Chapter 6 Part 2 Flashcards
Autoimmune diseases effect mostly?
Woman
-IgG4 diseases effect men
Do autoantibodies mean there is an autoimmune disease
no, could be something else
3 things need to be met for autoimmune
- Immune reaction for self
- Not secondary to tissue damage (needs to be primary)
- Absence of other causes
Systemic diseases discussed in this chapter?
- Systemic Lupus erythematosus
- Rheumatoid arthritis
- Systemic Sclerosis (Sjogren syndrome)
- Polyarteritis nodosa
- Inflammatory myopathies
How does the immune system generate autoanitbodies?
Somatic recombination remember?? We need to eliminate these
There are 2 types of immune tolerance, what are they?
- Central (thymus and bone marrow)
2. Peripheral
How does central tolerance eliminate autoanitbodies (t-cells)?
- T cells for self are apoptosed in thymus.
2. Some CD4 cells allowed to live as regulatory T-cells
Central tolerance for B-cells?
- RECEPTOR EDITING is how B-cells are fixed.
2. Apoptosed if not
What is another word for peripheral tolerance?
- Anergy
How does peripheral tolerance work?
- Lymphocytes for self rendered functionally unresponsive
- eliminate co-stimulater after APC presentation. - Without TH, B-cells don’t function adequately
What allows fetus to be accepted?
Regulatory T-cells
Where are immune privileged sites?
- Testes, eyes, Brain
2. Sites where Ags are hidden from immune system
Changes contributing to autoimmunity (3)
- Defective tolerance
- Abnormal Ag display
- Inflammation or initial innate immune response
What disease is associated with the HLA-B27?
Ankylosins spondylitis (greater liklihood of happening)
HLA -DQA1?
Celiac disease
Role of Infections leading to autoimmune (the dark side): (3)
- Infection provides co-stimulation needed to cause self-antigen
- Molecularmimicry: microbe that looks like self Ag
- Viruses: (EBV or HIV) can drive B-cell activation that causes problems
Role of infections (the good side):
- Infections can help develop immunity.
2. Infections can decrease IL-2 and reg T-cell
What common disease decreases the likelihood of autoimmune problems?
Type 1 diabetes
Gen features of Autoimmune (AI)
- Chronic
- Relapse
- Damage=progressive
- Epitope spreading (1 bad Ag causes tissue damage and then stim other Abs
- Abnormal/excessive Th1 and 17
This disease effects skin, joints, kidney and serosal membranes. Pt has a malar rash, oral ulcers, renal problems and tests positive for syphilis.
Systemic Lupus Erythematosus (SLE)
Specific Abs for SLE?
- Double stranded DNA
2. Smith (SM) Ag
Antinuclear ABs are found in all AI and can be for? (4)
- DNA
- Histones
- Non-histone proteins on RNA
- Nuclear Ags
What can cause a false-+ syphilis test in SLE?
Antiphospholipid Abs
VDRL
What else can Antiphospholipid Abs do?
Cause hypercoagulable PTT test
What drugs are associated with SLE? (3)
- Hydralazine
- Procainamide
- D-penecillamine
What is linked to anti-DS DNA and Anti smith?
HLA-DQ
what in the Env may cause SLE?
UV-light
Morphologic effects of SLE are seen where? (5)
- Blood vessels
- Joints
- Kidneys
- Skin
- Pericardium/serosal surfaces
What are the morphologic changes of blood vessels?
Acute necrotizing vasculitis of small blood vessels
What are the morphologic changes of Joints?
Non-erosive synovitis, Just inflammed
!Rheumatoid arthritis is deformed joints!
What are the morphologic changes of Kidneys
Glomerular lesions related to the immune complex
What are the morphologic changes of Skin
Butterfly rash on face!
What are the morphologic changes of Pericardium/serosal surfaces
Inflammation
- Acute = fibrisous exudate
- Later = thickened
SLE can cause what cardiac problems?
- Tachycardia (due to myocarditis)
- Coronary artery disease
- Valvular abnormalaties
Other organs effected by SLE (3)
- CNS (due to vasculitis of small blood vessels)
- Splenomegaly
- Liver: pleural effusion/pleuritis
Clinical features of SLE
- Young woman
- Renal involvement (blood/protein in urine)
- Increased infections
- Disease can flare (corticosteroids help)
What is associated with Raised skin lesions that are deep and promote scarring?
- Chronic Discoid Lupus
What is associated with wide spread rash and no scars?
Subacute Cutaneous Lupus
Drug induced lupus
- Hydralazine
- Procainamide
- D-penecillamine
- Spare CNS and Kidneys
Pt comes in complaining of dry eyes (keratoconjuctivitis sicca) and Dry mouth (xerostomia):
What is the disease and what causes these symptoms
- Sjogren Syndrome
2. Destruction of lacrimal and salivary glands
Will you find Sjogren syndrome on its own?
Generally not. Usually in conjunction with other diseases
How do you diagnose Sjogren syndrome?
- Biopsy the lip and look for intense lymphocytic response
- Early onset = T and B mix
- Late = mostly B
Sjogren syndrome mostly effects who?
Women ages 50-60
This disease causes widespread damage to small blood vessels, progressive interstitial and perivascular Fibrosis in the skin and organs.
Pt with thick skin and Raynaud phenomenon.
What is the disease?
What causes death?
- Systemic Slerosis or Scleroderma
2. Fibrosis of kidney, heart or pulm
Clinical features of Scleroderma? (6)
- Skin Thickening
- Raynaud phenomenon (vasoconstriction of extremities and discoleration in fingers)
- Dysphasia from esophageal fibrosis
- Resp diff
- Myocardial fibrosis
- Renal issues
Pt with calcinosis, Raymond phenomenon, esophagea and scleradoma issues?
CREST syndrome.
-Limited form of scleroderma
AI more likely in men?
IgG4 related
-Autoimune pancreatitis
What is the major factor in Human organ transplants?
HLAs
Rec of alloantigins in organ grafts, direct vs indirect?
direct: both CD8 and CD4
Indirect: CD4 only (IFN-gamma)
Acute cellular rejections include
- Cytokines (CD4+ T-cells)
2. Increase vasc. perm and local mononuclear cells
Chronic rejection includes?
- Lymphocytes react against alloantigens in vessel walls
2. Secrete cytokinse for local inflammation
Hyperacute rejection includes
- Preformed antidonor Abs
2. Extremely rapid
Acute ab-mediated rejections (2)
- Antidonor abs produced after transplant
2. graft vasculature is targeted
Chronic AB-mediated
- Insidious
2. Also vascular components
How to increase graft survival? (5)
- HLA matching
- Immunosuppressive Therapy
- T + B cell depleting Abs
- Pooled IgG
- Plasma Pherisis (pull out plasma from blood)
HLA matching required for Kidney? (3)
HLA A, B and DR
-not done for liver, heart or lungs
Immunosuppressive Therapies include? (2)
- Steroids = decreased inflammation
2. Mycophenolate mofetil = inhb lymphocytes
This virus can reactivate, infect renal tubules and cause graft failure
Polyoma Virus
Infections that increase AI risk? (3)
- EBV-induced lymphomas
- HPV
- Kaposi Sarcoma (HHV8)
Where are hematopoitic cells taken from?
Peripheral blood (use colony stimulating factor to generate more stem cells)
What is required for a bone marrow transplant?
Need to destroy immune system of recipient
Graft vs host disease: Acute (2)
- Days to weeks.
2. Effects Immune system, skin, liver and intestines
Graft vs host disease: Chronic
- Involution of thymus (some autoimmunity)
- gen same as acute but worse
Graft vs host disease: is mediated through? (2)
- T-lymphocytes (if donor t-lymph killed than GVHD removed)
2. If you remove T-cells, Leukemia could come back and increase risk of graft failure
B-cell related Immunodeficiency syndromes? (4)
- X-linked Agammaglobulinemia
- CVID
- Hyper-IgM syndrome (CD40L)
- IgA deficiency
T-Cell Related Immunodeficieny syndromes (4)
- APA deficiency
- X-linked SCID (gamma chain)
- DiGeorge Syndrome
- MHC Class 2 deficiency
What disease is a bubble boy?
What happens to da bboy?
- Severe combined Immunodeficiency (SCID)
2. Pro T-cell can’t become Immature T-cell thus effecting T-cell development
Features of SCID?
- X-linked
- Infants w/early thrus
- Pt dies w/out bone marrow transplant
Disease that is due to fail of B-cell precurssors and when do you see it?
- X-linked Agammaglobulinemia
2. At 6 months (when mothers Abs are gone)
X-linked Agammaglobulinemia: do pt have Igs?
NOOOOO!
X-linked Agammaglobulinemia: what is associated (3)
- giardia
- Blood stream viruses
- AI arthritis
X-linked Agammaglobulinemia: Tx
Provide Immunoglobins
Disease associated with a failure of 3rd and 4th pharyngeal pouches to close, t-cell deficiency and tetany.
DiGeorge syndrome
DiGeorge syndrome features (4)
- Fail of 3rd and 4th pouch to close
- T-cell deficiency
- Hypoparathyroid = Hypocalcemia and tetany
- abnormal mouth and ears
Can’t produce IgE, IgG or IgA
Hyper IgM syndrome
Hyper IgM syndrome Features:
- CD40L mutation (Th to B messed up)
- X-linked
- Pyogenic infections
What happens if IgM reacts w/blood cells?
hemolytic anemia
Hypogamma globulinemia (blocking IgG) is a result of what disease?
Common Variable Immunodeficiency (CVID)
CVID-do B-cells become plasma cells?
No, but they are normal
Find this disease with blood transfusions
Isolated IgA
IgA is usually
asymptomatic which is why you find it in transfusion pts.
Immunodeficiencies Associated w/systemic diseases (2)
- Wiskoff-Aldrich syndrome
2. Ataxia Telangiectasia
Wiskoff-Aldrich syndrome: facts (3)
- X-linked
- Thrombocytopenia
- Hematopoietic stem cell transplant = Tx
Ataxia Telangiectasia: facts (3)
- Autosomal Recessive
- Abnormal gait and vascular malformations
- neurologic issues and increased tumors
Acquired Immunodeficiency syndrome (AIDS): caused by?
HIV and transported by sexual, needles, mother to infant
2 forms of HIV
- HIV 1 (Developed nations and Central america)
2. HIV 2 (3rd world)
Virus core proteins of HIV
- Major Capsid Proteins-P24 (ELIZA test for this)
- copies of RNA
- Viral Enzymes
HIV Matrix protein?
p17
Proteins studding HIV envelope?
Gp120 and GP41
HIV infection involves what cells?
- T cells
- Dendritic Cells
- Macrophages
Chemokine receptors for HIV isolates (3)
- R5 => CCR5
- X4 => CXCR4
- R5X4 => dual tropic
R5 => CCR5?
- Monocytes
2. Acute strain
X4 => CXCR4
- T-cells
2. gradually accumulates
HIV infects…
- Memory and active T-cells
2. Can’t infect Naive T-cells
Why can’t HIV infect Naive T-cells?
ApoBEC36 gene/enzyme blocks it
-HIV’s VIF is learning to counteract this
HIV thrives when…
- Host T-cell and macrophages activated
- Stim NF-kB and increase monocytes
Polyclonal B-cells can
cause problems
Macrophages from HIV1… (2)
- depend on VPR gene
2. Resevoirs of infection
Dendritic Cells…
- Bring mucosal dendritic cells to lymph and CD4+
Follicular cells…
- HIV resevoir
2. Trap virions and maintain CD4+ ability to infect
