Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Haematology > Immunopatholgy > Flashcards

Immunopatholgy Flashcards

1
Q

What is meant by Immunological tolerance

A

When we are exposed to foreign antigens early on we more easily become tolerant to them

We produce T and B cells that react against our own antigens

Most of these cells are deleted before leaving the thymus or bone marrow (central tolerance).

Some self reactive T and B cells escape this but are kept under some control (peripheral tolerance)

– There are anergic (“↓energy”) B cells that are acƟvated by high concentrations of antigens

– T regulatory cells (Tregs) are CD25+ suppress autoreactions

Antigens may also be hidden (sequestered) e.g. in the eye

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is Autoimmunity and the reasons why it occurs.

A

“Friendly fire”

When antibodies attack their own antigens/cells/tissues

Sometimes tolerance breaks down or is overcome and the could be as a result of a Genetic or Environmental factor/reason

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List the Genetic reasons ass. with Autoimmunity

A

Associations with certain HLA antigens:

  • SLE, myasthenia gravis, and type I diabetes: HLA DR3
  • Rheumatoid arthritis: DR4 allele
  • Ankylosing spondylitis ‐ HLA class I allele B27

Defective clearance of complement proteins:

• Causes excessive deposition of immune complexes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

List the Environmental reasons ass. with Autoimmunity

A. P. D.

A
  1. Antigen mimicry (rheumatic fever: cardiac myosin ~ Strep.)
  2. Polyclonal activation of B cells by Gram neg bacteria
  3. Drugs: penicillin (red cells) and others: SLE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List the classification of the most common Autoimmune Diseases

A

Autoimmune haemolytic anaemia(AIHA)

Graves’ disease

SLE-Systemic Lupus Erythematosus

Idiopathic thrombocytopenic purpura (ITP)

Multiple sclerosis

Type I diabetes mellitus

Rheumatoid arthritis

Psoriasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Autoimmune haemolytic anaemia:

Autoantigen Major Effector

A

Blood group antigens

B cells/autoantibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Graves’ disease:

Autoantigen
Major Effector

A

TSH receptor

B cells/autoantibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

SLE:

Autoantigen
Major Effector

A

dsDNA histones; ribonucleoproteins
(snRNPs)

B cells/autoantibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Multiple sclerosis:

Autoantigen
Major Effector

A

Myelin basic protein; myelin oligodendrocyte protein,
proteolipid protein

T cells; important role for B
cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Type I diabetes mellitus:

Autoantigen
Major Effector

A

Pancreatic ‐islet cell antigen

CD4+ T cells; CTL-cytotoxic lymphocytes; B
cells/autoantibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Idiopathic thrombocytopenic purpura (ITP):

Autoantigen
Major Effector

A

Platelet membrane protein

B cells/autoantibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Rheumatoid arthritis:

Autoantigen

A

lgG; citrullinated and carbamylated proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Psoriasis:

Autoantigen
Major Effector

A

Unknown

CD4+ T cells (THI and TH17)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is Systemic Lupus Erythematosus

A

Chronic systematic inflammatory disease
• 1 in 2000 (trippled over last 40 yrs), mostly women
• Onset usually between 20‐40 years
– Usually follows a chronic and irregular Involves
kidneys, heart, GI tract, central nervous system,
muscles and joints

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Problem which may arise from Systemic Lupus Erythematosus

A

Pleural Effusions

Heart Problems

Lupus Nephritis

Arthritis

Raynaud’s Phenomenon: A condition in which some areas of the body feel numb and cool in certain circumstances

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Rheumatoid arthritis

A

A progressive inflammatory disease of the joints, the
disease can be very mild or severe.

Rheumatoid Factor: An IgM antibody that reacts against a patient’s own IgG antibodies, in 70-80% of patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Grave’s disease

A

Overproduction of thyroid hormones

Goiter that is soft instead of rubbery

Leads to hyperthyroidism
(overactive thyroid)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Hypersensitivity

Number:Type of hypersensitivity:Mediator:Example

A

I Anaphylactic IgE Hay fever, bee sting

II Cytotoxic Antibodies Goodpasture’s, AIHA-Autoimmune Hemolytic Anaemia

III Immune complex Antibodies SLE, Rheumatoid arthritis

IV Delayed T cells Contact sensitivity to nickel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Immunodeficiencies and their manifestations

A

B‐lymphocyte deficiency:
deficiency in humoral or antibody
mediated immunity

T‐lymphocyte deficiency:
deficiency in cell‐mediated
immunity

T‐ and B‐lymphocyte deficiency :
combined deficiency of antibody
and cell‐mediated immunity

Phagocytic cell deficiency

NK cell deficiency

Complement component deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

B‐lymphocyte deficiency:
deficiency in humoral or antibody
mediated immunity

A

Recurrent bacterial infections such as otitis media

and recurrent pneumonia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

T‐lymphocyte deficiency:
deficiency in cell‐mediated
immunity

A

Increased susceptibility to viral, fungal, and

protozoal infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

T‐ and B‐lymphocyte deficiency :
combined deficiency of antibody
and cell‐mediated immunity

A

Acute and chronic infections with viral, bacterial,

fungal, and protozoal organisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Phagocytic cell deficiency

A

Systemic infections with bacteria of usually low
virulence; infections with pyogenic bacteria;
impaired pus formation and wound healing

24
Q

NK cell deficiency

A

Viral infections, associated with several T‐cell
disorders and X‐linked lymphoproliferative
syndromes

25
Q

Complement component deficiency

A

Bacterial infections; autoimmunity

26
Q

Fairly common immunodeficiencies

A
  • IgA deficiency

* Transient hypogammaglobulinemia.

27
Q

• IgA deficiency

A

‐ 1:800 individuals.
– Decreased release of IgA by B lymphocytes.
– Recurrent sinopulmonary viral or bacterial infections and/or celiac disease (defective absorption in the bowel);
– Isolated IgA deficiency may also precede full‐blown expression of CVID (chronic variable immunodeficiency); the two disorders are often
found in the same families.
– Treatment:
• Hygiene, physio, antibiotics
• No infusions of immunoglobulins. These contain traces of IgA,
which is foreign to them, so they develop hypersensitivities
• The prognosis for selective IgA deficiency is generally good

28
Q

Transient hypogammaglobulinemia.

A

Occasionally infants do not make enough antibodies to replace the antibodies their mothers have given them (5‐6 months of age)

29
Q

Secondary (acquired) immunodeficiencies

A

• Immunosuppression:

– Treatment of autoimmune conditions
– Many forms of chemotherapy-kill off cells of the immune system as innocent bystanders

  • Infection: HIV, TB, measles
  • Malignancies: Hodgkin disease, leukeamia, solid tumours
  • Disorders of biochemical homeostasis: DM, chronic renal failure
  • Autoimmune disease: SLE
  • Trauma, burns
  • Environmental exposure: nuclear power station accidents

• Others: malnutrition, allogeneic blood transfusion, pregnancy, stress
(endogenous cortisol secretion?), aging

30
Q

Immunology of HIV

A
  • HIV infects cells of the immune system via CD4 and chemokine coreceptors (either CCR5 or CXCR4).
  • The reverse transcriptase enzyme used by HIV is particularly prone to errors. HIV is extremely adept at generating so‐called ‘escape mutants’.
  • Both virus‐specific T helper cells (TH) and cytotoxic T lymphocytes (CTL) are required to effectively eliminate an infected cell.
  • The pro‐virus can remain safely inside long‐lived cells (such as memory T‐cells), for years before being activated
  • Hallmark of HIV: progressive loss of activated CD4 cells and immunodeficiency. High affinity antibodies are lacking.
  • The emergence of HIV‐specific CTL responses is important for initial viral control. The lack of protective immunity in chronic infection is likely a result of multiple mechanisms that the virus uses to evade the host immune response.
  • Certain HLA haplotypes influence the rate of disease progression.
  • Individuals who are homozygous for a thirty-two base pair deletion in the CCR5 gene are more resistant to infection and individuals heterozygous for this deletion tend to have slower rates of disease progression.
  • Evidence of superinfection with a second strain of HIV suggests that immunity to the virus is incomplete and raises concerns about the ability to generate an effective vaccine.
  • Destruction of the cellular immune system is inevitable in the vast majorityof patients. The introduction of antiretroviral therapy leads to immune restoration
31
Q

Types of transplantation

MHC = Major histocompatibility complex
G

A

Autograft: Taking from the thigh to the face

Isograft/Syngraft: Twins

Allograft: Two different individuals

Xenograft: Different animals

32
Q

Human leucocyte antigens (HLA) genes

A

There are two different classes:

Class I and Class II

Class I: Expressed on all nucleated cells and Comprised of a chain bound to a B2 microglobulin/ A, B and C

Class II: Expressed on antigen presenting cells,Upregulated on endothelial and epithelial cells in in inflammatory conditions and comprised of two chains a and b / D(P,Q,R)

33
Q

Rejection of grafts

A

Blood group antigens occur mainly on red cells. Blood groups (ABO en Rh) are not so polymorphic.

Blood group crossmatching is easier.

HLA occurs on all cells except red cells. Very polymorphic. More complex crossmatching.

Hyperacute rejection:
– from preformed antibodies already in the circulation resulting from an immune response to previous blood transfusions (HLA or ABO)

Acute rejection:
– From immune response after the transplant

Chronic rejection:
– Subclinical microvascular inflammation (antibodies)

Tx: Immunosuppression

34
Q

Haematopoietic stem cell transplantation

Method:

Advantages:

Donors:

A

• Previously: bone marrow transplantation
• Done by isolating circulating stem cells
especially with blood cancers
• Transplant the immune system also-the transplanted immune system can often attack the blood cancer better:\

• Graft versus leukaemia
– Can attach the foreign environment around it

• Graft versus host disease

Donors: amongst siblings best, bone marrow registries

35
Q

Tumour immunology

A
  • The immune system does “immune surveillance”
  • Cancers can express fetal antigens, or new antigens resulting from mutated oncogenes
  • Everything from NK cells to Tregs can be involved
  • The tumour antigens can be only slightly different from normal, poorly expressed, or hidden, and not elicit a good immune response

• Treatment with recombinant antibodies:
– antiCD20(B-cell) and antiCD56 antibodies used for hematological cancers

36
Q

Which tests are conducted for cellular immunity

A

Full blood count

Flow cytometry

37
Q

Full blood count

A

This counts the total number of lymphocytes

in the blood (of which 80% are T cells)

38
Q

Flow cytometry

A

This can count the number of cells that have various Ags on their membranes, e.g. CD4+ cells

This helps to monitor the cellular immune system in HIV (normal CD4 count 500‐2000)

39
Q

What is meant by Antibody “strength” or titre

A
  • The strength of an antibody response can be roughly measured by serially diluting it.
  • It is diluted (titrated) until it shows no reaction.
  • A strong antibody reaction has a high titre (has to be diluted multiple times before there is no more reaction).

A tire of 1:32 is stronger than a titre of 1:4.

Antibody concentrations can be measured in other units also e.g. International Units

– An anti-HBsAg concentration > 10 mIU/mL is protective.

40
Q

A 22-year-old male, with significant cat allergies, visits a home with multiple cats. Two hours later, he arrives at an urgent care center with a severe exacerbation of asthma. He is treated with a short-acting bronchodilator and epinephrine. Initially, his symptoms resolved after treatment; however, 8 hours later he is forced to go the emergency room with another exacerbation. What is the most likely cause of his symptoms?

A) additional IgE cross-linking on mast cells leading to lipid mediator and cytokine release

B) CD4+ TH1 cell production of IFN-γ
C) complement activation leading to mast-cell degranulation by C5a and C3a

D) eosinophil and basophil infiltration leading to the release of proinflammatory mediators

E) neutrophil recruitment and the release of cytoplasmic granule components

A

D. The timing of the symptoms exhibited in this individual are characteristic of late-phase allergic reactions in which eosinophil infiltration occurs. This recruitment of eosinophils, as well as the passage of other leukocytes from the circulation to the tissue, is facilitated by the increased vascular permeability caused by proinflammatory cytokines and histamine.

41
Q

A 21-year old male who is allergic to cat dander is exposed to a friend’s cat while wearing a facial mask to reduce his contact with the allergen. Nevertheless, several hours later, he is wheezing and coughing.

Which of the following best explains this individual’s allergic reaction?

A) Mast cells in his gastrointestinal tract degranulated following the cross-linking of allergen-specific IgE on their surface, and the inflammatory mediators traveled to his lung.

B) Mast cells in his blood vessels degranulated following the cross-linking of allergen-specific IgE on their surface, causing a systemic inflammatory response.

C) Mast cells in his lung degranulated following the cross-linking of allergen-specific IgE on their surface.

D) Mast cells in his skin degranulated following the cross-linking of allergen-specific IgE on their surface, causing a systemic inflammatory response.

A

C. Despite the use of protective barriers such as facial masks to prevent an individual’s inhalation of allergens, small amounts of airborne antigens such as cat dander can enter by this route and cause degranulation of IgE-sensitized mast cells in the lung.

42
Q
  1. The usual sequence of events in an allergic reaction is as follows:

A) The allergen combines with circulating IgE, then the IgE-allergen complex binds to mast cells.

B) The allergen binds to IgE fixed to mast cells.

C) The allergen is processed by antigen-presenting cells and then binds to histamine receptors.

D) The allergen is processed by antigen-presenting cells and then binds to mast cells.

E) The allergen combines with IgG.

A

B. Allergic individuals have already made IgE responses to specific allergens. IgE binds passively to cells expressing highaffinity Fc receptors for IgE (e.g., mast cells) and interacts with the allergen when present. This results in cross-linking of the high-affinity FcεR, resulting in mast-cell degranulation. The allergen does not need to be processed by APCs in order to bind to IgE.

43
Q

Epinephrine

A) causes bronchodilation

B) is effective even after anaphylactic symptoms commence

C) relaxes smooth muscle

D) decreases vascular permeability

E) all of the above

A

E. All are effects of epinephrine and make it useful for treatment of acute anaphylactic symptoms.

44
Q

A human volunteer agrees to be passively sensitized with IgE specific for a ragweed antigen (allergen). When challenged with the allergen intradermally, he displays a typical skin reaction due to an immediate hypersensitivity reaction. If the injection with sensitizing IgE was preceded by an injection (at the same site) of Fc fragments of human IgE followed by
intradermal injection with allergen, which of the following outcomes would you predict?

A) No reaction would occur because the Fc fragments would interact with the allergen and prevent it from
gaining access to the sensitized mast cells.

B) No reaction would occur because the Fc fragments would interact with the IgE antibodies, making their
antigen-binding sites unavailable for binding to antigen.

C) No reaction would occur because the Fc fragments would interact with FcεR receptors on mast cells.

D) The reaction would be exacerbated due to the increased local concentration of IgE Fc fragments.

E) The reaction would be exacerbated due to the activation of complement

A

C. Since the IgE Fc fragments would bind to the high-affinity FcεR expressed on the surface of mast cells, the allergen specific IgE would not have access to these receptors and therefore would not bind to these cells. When the allergen is introduced intradermally, it would bind to the allergen-specific IgE at the site, but this would not result in cross-linking of FcεR, which is saturated with soluble IgE Fc fragments. Hence no immediate hypersensitivity reaction would take place.

45
Q

The following mechanism(s) may be involved in the clinical efficacy of desensitization therapy to treat patients with allergies to known allergens:

A) enhanced production of IgG, which binds allergen before it reaches mast cells

B) skewing of T-cell responses from TH2 to TH1

C) decreased sensitivity of mast cells and basophils to degranulation by allergen

D) decreased production of IgE antibody

E) all of the above

A

E. All are considered to be involved to varying degrees in injection therapy.

46
Q

Antihistamines

A) block H1 receptors and inhibit smooth muscle contraction, dilatation of small blood vessels, and mucus production
B) directly bind to histamine, blocking its inflammatory effect

C) influence the activity of leukotrienes

D) inhibit binding of IgE to mast cells

E) are adrenergic agents that mainly relax the bronchioles

A

A. Antihistamines act by blocking H1 histamine receptors, NOT histamine itself. They do not act by influencing the
activity of leukotrienes or by binding to IgE on mast cells and are not adrenergic agents.

47
Q
  1. Which of the following remains the gold standard for asthma management?
A) adhesion molecule antagonists
B) corticosteroids
C) antihistamines
D) allergen desensitization therapy
E) epinephrine
A

B. Corticosteroids remain the gold standard for asthma management and for several decades have been considered the cornerstone for asthma control. While it improves asthma symptoms, it does not alter the natural course of asthma or offer clear long-lasting improvement of respiratory performance. Therefore, the development of drugs capable of mitigating or avoiding CST side effects, toxicity, and resistance could usher in the development of new asthma
therapies.

48
Q
  1. Anaphylactic reactions

A) evolve in minutes and abate within 30 minutes

B) may be followed by inflammatory reactions hours later

C) are the consequences of released pharmacologic agents

D) may involve components of mast-cell granule matrix

E) all of the above

A

E. All are true. A and C are true of the classic wheal and flare type response, while B and D describe features of the late phase response, which is a complication of some anaphylactic reactions.

49
Q

Graves’ disease is an example of type II hypersensitivity whose pathophysiology is best explained by:

A) disease-causing antagonistic autoantibodies to cell surface receptors

B) disease-causing agonistic autoantibodies to cell surface receptors

C) disease-causing autoantibodies to nuclear antigens

D) disease-causing autoantibodies to acetylcholine receptors

A

A. In Graves disease, agonistic autoantibodies (as opposed to choice B, antagonistic autoantibodies) directed against thyroid-stimulating hormone receptors on thyroid epithelial cells stimulate the cells, resulting in hyperthyroidism. These antibodies are not generated in response to nuclear antigens or acetylcholine receptors. Therefore, choices C and D, respectively, are incorrect.

50
Q

Which of the following is most likely to involve a reaction to a hapten as its etiologic cause?

A) Goodpasture’s syndrome following a viral respiratory infection

B) hemolytic anemia following treatment with penicillin

C) rheumatoid arthritis following a parasitic infection

D) farmer’s lung following exposure to moldy hay

A

B. Penicillin can function as a hapten, binding to red blood cells and inducing a hemolytic anemia. A, C, and D are examples of immune aggregate (type III) reactions requiring complement and neutrophils for pathologic effects.

51
Q

In an experimental mouse model for the study of autoimmune hemolytic anemia, intravenous administration of a monoclonal IgA antibody specific for a red blood cell antigen did not cause anemia to occur.
The best explanation for this observation is that:

A) the IgA would localize in the gastrointestinal tract

B) the Fc region of the IgA antibody does not bind receptors for Fc receptors on phagocytic cells

C) IgA cannot activate complement beyond the splitting of C2

D) the IgA used has a low affinity for the red blood cell antigen

E) the IgA used requires secretory component to work

A

B. Since phagocytic cells have Fc receptors for IgG and not IgA, bound IgA would not cause engulfment and damage. Thus, A, C, D, and E are false.

52
Q

The glomerular lesions in immune complex disease can be visualized microscopically with a fluorescent antibody against:

A) IgG heavy chains

B) κ light chains

C) C1

D) C3

E) all of the above

A

E. The lesions in immune complex disease are dependent on the presence of antigen, antibody, and complement. Hence all can be demonstrated by immunofluorescence at a lesion: A and B, because they are parts of IgG; C and D, because they are the early components of complement activated by the immune aggregates.

53
Q
  1. The final damage to vessels in immune complex-mediated arthritis is due to:

A) cytokines produced by T cells

B) histamine and SRS-A

C) the C5, C6, C7, C8, C9 membrane attack complex

D) lysosomal enzymes of polymorphonuclear leukocytes

E) cytotoxic T cells

A

D. Neither T cells nor mast cells are responsible for the final tissue damage in immune complex disease. Therefore A, B, and E are eliminated. The final lytic complex of complement is similarly not involved, since complement activation up to C5 is sufficient to bring in the polymorphonuclear leukocytes, whose lysosomal enzymes cause the tissue damage.

54
Q

Serum sickness is characterized by:

A) deposition of immune complexes in blood vessel walls when there is a moderate excess of antigen

B) phagocytosis of complexes by granulocytes

C) consumption of complement

D) appearance of symptoms before free antibody can be detected in the circulation

E) all of the above

A

E. All are characteristics of serum sickness

55
Q

Type II hypersensitivity

A) is antibody-independent
B) is complement-independent
C) is mediated by CD8+ T cells
D) requires immune complex formation
E) involves antibody-mediated destruction of cells
A

E. Type II hypersensitivity reactions occur following development of antibodies against target antigens expressed on normal cells or cells with altered membrane determinants.

Antibodies bind to the surface of these cells and mediate damage or destruction by one or more mechanisms, including complement-mediated reactions. CD8+ cytotoxic T cells and immune complexes are not involved in these reactions.

56
Q

Immune complexes are involved in the pathogenesis of which of the following rheumatic fever-associated diseases:

A) poststreptococcal glomerulonephritis

B) pigeon breeder’s disease

C) serum sickness

D) autoimmune hemolytic anemia

A

A. Rheumatic fever is a disease associated with infections caused by group A streptococci. It involves the development of anti-streptococci antibodies that are cross-reactive with antigens present in human heart muscle, cartilage, and glomerular basement membrane.

57
Q

A patient is suspected of having farmer’s lung. A provocation test involving the inhalation of an extract of moldy hay is performed. A sharp drop in respiratory function is noted within 10 minutes and returns to normal in 2 hours, only to fall again in another 2 hours. The most likely explanation is that:

A) the patient has existing T cell-mediated hypersensitivity

B) this is a normal pattern for farmer’s lung

C) the patient developed a secondary response after the inhalation of antigen

D) the symptoms of farmer’s lung are complicated by an IgE-mediated reactivity to the same antigen

E) all of the above

A
  1. D. Type III hypersensitivity reactions in farmer’s lung and similar occupational diseases have an onset of symptoms that usually occur several hours after exposure to the causal antigen. The appearance of breathing difficulties within minutes would create a strong suspicion that a type I anaphylactic response is also present. Presumably the patient made both
    IgE and IgG antibodies to the actinomycete antigens. A positive wheal and flare reaction on skin testing would provide further confirmation.

Haematology (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions