Ch6 Flashcards
NF-Kb TF does what when turned on?
Causes production of cytokines leading to destruction of microbe by phagocytosis
T cell receptor has what structure?
Alpha and beta chain with disulfide bonds
Each T cell receptor is linked to what? 2
CD3 complex
2 zeta chains
CD3 complex has what in it?
gamma
delta
epsilon
First signal to T cell?
Antigen/MHC presentation
Second signal to T cell?
CD28 and B7/CD80/CD86
Polyclonal T cell proliferation is described how?
Non-neoplastic
Monoclonal T cell proliferation is described how?
Neoplastic
CD means what?
Clusters of differentiation
CD3 and CD5 define what type of cells?
T cell
CD19 and CD20 define what cells?
B cell
T lymphocytes are what percentage of lymphocytes?
60-70
B lymphocytes are what percentage of circulating peripheral lymphocytes?
10 to 20
B cells form what when stimulated?
Plasma cells that secrete Ig’s
What 3 main receptors do B cells have?
Complement receptor
FC receptor
CD40
What is the complement receptor for Epstein-Barr?
Type 2 complement receptor (CR2, CD21)
What are the two signals to a B cell when interacting with external free antigen-complement?
- Igalpha and Igbeta coreceptor signaling
2. Complement binding to CR2/CD21
Two types of dendritic cells?
Interdigitating Dendritic cells
Follicular dendritic cells
Interdigitating dendritic cells have what important title?
Most important APC for initiating T cell response again protein antigens
Immature dendritic cells in epidermis are called what?
Langerhans cells
Nucleus of dendritic cell is described how?
Reniform
What receptors do follicular dendritic cells have?
Fc receptors for IgG and C3b
What do follicular dendritic cells do?
Present antigens to B cells
How are macrophages involved in CMI?
T cells activate them to let them kill microbes
How are macrophages involved in HI?
Phagocytose and destroy microbes that are opsonized by IgG or C3b
What makes NK cells different?
Can kill infected cells without prior exposure to a microbe or antigen
NK cells are positive for what CD’s?
CD16 and Cd59
CD16/FCgammaRIII is the receptor for what?
NK IgG receptor
What main cytokine do NK cells release?
IFN-gamma to activate macrophages
What stimulates proliferation of NK cells?
IL-2 and IL-15
What stimulates NK cells to kill and secrete IFN-gamma?
IL-12
More than half of the body’s lymphocytes are where?
Mucosal tissues
B cells are concentrated where in lymph node?
Follicle cortex of lymph nodes possibly with germinal center
T cells are where in lymph nodes?
Paracortex
Follicular dendritic cells are where in lymph node? 2
Follicles (present to B) and paracortex (present to T)
Where are T cells in the spleen?
PALS
Where are B cells in spleen?
Follicles
Where do plasma cells go to respond to an antigen?
Stay in lymph node
Where are the genes for HLA encoding?
Chromosome 6
what type of antigen do MHC-1 molecules present?
Intracellular, usually viruses
Class I MHC have what genes?
HLA-A, HLA-B, HLA-C
Class II MHC have what genes?
DP, DQ, DR
What removes the CLIP from MHC II?
HLA-DM
How is the expression of HLA described?
Codominant: one allele from mom, one from dad
Ankylosing spondylitis and postinfectious anthropathies are associated with people that have what antigen?
HLA-B27
Rheumatoid arthritis involves what HLA allele?
DR4
Type 1 diabetes involves what HLA allele? (3)
DR3
DR4
DR3/DR4 (the worst risk)
21-hydroxylase deficiency is involves with what antigen?
HLA-Bw47
Hereditary hemochromatosis is associated with what antigen?
HLA-A
What mainly makes the cytokines for innate immunity? (3)
- macrophage
- dendritic
- NK cells
What are the 6 cytokines of innate immunity?
- TNF-alpha
- IL-1
- IL-2
- Type 1 IFN’s (alpha and beta)
- IFN-gamma
- chemokines
What are the cytokines of adaptive immunity?
- IL-2
- IL-4
- IL-5
- IL-17
- IFN gamma
What makes most of the adaptive cytokines?
CD4+ lymphocytes
Early response of CD4 t cells to antigen is what? (2)
Secrete IL2
Express receptor for IL-2
What mediates functions of helper T’s?
CD40
Cytokines
memory cells respond when?
When re-exposed to an antigen
What is the main basis of HS disorders?
Imbalance in effector mechanisms of immune responses and control mechanisms that limit these responses
What cells play a role in initiation and propagation of Type I hypersensitivity?
TH2 cells –> promote IgE production
What triggers mast cells to activate? (2)
- Cross linking IgE Fc receptors
2. C5a and C3a
What happens in immediate reaction of Type I?
Vasodilation, leaky vessels due to prostaglandin and leukotrienes
Histamine has what effect? 3
- Vasoconstriction
- Leaky vessels
- increase mucus
Leukotrienes C4 and D4 do what?
Vasoactive and spasmogenic
Leukotriene B4 does what?
Chemotaxis for leukocytes
Prostaglandin D2 does what? 2
Bronchospasm
Increased mucus secretion
What cells cause late response of HS Type I?
Eosinophils
What is it called if you are more likely to have Type I immediate eractions? (2)
- Higher serum IgE
2. More IL-4 producing Th2 cells
Different Type II reactions? 4
- transfusion rxn
- Autoimmune hemolytic anemia
- agranulocytosis
- thrombocytopenia
Type II is due to what pathways?
Complement
Fc-receptors
Results of Type II HS?
Glomerulonephritis
Vascular rejection
5 examples of Type II?
Myasthenia gravis Graves disease acute rhematic fever Goodpasture Autoimmune hemolytic anemia
Examples of Type III? 4
Systematic lupus erythematosus
Poststreptococcal glomeruonephritis
Serum sickness
Arthus reaction
What is arthus reaction?
Localized tissue necrosis from acute immune complex vasculitis
Type IV HS is mediated by who?
CD4 and CD8 t cells
Examples of type IV?
Type 1 diabetes multiple sclerosis rhematoid arthritis crohn disease contact dermatitis
What is granulomatous formation?
DTH due to persistent antigens in which CD4 cells are replaced by macrophages that form giant cells
CTL is important for what? 2
- Virus infections
2. tumor rejection
What enzymes do cytotoxic T cells have?
What special killing receptor
Perforins and granzymes
Fas
3 requirements for autoimmunity?
- Presence of an immune reaction specific for self antigen
- Reaction is of primary pathogenic significance
- Absence of another well-defined cause
Autoimmune diseases encompass what HS diseases?
II, III, IV
What is self-tolerance?
Lack of response to one’s own antigens
What causes anergy in B cells?
T cells?
B: Encounter self antigen but have no T cells, so unable to respond and are excluded from follicle
T: If antigen is presented without costimulator
Regulatory T cells have what protein?
Mutation in this causes what?
FoxP3
IPEX
What regulatory T cell gene has polymorphisms in MS?
CD25
What does PTPN-22 cause? 2
RA
Type 1 DM
NOD-2 causes what?
Crohn
IL-2 and IL-7 receptor alpha chain defect causes what?
MS
What characterizes SLE?
Anti-nuclear Autoantibodies against all parts of body
What is the lupus pneumonic?
Malar Rash Discoid Rash Serositis Oral Ulcers Arthritis Photosensitivity Blood abnormalities Renal ANA antibodies Immune abnormalities Neurologic
Antinuclear antibodies are directed against what? 4
DNA
Histones
Proteins on RNA
Nucleolar antigens
Test for ANA’s?
Indirect immunofluorescence or EIA
Homogeneous ANA’s find what?
Chromatin and histones
Rim ANA’s find what?
dsDNA
Speckled pattern ANA’s find what?
Histones and RNP’s
Which is most common ANA pattern?
Speckled
Nucleolar ANA pattern means what?
RNA
antiphospholipid antibodies are found in what percentage of SLE patients?
40-50
This anti-phospholipid of SLE is used in detecting what disease?
Syphilis
What happens to people with anti-phospholipid SLE?
Recurrent spontaneous miscarriages
Focal cerebral or ocular ischemia
What is the genetic link of SLE?
HLA-DQ
When does SLE show up in patient?
20 or 30’s
Who gets SLE more, females or males?
Females 9 to 1
Lupus nephritis as a result of SLE means what?
Immune complex deposition in glomeruli
Five patterns of lupus nephritis?
- Minimal mesangial (Class I) – Mesangial proliferative (Class II) – Focal proliferative (Class III) – Diffuse proliferative (Class IV) – Membranous (Class V)
Classes I and II of lupus nephritis see an increase in what?
Mesangial matrix and cells due to proliferation and complex deposition
Class III of lupus nephritis have glomeruli that show what?
- crescent formation
- fibrinoid necrosis
- Proliferation of endothelial and mesangial cells
Which is most severe class of lupus nephritis?
Class IV
In class IV lupus nephritis how many glomeruli are involved? Is this class symptomatic?
over 50%
Yes: HTN and renal insufficiency
Class V lupus nephritis sees what?
Diffuse thickening of capillary wall causing very severe proteinuria or nephrotic syndrome
Deposits in SLE can be identified with what?
Immunofluorescence
Membranous lupus nephritis deposits where?
Subepithelial
Focal and diffuse proliferative deposit where?
Subendothelial
What lesion results from class III and IV?
Wire loop
Main characteristic of SLE on skin?
What makes it worse?
Facial butterfly
Sunlight
What happens to heart in SLE?
Valvular endocarditis (Libman sacks)
What is seen in nearly every case of SLE?
Hematologic derangement: Anemia or thrombocytopenia
Chronic discoid lupus drythematosus is similar to SLE how?
Skin manifestations are the same
In Chronic DLE, what is the main sign?
Skin plaques surrounded by an elevated erythematous border of face and scalp
Subacute cutaneous lupus erythematosus is similar to SLE how?
Mild systemic symptoms similar
What is the mutation in subacute cutaneous lupus erythematosus?
Antibodies to SS-A antigen and HLA-DR3 genoptype
Sjogren syndrome has what two main symptoms?
Dry eyes
Dry mouth
What are the two forms of sjogren syndrome?
Primary = sicca syndrome Secondary = sjogren + another autoimmune disease
What happens in Sjogren syndrome?
Lymphocytic infiltration and fibrosis of lacrimal and salivary glands with ANA’s against SS-A and SS-B
What is Mikulicz syndrome?
Anything that can cause a lacrimal and salivary gland enlargement
What needs to be done to diagnose sjogren syndrome?
Biopsy of lip
Systemic sclerosis/Scleroderma means what?
Fibrosis throughout the body and mainly skin
Two cattegories of sclerosis?
Diffuse
Limited
