Pathophysiology ch11 presentation Immune system

Lymphoid cells, WBCs, and the immune system.

1. Ch. 11 Disorders of WBCs and Lymphoid Tissues

2. Neutropenia ( Agranulocytosis ) Aplastic anemia – all myeloid stem cells are affected Agranulocytosis – absence of neutrophils Neutrophil normal range – 1500-8000 cells/microliter Neutropenia – less than 1500 Benign Ethnic Neutropenia Which colony stimulating factor may be administered to treat neutropenia?

3. Causes of Neutropenia Congenital Kostmann Syndrome Acquired Chemo or radiation therapy Neoplastic cell growth Splenomegaly Felty Syndrome – variant of RA – increased destruction in spleen Infections Drug related

4. Clinical Features of Neutropenia Gram -, gram+, fungi Characteristic feature – absence of ___________.

5. HSV-1 HSV-2 HHV-3 HHV-4 HHV-5 Infectious Mononucleosis - Cause Herpesviridae

6. Infectious Mononucleosis Cause  Characterized by  fever, pharyngitis, lymphadenopathy, splenomegaly, tonsillitis, mononucleosis cells in the blood, heterophile antibodies (antibody that reacts with antigens from another species) Classic Triad  Pharyngitis, fever, and lymphadenopathy Most common presenting symptoms  sore throat, malaise/fatigue Age of infected persons  Transmission 

7. Cells that EBV infects Infected B cells produce heterophile antibodies T-cell division lymphoid tissues is mainly responsible for lymphadenopathy & splenomegaly

8. Infectious Mononucleosis - atypical CD8+ T-lymphocytes are characteristic

9. Infectious Mononucleosis – Clinical Course/Features Swollen lymph nodes Exudative pharyngitis in a person with infectious mononucleosis Esp. cervical, axillary and groin Insidious onset Incubation period Prodromal period – malaise, anorexia, chills Fever, Severe pharyngitis, Lymphadenopathy Splenomegaly Hepatitis – nausea, hepatomegally , jaundice but resolves completely CNS complications How long does it last? Treatment

10. 1.What are the large cells and what causes them? 2.Why do they have this appearance? 1.Downey cells, EBV infection

11. 1.What test is this and what disease does it test for? 2. How does this test work? Mixes serum from patient with color-enhanced sheep/horse RBC EBV

12. Dx Heterophile antibody Anti-VCA Anti-EBNA

13. Leukemias  Classification  Lymphocytic Myelogenous 4 types Most common Among children and adolescents is ______________. Adults (over 20) _________ and ____________.

14. Leukemia Etiology Disruption or dysregulation of genes Translocations Inversions Deletions

15. Found in > 90% of those with CML BCR-ABL is tyrosine kinase that is continually active. Imatinib ( Gleevec ) 5 yr survival rate has doubled Awards $$$

16. Acute Leukemias 2 main forms  85% are pre B cell origin

17. Manifestations of ALL and AML Cross BBB  HA,N/V, confusion,seizures,coma Cerebral and pulmonary leukostasis Hyperuricemia

18. Diagnosis and Tx of Acute Leukemias Bone marrow biopsy- Cytogenic studies- looking for chromosomal abnormalities and cell markers Lumbar puncture- CT scan of chest, abdomen, and pelvis- Chemotherapy- ALL 5-yr survival rate is 80% in children AML – overall only 30% long-term survival rate Bone marrow or stem cell transplantation-

19. Chronic Leukemias  involve proliferation of more fully differentiated myeloid and lymphoid cells 2 main forms CLL 1/3 of all leukemias and is mostly in older adults CML 10-15% of all leukemias and is mostly in older adults

20. CLL 2 forms Indolent – often asymptomatic at time of diagnosis Aggressive - lymphadenopathy, hepatosplenomegally , fever, abdominal pain, weight loss, progressive anemia, and thrombocytopenia, with a rapid rise in lymphocyte count. Have greater amounts of CD 38 antigen Diagnostic hallmark – isolated increase in lymphocytes Treatment – if aggressive form, chemo, stem cell transplant Do you think antibodies would be high or low ?

21. CML  excessive granulocytes, erythroid precursors, and megakaryocytes but they don’t develop into useful cells 3 phases Chronic phase – 4 years - weakness and weight loss Short accelerated phase (6-12 months) - splenomegally - constitutional symptoms – fever, night sweats, bone pain 3. Terminal blast crisis phase ( 3 months) - leukostasis Hallmark – BCR-ABL gene product can be detected in the peripheral blood

22. CML blast crisis – WBC - 150,000 per microliter

23. Malignant Lymphomas – of the two, which has a better survival rate? NHL – more common; usually seen in those > 50 YO HL Reed-Sternberg cell HL NHL With NHL there is a poor humoral response , rather than the impaired cellular immunity seen with HL.

24. Non-Hodgkin Lymphomas (NHL) Risk factors  chemical and radiation exposure, and immune dysfunction Cause  genetics; impaired immunity and infectious agents play a role Origination T or B cell transformation Proliferation location Spread – potential to spread to liver, spleen or bone marrow

25. 40 different NHLs based on appearance, surface markers (antigens, CD markers), and genetic features. Classification based on: B or T cell Level of maturation Anatomic sites Surface markers and genetic features Aggressiveness *

26. EBV latent and malarial infection brings it out

27. NHL – causes poor humoral response Clinical Manifestations Indolent Present w/ painless adenopathy Aggressive Constitutional symptoms

28. Hodgkin Lymphoma (HL)  causes poor cell mediated response Differences from NHL Arises from single node Distinctive morphological features Cause  Viruses ( Hx of mono) Carcinogens Genetics, immune mechanisms Atypical mononuclear tumor B cell; expresses CD30 ________________________________

29. HL Clinical Manifestations Enlarged nodes – above diaphragm Fevers, chills, night sweats, weight loss Fatigue, anemia – Prone to viral, fungal, protozoal infections Cell-mediated responses are most lacking

30. HL Diagnosis Definitive Diagnosis – CT scan of chest and abdomen – Staging – location and number of nodes involved Stage A – no constitutional symptoms Stage B – weight loss and night sweats

31. Dx – classic triad >10% plasma cells in bone marrow Bone lesions M-protein spikes(serum) or Bence Jones proteins(urine) Multiple Myeloma Expansion of a single clone of immunoglobulin producing plasma cells  impairs production of RBCs, WBC, platelets This should be a picture of plasmacytomas Amyloid is from breakdown of light chains