immunology notes and answers

7/29/2019 Immunology Notes and Answers

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2/1: Functional anatomy of immune system (ch 4 robbins pg 100-104)

1. Define and use in proper context:a. Antigen processing cellsb. Bursa of Fabricusc. Dendritic cells (follicular - B cells, interdigitating - T cells)d. GALT (gut associated lymphoid tissue)e. Innate vs adaptive immunityf. Cellular vs humoral immunityg. Immunoproliferative diseaseh. Autoimmunityi. Immunodeficiencyj. Lymph nodek. Lymphocyte (B, T, plasma cell)l. Lymphoid stem cellsm. Monoclonal/polyclonaln. Monocyte/histiocyte/macrophageo. Phenotypep. Spleenq. Thymusr. Tonsil

2. List major subtypes of T lymphocytes and explain the general role of each, if known, in theimmune process

3. Describe relation of B lymphocytes4. Describe role of macrophages (monocytes) in immune response5. List the major phenotypic (CD) markers and state their diagnosis utility6. Describe the cellular content and microanatomy of tonsils, lymph nodes, spleen, thymus, gut-

associate lymphoid tissues and bone marrow.

7. Relate function to microanatomy in immune system, specifically for Reactive Hyperplasias andLymphadenopathy, and for Lymphoma

2/1: Allergy and hypersensitivity (basic immune: 205-221)

1. Define the termsa. Inflammationb. Hypersensitivityc. Allergyd. Atopy

2. Describe the pathophysiologic mechanisms of Types I, II, III, and IV hypersensitivity3. Describe the cellular mechanisms of IgE-initiated hypersensitivity.4. Describe the differences between mast cells and basophils.5. Outline the mast cell-associated mediators of inflammation.6.

Describe eosinophil involvement in inflammatory injury.7. Define and use in the proper context the following terms:

a. Immediate hypersensitivityb. Late phase reactionc. Delayed hypersensitivityd. Immediate hypersensitivity skin teste. Delayed hypersensitivity skin testf. Radioallergosorbent test (RAST)

2/1: SPP case 1: asthma

1. identify clinical syndromes which characterize IgE- mediated hypersensitivities


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2. Describe the clinical features of allergic rhinitis and asthma.3. List the laboratory tests that are useful for confirming the presence of IgE-mediated allergic

reactivity.

4. Describe overall approach to the management of allergic disease.5. Describe the mechanistic classes of medications used for the treatment of asthma and allergic

rhinitis

2/4: Immunologic tolerance and Autoimmunity I/II (Ch 9 basic immune)

1. Compare and contrast peripheral and central tolerance for T- and B- lymphocytes.2. Describe anergy in peripheral B-and T-lymphocytes.3. What is activation-induced cell death?4. Why are T-reg cells important?5. Describe immune effector mechanisms that mediate autoimmune disease.

Proposed Mechanism Antigens Involved in

Pathogenesis

Reason for or Cause of Mechanism Resulting Autoimmune

Disease

1. Emergence of

sequestered antigen

Thyroglobulin (?) Antigen isolated in thyroid follicle Hashimoto's thyroiditis

Lens protein Antigen isolated from bloodstream Sympathetic ophthalmitis

Spermatozoal antigens Antigen developed in adult life Infertility (male)

2. Alteration of self antigens Drugs, viruses, other

infections

Attachment of hapten, partial

degradation

Hemolytic anemias, SLE /

rheumatic fever (?)3. Loss of serum suppressor

Abs

Many types B cell deficiency; congenital

Bruton's agammaglobulinemia

Many types

4. Loss of suppressor T cells Many types T cell deficiency; postviral infection Rare

5. Activation of suppressed

lymphocyte clones

Epstein-Barr virus;

other viruses (?)

B cell stimulation Rheumatoid arthritis (?)

6. Emergence of forbidden

clones

Many types Neoplastic transformation of

lymphocytes; malignant lymphoma

& lymphocytic leukemias

Hemolytic anemia,

thrombocytopenia

7. Cross-reactivity btwn self

and foreign antigens

Antistreptococcal ab &

myocardial antigens

Antibody against foreign antigen

reacts against self antigen

Rheumatic fever

8. Abnormal immune

response genes: Ir genes

Many types Loss of control of the immune

response due to lack of Ir genes

Many types

6. What genetic loci have been associated with autoimmune disease?7. How can infection influence autoimmunity?8. Why are animal models that mimic human autoimmune disease so important?

2/4: Hereditary Immunodeficiency disease (pg223-240 basic immune)

1. Outline selected clinical examples of hereditary deficiencies or dysfunctions in phagocytic cells, T-cells, and B-cells.

2. Outline characteristics, infections seen in patients with phagocytic cell, T cell and B celldeficiencies and the mechanisms resulting in increased susceptibility to these specific infections.

3. Define the following:a. Chronic granulomatous diseaseb. Hyposplenismc. DiGeorge syndromed. Severe combined immune deficiencye. X linked agammaglobulinemiaf. Selective IgA deficiencyg. Common variable immune deficiency

2/4: Clinical Care case discussion

1. Identify common presenting clinical feature of primary immune deficiency


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2. Describe how antibody deficiency causes clinical disease3. Describe the tests that would identify an antibody deficiency4. Define immune dysregulation5. Identify current therapy for immunoglobulin /antibody deficiency6. Define newborn screening (NBS)7. Describe how NBS is used for primary immunodeficiencies8. Describe the use of flow cytometry in diagnosis of immunodeficiency9. Describe how t cell deficiency cause clinical disease10.Describe current therapies for SCID

2/5 Granulocyte production

1. Know relation btwn marrow reserve pool and propensity to infection in neutropenia2. Know the clinical presentation of neutropenia3. Know when you need to do a detailed workup of neutropenia4. Know how GCSF works5. Know the presentation of neutrophil dysfunction6. Understand the process of how neutrophils get from the blood to the site of infection7. Know the major mechanisms of intracellular killing of bacteria

2/6 Role of chemokine Networks in disease

1. Describe the structure and function of chemokines and their receptors2. What is the role of IL-8 in the immune response3. How do chemokines assist in the trafficking of leukocytes4. Which families of adhesion molecules are involved in cell migration5. How can decoy chemokine receptors modulate the immune response6. Describe the role of CCR5, mutant CCR5 and CXCR4 in HIV infection.

2/6 - HIV Basic Virology (BI 231-237)

1. Recognize HIV as a zoonosis from chimpanzees2. Describe HIV structure3. Describe the life cycle of HIV including:

a. Receptors on target cells CD4 and CCRsb. Virus-specific enzyme functions reverse transcriptase, integrase, protease.c. Virus-specific regulatory proteins.

4. Identify properties of HIV that are associated with immune evasion and immune deficiency.5. Describe current concepts of HIV disease pathogenesis

2/6 - Clinical presentation of HIV infection

1. Recognize current epidemiological trends2.

Walk through the life of an HIV patient3. Learn appropriate diagnostic tests for HIV

4. Identify manifestations of acute and chronic HIV infection2/6 - Principles of Therapy for HIV

1. Review parts of viral life cycle where we can interfere with drugs2. Discuss appropriate time to intervene and current controversies regarding when to treat3. Review the March 2012 DHHS recommendations for initial antiretroviral treatment4. Describe the common toxicities of common drugs5. Emphasize the critical importance of adherence6. Discuss prevention and management of drug resistance


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2/6 Transfusion Transmitted Diseases I and II

1. Understand the differences between viral and protein infectious agents2. Differentiate classic CJD from variant CJD (etiology, neuropath, onset age, transmission routes, etc)3. Explain the structural and behavioral differences between PrP-C and PrP-Sc.4. Know the general symptomatology of CJD.5. Understand the acute, intermediate, and chronic stages of T. cruzi and the associated symptoms.6. Know the differences between primary, latent, and recurrent CMV disease.7. Understand why immunocompromised individuals are more prone to CMV recurrences.8. Understand how CMV infection affects healthy immunocompetent individuals, fetus/neonates, and

immunocompromised individuals differently.

9. Understand the mechanisms by which CMV escapes the host immune defense of CD4 T cells, CD8 Tcells, and NK cells.

10.Describe the clinical diseases (WNF and WNE/M) caused by WNV infection.11.List the methods/tests to detect WNV infection.

2/7: Sepsis

1. Define sepsis and related terms2. Describe pathophysiology of sepsis3. Understand treatment modalities for sepsis

2/7 Dengue Virus and other Hemorrhagic fevers

1. Define the term FUO and discuss major diagnostic possibilities2. Understand mechanisms causing viral hemorrhagic fever3. List common etiologies of viral hemorrhagic fever

2/7 EBV and immune control: SPP case 3

1. Describe properties of Epstein-Barr virus2. Understand epidemiology and pathophysiology of EBV infection3. Describe symptoms of acute EBV infection4. Discuss chronic conditions associated with EBV infection

2/7: Transplant immunology

1. Determine /define 3 types of organ transplant rejectionActive Immunologic Factor

in Recipient

Type of

Hypersensitivity

Target Sites in

TransplantPathologic Effect

Type of

Rejection

Preformed antibody against

donor transplantation

antigens

Type II cytotoxic Small blood vessels

in donor tissue

Fibrinoid necrosis / thrombosis of

small vessels; ischemic necrosis of

parenchymal cells.

Hyper-

acuteType III immune

complex formation

(local, Arthus-type)

Circulating antibody formed

due to humoral immune

response against donor

transplantation antigens

Type II cytotoxic Parenchymal cells Acute necrosis of parenchymal cells Acute

Type III immune

complex formation

(local, Arthus-type)

Small blood vessels Fibrinoid necrosis/thrombosis in

acute phase; intimal fibrosis /

narrowing in chronic phase

Acute,

chronic

Activated T cells elicited by

cellular immune response

against donor

transplantation antigens

Type IV Parenchymal cells Progressive, slow loss of

parenchymal cells.

Chronic

2. Define strategies to prevent rejection3. Define mechanism of action commonly used immunosuppression medications


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4. Define complications of over immunosuppression

2/8: Allogeneic Hematopoietic Stem Cell Transplant

1. Understand the indications for allogeneic HSCT for hematologic malignancies and immune systemdisorders

Cytokine-mobilised peripheral blood stem cells have largely replaced bone marrow as the source

of cells in autologous transplantation because of more rapid neutrophil and platelet recovery and

faster immune reconstitution. Allogeneic peripheral blood stem cells similarly lead to fasterhematologic recovery: however, their effects on GVHD, relapse, survival, and immune

reconstitution are less certain. Peripheral blood stem cells transplantation (PBSCT) and bone

marrow transplantation involve the transfer of pluripotent haematopoietic stem cells capable of

regenerating all cellular elements of the blood and immune system. It has become the

conventional form of treatment for congenital immunodeficiency diseases, selected malignancies

and aplastic anaemia for patients who have an HLA-identical sibling or an identical twin. For

patients who lack an HLA-matched sibling, a closely HLA-matched unrelated individual or an

imperfectly HLA-matched relative may act as donors.

The reason why HLA matching needs to be especially stringent in HSCT is because the recipient is

either immunodeficient or needs to be conditioned, i.e. undergo profound chemoradiotherapy to

eliminate residual disease and create space for the new marrow. This results in ablation of the

recipient's immune system. The immunoincompetent recipient is, therefore, at high risk of

developing life-threatening GVHD.

Donor selection is done in sequential steps starting from the search for the best match, namely a

genotypically identical sibling. Information regarding genotypic identity for HLA class I and II

determinants can be readily obtained within families by determining the HLA class I and class II

antigens of the four parental haplotypes and analysing their segregation in the family. If

genotypically identical siblings are unavailable, the second best choice is to obtain bone marrow

from HLA-haploidentical relatives. Parents and offspring are always HLA haploidentical. The

degree of disparity between HLA-haploidentical donorrecipient pairs depends on the similarity

of the non-shared haplotypes. The risk of GVHD increases progressively with the number of HLA

disparities in the recipient compared with the donor. Bone marrow can be obtained from

unrelated donors, if neither genotypically identical siblings nor haploidentical relatives are

available. In this case, the donors are HLA phenotypically identical unrelated volunteers. Serologic

typing alone does not ensure that the individuals share the same HLA genes. DNA-based

techniques now permit molecular typing and a high degree of matching. Patients who are truly

highly matched appear to have better outcomes. Worldwide, approximately 3040 000 HSCTs areperformed yearly, with an annual increase of 1020% each year. More than 20 000 people have

now survived 5 years or longer after HSCT.

The indications for bone marrow transplant are numerous and are increasing. Allogeneic bone

marrow transplantation has been successful in treating children with a range of congenital

immunodeficiency disorders (see Ch. 19). In aplastic anaemia, marrow transplantation is the

preferred method of treatment if an HLA-identical sibling is available, and in this setting 85%

long-term survival is achieved. In children with homozygous beta-thalassaemia, allogeneic bone

marrow transplantation has led to disease-free 1-year survival of 75%. Non-transplanted patients

undergo iron overload and usually die in their twenties.

In haematological malignancies, long-term survival and cure rates of up to 70% have been

reported. In acute lymphoblastic leukaemia, bone marrow transplantation is indicated in those


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50% of children who are not cured by a primary chemotherapy regimen. Interestingly, patients

with leukaemia treated with bone marrow transplantation experience the beneficial graft-versus-

leukaemia (GVL) effect (see Clinical Box 11.2 ) that occurs in association with GVHD. In chronic

myelogenous leukaemia (CML), allogeneic transplantation with marrow from an HLA-matched

sibling donor is the treatment of choice for patients who are in the stable phase. If the patient with

CML has no HLA-identical family donor, transplantation should be undertaken only when the

clinical condition deteriorates, in order to justify a riskier procedure. Long-term disease-free

survival has been achieved in patients with both Hodgkin's disease and non-Hodgkin's lymphoma.

In both conditions, the results are better when the treatment is performed soon after a relapse, ata time when the disease is minimal. Under these circumstances, a disease-free survival of up to

70% can be achieved. A lower mortality rate is associated with the use of an autologous graft, and

this is the preferred mode of treatment in most centres. Though autologous HSCT does not cure

multiple myeloma, event-free survival rates and overall survival rates are prolonged

approximately 1 year compared with survival rates achieved by chemotherapy. Bone marrow

transplantation is being tested in non-haematological malignancies, where extremely aggressive,

bone marrow impairing chemotherapeutic regimens may be desired to treat the original

malignancy. Anecdotal successes have been reported in neuroblastoma, breast cancer, testicular

tumours and gynaecological cancers.

Before HSC are infused, the recipient must undergo chemotherapy and/or radiotherapy

conditioning to suppress the immune system, to create space in the bone marrow and toeliminate malignant cells in cases where malignancy was the reason for the transplantation. The

major complications of marrow transplantation are graft rejection, GVHD, opportunistic infection

and recurrence of malignancy. In the setting of recipients receiving marrow from an HLA-identical

sibling, this complication is fortunately rare. Predisposing factors include previous blood

transfusions and insufficiently aggressive conditioning regimens. A complication peculiar to bone

marrow transplantation is veno-occlusive disease of the liver, which consists of three main

symptoms: jaundice, tender hepatomegaly and ascites. It is present in up to 50% of the patients.

Progressive liver failure can develop and a fatal outcome is not unusual.

2. Understand principles of stem cell mobilization and types of hematopoietic stem cell grafts.3. Understand the immunobiology of allogeneic HSCT with particular reference to pathophysiology

of graft-versus-host disease.

4. Discuss the complications of allogeneic HSCT

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