Immunology — USMLE Step 2 CK Notes

Trace Mineral Deficinecies

RF: PRN

Malabsorption eg IBD, Bowel resection

Zinc deficiency

Patchy Alopecia

Pustular crusting skin rash with scaling and erythema (perioral region & extremities)

Hypogonadism

Impaired wound healing and Impaired Taste

Immune dysfunction

Dietary supply: Meat, nuts and fortified cereal

Absorbed in duodenum and jejenum

Chromium deficiency: Impaired glucose control in diabetes

Selenium Deficiency: Thyroid dysfunction + Cardiomyopathy

Immune dysfunction

Copper deficiency: ataxia; periph neuropathy RF: Excessive ingestion of Zn (competes for absorption); malabsorption issues

Brittle hair

Skin depigmentation

Microcytic Anemia

Osteoporosis

Pellagra: B3 Deficiency (niacin)

Dermatitis, diarrhoea and dementia

Rash is rough, scaly and hyperpigmented and occurs symmetrically in sun exposed areas

Dementia: memory or affective sx such as depressed mood and psychosis

Diarrhoea often accompanied by Abdo pain, nausea and anorexia

Glossitis

B1 (Thiamine) Deficiency

Beriberi: periph neuropathy, High Output HF

Wernicke Korsakoff Syndrome

B2 (Riboflavin) Deficiency

Angular cheilosis, stomatitis and glossitis

Normocytic anemia

Seborrheic dermatitis

B6 Deficiency (pyridoxine)

Cheilosis, stomatitis, glossitis

Irritability, confusion and depression (needed for serotonin production)

Periph neuropathy (rare)

Sideroblastic anemia

2 x 6 gives 12 for anaemia

B9 Deficiency (Folate)

Megaloblastic anemia; Gingival hyperplasia

NTDs in foetus

B12 (cobalamin) Deficiency

Megaloblastic anemia

Neurological deficits: confusion, parathesias, ataxia, depression

Vitamin C Deficiency —> impairs collagen crosslinking

—> fragile capillary walls

Scurvy: punctate hemorrhage, gingivitis, corkscrew hair

Mucosal bleeding and periodontal disease

Poor wound healing; ecymosis and petechiae

Even more severe in kids: hemorrhages, bone deformities; subperiosteal and join the hematomas

Constitutional; arthralgias, depression

Vitamin A Toxicity

Dry skin w desquamation; cerebral edema; visual disturbances; fatigue

Anorexia and GI upset

Periosteal reaction

Vitamin A Deficiency

Xerophthalmia (eye dryness), night blindness, follicular hyperkeratosis (not palms/feet as no hair)

Blood Transfusion Reactions

Anaphylaxis

Seconds - minutes

Angioedema and edema of hands

Trachea can show subglottic narrowing

Recipient has IgA Abs —> washed RBCs used if IgA Deficiency

Acute Hemolytic: ABO Incompatibility

Within 1hr

Anxious and SOB w norm O2 SATS

Fever, Hemonglobinuria

——->>> ATN——>> Acute renal failure

——->>> Flank pain DIC, Shock

Positive Coombs Test

Management: Aggressive hydration to prevent renal insult; supportive

Febrile Nonhemolytic: Most Common Reaction

Within 1-6hr

Cytokines accumulation during blood storage

Transient Fever and chills

Prevent via leukoreduction thereby minimising cytokines production by WBCs

Tx: Acetaminophen+fluids to blunt hypothalamic response to cytokines

Urticarial

Within 2-3hr

Recipient has IgE against blood product component

Tx: cessation of transfusion; antihistamines; resume transfusion if otherwise asymp

No additional evaluation

Transfusion-related Acute Lung Injury (TRALI)

Within 6hr

Donor has anti-leukocyte Abs

Resp Distress: Acute SOB; Crackles and Rales

Non cardiogenic pulm edema with diffuse bilateral infiltrates

———>>>>> No JVP and norm EF

Tx: Respiratory supportive care; high mortality

TACO: Transfusion related circulatory overload: Raised JVP and decreased EF Acute SOB with Crackles and Rales

Diffuse bilateral infiltrates

S3

High BNP

Tx: Diuresis (furosemide) and O2

ARDS: No Fever

Delayed hemolytic

Within days to wks

Anamnestic Ab Response

Often asymptomatic; lab evidence of hemolytic anemia

Positive Coombs and new antibody screen

Graft v Host

Within wks

Donor T Lymphocytes. (Type 4 HSR)

Rash, fever, GI sx and Pancytopenia

Solid organ transplant recipients high risk for PCP and CMV

—> TMP SMX prophylaxis (also fights Toxo and Listeria)

Hep B and pneumococcus vaccine given prior to transplant

Ganciclovir/valganciclovir prophylaxis for CMV common

IM Influenza vaccine annually

Rejection reactions

Hyperacute

Type 2 HSR

Mins to hrs

Capillary thrombosis prevents graft vascularisation

Acute Graft Rejection (acute cellular rejection)

Acute cellular Rejection: lymphocytic infiltrates (type 4 HSR)

Within first 3 months after transplant

Most reliable sign: Endotheliitis of transplant organ:

Eg lymphocytic invasion of hepatic and portal veins

Interlobular duct destruction (nonsuppurative cholangitis)

Mononuclear infiltrate: eosinophils and lymphocytes

Tx: High dose corticosteroids

Mononuclear cells —> agranulocytes

Acute Graft versus host Disease

Within 100 days

Potentially reversible

Hematopoeitic SCTs

D/t CD8 T cells (type 4 HSR)

Maculopapular rash: often painful and can become confluent (like SJS)

Profuse, watery diarrhoea (has secreatory pattern))

Liver inflamm with damage to biliary tract epithelium

——>> elevated Bilirubin, Alk phos and transaminases

Dx: Allograft Biopsy

Tx: IV steroids

Calcineurin Inhibitors (Tacrolimus, cyclosporine)

Hepatically cleared and metabolised by P450 enzymes

—> certain drugs can cause acute toxicity years after transplant

Vasoconstrictive ——> acute toxicity HTN and AKI (Prerenal)

Reversible

Chronic toxicity slower and irreversible

Impair secretion of insulin —- hyperglycaemia (tacrolimus)

Gingival hypertrophy (cyclosporine); hirsutism; alopecia

GI upset

Neurotoxicity eg tremor

Nephrotoxic

Increased infection and malignancy risk (all immunosuppressants)

Transplant renal artery stenosis

Renovascular HTN (resistant)

Decline in renal function after ACEI/ARB

Patient looks well (cf graft rejection)

Lateralising abdo bruit and flash pulm oedema

Associated with operative abnormalities (trauma during organ procurement; abnorm suture)

Viral infection (CMV; BK) and atherosclerosis of donor artery

First 2 years post transplant

Management: Angioplasty +/- stent

Hypersensitivity

Type 1: IgE mediated: Anaphylaxis; Urticaria

Type 2 (cytotoxic): IgG & IgM mediated: Autoimmune hemolytic anemia; Goodpastures

Type 3 (immune complex): Serum sickness; PSGN; Lupus nephritis

Type 4 (delayed): T Cell and macrophage: >12hrs post contact

Erythema, edema, vesicles

Contact dermatitis (poison ivy/nickel/neomycin)

Tuberculin skin test

Anaphylaxis:

Allergic SX in >/= 2 organ systems: Skin; resp; GI; CV

OR. Hypotension after exposure to allergen

Skin findings absent in 20%

Tx: IM Epi

Steven Johnson Syndrome

SJS: <10% Body surface area

TEN: >30%

Overlap in between

Mucosal involvement; systemic sx

Medications; Mycoplasma; Vaccinations; Graft vs Host Disease

Tx: Supportive (similar to burn care)

DRESS Syndrome

Potentially life threatening drug reaction

MCC is allopurinol and antiepileptics (phenytoin and carbamazepine)

Morbilliform eruption starting on face/upper trunk that becomes diffuse and confluent

——> often >50% body surface

Facial edema common

Eosinophilia

Systemic sx w involvement of >1 organ system in 90%

Diffuse LAD

Unusually long latency (2-8 wks) between drug initiation and sx manifestation

Poss d/t HHV6 reactivation

Serum Sickness-Like reaction

Immune complex formation; Abs (beta lactam; sulfa); Acute Hep B

Sx 1-2 wks post exposure

Fever, skin rash, polyarthralgia

Tx: Steroids/plasmapheresis if severe

Complement deficiency

SLE, Antiphospholipid Antibody Syndrome

Increased risk of encapsulated bacteria

Common variable immunodeficiency: Impaired B cell isoswitching

Acquired (sporadic mutation) —> teenager/adult dx.

Decreased Igs but norm B cell numbers

Increased lymphoid tissue —->> Autoimmune disease and Lymphoma risk

Selective IgA deficiency

Most common B cell defect

Recurrent URT Infections and diarrhoea

Anaphylaxis if given blood contains IgA

DiGeorge Syndrome (22q11.2 deletion) Defective development of pharyngeal pouches

Cellular immune deficiency

Seizure, truncus arteriosus, micrognathia

Conotruncal cardiac defects:

No Thymus/hypoplastic: Candida, viruses, PCP pneumonia

Craniofacial abnormalities (cleft palate; micrognathia)

Micro deletion on chromosome 22

LAD

Impaired chemotaxis

Recurrent bacterial infections of skin and mucosa (omphalitis; peridonitis)

No pus at inflamm site (late of neutrophils)

Prolonged falling off of umbilical stump (>21 days)

Marked periph leukocytosis w neutrophils

CGD: Staph aureus skin abscesses X linked recessive

Impaired oxidative burst

Recurrent swollen, infected LNs in groin

Recurrent bacterial or fungal infections d/t catalase positive organisms

Dx: negative Nitrotetrazolium dye test (yellow means they have disease);

flow cytomegalovirus with DHR 123

Wischkott Aldrich Syndrome: high IgA and IgE w Microthrombocytopenia + eczema X linked recessive defect in WAS protein gene

Often presents with prolonged bleeding after circumcision

Impaired cytoskeleton changes in WBCs and PLts

Petechiae and recurrent ear infections

Low IgM and IgG, Tx: SCT

Asplenia

Increased risk of encapsulated organisms: S Pneu, haem influenza, Neisseria men. (SHiN)

—-> AmoxiClav and Levofloxacin (Pen allergy) cover encapsulated orgs

Decreased antibody mediated phagocytosis (opsonisation)

Brutons X Linked agammaglobulinaemia

Infants start at 6-9 months

No/small tonsils (B cell issue!)

Absence of B cells on flow cytometry, low levels of all Igs

Chronic Enterovirus infections

Tx: prophylactic Abs and IVIg

Hyper IgM Syndrome

Normal B cells w decreased IgA and IgG; high IgM

X linked defect in CD40 Ligand —> B Cell isoswitching

CD40 Ligand deficiency

Needed for maturation of other WBCs eg T Cells and macrophages —-> pancytopoenia

Hyper IgE (Jobs) —> cold abscess

Defective neutrophil chemotaxis

Jak Stat

Retained teeth

Eczema

SCID

No thymus or tonsils

Severe lymphopoenia

Most common is X linked recessive: Gamma chain issue -> ILR

Also AR form —->. ADA Deficiency

Tx: BM Transplant by age 1 or death (paediatric emergency!)

Polysaccharide vaccine produces relatively T cell independent B cell response

Conjugate produces T cell dependent B cell response

Myeloperoxidase Deficiency

Impairs neutrophil killing and monocytes action (endocytosis and digestion)

Susceptibility to Candida infections

Hereditary Angioedema

C1 I Deficiency/dysfunction ==> excessive bradykinin

Swelling w/o urticaria (face, extremities, genitals) ; laryngeal edema (life threat)

Colicky abdo pain, vomiting and diarrhoea (bowel wall oedema)

Dx: Low C4 and C1I protein/function

Management: C1I concentrate

Tx of acute swelling: Bradykinin Antag (icatibant) or kallikreain I (ecallantide)

Triggers: Dental procedures; STRESS; trauma

Skin Testing —> T Cell dependent TYPE 4 HSR

Killed vaccines —> no long immune activation —> need multiple doses