Brainscape's Knowledge GenomeTM

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


See full index

Pathobiology > Immunopathology > Flashcards

Immunopathology Flashcards

1
Q

What are the steps of neutrophils getting into the interstitium and initiating phagocytosis?

A
  1. Margination (blood stasis)
  2. Rolling (via selectins on endothelium / sialyl-lewis receptors on leukocytes)
  3. Adhesion (integrins on leukocytes / ICAM/VCAM on endothelium)
  4. Transmigration (PECAM-1/CD-31 and collagenases)
  5. Activation and attachment - via TLRs and receptors for cytokines / opsonins
  6. Phagocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What cells in the tissue release inflammatory cytokines initiating the innate immune response?

A

Mast cells and dendritic cells (note that DCs make IL-1 / TNF)

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

What can be seen in the cytoplasm of natural killer cells, and what two types of killing to they participate in?

A

Large granules - contain perforin / granzymes

  1. More activating receptors than inhibitory receptors activated (inhibitory receptors activated by MHC Class 1 binding typically, indicating a normal, healthy cell). These theoretically scoop up virally infected cells which CD8+ T cells cannot recognize
  2. Antibody-dependent cell-mediated cytotoxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Do NK cells secrete cytokines?

A

Yes - They also secrete IFN-y (stimualte macrophages, which stimulate them by IL-12) and TNF like DCs

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

What are the two arms of the adaptive immune system, and what are they typically directed towards?

A

Cell-mediated - effective against intracellular pathogens (i.e. viruses, intracellular bacteria, fungi, etc)

Humoral / antibody-mediated - targeted against extracellular microbes

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

How does the adaptive system help the innate immune system?

A

While the innate system already has complement and C-reactive protein for opsonization, the antibodies produced by humoral immunity are also effective opsonins for macrophage / PMN phagocytosis. Furthermore, signalling via cytokines from innate immunity also helps increase phagocyte activation.

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

Are T or B cells more mobile? How does the more mobile one get to lymph nodes?

A

T cells - since they must directly interact with cells to have a function (2/3 of all circulating lymphocytes)

Chemokines attract T cells to lymph nodes from the blood stream, and they are naive since they haven’t encountered antigen.

They undergo the normal process of margination / adhesion, etc, and enter through the high endothelial venules in the paracortex region, where they will sit in the paracortex.

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

Where does T cell development occur? What is associated with the receptor?

A

Occurs in the thymus (also they are produced by lymphoid line in the bone marrow)

Associated with TCR is two CD3 receptors, as well as two zeta or two eta chains.

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

Why do CD8 cells require a professional APC for activation if MHC Class 1 is constitutively expressed on all nucleated cells?

A

Professional APC will use its B7 to bind the CD28 co-receptor on T cells to provide the second activation signal, thus activating that CD8 T cell into a T-memory or T-effector cell which can go kill all nucleated cells expressing that ligand on MHC Class 1.

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

What type of MHC do CD4+ T cells bind, and what important cytokines do they secrete / ligands to they express for maturation of the immune response (humoral immunity)? What will result if this ligand is not expressed?

A

Bind MHC Class 2, since 2x4 = 1x8

Secrete IL-2 for clonal expansion of T cells, as well as other cytokines to direct the exact immune response

Important ligand: CD40L -> binds CD40 on B cells to activate a specific class switching, in a specific cytokine environment.

If CD40L or CD40 is deficient -> Hyper-IgM syndrome, with decreased IgA/IgG/IgE because of defective class switching

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

What cytokines does the Th1 subset secrete and what does this do? What causes formation of this subset?

A

Secretes IFN-y -> activates macrophages, induces class switching to IgG, suppresses Th2 response

Induced by macrophages secreting IL-12, IFN-y

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

What cytokines does the Th2 subset secrete and what does this do? What causes formation of this subset?

A

Secretes IL-4, IL-5, and IL-13

IL-4 - Class switching to IgE, inhibits Th1
IL-5 - Eosinophil chemotactic agent

Induced by IL-4, IL-2 from APCs

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

What cytokines does the Th17 subset secrete and what does this do? What causes formation of this subset?

A

Secretes IL-17 -> recruits inflammatory response via neutrophils and monocytes

Induced by TGF-beta in combination with IL-6

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

What are the two types of Treg cells and what cytokines do they release? What causes formation of these subsets?

A

All secrete IL-10 / TGF-beta, which suppress the immune response

Natural T-regs = CD4+,CD25+, FoxP3+ T cells which were developed in thymus, suppress autoreactive T cells

Adaptive regulatory T cells = Originally CD4+ cells which are induced to express CD25 marker in the periphery, typically involved in mucosal immunity (i.e. MALT)

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

What are the two CD8+ killing mechanisms?

A
  1. Perforin / granzyme pathway of direct killing, also induces apoptosis
  2. Induction of apoptosis via FasL binding Fas receptors on cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Where do B cells live, and what is a primary vs secondary lymph follicle?

A

They make up less than 1/3 of circulating lymphocytes, living primarily in the cortex of lymph nodes

Primary follicles - small, naive B cells
Secondary - Contain a germinal center with pale area representing replicating B cells which have encountered antigen, undergoing class-switching and affinity maturation

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

What is the sequence of events which results in B and T-cell dependent antigens co-activating these two cell lines.

A

A B cell binds an extracellular antigen via its B cell receptor (immunoglobulin), then internalizes and processes this antigen. It will present a portion of the antigen on its MHC Class 2 (acts as a professional APC).

CD4+ T cell will bind MHC Class 2 if it can recognize the same antigen as that B cell. The B7 of the B cell will bind CD28 on T cell, signalling its activation.

For further maturation of the immune response, CD40L of the T cell binds CD40 receptor on B cells, activating it / inducing class switching.

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

How does Thymic Independent (TI) activation of B cells work, and why is it not always preferable to T cell activation?

A

Certain large peptides like LPS or the pneumococcal capsule sugars can activate B cells in the absence of T cell recognition.

The response will be IgM only (no class-switching is available without T cell help), will generate no memory, and are generally poorly immunogenic. This is why we conjugate the pneumococcal vaccine with an immunogenic protein, so T cell help will activate memory and a sustained immune response.

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

Where do dendritic cells exist and what is their primary function?

A

Widespread in epithelial surfaces and interstitium of tissues, can be recruited to paracortex of lymph nodes via chemokines

-> function to present antigen primarily to CD4 T cells.

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

Where are follicular dendritic cells present and what is their function?

A

Exist in germinal centers of lymphoid follicles, function to hold onto antigens for long periods of time and present these to B lymphocytes, promoting their activation. They sit there and accept antigens from them and hold onto them while they mutate and adapt.

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

What are the 6 HLA / MHC loci and what chromosome do they exist on?

A

Like their number, chromosome 6!

1 letter for MHC Class 1: HLA-A, HLA-B, HLA-C
2 letters for MHC Class 2: HLA-DP, HLA-DQ, HLA-DR

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

What is the function of MHC Class 1?

A

Expresses cytoplasmic proteins (proteins made within the cell). These are degraded on proteasome, transported into the ER via TAP-1/TAP-2, and put into MHC Class 1 molecules on all nucleated cells + PLATELETS.

They present these peptides on the surface of the cell to CD8+ T cells.

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

What cells have MHC Class 2 and what can increase their expression?

A

Located on B cells, dendritic cells, and macrophages, but only constitutively expressed in dendritic cells. Upregulated via IFN-y.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the function of MHC Class 2?

A

Expresses exogenous antigens which were cleaved in intracelullar vesicles, presenting peptides to CD4+ T cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How do NK cells activate antibody-dependent cell-mediated cytotoxicity?

A

Their Fc receptors bind an immunoglobulin which has bound a cell (part of adaptive immune response), and they release perforin / granzymes into the target cell. Can also use FasL death receptor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is Type 1 Hypersensitivity and what antigen-presenting cells are involved in the sensitization phase? How does this occur?

A

Immediate Hypersensitivity Reaction

2 APCs involved

  1. Dendritic cells - present allergen via MHC Class II, while secreting IL-4 -> turn naive T-cells into allergen-specific Th2 cells, with clonal expansion
  2. B cells - bind allergen via their BCR’s, internalize, and present via MHC Class II. This further activates Th2 cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Once sensitized Th2 cells are made, how does the sensitization phase of Type 1 hypersensitivity complete?

A

Allergen-specific active Th2 cells use their CD40L to stimulate class-switching of antigen-specific B cells (via CD40) in the presence of IL-4 stimulation. This creates IgE-secreting plasma cells.

IgE will attach to Fc receptors on basophils and mast cells, ready for next immune challenge.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What generally occurs in subsequent exposures of allergen in Type 1 hypersensitivity (following sensitization)?

A
  1. Eosinophil development, recruitment, and activation (via IL-3, IL-5, and GM-CSF)
  2. Cross-linking of IgE on mast cells / basophils, with activation and degranulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What mediates the immediate reaction in Type 1 Hypersensitivity?

A
  1. Biogenic amines -> histamine
  2. Chemotactic factors for eosinophils
  3. Enzymes (i.e. proteases)
  4. Proteoglycans, which account for the metachromatic staining of basophils / mast cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What two processes mediate the late phase reaction of Type 1 hypersensitivity?

A
  1. Activation of phospholipase A2.
    From arachidonic acid: make leukotrienes B4,C4, and D4 and PGD2 from cell membrane
    From phospholipids: makes platelet-activating factor.
  2. Secretion of cytokines/chemokines: i.e. IL-4, IL-5, TNF, and IL-1 -> proinflammatory and pro-TH2.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the major histopathologic findings of someone with chronic Type 1 hypersensitivity reactions?

A

As in asthma:

  1. Bronchial smooth muscle contraction leading to hyperplasia
  2. Increased respiratory glandular secretions (PSCC -> goblet cells via mucinous metaplasia)
  3. Infiltration of chronic inflammatory cells, especially eosinophils
  4. Exudative edema due to increased vascular permeability / vasodilation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are the clinical features that can result from increased vasodilation, increased edema, bronchoconstriction, and increased glandular / mucinous secretions?

A

Vasodilation -> localized erythema which may cause shock

Edema -> hives on skin, or nasal / laryngeal edema

Bronchoconstriction -> wheezing / airway constriction following bronchospasm

Glandular / mucinous secretions -> rhinorrhea and even mucous plugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What must antibodies be reacting to to constitute a Type II hypersensitivity reaction?

A

Antibodies bind to a fixed cell surface or tissue antigen.

The tissue antigen can be native to the tissue, or adsorbed onto the tissue (i.e. a microbial product or a drug like penicillin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What are the ways in which a cell can be phagocytosed in Type II hypersensitivity?

A

Both are facilitated an antibody binding a cell antigen (definition of type 2 hypersensitivity)

  1. Fixation of complement following the cascade, via C3b receptors
  2. Direct target phagocytosis using immunoglobulin Fc as receptors.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Other than opsonization, give two other ways complement can cause tissue damage in T2 hypersensitivity?

A
  1. Cell lysis -> formation of MAC

2. Acute inflammation leading to tissue injury -> via C3a / C5a anaphylatoxins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Name those two Type II hypersensitivity diseases.

  1. Antibodies to epidermal desmosomes
  2. Antibodies direct against glomerular and pulmonary basement membranes
A
  1. Pemphigus vulgaris

2. Goodpasture syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Other than complement mechanisms, give to other broad categories of Type II hypersensitivity mechanisms.

A
  1. Antibody-dependent cell-mediated cytotoxicity (ADCC)

2. Antibody-mediated cellular dysfunction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How does ADCC work? Give one example.

A

Antibody binds target cell, facilitates killing of the cell via natural killer perforin/granzymes pathway.

Example is killing of tumor cells in cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is the difference between ADCC and antibody-mediated cellular dysfunction? Give two examples of the latter.

A

Antibody-mediated cellular dysfunction does not cause cell death, just impairs the function of the cell.

  1. Myasthenia gravis - antibodies to Ach receptors in motor end plate
  2. Graves disease - antibodies which stimulate TSH receptors on thyroid follicular cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is the definition of Type III hypersensitivity?

A

Immune complexes form and deposit in tissues, or the immune complexes form when antigens get lodged in tissues.

These immune complexes cause activation of complement once deposited, which mediates the tissue injury via influx of acute inflammatory cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is the main difference between Type II and Type III hypersensitivity?

A

Type III hypersensitivity is forming immune complexes to a SOLUBLE antigen, which may be circulating or planted

Complement will ALWAYS be involved in tissue damage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are some examples of exogenous antigens which can cause Type III hypersensitivity?

A

Microbial antigens
Drugs
Animal serum (serum sickness)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What types of “self” antigens can generate type III hypersensitivity?

A

Things that are soluble -> i.e. nuclear antigens in lupus.

Will fix complement and mediate cellular damage.

Also cancer cells, if mechanism is not ADCC (which would be a type II hypersensitivity), but rather complement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What is an example of a local Type III hypersensitivity and how does it work?

A

Arthus reaction -> antigen is injected, circulating antibody neutralizes it and forms immune complexes directly in the area where the antigen was injected. Complement is fixed in tissues and a skin rash is formed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

How can an exogenous antigen cause systemic immune complex disease? What factors control the rate of deposition

A

Example: serum sickness

Controlled by factors of 1. the immune complex: how large, the charge, the structure, as well as 2. host factors (how well are phagocytes clearing these immune complexes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Where in the body do immune complexes tend to deposit and why?

A

Areas where the complexes are present or being filtered

i.e.
Small / medium sized vessels -> complexes lodged from blood stream

Renal glomeruli -> where complexes are filtered out and get lodged in basement membrane

Joints -> synovial fluid made as an ultrafiltrate of plasma

Skin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What initiates the tissue damage in Type III hypersensitivity?

A

Everything initiated by complement, including vasodilation, increased vascular permeability, opsonization, chemotaxis of inflammatory cells, and cell lysis by MAC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What causes secondary damage following complement in Type III hypersensitivity?

A

Degranulation and ROS via PMNs and macrophages, with resultant endothelial damage and activation of primary / secondary hemostasis and coagulation cascade.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What histologically characterizes Type III hypersensitivity?

A

Typically fibrinoid necrosis of small to medium-sized blood vessels from chronic activation of the clotting cascade -> deposition of fibrin in vessels

This will be accompanied by acute inflammatory cells, edema / hemorrhage, and possible thrombosis of vascular lumen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

How can Type III hypersensitivity lead to ischemic necrosis?

A

Lodging of immune complexes in blood vessels with formation of vascular luminal thromboses cause clotting which reduces blood supply to a tissue.

-> ischemic / coagulative necrosis results

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What laboratory visualizing techniques are commonly utilized to assess presence of antibody complexes in tissues?

A
  1. Most common - Direct immuno-fluorescence (anti-Ig or anti-complement)
    - > antibodies are tagged with fluorescent marker
  2. More rarely -> electron-dense deposits on electron microscopy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Give two examples of type III hypersensitivity disease.

A
  1. Acute poststreptococcal glomerulonephritis

2. Systemic lupus erythematosus (SLE)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What are the two types of Type IV hypersensitivity? Give two examples of each.

A
  1. Delayed-type hypersensitivity
    - > contact dermatitis due to poison ivy (atopic dermatitis is Type 1)
    - > tuberculosis skin testing
  2. Cytotoxic T-cell mediated hypersensitivity.
    - > Graft-versus-host disease
    - > Hashimoto’s thyroiditis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What are the two phases of delayed-type hypersensitivity, and what happens in the first phase?

A
  1. Sensitization phase -> APC presents peptide via MHC Class II to response CD4+ T cell, becomes Th1 cells via stimulation via IL-12. This takes 1-2 weeks.
  2. Effector phase - happens after 1-2 days following secondary exposure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

How does the sensitization phase of Type IV hypersensitivity differ from Type I hypersensitivity?

A

Type I hypersensitivity - IL-4 stimulates CD4 differentiation into Th2 cells, which facilitate B cells to make IgE

Type IV hypersensitivity - IL-12 stimulates CD4 differentiation into Th1 cells, which facilitate secretion of IFN-y

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What occurs in the effector phase of Type IV hypersensitivity?

A
  1. Activation and proliferation memory Th1 cells
    - > secrete IFN-y, IL-2, TNF, and chemokines to recruit monocytes
  2. Monocytes are activated to M1 macrophages via IFN-y, and stimulate further Th1 proliferation via their IL-12. More TNF, IL-1, and chemomkines are made.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What are the initial and late histopathological findings of Type 4 hypersensitivity effector phase?

A
  1. Initial -> diffuse infiltrate of Th1 cells
  2. Later -> collections of activated macrophages, surrounded by Th1 lymphocytes. This is the granulomatous inflammation we know and love.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What is the pathogenesis of the cytotoxic T cell-mediated hypersensitivity (a subset of Type 4)?

A

APC like macrophage or dendritic cell presents via MHC Class 1 a cytoplasmic peptide of a cell class you don’t want killed.

CD8 T cells begin killing good cells via perforin / granzymes or Fas/FasL pathway (i.e. Type 1 diabetes, Hashimotos, Graft-vs-host)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What is the direct pathway of graft recognition?

A

Usage of donor’s APCs to stimulate host CD4 or CD8 T cells via the proper MHCs to result in activation

  1. CD8 cells are activated by cytoplasmic peptides of the graft APCs being presented on MHC Class I, which are recognized as foreign by the receipient’s T cells.
  2. CD4 T cells are activated by APCs presenting any extracellular peptides on MHC Class II, thus allowing recognition of donor MHC.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What is the effect of the direct pathway in terms of graft rejection?

A

Results in acute rejection (cell-mediated)

CD8 T cells directly kill graft cells

CD4 T cells activate macrophages via IL-2 and IFN-y and amplify the inflammatory response, leading to graft damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What seems paradoxical about the direct pathway of graft rejection?

A

Our T cells should not be able to be activated by another person’s MHC -> there must be some molecular mimicry going on where foreign MHC + foreign peptide looks somewhat like self MHC.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What is the indirect pathway of graft recognition important for, and which type of T cell participates? Why?

A

Important for development of chronic rejection

CD4+ T cell participates, but not CD8 T cell since the indirect pathway relies on host APCs presenting to T cells. Host APCs will not be able to present graft material as intracellular / cytoplasmic foreign material, only extracellular (CD4 pathway only).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What type of hypersensitivity are the indirect and direct pathways of graft rejection?

A

All type-4, cellmediated hypersensitivities.

Only the direct path contains CD8+ T cells which participate in Cytotoxic T-cell mediated hypersensitivity, the rest are CD4+ delayed-type hypersensitivities.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What causes hyperacute rejection, and what provides the prior sensitization stimulus?

A

When the recipient has preformed antibodies towards donor antigens

-> can be due to previous transplant, blood transfusions (contain WBCs), or pregnancies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

How does acute humoral rejection differ from hyperacute?

A

Acute humoral rejection involves newly-formed antibodies in the recipient directed against the graft, overtime. Requires T cell help for the most part, and normally days to weeks later weeks to manifest.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What type of hypersensitivity is hyperacute graft rejection, and what does it look like?

A

It is a type 2 hypersensitivity (tissue antigen, insoluble), looks like type 3 because of high levels of complement deposition in tissues, but it’s the donor’s tissues.

  • > edema
  • > acute inflammatory infiltrate
  • > endothelial cell damage, fibrinoid necrosis, hemorrhage, and thrombosis
  • > tissue infarct
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What are the symptoms of acute rejection of kidney transplant?

A

Increased serum creatinine, decreased urine output, and development of renal failure days to weeks after transplantation / reduction in immunosuppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What are the two primary mechanisms of acute rejection, and which is more easily treatable?

A
  1. Cell-mediated - due to T-cell overactivity (from direct pathway)
    - > easily treated by increasing immunosuppression (most immunosuppressives effective against T-cell proliferation)
  2. Humoral - due to antibodies formed after transplantation. More difficult to treat.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

How does acute, cell-mediated rejection appear histologically?

A

Interstitial inflammatory infiltrate with T cells and macrophages, injuring tubules (tubulitis) and vascular endothelium (endothelitis and edema)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

How does acute, humoral rejection appear histologically? There are really two presentations here, and one is more common.

A

Since it is due to antibodies, it usually appears exactly like hyperacute rejection (just later).

  1. Most common - A type 2 hypersensitivity which looks like type 3 w/ associated vasculitis and fibrinoid necrosis.
  2. Alternatively, can present with vascular intimal thickening via foamy macrophages which are recruited by antibodies which cannot fix complement (low avidity). Fibroblasts and SMCs will proliferate due to cytokine production and lead to tissue atrophy. Not associated with vasculitis, more vessel stenosis by thick intima.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What is the timescale of chronic rejection and what lab values are associated with it?

A

Typically years after transplantation, may follow acute rejection which did not resolve, multiple resolved acute rejections, or indolent course without any past history of rejection.

Associated with: slowly increasing serum creatinine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What immunologic mechanism is behind chronic rejection?

A

Indirect pathway of CD4+ T cell activation
-> activated macrophages and APCs present alloantigens from broken down graft / areas of ischemia, which leads to further T cell activation and subsequent inflammation & breakdown of graft for more antigen presentation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

What are some non-immunologic mechanisms of graft rejection?

A
  1. Insufficient nephron mass (small kidney in bring person leading to glomerular hyperfiltration)
  2. Reperfusion injury at engraftment
  3. Infections due to immunosuppressive therapy
  4. Immunosuppressive drug toxicity
  5. Increasing age of recipient with atherosclerosis / hypertension
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

What are atubular glomeruli?

A

A mechanism of graft breakdown whereby autoimmune destruction of the tubules will lead to loss of glomeruli which supply them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

What is the dominant pathologic feature of chronic graft rejection?

A

Scarring -> vascular fibrosis with intimal thickening, interstitial fibrosis, tubular atrophy, and chronic inflammatory infiltrate.

-> fibroblasts and interstitial fibrosis aplenty

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What is the most important thing to prevent hyperacute rejection?

A

ABO blood group compatibility

-> check this to make sure graft won’t be instantly rejected due to blood in it when you first put it in

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Other than ABO compatibility, what three things are done to prevent solid organ transplant rejection?

A
  1. HLA matching (especially in renal transplants)
  2. Immunosuppressant therapy
  3. Induction of immune tolerance by using agents which selectively block co-stimulatory molecules, inducing anergy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Can antibodies play a role in chronic rejection?

A

Yes, if Th1 cells stimulate the proliferation of B cells.

79
Q

What mediates transplant rejection in allogeneic hematopoeitic stem cell transplant?

A

Recipient’s surviving T cells and NK cells (immune system is supposed to be ablated prior to transplantation)

80
Q

Give two reasons why a little bit of graft versus host disease (GVHD) might be good?

A
  1. Reduces chances of graft rejection -> remaining recipient T cells which were not ablated will be killed by the donor’s immune system
  2. Donor cells are often given in malignancy conditions, and if the graft immune system can recognize the host tumors, it can serve better anti-tumor properties
81
Q

What are the common manifestations of GVHD in terms of which tissues are affected?

A
  1. Skin -> often maculopapular rash acutely, with dermal fibrosis chronically
  2. Liver - often jaundice due to injured bile ducts
  3. Mucosal surfaces like GI tract, eyes, and mouth can be damaged leading to N/V, eye dryness
  4. Lymphoid organs -> destruction of thymus and LN
82
Q

What is central tolerance? What different processes do T / B cells undergo? What must occur if these mechanisms fail?

A

Prevention of auto-reactivity of T-cells or B cells during the maturation process within the primary lymphoid organs.

T cells will be eliminated via apoptosis, with a small amount becoming Tregs

B cells will be eliminated via apoptosis in the bone marrow, undergo anergy, or may undergo receptor editing (via light chain editing)

If these mechanisms fail - need peripheral tolerance to prevent autoreactivity (backup systems in the periphery)

83
Q

How does peripheral anergy of T cells occur?

A

T cell binds MHC + self antigen, and does not see a costimulatory signal, or its CD28 binds an inhibitory signal (CTLA4 rather than B7)

84
Q

How does peripheral anergy of B cells occur?

A

Usually due to lack of self-reactive helper T cells.

85
Q

How are T cells suppressed by Tregs?

A

T-regs recognize that self-antigen is being bound, and locally release regulatory cytokines, suppressing this autoreactivity (Remember that Tregs have intermediate self-antigen reactivity)

86
Q

How does activation-induced cell death of T-cells occur?

A

Initially, T-cells are resistant to Fas-mediated apoptosis. However, as they become overactive, they will T cells will overexpress Fas / FasL, allowing for paracrine / autocrine deletion via apoptosis.

87
Q

What are a few immune-privileged areas, and how do they deal with the immune system targeting self-antigens there?

A

Brain, testes (brain-testis barrier via sertoli cells), and eyes (prevent clouding of cornea)

Two main mechanisms
1. Hiding of self antigen

  1. Expression of FasL on tissues to induce apoptosis in any cell that comes near.
88
Q

What are genetic factors that can lead to loss of tolerance?

A

Usually, expression of problematic MHC molecules, or loss of a self-tolerance mechanism due to a single gene mutation

89
Q

How can a microbial infection initiate an autoimmune reaction?

A
  1. Increases expression of co-stimulatory molecules on APCs which are also presenting self antigen.
  2. Creating an immunologic cross-reaction via molecular mimicry (amplification of autoreactive T cells), as in S. pyogenes infection
90
Q

How can autoimmune conditions become progressively worse after initiation?

A

Via the process of epitope spreading -> antigens not normally seen without tissue damage will become expressed, further continuing lymphocyte activation vs self-antigens

91
Q

Who is typically diagnosed with systemic lupus erythematosus?

A

African American Women in their early 20s.

92
Q

What two auto-antibodies are very specific but not sensitive for SLE?

A
  1. Anti-dsDNA

2. Anti-Smith antigen

93
Q

How can inherited complement deficiencies predispose to SLE T3 hypersensitivity?

A

RBCs express C4 receptors. When in circulating, immune complexes can attract the early stages of complement cascade, and the C4 component can stick to these RBCs, clearing them out of circulation when they get to the spleen.

If you have complement deficiencies, these Ab complexes cannot be cleared as well -> worse autoimmune manifestions

94
Q

What are some environmental triggers of SLE?

A

Certain medications (i.e. hydralazine, drug-induced lupus)

Exposure to UV radiation -> exposes nuclear antigens in the epidermis.

95
Q

What is the general pathogenesis of SLE? Include the three major classes of antibodies which are formed.

A

Loss of self-tolerance and activation of auto-reactive CD4+ T cells -> activation of B cells specific to self antigens.

  1. Anti-nuclear antibodies (ANAs)
  2. Antibodies vs formed blood elements (RBCs, platelets, WBCs)
  3. Antiphospholipid antibodies
96
Q

What are the clinical manifestations of these three antibody types? What type of hypersensitivity are these, when relevant?

A
  1. Anti-nuclear antibodies (ANAs) - immune complex formation in small blood vessels (i.e. glomeruli) - Type III hypersensitivity
  2. Antibodies vs formed blood elements (RBCs, platelets, WBCs) - anemia, thrombocytopenia, or leukopenia (Type II hypersensitivity)
  3. Antiphospholipid antibodies
    - > delayed coagulation in vitro -> lupus anticoagulant antibodies
    - > hypercoagulability in vivo -> antiphospholipid antibody syndrome
97
Q

What does SLE do to your arteries?

A

Type 3 hypersensitivity -> Leads to fibrinoid necrosis & inflammation, with fibrous scarring in multiple organs

-> can even lead to non-inflammatory occlusions especially in kidneys and CNS (i.e. strokes) due to antiphospholipid antibodies predisposing to thrombus formation

98
Q

What kidney condition does SLE cause and why?

A

Diffuse proliferative glomerulonephritis, due to Type 3 hypersensitivity, and resultant fibrinoid necrosis, acute inflammation, and thrombosis

99
Q

What are “wire loops” of SLE?

A

Very thick glomerular capillaries seen in SLE due to extensive immune complex deposition

100
Q

What is the most common type of skin involvement for lupus? Why?

A

Erythematous rash on the face (butterfly / malar rash) -> sun exposure areas receive UV radiation damage and expose the epidermal nuclear antigens

101
Q

Where do antibodies tend to get stuck in the skin and what does this cause on a histological level?

A

Usually get stuck at the dermo-epidermal junction, especially affects basal cells - can be seen by direct immunofluorescence

-> this is often associated with some dermal vasculitis (T3 hypersensitivity)

102
Q

How will direct immunofluorescence findings differ between systemic and local lupus syndromes?

A

Systemic -> immune complexes will be deposited at DE junctions even where there’s no rash

Local -> complex deposition will only occur where there is active pathology

103
Q

Other than skin, kidneys, and arteries, give a few other places where immune complexes are known to cause problems in lupus?

A
  1. Joints -> ultrafiltrate of plasma, type 3 hypersensitivity
  2. Serosal surfaces -> fibrinous inflammation of peritoneum and especially pericardium
  3. Heart -> especially valves (vegetations) and pericardium (pericarditis)
104
Q

How does lupus predispose to atherosclerosis, especially coronary arteries?

A

High levels of constant inflammation -> elevated C-reactive protein = risk factor for atherosclerosis

105
Q

How are lymphoid organs affected by lupus?

A

Follicular hyperplasia in lymph nodes and spleen due to increased number of plasma cells

106
Q

How is lab detection of anti-nuclear antibodies different than detection of antibody-complexes present within tissues normally? Is this test specific or sensitive?

A

Uses indirect immunofluorescence -> use patient’s serum on cells with exposed nuclei, then apply fluorescently tagged anti-immunoglobulins

Sensitive but not specific -> lupus almost always associated w/ positive ANA, just don’t know which Ab

107
Q

What are two common, nonspecific patterns of fluorescence via the ANA indirect immunofluorescence test?

A
  1. Homogenous pattern -> antibodies to diverse nuclear complements including DNA
  2. Speckled pattern -> antibodies to non-DNA nuclear components (i.e. Smith antigen)
108
Q

What does a rim (peripheral) pattern mean via the ANA indirect immunofluorescence test?

A

Very specific pattern for SLE -> antibodies to dsDNA

109
Q

What does a nucleolar pattern mean via the ANA indirect immunofluorescence test?

A

Seen in systemic sclerosis normally -> antibodies to nucleolar RNA

110
Q

What does a centromere pattern (with glowing of the mitosis / division) mean via the ANA indirect immunofluorescence test?

A

Seen in limited system sclerosis (CREST syndrome)

111
Q

When is specific ANA characterization done?

A

Following a positive IF-ANA test

-> more expensive, can tell if anti-dsDNA or anti-Smith specifically

112
Q

What lab value do antiphospholipid antibodies elevate, and what test will be interfered with due to their presence?

A
  1. Prolonged aPTT (contact activator, intrinsic pathway)
  2. Syphillis test - FTA-ABS -> will react with cardiolipin, seem as nonspecific antibodies generated in syphillis infection.
113
Q

What are LE cells / hematoxylin bodies?

A

An old test for lupus -> can shake up patient’s anticoagulated blood.

If you see neutrophils or macrophages which have eaten nuclei of injured cells from shaking (nuclei were opsonized by ANAs) -> they have lupus

LE cell = Lupus erythematosus cells

114
Q

What are common general complaints / clinical findings in lupus? How is it treated?

A

Fever, malaise, malar rash, joint pain, hematuria / RBC casts, proteinuria

Treated with immunosuppressants

115
Q

What is the highly local lupus variant, and what are its clinical manifestations? How do lesions appear grossly and microscopically?

A

Chronic discoid lupus erythematosus -> a scarring dermatosis

Involvement of sun-exposed skin on face and scalp, with no antibodies in non-lesional skin

116
Q

How do lesions of chronic discoid lupus erythematosus appear grossly and microscopically?

A

Lesions will appear as scaly skin plaques with red border, and will form scars.

Microscopically, there will be epidermal atrophy, and chronic inflammation around the DE junction (involves basal cells)

117
Q

How does subacute cutaneous lupus erythematosus differ from chronic discoid lupus erythematosus?

A

Different ANA antibodies cause it, and it results in a mild, non-scarring rash.

Importantly, it will also have some systemic manifestations (not totally local)

118
Q

Does drug-induced lupus go away after the drug is removed? Will there be ANAs?

A

Yes - it goes in remission

And yes, there will be ANAs, although not anti-dsDNA or anti-Smith

119
Q

What is Sjogren syndrome and its two forms? What is the secondary form commonly associated with?

A

Chronic autoimmune disorder of lacrimal and salivary glands, common in middle-aged women

Primary - sicca syndrome (dry eyes / mouth)

Secondary - associated with another immune disease -> especially rheumatoid arthritis

120
Q

What are antibodies typically direct against in Sjogren syndrome?

A

Rheumatoid factor (in secondary) and ribonucleoproteins SS-A (Ro) and SS-B (La)

SS = Sjogren syndrome

121
Q

What are the early and late manifestations of Sjogren syndrome in lacrimal / salivary glands?

A

Early - lymphocytic and plasma cell infiltration with ductal epithelial hyperplasia

Late - Glandular fibrosis / atrophy

122
Q

Other than lacrimal / salivary glands, what other surfaces can be affected in Sjogren’s syndrome?

A
  1. Mucosal surfaces like cornea, mouth, and nose
    - > ulceration and inflammation secondary to drying (loss of lacrimal / salivary glands)
  • keratoconjunctivitis sicca in eyes
  • xerostomia of the mouth
  1. Enlargement of parotid gland (secondary to lymphocyte buildup)
123
Q

What condition do these autoimmune conditions like SS and SLE predispose you to because of stimulation of B cell proliferation?

A

B cell lymphomas

124
Q

What characterizes systemic sclerosis (scleroderma) and what are the two broad types?

A

Excessive fibrosis, affecting middle-aged women

  1. Diffuse systemic sclerosis
  2. Limited systemic sclerosis
125
Q

What is diffuse systemic sclerosis?

A

Rapidly progressing variant

-> initial involvement of skin, followed by abnormalities in many visceral organs

126
Q

What is limited systemic sclerosis?

A

Slowly progressing variant, confined to skin of face / distal upper extremities
-> does not extensively involve visceral organs

127
Q

What is CREST syndrome?

A

A subset of limited systemic sclerosis, characterized by:

Calcinosis
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangectasia
128
Q

What causes sclerodactyly?

A

Skin gets very tight due to scarring and contracture, which leads to warping of the hands

129
Q

What ANAs are fairly specific for diffuse systemic sclerosis and CREST syndrome?

A

Diffuse systemic sclerosis - anti-Scl 70 (DNA topoisomerase I)

CREST syndrome - anticentromere antibody

130
Q

How do T cells contribute to the pathogenesis of systemic sclerosis?

A
  1. Stimulation of B cells for ANAs
  2. Secretion of growth factors for fibroblasts -> excessive collagen production
  3. Secretion of inflammatory cytokines which lead to persistent injury of microvascular endothelium
131
Q

How does microvascular damage contribute to worsening of systemic sclerosis?

A

Increases platelet activation, release of growth factors for fibroblasts -> excessive collagen production

Over time, fibrinoid necrosis w/ vessel narrowing can result in tissue ischemia, resulting in more necrosis and scarring

132
Q

Where is the skin affected first in systemic sclerosis, and what is the worse possible manifestation of this?

A

Affected first in distal upper extremities (then face and upper trunk)
-> worst manifestation is autoamputation due to extensive scarring and microvascular hyalinization -> ischemia

133
Q

What does systemic sclerosis do the GI tract?

A

Collagenization of wall with muscular atrophy

Esophageal dysmotility results (especially in CREST), as well as GE reflux

Can also impair absorption.

134
Q

What part of the kidney is affected in systemic sclerosis and what systemic effect can this cause?

A

Affects the afferent arterioles due to excessive fibroblast proliferation -> leads to stenosis of the intima

Decreased renal blood flow will lead to increased renin-angiotensin-aldosterone pathway
-> high blood pressure

135
Q

Why does epidermal atrophy occur in the skin in systemic sclerosis?

A

Because involvement of the vessels with excess collagen production and fibroblast proliferation + fibrinoid necrosis, microvasculature will be injured and decrease blood flow.

Cells will atrophy in response to this.

136
Q

What are the two most problematic manifestations of systemic sclerosis now?

A
  1. Lungs - Pulmonary interstitial fibrosis -> pulmonary hypertension
  2. Heart - myocardial fibrosis with possible pericarditis
137
Q

What are the three primary clinical features of Mixed Connective Tissue Disease? What feature is notably not present?

A
  1. SLE characteristics - fever, cytopenias
  2. Systemic sclerosis characteristics - Hand swelling, Raynaud phenomenon, esophageal dysmotility, pulmonary interstitial fibrosis
  3. Polymyositis - inflammation of muscles

Actually minimal kidney involvement as well despite SLE / Scleroderma manifestations

138
Q

What antibody is associated with Mixed Connective Tissue Disease, and what is the treatment?

A

anti-U1 RNP (a ribonucleoprotein)

Treatment: Corticosteroids -> responds quite well.

139
Q

What types of infections B cell deficiencies predispose you to?

A

B cell - infections with pyogenic bacteria which are often encapsulated, certain viruses (i.e. enteroviruses, hepatitis, polio), and intestinal parasites like Giardia

140
Q

What types of infections do T cell deficiencies predispose you to?

A

T cell - viruses, fungi, intracellular bacteria, and protozoa

141
Q

What is typically the cause of impaired humoral immunity in SCID?

A

Secondary to abnormal T-cell functioning (abnormal differentiation or activation)

->however, may be a bone marrow stem cell defect

142
Q

What is the most common cause of SCID? Its pattern of inheritance?

A

X-linked

  • > due to a defect in IL-2 receptor gamma-chain.
  • > deficient T cell proliferation
143
Q

What is the second most common cause of SCID? Its pattern of inheritance?

A

Autosomal recessive

  • > Adenosine deaminase (ADA) deficiency
  • > involved in metabolism of purines, leads to accumulation of metabolites which inhibit DNA synthesis and are toxic to developing T cells (5’ nucleotidase deficiency)
144
Q

How is ADA deficiency treated?

A

With gene therapy -> harvest patient’s bone marrow, use a retroviral vector to “transfect” stem cells with normal ADA gene, expand infected cell line it in vitro, and infuse back into the patient

145
Q

What are the anatomic features of SCID?

A

Systemic lymphoid tissue is absent or hypoplastic

Thymus is underdeveloped and lacking lymphoid cells. Lacks thymic (Hassel’s) corpuscles.

146
Q

Does SCID always present with severe lymphopenia?

A

No, depending on the defect there will occasionally be normal lymphocyte counts but they are dysfunctional

147
Q

Why will patients with SCID often have scant amounts of IgG in their blood when diagnosed?

A

Diagnosed as infants -> will have some IgG transferred from their mother passively across the placenta

148
Q

Give two ways in which SCID patients can develop graft-versus-host disease?

A
  1. Transplacental transfer of maternal T cells -> no immune system to fight it
  2. Blood transfusion -> make sure to inactivate T cells by first irradiating blood products
149
Q

What is the treatment for SCID, and how to we prevent GVHD?

A

Early allogeneic stem cell transplant (before 1 year)

  • > prevent via depletion of mature T cells in donor sample (will be active against recipient HLA)
  • > all new T cells will develop properly in the patient’s thymus
150
Q

What will be absent in the immune defect of DiGeorge Syndrome?

A

Since it affects the development of the 3rd and 4th pharyngeal pouches

  • > Thymus will be affected (will be absent or very small)
  • > little T cell maturation can occur
  • > B cells will be unaffected
151
Q

What anatomical defects are present in DiGeorge syndrome (22q11)? Include non-immunologic things

A
  1. Hypoplastic or absent thymus
  2. Absent or rudimentary parathyroid glands -> tetanus due to hypocalcemia secondary to increased neuronal excitability
  3. Congenital defects of heart
  4. Facial deformities (small mouth / chin)
152
Q

What infections is a DiGeorge patient susceptible to?

A

All infections requiring cytotoxic or delayed hypersensitivity
->viral, fungal, and TB infections

(serum Ig levels, and antibody response to most bacteria is normal assuming there’s any T function at all)

153
Q

What is the treatment for DiGeorge?

A

Transplantation of fetal thymus or thymic epithelium, but this is often not needed since there is enough thymus remaining to seed the remaining gland

154
Q

What causes Bruton’s Agammaglobulinemia and what is the mode of inheritance?

A

X-linked -> seen mostly in males

Caused by BTK mutations (B-cell tyrosine kinase) which is required for maturation from pre-B cells to B cells.

155
Q

What will be the anatomical consequences of Bruton’s agammaglobulinemia (XLA)?

A

Absent B cells in blood / lymphoid tissues (but normal pre-B cells in bone marrow)

Germinal centers absent, tonsils poorly developed

Lack of plasma cells!

Virtual absence of serum Igs with normal T cell function

156
Q

What are the pyogenic bacterial infections that Ig deficiency will lead you to?

A

S. aureus, S. pneumoniae, H. influenzae

157
Q

What is the treatment for XLA?

A

Periodic gamma globulin infusions

158
Q

What disorders are associated with XLA and why?

A

Arthritis and autoimmune diseases like lupus-like disorders (the few autoreactive B cells that make it into the periphery may become active due to defective BTK signalling (required for destroying sell-reactive B-cells))

159
Q

What causes Hyper IgM syndrome and what lab values will be associated? What is the mode of inheritence?

A 
X-linked
Defect in CD40L required for class switching

Associated with normal or high IgM, and low IgA, IgG, and IgE (AGE)

160
Q

What is the most common primary immunodeficiency? How do you get it?

A

Selective IgA deficiency

Can be congenital or acquired (toxoplasmosis, viral infections, drug exposures)

161
Q

What is one important consideration when treating someone with selective IgA deficiency?

A

~40% will have serum antibodies to IgA

  • Most are IgG and would just cause serum sickness, but some have IgE which can cause anaphylaxis
162
Q

What types of infections are those with secretory IgA deficiences susceptible to?

A

Sinopulmonary infections (mucosal immunity) and diarrhea (GI - mucosal immunity to Giardia, enteroviruses)

163
Q

What disorders are associated with selective IgA deficiency?

A

Increased respiratory allergies, autoimmune diseases like RA / SLE, and Celiac disease

164
Q

What is common variable immunodeficiency (CVID)? How does it differ from the other similar condition?

A

The common variable is “hypogammaglobulinemia”

  • > group of heterogeneous disorders which decrease Ig’s sometimes only IgG
  • > differs from Bruton’s because it is autosomal recessive and not X-linked

(seen in girls now)
-> also tends to be diagnosed much later than Bruton’s, in teenage years

165
Q

For common variable immunodeficiency, is a B-cell deficit always present? What is it normally? How could it not be present?

A

Normally a defect to differentiate into plasma cells to produce antibody

B cell deficit does NOT need to be present -> can just be T-cell disorder with excessive immunosuppression or failure to help develop Abs.

166
Q

What finding is common in lymphoid tissue in the duodenum due to CVID?

A

Nodular lymphoid hyperplasia -> persistent antigen stimulation of B cells, but plasma cells are absent

167
Q

Why are non-caseating granulomas present in CVID?

A

Pyogenic bacteria which cannot be neutralized via antibodies must be surrounded by T-cells and macrophages

168
Q

What disorders are associated with CVID, and what is the treatment?

A

Autoimmune disorders like RA, and B-cell lymphomas

-> treatment: periodic IV immunoglobulin (same as XLA)

169
Q

What is the diagnostic triad of Wiskott-Aldroch syndrome?

A 
WATER
Wiskott
Aldroch
1. Thrombocytopenia
2. Eczema
3. Recurrent infections (immunodeficiency)
170
Q

What causes Wiskott-Aldroch Syndrome?

A

Mutation in WASp, which functions in reorganizing cytoskeletal actin.

This is required for B cell, T cell, and platelet function

171
Q

Early on, what type of infection are Wiskott-Aldroch patients susceptible to? What poses their greatest risk of death?

A

Susceptible to encapsulated pyogenic bacterial infection (poor polysaccharide antibody response, peptide is okay)

-> Bleeding risk due to low, small platelet count risks death

172
Q

What happens in WA patients as time goes on?

A

Progressive depletion of lymphocytes in blood and T-cells as well -> loss of cellular immunity (was present before)

173
Q

What is the treatment and associated disorders with WA?

A

Treatment - stem cell transplant

Associated - Lymphoma

174
Q

What causes Ataxia-Telangectasia?

A

Autosomal recessive defect in ATM gene

-> unable to repair double-strand DNA breaks

175
Q

What is the diagnostic quad of ataxia-telangectasia?

A

4 A’s

Cerebellar Ataxia

spider Angiomas (telangectasia)

IgA deficiency -> sinopulmonary infections

elevated Alpha-fetoprotein (impaired organ development)

176
Q

Why is there variable immunodeficiency in ataxia-telangectasia?

A

DNA breaks are required for antigen-receptor splicing in immune cells

177
Q

What causes LAD-1?

A

CD18 defect, an integrin required for phagocyte adhesion, migration, and chemotaxis

Autosomal recessive

178
Q

What are the clinical manifestations of Leukocyte Adhesion Deficiency (LAD-1)?

A

Recurrent skin / mucosal bacterial / fungal infections, lack of pus formation (neutrophils cannot migrate out), leukocytosis from high neutrophils in the blood, impaired wound healing, and periodontal disease

179
Q

What are bare lymphocyte syndrome types II and III a subset of, and what causes them?

A

Subset of autosomal recessive SCID

-> caused by a deficiency in Class II MHC molecules, and markedly impaired cellular and humoral immunity, predisposing to all infections.

180
Q

What causes Chronic Granulomatous Disease (CGD)? How is it inherited?

A

Defect in NADPH oxidase to generate superoxide anion for respiratory burst

  • > need to make HOCl from H2O2 and MPO
  • > Mostly X-linked recessive, but 1/3 autosomal recessive
181
Q

How are lesions in chronic granulomatous disease histologically unique?

A

Central core of neutrophils surrounded by a T-cell / macrophage lymphoma
-> can’t kill the bacteria via ROS, but can surround and contain the infection in granulomas of subcutaneous tissue

182
Q

What organisms are most dangerous for CGD?

A

Catalase-positive bacteria

183
Q

What are two tests for diagnosis of CGD?

A
  1. Dihydrorhodamine (DHR) flow cytometry test -> CGD neutrophils can’t oxidize DHR to fluoresce rhodamine
  2. Nitroblue tetrazolium (NBT) -> CGD neutrophils can’t turn yellow NBT to insoluble, black NBT
184
Q

What is the treatment for CGD?

A

gamma-interferon (not well understood, probably makes neutrophils better at using non-oxidative pathway)

185
Q

What causes Chediak-Higashi (CH) syndrome and what is the pattern of inheritance?

A

Autosomal recessive

Lysosomal trafficking regulator protein dysfunction

186
Q

What happens to granular cells in CH?

A

They have giant granules due to fusion of cytoplasmic granules (defective lysosomes)

187
Q

What happens to neutrophils in CH and why is this relevant ?

A

Enlarged lysosomes with impaired neutrophil function -> poor phagolysosome formation and bactericidal activity
-> recurrent pyogenic infections

188
Q

What happens to the skin in CH?

A

Giant melanosomes in melanocytes -> partial albinism due to poor spreading of melanin

189
Q

What happens to platelets in CH?

A

Abnormal dense bodies -> mild bleeding tendency

190
Q

How is the nervous system affected in CH?

A

Progressive dysfunction and peripheral neuropath, not well understood (likely microtubule dysfunction)

191
Q

What will C1, C2, and C4 deficiencies cause?

A

Poor clearing of immune complexes via C4 receptors on RBCs -> autoimmune or immune complex diseases (like SLE glomerulonephritis)

-> MBL and alternate pathway will still allow for MAC killing

192
Q

What will C3 deficiency cause?

A

Frequent, serious pyogenic infections

193
Q

What will C5-9 deficiencies cause?

A

Recurrent, disseminated Neisseria infections

Pathobiology (20 decks)

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