UPenn Anatomy Notes

Risks for SLE

Genetics, smoking, alcohol, autoimmune

mechanism of SLE

1. Usually, when cells are not able to be repaired after damage, apoptosis ensures
2. If these bad cells are NOT CLEARED efficiently, the nuclear material of these cells will be exposed to macrophages (cytoplasmic proteins-Ro, membrane-cardiolipin proteins, histones)
3. Overtime, immune system develops immunity against these nuclear material, by producing autoantibodies which can target our own cells
4. It is said complement protein deficiency can cause SLE

symptoms of SLE

Flare Ups (immunologic memory): when apoptosis exposes immune cells to imune system (i.e. sun, stress, surgery)

* Elevated T and B cell count (IL6 & IL10, B Lymphocyte stimulator)
* Women more at risk

Symptoms Include: Fatigue, Myalgia, Weight Loss, Fever, Butterfly Rash (50% of patients), photosensitivity, cognitive impairment, headaches, seizures, delirium, fibrosis, pleuritis, chest pain, hypertension, digestive issues

SLE Serum Markers

Autoantibodies, nuclear proteins, cell membrane components include (anti-ro, anti nRNP, anti-histone, anti ds DNA), reduced complement 3 and 4 protein

treatment of SLE

Management: Avoid light, reduce cardiovascular risk, weight loss, Vitamin D Supplements

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Drugs:


1. Tacrolimus: Inhibit IL2 production & function, suppress T-cell activity
2. Mycophenolate & Plantiopurine: Reduce lymphocyte activity
3. Belimumab: Inhibit BAFF/BLys
4. Glucocorticoids & NSAIDS: Suppress inflammation & pain;

complications of SLE

increased risk of Non-Hodgkin’s Lymphoma, Osteoporosis, Antiphospholipid Syndrome (1/3 patients w/ SLE)

symptoms of Dermatomyositis

Skin: Heliotrope Rash (purple/blue which can change to red on upper eyelids that is associated w/ edema)

Rash on Face (Malar)

Gottron’s Papules: Occur over joints on hands/feet, mistaken for warts but are softer

Calcinosis: Calcium deposits underneath the skin/within muscle

Shawl Sign: Redness Present over shoulder & back, photosensitive

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Proximal Muscle Weakness: Difficulty Climbing stairs, brushing hair, lifting objects out of chair; elevated muscle enzymes

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Inflammatory Myopathy, Muscle Biopsy (Perivascular inflammation & necrosis) - upregulation of MHC I on muscle fibers, increase immune system signaling, complement activation

treatment & complications of dermatomyositis

No FDA approved medications, but IV steroids, IVIG Methotrexate, MMF, Azathioprine, Cyclosporine, & Rituximab have all been used

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Complications: Sign of underlying disease, increased risk of lymphoma

two types of Scleroderma & overall problem

Limited Cutaneous Systemic Sclerosis & Diffuse Cutaneous Systemic Sclerosis

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Problems: Hardening of skin, a fibrotic disease that affects the skin in all areas; Presence of autoantibodies & Anti-SCL 70 antibodies

symptoms of limited cutaneous systemic sclerosis

C - Calcinosis

R - Raynaud’s - white, blue discoloration of fingertips & Vasoconstriction

E - esophageal dysmotility

S - Sclerodactyly, or restricted range/impairment of motion in joints

T - Telangiectasia - dilated blood vessels with fine appearance

fat pads lost

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\*\*ANTI-CENTROMERE ANTIBODIES PRESENT

Diffuse Cutaneous Systemic Sclerosis symptoms

CREST + INTERNAL ORGAN ISSUES (Lung problems, cardiovascular issues, kidney issues, scleroderma renal crisis with renal system)

diagnosis & treatment of sclerosis

Nailfold Capillaroscopy: Examine where base of fingernail meets skin, examine peripheral capillaries to indicate systemic sclerosis

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Treatment: Steroids, immunosuppressants, avoid smoking; skin stretching, avoid colds, therapy

* Nifedipine: Treat Raynaud’s
* Antacids: Stomach discomfort
* Analgesia: Joint pain
* Antibiotics: Skin infections

general mechanism of Psoriasis

a chronic autoimmune disease that speeds up the growth cycle of skin cells; typical skin appearance that primary care doctors recognize

* hyperproliferation of keratinocytes in epidermis; increase in epidermal cell turnover rate

symptoms of Psoriasis

raised plaques, rash, scaling spots, cracked skin that may bleed, itching, burning, soreness, cyclic rashes

types of Psoriasis

Plaque - most common, raised skin patches with scales

Nail - fingernails/toenails with abnormal nail colors and growth, may separate from nail bed

Guttate - young children, drop shaped spots on trunk & appendages

Inverse - groin, butt, breasts, cause smooth patches of inflamed skin worsening w/ friction & sweating; triggered by fungus

Pustular - rare, pus-filled blisters; occur in widespread patches or small areas on palms

Erythrodermic - rarest, peeling rash covers entire body that can itch or burn intensely

psoriatic arthritis

form of arthritis that affects those with psoriasis, lead to joint pain, inflammation, stiffness, swelling

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treatment: immunosuppressants, methotrexate

compare the epithelium of esophagus, stomach, small intestine

Esophagus: protection from abrasive effects of food

Stomach: Specialized for production of digestive acid/enzymes; contains cells to protect against self-digestion

Intestine: Specialized for absorption of nutrients; consists of absorptive cells known as enterocytes/goblet cells; secrete mucus for lubrication

lamina propria comparison across different parts of digestive system

Esophagus: Unspecialized, supports epithelium

Stomach: Not visible and fills interstices between gastric glands

Intestine: Occupies cores of villi, increase SA for absorption

muscularis comparisons

Esophagus: Muscle fibers/push food towards stomach

Stomach: Thin/pushes food through

Intestine: Thin, pushes food through gastrointestinal tract

sepsis

bacteria infects bloodstream when appendix ruptures

t follicular helpers vs. t-helper 1

t-follicular helpers help b cells become plasma cells while t-helper 1 activates macrophages & cytotoxic t cells

memory b cells vs. naive b cells

memory: present at greater precursor frequency, favor use of higher affinity IgG b-cell receptors; fight infections faster because more terminally differentiated

immunodeficiency compare & contrast

CVID: Deficiency of antibody response (IgG, IgM, IgA)

Severe Combined: Associated w/ viral/fungal/bacterial infections

XLA: inability to produce b cells or antibodies that b cells make

immunoglobulin class switching & SHM

process whereby activated b cells change antibody production from IgM to either IgA, IgG, IgE depending on functional requirements

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Somatic Hypermutation (SHM) - cellular mechanism by which immune system adapts to new foreign elements that confront it

Monoclonal antibodies

Anti-CLTA-4 Ipilimumab: blocks CTLA-4 on surface of T cells preventing it from binding B7 on dendritic cells; blocks co-inhibitory signaling pathway; cause t-cells to be suppressed; leads to cd28 on t cells to bind with cd80/86, causes t cell activation to launch anti-tumor immune response + kill tumor cells

\*Ipilimumab increases t-cell activation which increases t cells directed at attacking transplant which leads to rejection

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Anti CD20 Rituximab: IgG antibody causing B cell depletion; uses antibody-dependent, complement-dependent cytotoxicity; induction of Apoptosis

WBC reaction to bacteria

1. Bacteria enters open wound
2. Sugars on bacteria bound by TLRs on macrophages
3. Macrophages secrete inflammatory cytokines
4. Neutrophils, DC, other cells recruited to site of infection
5. Bacterial antigens trafficked by dendritic cells to lymph nodes
6. Plasma cells produce antibodies that bind the bacteria
7. Macrophages phagocytose antibody-coated bacteria

classes of immunosuppresants

TNF-Alpha Inhibitors: Used to reduce chronic inflammation; may cause reactivation of latent tuberculosis

Methotrexate: Competitively inhibit enzyme necessary for purine/pyrimidine synthesis

Cyclosporine: Prevent dephosphorylation of NFAT transcription factor in T cells

CAR-T advantages & overall mechanism

kills b cells producing autoantibodies

higher specificity & retain b cells with protective immunity (Lupus is least likely to be suitable for CAAR because it is literally autoantibodies)

chylomicrons

lipids combining with proteins, phospholipids, and cholesterol to produce lipoprotein complex during absorption

lacteal

lymphatic vessel from which chylomicrons are absorbed

peritonitis

swelling/inflammation of lining of abdomen, known as peritoneum and caused by infection from hole in bowel or burst appendix

napkin ring sign

constriction of lumen of large intestine; feature of high-risk coronary artery plaque

intrinsic factor is absorbed where

ileum

circulation pattern of lymphocytes through lymphatic system

lymph nodes → efferent lymphatic vessels → thoracic duct → left brachiocephalic vein → post-capillary venules → afferent lymphatic vessels → lymph nodes

positive coopertivity

accounts for sigmoidal shape of HbA; once one oxygen molecule binds to ferrous iron of heme molecule, oxygen affinity of hemoglobin increases; allow second molecule to bind more easily; and everyone else to bind more easily as well

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Allow hemoglobin to lose oxygen more when any oxygen molecules are released; facilitate systemic oxygen delivery to tissues

stages of hiv life cycle

binding, fusion, reverse transcription, integration, replication, assembly, budding

3 components of white pulp

marginal zone, follicles, periarteriolar lymphoid sheath