspnea, bronchospasm, hypotensionm respiratory arrestm shock
Which kind of Hypersensitivity disorder is Febrile nonhemolytic transfussion reaction?
Type II hypersensitivity reaction
What happens in Febrile nonhemolytic transfussion reaction?
Host antibodies against donor HLA antigens and leucocytes
These are the manifestations Febrile nonhemolytic transfussion reaction
Fever, headachesm chills, flushing
Which kind of Hypersensitivity disorder is Acute hemolytic transfussion reaction?
Type II hypersensitivity reaction
How is Acute hemolytic transfussion reaction classify?
Intravascular hemolysis
Extravascular hemolysis
What happens in Intravascular hemolysis in Acute hemolytic transfussion reaction?
ABO blood group incompatibility
This is what happens in Extravascular hemolysis in Acute hemolytic transfussion reaction
Host antibody reaction against foreign antigen in donor RBCs
Clinical presentation of Acute hemolytic transfussion reaction
Fever, hypotension, tachypnea, tachycardia, flank pain, hemoglobinemia (intravascular), jaundice (extravascular hemolysis)
Which could be the complication caused by bacterias in case of No T cells?
Sepsis
In case of No B cells which bacterias can caused disease?
Encapsulated (SHiNE SKiS) S. pneumoniae H. influenzae type B Neisseria meningitidis Escherichia coli Salmonella Klebsiella pneumoniae Strep group B
We are at risk of these bacterias infection in case of no granulocyte
Staphylococcus
Burkholderia cepacia
Serratia
Nocardia
Which bacteria is the principal that affects in case of no complement?
Neisseria (No membrane attack complex)
These viruses increased the risk of infection if No T cells
CMV, EBV, JCV, VZV
Chronic infection with respiratory/ GI viruses
Which vaccines are contraindicated in patients with no B cells?
Live vaccines
Which viruses infect in patients without B cells?
Enteroviral encephalitis
Polivirus
For patients with no T cells, are at higher risk for these Fungi infections
Candida
Pneumocystis Pneumoniae
For patients without IgA this is the most common parasite infection
GI giardiasis
No granulocyte patients are at higher risk of these fungi infection
Candida, Aspergillus
Patients with no B cells are at higher risk of recurrent infection by…
Bacterias
For patients with no T cells these microorganism are the most probable cause of infection
Fungal and Viral infection
Which are B cell disorders?
X-linked agammaglobulinemia
This is an alternative name for X-linked agammaglobulinemia
Bruton agammaglobulinemia
Which inheritance mode does Bruton agammaglobulinemia has? who are affected?
X linked recessive
Increase in boys
What is defective in X-linked agammaglobulinemia?
Defect in BTK, atyrosine kinase gene→ No B cell maturation
Which is the clinical presentation of X-linked agammaglobulinemia?
Recurrent bacterial and enteroviral infections after 6 months (Decreased maternal IgG)
These could beclinical findings in X-linked agammaglobulinemia
Absent/ scanty lymph nodesand tonsils
Which are the findings in Bruton agammaglobulinemia?
Normal CD19+ B cell count
↓ Pro B, ↓ Ig of all classes
Which is the most common immunodeficiency?
Selective IgA deficiency
Which is the defect in selective IgA deficiciency?
Unknown
Which is the clinical presentation of selective IgA deficiciency?
Majority Asymptomatic
Can see:
Airway and GI infection. Autoimmune disease, Atopy, anaphylaxia to IgA containing products
These are the lab results in selective IgA deficiciency
IgA <7 mg/ dL with normal IgG, IgM levels
What is wrong in Common variable immunodeficiency?
Defect in B cell differentiation
Many causes
When can Common variable immunodeficiency be acquired?
In 20-30s
These could be findings in patients with Common variable immunodeficiency
Increase risk of autoimmune disease
Bronchiectasis, lymphoma, sinopulmonary infections
Which labs are affected in Common variable immunodeficiency?
Decreased plasma cells
Decreased Immunoglobulins
These are T cell disorders
Thymic aplasia
IL-12 receptor deficiency
Autosomal dominant hyper IgE syndrome
Chronic mucocutaneous candidiasis
Thymic aplasia is also known as…
DiGeorge Syndrome
What is affected in DiGeorge syndrome?
22q11 deletion; failure to develop 3rd and 4th pharyngeal pounches→ Absent thymus and parathyroids
Which are the clinical manifestations of DiGeorge syndrome?
Tetany (hypocalcemia)
Recurrent Viral/Fungal infections (T cell deficiency)
Conotruncal abnormalities
Name Conotruncal abnormalities
Tetralogy of Fallot
Truncus arteriosus
Which are the findigs in Thymic aplasia?
↓ T cells, ↓ PTH, ↓ Ca2+
Absent Thymic shadow on CXR
22q11 deletion defected by FISH
What is wrong in IL-12 receptor deficiency?
↓ Th1 response
Which is the inheritance mode of IL-12 receptor deficiency?
Autosomal recessive
When can IL-12 receptor deficiency be presented?
After administration of BCG vaccine
This is how IL-12 receptor deficiency can manifest
Disseminated mycobacterial and fungal infections
What is decreased in IL-12 recetor deficiency?
↓ IFN γ
Also known as Job syndrome
Autosomal dominant hyper IgE syndrome
What is the defect in Autosomal dominant hyper IgE syndrome?
Deficiency of Th17 cells due to STAT3 mutation→ Impaired recruitment of neutrophilstp sites of infection
These are the clinical findings in Job syndrome
FATED
coarse Facies, cold (noninflamed) sthapylococcal Absceses, retained primary Teeth, ↑ IgE, Dermatologic problems (eczema)
We see this lab alteration in Autosomal dominant hyper IgE syndrome
↑ IgE, ↓ IFN γ
What is altered in Chronic mucocutaneous candidiasis?
T cell dysfunction. Many causes
This is the presentation of Chronic mucocutaneous candidiasis
Noninvasive Candida Albicans infections of skin and mucous membranes
What can be found in Chronic mucocutaneous candidiasis?
Absent in vitro T cell proliferation in response to Cnadida Antigens
Absent cutaneous reaction to Candida antigens
Which are B and T cell disorders?
Severe combined immunodeficiency (SCID)
Ataxia Telangiectasia
Hyper IgM syndrome
Wiskott Aldrich syndrome
How can we classified the defects in SCID?
Defective IL-2R gamma chain (most common, X linkes)
Adenosine Deaminase Deficiency (Autosomal recessive)
This is how SCID can be presented
Failure to thrive, chronic diarrhea, thrush
Recurrent viral, bacterial, fungal and protozoal infections
Which is the treatment for SCID?
Bone marrow transplant
Is it possible to have a Bone marrow transplant rejection in SCID?
No concern for rejection
These are the findings in SCID
↓T cell receptor excision circles (TRECs) Absence of thymic shadow (CXR) Germinal centers (lymph node biopsy) and T cells (flow cytometry)
Which is the problem in Ataxia Telangiectasia?
Defects in ATM gene → DNA double strand breaks → cell cycle arrest
Which is the triad for Ataxia Telangiectasia?
Cerebellar Defects (Ataxia) Spider Angiomas (telangiectasia) IgA deficiency
These are the findings in Ataxia Telangiectasia
↑ AFP
↓ IgA, IgG and IgE
Lymphopenia, cerebellar athrophy
What is the defect in Hyper IgM syndrome?
Most commonly due to defective CD40L on Th cells= class swithcing defect
How is Hyper IgM syndrome genetically classify?
X linked recessive
Which are the infection that can occur in Hyper IgM syndrome?
Severe pyogenic infections early in life
Oportunistic infection with Pneumocystis, Cryptosporidium, CMV
In Labs what is altered in Hyper IgM syndrome?
↑ IgM
↓↓ IgG, IgA, IgE
Which is the mutation in Wiskott- Aldrich syndrome?
Mutation in WAS gene
Which is the inheritance mode of Wiskott- Aldrich syndrome?
X linked recessive
What is the problem with T cells in Wiskott- Aldrich syndrome?
T cells unable to reorganize actin cytoskeleton
These is the mnemonic for Wiskott- Aldrich syndrome
WATER Wiskott- Aldrich syndrome Thrombocytopenic purpura Eczema Recurrent infections
Which risk are higher in Wiskott- Aldrich syndrome?
Increased risk of Autoimmune disease and malignancy
These are the lab alterations in Wiskott- Aldrich syndrome
↑ IgE, IgA
↓ to normal IgG, IgM
Fewer and smaller platelets
These diseases are classified as Phagocyte dysfunction
Leukocyte adhesion deficiency (type 1)
Chédiak- Higashu syndrome
Chronic granulomatous disease
Which is the defect in Leukocyte adhesion deficiency (type 1)?
Defect in LFA-1 integrin (CD18) protein on phagocytes;
What happens if there is a defect in LFA-1 integrin (CD18) protein on phagocytes?
Impaired migration and chemotaxis
Inheritance mode of Leukocyte adhesion deficiency (type 1)?
Autosomal recessive
These are characteristics of clinical presentation of Leukocyte adhesion deficiency (type 1)
Recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed separation of umbilical cord (>30 days)
What is increased in Leukocyte adhesion deficiency (type 1) ?
Neutrophils
Although Neutrophils are increased in Leukocyte adhesion deficiency (type 1) what is the problem with them?
Absence of neutrophils at infection sites
In this phagocyte dysfunction there is a defect in lysosomal trafficking regultator gene (LYST)
Chediak Higashi syndrome
Which is other problem in Chédiak Higashi syndrome?
Microtubule dysfunction in phagosome lysosome fusion
Which is the inheritance pattern for Chédiak Higashi syndrome?
Autosomal recessive
Who are the main bugs who cause recurent pyogenic infections in Chédiak Higashi syndrome?
Staphylococci and streptococce
These are the clinical manifestations of Chédiak Higashi syndrome
Recurrent pyogenic infections Partial albinism Peripheral neurophaty Progressive neurodegeneration Infiltrative lymphohistiocytosis
These lab result are altered in Chédiak Higashi syndrome
Giant granules in neutrophils and platelets
Pancytopenia
Mild coagulation defects
What is the defect in Chronicgranulomatous disease?
Defect in NADPH oxidase→ ↓ reactive oxygen species (superoxide) and absent respiratory burst in neutrophils
This is the inheritance mode in Chronic granulomatous disease
X linked recessive
From which microorganisms are patients suceptible in Chronic granulomatpus disease?
↑ Suceptibility to catalase + organisms (PLACESS) Pseudomona Listeria Aspergillus Candida E. Coli S. aureus Serratia
Which lab test help in the diagnosis of Chronic Granulomatous?
Abnormal dihydrorhodamine (flow cytometry) test Nitrobuline tetrazolinum test is - (test out of favor)
Name all types of Graft
Autograft
Syngeneic graft
Allograft
Xenograft
What is a autograft?
From self
This kind of graft comes form identical twn or clone
Syngeneic graft
What is a Allograft?
From nonidentical individual of same species
This type of Graft comes from different species
Xenograft
These are all the Transplant rejection types
Hyperacute
Acute
Chronic
Graft versus host disease
How long does it take for rejection to be categorized as Hyperacute?
Within minutes
Which is the pathogenesis in Hyperacute rejection?
Pre-existing recipient antibodies react to donor antigen (Type II reaction)
What is activated in Hyperacute reaction?
Activates complement
These are the results of Hyperacute reaction
Widespread thrombosis of graft vessels → Ischemic/necrosis
Which are the alternatives if treatment in Hyperacute transplant reaction?
Graft must be removed
In this kind of Trasnplant rejection it takes weeks to months for the onset
Acute rejection
Which are the types of Acute transplant rejection?
Cellular
Humoral
What happens in the cellular Acute Rejection?
Cytotoxic T lymphocites activated against donor MHCs
Which is the difference between Hyperacute and Acute Humoral rejection?
Humoral is similar to Hyperacute, except antibodies develop after transplant
Which is the pathogenisis in Acute Transplant rejection?
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
How do you manage Acute transplant rejection?
Prevent/ reverse with immunosupressants
How long does it takes for Chronic transplant rejection to onset?
Months to years
Recipient T cells perceive donor MHC as recipient MHC and react against donor antigens presented
Chronic Transplant rejection
Does Chronic Transplant rejection has cellular or Humoral components?
Both
How do you manage chronic transplant rejection?
Irreversible. T-cell and antibody mediated damage
Which organs could be the main affected by Chronic Transplant rejection
Heart
Lungs
Liver
Kidney
This is the main damage in chronic transplant rejection to the heart
Atherosclerosis
How is manifested the chornic transplant rejecetion in Lungs?
Bronchiolitis obliterans
What is the effect of Chronic transplant rejection in Liver=
Vanishing bile ducts
Which are the main features in Kidneys during chronic transplant rejection?
Vascular fibrosis
Glomerulopathy
How much times does Graft versus host disease takes to onset?
Varies
What happens in Graft versus host disease?
Grafted immunocompetent T cells proliferate in the immunocpromised host and reject host cells with foreign proteins
Which is the result of Graft versus host disease?
Severe organ dysfunction
Which are the clinical features of Graft versus host disease?
Macupapular rash
Jaundice
Diarrhea
Hepatosplenomegaly
In which kind of transplants is more common to see Graft versus host disease?
Usually in bone marrow and liver transplant (rich in lymphocytes)
When is beneficial Graft versus host disease?
Potentially beneficial in bone marrow transplant for leukemia (Graft versus tumor effect)
