Immunology Flashcards
Inheritance of Wiskott-Aldrich Syndrome (WAS) and antibody findings
X-linked recessive
- Elevated IgA & IgE
- IgM low
**WASP protein normally allows cytoskeleton rearrangements for antigen binding, but this is dysfunctional and T cells under-respond
Characteristic signs of WAS (Wiskott-Aldrich syndrome)
- Thrombocytopenia w/ hepatosplenomegaly
- Eczema
- Immunodeficiency (recurrent infections: respiratory & skin)
*The problem is lymphocytes are dysfunctional due to WASP protein
Who does WAS (Wiskott-Aldrich syndrome) effect?
Young boys
*Usually die by 6 from infection
What malignancy is WAS (Wiskott-Aldrich syndrome) inclined to develop?
Lymphoid
Treatment & cure of WAS (Wiskott-Aldrich syndrome)
Bone marrow transplant from HLA identical sibling
*complete reversal of platelet & immune defect
Cellular immune responses are promoted by what?
CD4+ and Th1 cells
Secrete IFN-gamma & IL-12 to activate macrophages & CD8+ T cells
Which interleukins does Th2 secrete and what do they do?
IL-4, IL-5, IL-6
Induce B cell class switching and promote humoral immune response
IL4: IgE
IL5: IgA
IL6: Acute inflammation
Function of Th17
Induce pro-inflammatory cytokines that recruit & promote neutrophil responses against extracellular pathogens
Purpose of IL-7 and mutation of its gamma chain causes what?
PURPOSE: Causes pluripotent stem cells to differentiate down the T-cell lineage during hematopoiesis
DISEASE: SCID [severe combined immunodeficiency]
Phenotypically, what is demonstrated in patients with SCID?
Absent CD3 (T cell)
Present CD19 (B cell)
Phenotypically, what is demonstrated in patients with adenosine deaminase deficiency?
Absence of CD3 & CD19
*Accumulated metabolites due to deficiency of adenosine deaminase causes toxins metabolites to accumulate in lymphocytes, killing them
What is defective in hyper-IgM syndrome
CD40L
*Impossible for B cells to receive the signal to isotype switch
Phenotypically, what is demonstrated in patients with RAG gene mutation?
VDJ recombination can’t occur, thus no CD3 or CD19
Defective development of what (embryologically) causes DiGeorge syndrome?
3rd & 4th pharyngeal pouch
What chromosomal abnormality causes DiGeorge syndrome?
Deletion at 22q11.2
What CD markers are present on mature T lymphocytes?
CD3 & CD5
*In DiGeorge syndrome, they are reduced due to thyme hypoplasia/aplasia
What CD markers are present on NKCs?
CD16 & CD56
What CD markers are present on mature B lymphocytes?
CD19 & CD20
What is defective in ataxia-telangiectasia and what are the consequences?
ATM gene mutation causing impaired VDJ recombination
What condition is associated with c-ANCA
Granulomatosis with polyangiitis
*Formerly called Wegener granulomatosis
What condition is associated with p-ANCA
Churg-Strauss syndrome
2 key characteristics always seen together in c-ANCA condition
Granulomatosis with polyangiitis:
1) Necrotizing vasculitis of the upper & lower respiratory tract –> nasal septal perforation, sinus pain, cough/hemoptysis
2) Kidney: crescentic, rapidly progressive GN
Key characteristics in p-ANCA condition
Asthma
Eosinophilia
*Eosinophil-rich necrotizing vasculitis; systemic effects
Most important CHEMOTACTIC factors for neutrophils
C5a & IL-8
Toxoid vaccine examples
Diptheria
Tetanus
*Chemically inactivated
Attenuated vaccine examples
*Weakened virus
“Attention Teachers! Please Vaccinate Small, Beautiful Young Infants with MMR Regularly”
- Adenovirus
- Typhoid
- Polio (Sabin)
- Varicella
- Smallpox
- BCG
- Yellow fever
- Influenza (intranasal)
- MMR
- Rotavirus
Killed, whole-cell vaccine examples
“A TRIP could Kill you”
- Hepatitis A
- Typhoid
- Rabies
- Influenza
- Polio (SalK)
Example of toxoid + polyribitol phosphate vaccine
Haemophilus influenza type B
*The capsule (polyribitol phosphate) alone would only produce a weak IgM response (T-cell independent)
**Must conjugate capsule to a toxoid (diphtheria toxoid) to induce memory (T-cell dependent)
Cause of Lambert-Eaton Myasthenic Syndrome (LEMS)
Autoimmune neuromuscular disorder due to antibodies against presynaptic calcium channels
Symptoms of LEMS
- Proximal muscle weakness
- Decreased tendon reflex (improving with prolonged muscle contraction)
What is often associated with LEMS
SCLC
What cytokines are overproduced in a super antigen infection & why?
T CELL:
IFN-gamma
MACROPHAGE:
IL-1
IL-6
TNF-alpha
*Superantigen crosslinks MHC II (macrophage) with TCR, inducing huge cytokine overproduction
What organisms are splenectomized patients most at risk of infection from?
Gram +, catalase -
- S. pneumonia
- *Hib
- **N. meningitides
What organisms are patients with NADPH oxidase gene defect at risk for? Give examples
Catalase + infections
- S. aureus
- Aspergillus
- Nocardia
- Salmonella
- Candida
*They neutralize H2O2 quickly into water and oxygen
Subunit Vaccine examples
- HBV (HBsAg)
- HPV (6,11,16,18)
- N. meningitidis
- S. pneumonia (13,23)
- Hib
Cause & symptoms of LAD (leukocyte adhesion deficiency)
CD18 defect
- Delayed umbilical cord separation
- Omphalitis
- Recurrent bacterial infections
Common lab finding in LAD (leukocyte adhesion deficiency)
Increased neutrophils in the blood
*Neutrophils can’t migrate to sites of inflammation correctly and remain in the blood
Which hypersensitivity reaction is Goodpasture Syndrome
Type II, cytotoxic
In TSS (toxic shock syndrome), what cytokines are released and from what cells?
Macrophages: IL-1, IL-6, TNF-alpha
TH1: IFN-gamma
Characteristics of IgA deficiency
- Increased mucosal pathogens
- Atopic allergy (High IgE)
- Transfusion reaction
Why is IgE higher in IgA deficiency?
Increased isotope switching due to their inability to produce IgA
*anti-IgA & IgE antibodies
**Patients can only receive blood products from other IgA deficient donors
When do we use ELISA
Measure antibody titers against viruses & other pathogens
When do we use Northern blots?
Determine RNA levels in a cell
When do we use Southern blots
Study genomic DNA
When do we use subtractive hybridization?
Research technique, not clinical assay
*Subtracts out the RNA of a closely related cell type in order to see the RNA from genes that are transcribed by a specific cell type
How can we calculate amount of globulin in blood?
Total protein - albumin = globulins
Hallmark of LAD (leukocyte adhesion deficiency)
- Inability to form pus or abscesses, recurrent bacterial infections, severely delayed wound healing
- Delayed umbilical cord separation in newborns
- Neutrophilia (5-10x higher) due to inability of cells to extravasate into tissues
When do we use the microcytotoxicity test?
To determine HLA class I expression of recipient & potential donor cells in order to select a compatible match
When do we use a mixed lymphocyte reaction test?
Determine compatibility of transplant recipient and donor with regard to HLA class II molecules
**Microcytotoxicity test is for HLA class I
Cytotoxic VS noncytotoxic type II hypersensitivity reaction
CYTOTOXIC:
Antibodies binding to cells or tissues and causing death of the cells or tissues
ie) Mismatch blood transfusion
NONCYTOTOXIC:
Antibodies binding to cells or tissues and changing their function
ie) Graves or Myasthenia Gravis
Arthus Reaction
Varian of type III hypersensitivity in which local vasculitis induces tissue necrosis, usually of the skin
What deficiency is seen in Bruton agammaglobulinemia?
Bruton Tyrosine Kinase
*impaired B cell maturation from pre-B cell to mature B cel, causing a total absence of any circulating B cells (CD19)
When do symptoms present in x-linked agammaglobulinemia?
6 months, after which maternal antibodies are no longer active
What are XLA (x-linked agammaglobulinemia) patients susceptible to?
S. pneumonia
Hib
Pseudomonas spp
Sx:
Sepsis
Meningitis
Osteomyelitis
Infants with XLA will present with what?
Recurrent otitis media
Sinopulmonary infections
Pneumonia
Adults with XLA will present with what?
Skin infections caused by staphylococcus and group a streptococcus
Chronic upper & lower respiratory infections
Define allotype
Minor amino acid differences in the constant domains of antibody molecules, dictated by genetic inheritance
ie) Paternity test
Define idiotype
Antigen-recognition portions of immunoglobulin molecule specific to unique antigens we have been exposed to
*EVERY antibody has a different idiotype
Define isotype
5 classes of immunoglobulins:
IgG, IgA, IgM, IgE, IgD
Symptoms associated with hyper-IgM syndrome
Recurrent sinopulmonary infections
- Pneumonia
- Sinusitis
- Otitis Media
