Chapter 6-Immuno and Hypersensitivity Flashcards
What are Langerhans cells
Immature dendritic cells in the epidermis
What is the high affinity receptor on Mast cells and basophils
FcER1
How many days after antigen exposure does inflammation occur in type 3 hypersensitivity
10
What are the characteristics of the Ig alpha (CD79 alpha and beta) and beta in the BCR complex
Invariant proteins responsible for the signal transduction into the cell
What are drugs that can activate mast cells
Codeine, morphine, adenosine, melittin (in bee venom)
What are the characteristics of the autoimmune diseases
Chronic, with relapses and remissions, and damage is progressive
Innate immune receptors target what general characteristics of PAMPS on microbes
Microbial components that are essential for infectivity and thus can not be mutated to evade recognition
What disease is associated with HLA-B27
Ankylosis spondylitis
Many autoimmune diseases are associated with which HLA alleles
Class 2
What percentage of cells do natural killer (NK) cells make up in peripheral lymphocytes
5 to 10%
What percentage of reactions are nonatopic allergies
20-30% of immediate hypersensitivity
What are plasmablasts
Antibody secreting cells in the peripheral blood
How does the crosslinking in mast cells lead to compound production
1) Cross linking activated phospholipase A2
2) PL A2 take phospholipids into arachidonic acid
3) Activation of prostaglandin and leukotriene pathways
What is the gene that is most commonly associated with autoimmune diseases
PTPN22 (because the association with RA)
What are the primary costimulatory molecules for T cells
Binding of CD28 on T cells with B7/ CD80/86 on APCS
What cytokines activate NK cells and what are their function
IL2, 15 (Stimulate proliferation-NK from T line)
IL-12 (killing and IFN-gamma secretion)
What genes are located in 5q31
IL 4, 5, 9, 13, GM-CSF all which have a higher relation to asthma
What is the purpose of proteoglycans (chondroitin sulfate) in mast cells
Helps to package and store the amines
Which portion of MHC 2 does CD4 bind to
Beta 2
T helper cells use and stimulate other cells via which mechanism
Cytokines with CD40L binding to CD40 on APCs
What is occurring during the deposition of immune complexes
Antigen-antibody complexes are deposited into tissue. These complexes are of medium size, formed in slight antigen excess, and most pathogenic
What are the characteristics of the TCR
Noncovalent linked polypeptides (6 total)
CD3 and zeta chains are invariant (identical) in all cells
Where are C-type Lectin receptors (CTRs) located and what is their ligand
Expressed on the plasma membrane of macrophages and dendritic cells, where they detect fungal glycans
Inflamasome activation activates which caspase to form which product
Caspase 1 to produce IL-1
What receptors are not expressed on NK cells, and what kind of granules do they have
No TCRs or Igs, but contain azurophilic granules
What are the two receptors that help to limit autoreactive T cells
- CTLA4
- PD1
What are the characteristics of the late phase reaction of type 1 hypersensitivity
Infiltration of eosinophils, neutrophils, basophils, monocytes and CD4 T cells
In lymph nodes, where are the T cells located
Paracortex, next to the follicles
What are the likely sites of antigen-antibody complexes to be deposited
Where blood is filtered at high pressure into urine and synovial fluid, aka joints and glomeruli
What are the three phases in Type 3 hypersensitivity
1) Formation of immune complexes
2) Deposition of Immune complexes
3) Inflammation and tissue damage
Where are mature T cells found
Blood and T cell zones of lymphoid tissue
What are the four circumstances where Ab mediated cell destruction and phagocytosis result in type 2 hypersensitivity
1) Transfusion reaction
2) Erythroblastosis fetalis
3) Autoimmune hemolytic anemia
4) Drug reactions
What is a trigger for bronchial asthma
Viral infections
What are the characteristics of the MHC 1 chains
- Polymorphic alpha chain
- Nonpolymorphic beta2 chain
If a T cell expresses BIM, what likely happened
It was a self reactive T cells that is signaled to undergo apoptosis
What are the domanent cells of chronic inflammation
Macrophages
What are the characteristics of the MHC 2 chains
Alpha and beta are both polymorphic
For MHC1, which regions make up the peptide binding cleft
Alpha 1 and alpha 2
What is the timing fro the immediate reaction in type 1 hypersensitivity
Within minutes of allergen exposure
What is that cause of autoimmune lymphoproliferative syndrome (ALPS)
Mutations in the FAS receptor gene
What are the 4 major types of innate immune receptors
1) TLRs
2) NOD like receptors (NLRs)
3) C-type Lectin receptors (CLRs)
4) Rig-like receptors (RLRs)
What is CD21
Complement receptor 2 (CR2)
What is the timing of the late phase reaction in type 1 hypersensitivity
2 to 24 hours without the need of antigen exposure
What are the results of the enzymes released by granules in mast cells
Tissue damage, Kinin production, activation of complement proteins
What tends to be higher in atopy individuals
IgE and Th2 levels
What is the result of vasoactive amines being released
1) Smooth Muscle Contraction
2) Increased vascular permeability
3) mucus secretion of nasal, bronchial, and gastric
What is the significance of N-formylmethionyl
Initiates the transcription/creation of proteins in bacteria and mitochondria. Allows recognition of bacterial proteins and chemotaxis to them
Where are RIG-like receptors (RLRs) located and what are their ligands
Located in the cytoplasm of most cells where they detect viral nucleic acids and prevent replication
What is the condition of erythroblastosis fetalis
Antigenic difference between the mother and fetus, where the IgG antierythrocyte antibodies of the mother crosses the placenta and lysis fetal RBCs
What is the function of autoimmune regulator
Aka AIRE, which stimulates expression of self antigen
What is the role of prostaglandin D2 in the type 1 immediate hypersensitive reaction
Most abundant cyclooxygenase product and produces intense bronchospasms and mucus production
What are the enzymes released by mast cells
Neutral proteases (Chymase, tryptase) Acid hydrolases
What is responsible for the adhesion of T cells to APCs
Integrins
What do the HLA for MHC1 code for
The polymorphic portion of the Alpha chains
What is occuring in the formation of immune complex during type 3 hypersensitivity reactions
Protein antigen triggers an immune response, where about a week later, antibodies are made and form the antigen-antibody complex
What are systemic autoimmune diseases usually involving and what are the alternative names for it
Usually involve blood vessels and connective tissue. This leads to the alternative name of collagen vascular disease or connective tissue disorder
What is the function of the alpha3 portion of MHC1
It is nonpolymorphic and binds to CD8
What is the cause of autoimmune polyendocrinopathy
Mutations in the AIRE gene
How was peptides processed for MHC1 molecules
Cytosolic proteins are taken up and transported into the ER, where they are bound to freshly synthesized MHC
What determines being prone to immediate hypersensitivity reactions
Genetics
What percentage of T cells are CD4+
60%
What are the three requirements for something to be considered a autoimmune diease
1) Presence of immune reaction specific for self antigen or tissue
2) Evidence of damage is the primary pathogenic condition
3) Absence of any other well defined disease
What size of stimulus is required to illicit system anaphylaxis
Small amounts, where even skin testing amounts can trigger
What are the receptors that are characteristic of Natural killer cells (NKs)
1) CD16 (Fc receptor for IgG)
2) CD56
What type of cells have the antigen receptor genes and which cell lines have rearranged expression
All cells have the antigen receptors in the germline, but only immune cells express them, and only B/T lines have rearranged antigen receptors
What are the two major products of eosinophils and what are their functions
Major basic protein, cationic protein which both damage tissue
What is nonatopic allergy
Immediate hypersensitivity reactions to non-antigenic stimuli, ugh as extreme temperatures and exercise. This does not involve IgE or Th2 cells
Where do plasma cells reside
Bone marrow and lymphoid tissue because they do not need to migrate to infection sites
A defective PTPN22 results in disease via which mechanism
Defective Protein tyrosine phosphatase can not remove phosphate from tyrosines, so tyrosine kinases run unchecked and result in excessive lymphocyte activation
What is the primary mechanism responsible for depletion of cells coated with Abs
Phagocytosis
What are the triggers for activation of mast cells
Cross linking of IgE, C5a, C3a (aka anaphylatoxins), IL-8, drugs, and physical stimuli
Which lymph node is responsible for the responses to blood borne antigens
Spleen
What are the cytokines that cause THelpers to differentiate into Th17
IL1, 7, 23(close relative of 12)
What is the treatment for late phase type 1 hypersensitivity
Broad spectrum anti inflammatory drugs (steroids) rather than antihistamine (the mediator of the first phase)
What are the 3 stages involved in the innate immune system
1) Recognition of the microbe/damage
2) Activation
3) Elimination of unwanted substances
What is the function of dendritic cells
In the Initiation of the immune response via presentation, but not in the destruction of pathogens
What is the most important mast cell derived amine
Histamine
What infection is highly associated with atopic dermatitis
Bacterial skin infection
What percent of lymphocytes in the blood does mature T cells make up
60-70%
Which disease is associated with HLA-A
Hereditary hemochromatosis
How is antigen receptor diversity created
Somatic recombination of genes that code for receptor proteins
What is the main location of isotype switching
Germinal centers
What is the treatment for autoinflammatory syndromes
IL-1 antagonists
What is the function of recombination activating genes (RAG 1 and 2) and what is the result of a defect
Responsible for the recombination of gene segments in the creation of lymphocyte receptors. Defects result in lack of mature lymphcytes
What is the conditions of autoimmune hemolytic anemia, granulocytosis and thrombocytopenia based from
Autoantibodies against their own blood/platelet cells
Polymorphism with PTPN22 are associated with which disorders
RA, Type 1 diabetes, other autoimmune
What is the cause and result of autoinflammatory syndromes
Gain of function mutations in the NLRs result in periodic fever syndromes
What is the postulated mechanism for uveitis and post-traumatic orchitis
Damage or traumatic causing the release of sequestered antigens
What does contact with urushiol
The antigenic component of poison oak, causes vascular dermatitis
What is the result in FOXP3
Autoimmune disorders, leading to a condition known as Immune dysregulation, polyendocrinopathy, enteropathy, X linked, or IPEX
What are the two transcription factors that are activated by TLRs
1) NFkB (Cytokine synthesis and adhesion molecules for leukocyte recruitment)
2) interferon regulatory factors (IRFs)- production of type on interferons (alpha and beta)
Polymorphism in the gene NOD2 results in which disease
Crown disease
Where are eosinophils derived from
Bone marrow
What are the characteristic of systemic anaphylaxis
Vascular shock, widespread edema, difficulty breathing
What percentage of T cells are alpha Beta TCR
95% of T cells
What is perivascular cuffing
Accumulation of CD4 T cells and macrophages in the perivasculature
What are the two mechanisms of Type 4 hypersensitivity
1) CD4 mediated inflammation (major component)
2) CD8 destruction
What is the family of activating receptors on NK cells and what do they respond to
NKG2D, and respond to infection and DNA damage
Necrotizing vasculitis aka fibrinoid necrosis are characteristic of which type of hypersensitivity
Type 3 hypersensitivity
In the spleen, where are the T cells located
Periarteriolar lymphoid sheath
What is the cause of allergic asthma
Late phase type 1 reaction
What is the relationship between HLA-B27 and ankylosing spondylitis
100-200 times more likely to develop disease with this HLA
What mechanism of cytokines normally work through
Autocrine and paracrine, and very rarely endocrine
During a type 4 hypersensitivity, what is the function of TH1 and Th17
Th1= activation of macrophages Th17= Activation of neutrophils
What is the immediate reaction of a type 1 reaction characterized by
Vasodilation, vascular leakage, smooth muscle spasm or glandular secretion
What are the results of late phase type 1 hypersensitivity reactions
-Bronchospasms, edema, Mucus secretion, smooth muscle spasms
What is the major lipid mediators in immediate hypersensitivity
Arachidonic acid
Where are cutaneous and mucosal lymphoid systems located
Epithelia of skin,GI and respiratory systems
What receptor does EBV use to enter and infect B cells
Complement receptor 2
What are the results seen from inflammation in type 3 hypersensitivity
Fever, hives (urticaria), joint pain (arthralgias) LN enlargement, proteinuria
What percentage of circulating peripheral lymphocytes do mature B cells make up
10-20%
During inoculation of PPD, what is the accumulation of cells characterized by
PPD aka, tuberculin causes Mononulcear cells (CD4 cells, and macrophages)
What are the locations of TLRs
Plasma membrane and endosomal vesicles
Atopy individuals have what percentage of family history of allergies
50%
What are the three locations of PRRs
Cytosol, endoscope, membranes
What are the phagocytes in the blood
Monocytes and neutrophils
What are the three things released from the granules of activated mast cells
Vasoactive amines, enzymes, proteoglycans
What potion of the MHC2 make up the peptide binding cleft
Alpha 1 and beta 1
What are the location of basophils
In blood circulating in small amounts
How does polymorphism in the NOD2 gene result in inflammatory bowel syndromes
Mutation in MOD2, so it is unable to detect commensal bacteria, so there is chronic inflammation
How does EBV and HIV lead to autoimmunity
Causes polyclonal activation and autoantibodies by releasing self antigens, then structurally altering them so they are able to activate T cells
What is atopy
Increased propensity to develope immediate hypersensitivity reactions
What does the gene PTPN22 code for
Protein tyrosine phosphatase
Which disease is associated with HLA-BW47
21-hydroxylase deficiency
What are the ligands for the NOD-like receptors (NLRs)
1) Necrotic cell byproducts (ATP,uric acid)
2) Ion Disturbances (potassium loss)
3) Microbial products
What is fibrinoid necrosis associated with
Immune complex injury
What is epitope spreading
Immune responses to one self antigen causes the release of other antigens and newly activated self lymphocytes
What is the role of surfactant in immune protection
In the lungs and serves as an innate component against inhaled microbes
In the spleen, where are the B cells located
Follicles
Many NLRs activate inflammation via which structure
Inflammasomes
