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Systemic Lupus Erythematosus, CD4+ T cell, Complement protein, microbial…
Systemic Lupus Erythematosus
Pathogenesis
Trigger
Susceptibility genes alters B and T cell
Production of self antibodies
Immune complexes
Binds to Fc receptors of to B cell
:arrow_up: Type I Interferons :arrow_up:
More production of anti-nuclear IgG antibody
Binds to Fc receptors of to dendritic cell
Apoptosis of cells
Increased burden of nuclear antigens
Risk factors
Environmental
Exposure to UV light
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Increases risk of
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Enhancing recognition by TLRs
DNA Altering
Modulate immune response
Apoptosis
SLE prefers the X gene (more in women)
Hydralazine, procainamide, D-penicillamide
Genetic
Familial association
HLA Association
Genetic deficiencies of classical pathway complement
Immunologic
Failure of B cell tolerance
CD4+ T cells contributes to production of pathogenic antibodies
Large amounts of IFN-a
TLR9 & TLR7 produces signals that activate B cells
BAFF promotes B cell survival
Tissue Injury
Type III Hypersensitivity
DNA-anti-DNA complexes detected in the glomeruli & blood vessels
Deposition of immune complex in different regions
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Theory
Type II Hypersensitivity
Exposed nuclei binded by anti nuclear antibodies
Binding of antibodies to cells and tissues
Signs and Symptoms
Butterfly rash on the face
Fever
Joint pain
Pleuritic chest pain
Photosensitivity
Infections
Coronary artery disease
Hematuria
Pancytopenia
Immune system
Innate
Cellular receptors
TLR
Function
Detects microbes to be ingested in endosomes
Cell surface
TLR1
Bacterial lipopeptides
TLR 2
Bacterial peptidoglycan
TLR 4
LPS
TLR 5
Bacterial flagellin
TLR 6
Endosomes
TLR3
dsRNA
TLR8
TLR7
ssRNA
TLR9
CpG DNA
Activities
Blocks microbial infections with barriers
Destroys microbes generally
Controlling and eradicating infections
Instructs the adaptive immune system
Reactions
Inflammation
Typical steps
Recognition of the infectious agent
Recruitment of leukocytes and proteins to the infected site
Activation of leukocytes and proteins to eliminate infectious agents
Control of reaction
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Cardinal signs
Calor (heat)
Dolor (pain)
Tumor (swelling)
Functio laesa (loss of function)
Rubor (Redness)
Function
Clear the host from agents of injury
Clear the consequences of injury
Mediators
Leukocytes
Complement proteins
Antibodies
Antiviral defense
Steps
Plasmacytoid dendritic cell
Type I IFN
IFN bind to receptor on infected or uninfected cell
RNAase production
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Phosphorylation of translation initiation factor
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Inihibition of viral gene expression and virion assembly
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Virus-infected cell
Components
NK cells
Complement system
Function
Opsonization and phagocytosis
Inflammation
Cell lysis
B cell response
Regulation
C1 Inhibitor
DAF
Factor I
Pathways
Classical
Lectin
Alternate
Mast cells
Cytokines
Dendritic cells
Plasma proteins
Phagocytes
Innate lymphoid cells
Epithelial barriers
Adaptive
Humoral
Function
Block infections and extracellular microbes
Steps
T-dependent
Follicular B cells
IgM recognizes antigen and go through phagocytosis
B cell shows presents antigen to T helper cell with MHC II
B cell proliferation
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T cell activation by IL-2 autocrine
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T-independent
B-1 cells, marginal zone B cells
Recognition of polysaccharide antigen
Activation and proliferation of B cells
Differentiation of B cells
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General
Antigen recognition
B lymphocytes activation
Proliferation
Differentiation
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Antibodies
Actions
Agglutination
Precipitation
Neuteralization
Complement fixation
NK cell activation
Opsonization
Types
IgA
IgM
IgG
IgD
IgE
Cell-mediated
Mechanism of action
Dendritic Cell with antigen
Recognition by CD4+ T cells
Differentiates into effector and memory cells
Effector and memory cells enter the circulation
CD4+ T cells recognizes MHC II
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CD4+ T cells recognizes MHC I
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Recognition by CD8+ T cells
Differentiates into effector and memory cells
Treatment
Hydroxychloroquine & chloroquine
Non-steroidal anti-inflammatory drugs
Corticosteroid
Reduces CD4+ T cells
Suppressing proinflammatory cytokines
Hypersensitivity
Classification
Antibody-mediated (Type II)
Cause
IgG and IgM binds to self antigens
Diseases
Myasthenia gravis
Graves
Pernicious anemia
Autimmune hemolytic anemia
Immune complex-mediated (Type III)
Cause
Deposition of immune complex and inflammation
Diseases
Systemic Lupus Erythematosus
Serum sickness
Reactive arthritis
Immediate (Type I)
Cause
IgE antibodies
Mast cells
Secretes
Protease
Prostaglandin & Leukotrienes
Histamines
Pro-inflammatory cytokines
Th2 cells
Eosinophils
Diseases
Anaphylaxis
Bronchial asthma
Allergic rhinitis
Food allergies
T cell-mediated (Type IV)
Cause
Th1 and Th17 produce cytokines that induce inflammation and activate phagocytes
Diseases
Rheumatoid arthritis
Multiple sclerosis
Diabetes Melitus I
Contact sensitivity
Causes
Autoimmunity
Reaction against microbes and environmental agents
Lymphatic system
Components
Lymphatic trunks
Right lymphatic duct
Throacic duct
Lymphatic capillaries and vessels
Lymph
Lymphoid organs
Thymus
Tonsils
Lingual
Pharyngeal
Palatine
Lymph nodes
Appendix
Peyer's patches
Defintion
System for drainage of excess fluid and leaked plasma proteins in the interstitial space
Function
Returnes large molecules
Maturation of WBC
Retruns excess interstitial fluid
To the bloodstream
Immune system
Lymph flow
Factors that increase
Increased permeability of the capillaries
increased interstisial fluid coloid pressure
Decreased plasma coloid osmotic pressure
Elevated capillary hydrostatic pressure
Extrinsic factors
Arterial pulse
External compression
Body movement
Excercising
Muscle contraction
CD4+ T cell
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Complement protein, microbial product