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MOD Exam 2 > Pathology of Immunity > Flashcards

Pathology of Immunity Flashcards

1
Q

Pre-existing defense against pathogens

A

Innate Immunity

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2
Q

Specific, programmed defense in response to antigen presence

A

Adaptive Immunity

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3
Q

Components of Innate Immunity

A
  • Barrier defense (like skin)
  • Cells
  • Neutrophils
  • Dendritic cells
  • NK cells

•Proteins
- Complement

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4
Q

Components of Adaptive Immunity

A

•Lymphocytes

•Lymphocytes
- Antibodies

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5
Q

Physical/Chemical Barriers of Innate Immunity

A
  • Salivary glands - secretions cleanse oral cavity (chemical)
  • Skin and mucosae - form a physical barrier
  • Tears - bathe the conjunctivae (chemical)
  • Ciliated epithelium - protects lung mucosa
  • Acid pH of stomach- kills microorganisms (chemical)
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6
Q

Pattern Recognition Receptors

important for innate immunity

A
  • Toll like receptors
  • NOD-like receptors and the inflammasome
  • C-type lectin receptors
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7
Q

Complement Pathway Effector Functions

  • C5a, C3a
  • C3b
  • MAC
A
  • C5a, C3a = inflammation
  • C3b = Phagocytosis
  • MAC = lysis of microbe
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8
Q

3 Important things to remember about innate immunity

A
  • Nonspecific
  • Present at birth
  • Does not alter with antigenic exposure
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9
Q

Adaptive Immunity: Tissues

- Generative organs?

A

• Bone marrow

  • generation of lymphocyte stem cells.
  • B lymphocyte maturation

• Thymus
- Maturation of T lymphocytes

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10
Q

Adaptive Immunity: Tissues

- Peripheral organs/tissues?

A

• Lymph nodes
- Lymphocytes can interact with APC’s and antigens in circulating lymph

•Spleen
- Lymphocytes can interact with blood- borne antigens

• Mucosa-associated lymphoid tissues (tonsils, adenoids, Peyers patches)
- Allow lymphocytes and plasma cells to be in the vicinity of antigens within the mouth and intestinal tract

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11
Q

• Primary site of hematopoiesis, starting in embryonic period
• Origin of stem lymphocytes
- B cell maturation

A

Bone Marrow

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12
Q

What does the Medulla of the thymus contain?

A
  • Maturing T lymphocytes
  • Dendritic APC’s with high levels of MHC I and II molecules
  • Hassall corpuscles: SQUAMOUS CELL NESTS
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13
Q

In lymph nodes, APC’s interact with lymphocytes and you get?

A
  • T and B cell clonal expansion
  • B cell differentiation into plasma cells
  • Migration of T cells and plasma cells out of lymph nodes and into circulation
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14
Q

Where in the lymph nodes do T and B cells predominate?

A
  • T cell = paracortex

- B cells = germinal centers

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15
Q

Function of B lymphocytes?

A
  • Neutralization of microbe
  • Phagocytosis
  • Complement activation
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16
Q

Function of Helper T lymphocyte

A
  • Activation of macrophages
  • Inflammation
  • Activation (proliferation and differentiation) of T and B lymphocytes
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17
Q

Function of Cytotoxic T Lymphocyte (CTL)

A

Killing of infected cell

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18
Q

Function of Regulatory T Lymphocytes

A

Suppression of immune response

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19
Q

Function of Natural Killer cells

A

Killing of infected cell

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20
Q

MHC Class I

  • Type of cells?
  • Typically recognize?
  • Antigens are processed into peptides by the ?
  • Mode of transportation?
  • Presentation of the entire complex to ?
A
  • All nucleated cells (and platelets)
  • Intracellular antigens (viral, tumor)
  • Proteasome
  • Peptides transport to the endoplasmic reticulum, load into the groove of MHC, and the entire complex migrates to the surface
  • CD8+ (cytotoxic) T cells
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21
Q

MHC Class II

  • Type of cells?
  • Typically recognize?
  • Antigens are processed into peptides by the ?
  • Mode of transportation?
  • Presentation of the entire complex to ?
A
  • Antigen presenting cells
  • Extracellular antigens (bacterial, allergens)
  • Endolysosomal enzymes
  • Vesicles form with processed peptides and MHC II complex
  • CD4+ (helper) T cells
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22
Q

Extensive heterogeneity of HLA haplotypes is important for?

A
  • Differences in fighting off illness

- Differences in allergic sensitivities

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23
Q

Clinical Important of HLA Haplotypes

A
  • Transplanted organs

- Associated autoimmune diseases

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24
Q

Cell-mediated immunity

A
  • APC’s bring back intracellular pathogens while expressing MHC-associated peptide antigens
  • Recognition by T cells:
  • Proliferation
  • Differentiation
  • Migration
  • Killing

• Dendritic cells capture microbial antigens from epithelia and tissues and transport the antigens to lymph nodes. During this process, the DCs mature, and express high levels of MHC molecules and costimulators. Naive T cells recognize MHC-associated peptide antigens displayed on DCs. The T cells are activated to proliferate and to differentiate into effector and memory cells, which migrate to sites of infection and activate the phagocytes to kill the microbe; other subsets of effector cells enhance leukocyte recruitment and stimulate different types of immune responses. CD8+ CTLs kill infected cells harboring microbes in the cytoplasm. Some activated T cells remain in the lymphoid organs and help B cells to produce antibodies, and some T cells differentiate into long-lived memory cells

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25
Q

MHC class I evoke the killing of?

A

INTRACELLULAR pathogens by CD8+ cells

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26
Q

MHC class II evoke a response to?

A

EXTRACELLULAR pathogens by CD4+ RECRUITMENT of macrophages and other T lymphocyte subsets

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27
Q

Humoral Immune Response

A 
• Mediated by antibodies 
• Antibodies come from plasma cells, which come from B lymphocytes 
• Can be:
- T-cell independent 
- T-cell dependent 
~ Isotype switching 
~ Increasing affinity

• Naive B lymphocytes recognize antigens, and under the influence of TH cells and other stimuli, the B cells are activated to proliferate and differentiate into antibody-secreting plasma cells. Some of the activated B cells undergo heavy-chain class switching and affinity maturation, and some become long-lived memory cells. Antibodies of different heavy-chain classes (isotypes) perform different effector functions

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28
Q

Mediators for Class Switching in the humoral immune response

A

IFN-Y and IL 4

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29
Q

What part of the humoral immune response do Helper T cells get involved with

A
  • Affinity maturation

- Memory B cell

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30
Q

First Ig produced and a large pentamer?

A

IgM

doesn’t cross the placenta

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31
Q

Ig with the longest half life and important in fetal protection

A

IgG

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32
Q

Ig with mucosal defense and present in high levels in colostrum

A

IgA

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33
Q
  • Ig with the shortest half life
  • Regulates hypersensitivity reactions
  • High affinity binding to FC receptor on Mast cells, basophils, eosinophils
A

IgE

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34
Q

Functions of NK cells

A

• Innate lymphoid cells
- No TCR or Ig

  • Destroy stressed and abnormal cells
  • Turned off with MHC class I expression
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35
Q

What activates NK cells?

A
  • Damages cells (recognized by NKG2D receptors)
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36
Q

What inhibits NK cells?

A
  • Self MHC molecules

- Class I MHC (present on all nucleated cells)

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37
Q

What is clonal selection and immunologic tolerance?

A
  • Lymphocytes are killed if they recognize self antigens (clonal deletion)
  • On introduction of a pathogenic antigen, the particular lymphocytes specifically targeted against that antigen are preferentially activated and produce identical cells
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38
Q

How does antigen receptor diversity occur?

A

B and T cell receptors (BCR and TCR) are products of multiple germline and randomized somatic genetic programming

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39
Q

What if a large population of cells with the exact same genes is identified?

A
  • Abnormal clone
  • Neoplasia
  • Lymphoma
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40
Q

An immune reaction to foreign or self antigens that are excessive and harmful

A

Hypersensitivity reactions

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41
Q

Which does Type I hypersensitivity involve?

recognize on sight

A 
• Seasonal allergies 
• Asthma 
• Food allergies 
•Severe allergic reactions 
- Urticaria (hives) 
- Angioedema 
- Anaphylaxis
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42
Q

Type I Hypersensitivity:

  • DC’s present antigens to?
  • T cells differentiate to ?
  • B cells class-switch to ?
A
  • Naive T cells
  • Th2 cells
  • IgE
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43
Q

Type I Hypersensitivity:

What interleukins are involved?

A
  • IL- 4: class switching
  • IL- 5: Eosinophil activation
  • IL- 13: Enhanced IgE production
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44
Q

Type I Hypersensitivity:

What do mast cells do?

A

Get prepared by binding IgE to their very specific FCERI receptor

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45
Q

Type I Hypersensitivity: Mast Cell Activation
• Degranulation of?
• Lipid mediators?
• Cytokines and chemokines?

A
  • Histamine
  • Lipid Mediators
  • Leukotrienes B4, C4, D4
  • Prostaglandin D2
  • Platelet activating factor

• Cytokines and chemokine
- Leukocyte recruitment (late phase)

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46
Q

Immediate Response for Type I Hypersensitivity

A

Mast cell mediators –>

  • Vasodilation
  • Vascular leakage
  • Smooth muscle spasm
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47
Q

Late Phase Reaction for Type I Hypersensitivity

A

Inflammatory cells –>

  • Eosinophils, basophils, neutrophils
  • Leukocyte infiltration
  • Epithelial damage
  • Bronchospasm
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48
Q

Reactions of Type I Hypersensitivity

A
  • Bronchoconstriction
  • Increase bowel peristalsis
  • Increase vasodilation permeability
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49
Q

Food antigen-driven disease of childhood (food allergy for Type I hypersensitivity)

A

Eosinophilic esophagitis

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50
Q

Symptoms of Eosinophilic esophagitis

A
  • Recurrent dysphagia
  • Weight loss
  • Can’t swallow effectively
  • Hurts to swallow
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51
Q

What should doctors do when they encounter a Type I reaction?

A
  • DIAGNOSE that an allergic reaction is happening
  • TREAT the allergic reaction
  • Block Histamine
  • Airway support

• IDENTIFY the allergen

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52
Q

Steps for Skin-prick Testing

A
  • IgE bound to mast cells
  • Injected allergen binds to IgE molecules
  • IgE cross-linking activates mast cells
  • Vasodilation, increased interendothelial spaces: Redness and swelling
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53
Q

Reaction where antibodies directly react with antigens present on the cell surface or extracellular matrix

  • Autoantibodies
  • Exogenous antigens that are bound to cell surfaces
A

Type II Hypersensitivity Reaction

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54
Q

What are the 3 mechanisms for Type II?

A
  1. Opsonization and PHAGOCYTOSIS
  2. Complement and Fc receptor-mediated INFLAMMATION
  3. Antibody-mediated CELLULAR DYSFUNCTION
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55
Q

Type II:
Autoimmune Hemolytic Anemia
- Target Antigen ?
- MOD?

A
  • Antigen: Red cell membrane proteins (Rh blood group antigens, I antigen)
  • MOD: Opsonization and phagocytosis of red cells
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56
Q

Type II:

Autoimmune Thrombocytopenic Purpura

A
  • Antigen: Platelet membrane proteins (GpIIb: Illa integrin)

- MOD: Opsonization and phagocytosis of platelets

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57
Q

Type II:

Pemphigus Vulgaris

A
  • Antigen: Proteins in intercellular junctions of epidermal cells (epidermal cadherin)
  • MOD: Antibody-mediated activation of proteases, disruption of intercellular adhesions
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58
Q

Type II:

Vasculitis caused by ANCA

A
  • Antigen: Neutrophil granule proteins, presumably released from activated neutrophils
  • MOD: Neutrophil degranulation and inflammation
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59
Q

Type II:

Goodpasture Syndrome

A
  • Antigen: Noncollagenous protein in basement membranes of kidney glomeruli and lung alveoli
  • MOD: Complement- and Fc receptor- mediated inflammation
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60
Q

Type II:

Acute Rheumatic Fever

A
  • Antigen: Streptococcal cell wall antigen; antibody cross-reacts with myocardial antigen
  • MOD: Inflammation, macrophage activation
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61
Q

Type II:

Myasthenia Gravis

A
  • Antigen: Acetylcholine receptor

- MOD: Antibody inhibits acetylcholine binding, down-modulates receptors

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62
Q 
Type II: 
Graves Disease (hyperthyroidism)
A
  • Antigen: TSH receptor

- MOD: Antibody-mediated stimulation of TSH receptors

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63
Q

Type II:

Insulin-resistant diabetes

A
  • Antigen: Insulin receptor

- MOD: Antibody inhibits binding of insulin

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64
Q

Type II:

Pernicious anemia

A
  • Antigen: Intrinsic factor of gastric parietal cells

- Neutralization of intrinsic factor, decreased absorption of Vitamin B12

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65
Q

Type II: Complement and Fc receptor-mediated inflammation Mechanism

A

• Mechanism = damaged tissue!

  • Basement membrane proteins
  • Streptococcal proteins that cross-react with myocardium
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66
Q

Rheumatic heart

  • Type of hypersensitivity?
  • What occurs?
A

• Type II
• Acute and chronic forms
• Cross reactive antibodies!
- Molecular mimicry *: Streptococcal antigen looks like myocardial antigen so you end up destroying heart tissue

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67
Q

Type II: Antibody-mediated cellular dysfunction Mechanism

A

• Mechanism: dysfunction due to receptor blockade!

  • Disrupted endocrine signaling
  • Disrupted neural signaling
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68
Q

Which Type II diseases are associated with opsonization and phagocytosis?

A
  • Autoimmune hemolytic anemia

- Autoimmune thrombocytopenic purpura

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69
Q

Which Type II diseases are associated with complement and Fc receptor-mediated inflammation?

A
  • Vasculitis causes by ANCA
  • Goodpasture syndrome
  • Acute rheumatic fever
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70
Q

Which Type II diseases are associated with antibody-mediated cellular dysfunction?

A
  • Myasthenia gravis
  • Graves disease (hyperthyroidism)
  • Insulin-resistant diabetes
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71
Q

Type of hypersensitivity where antigen-antibody complexes FORM and DEPOSIT, causing DAMAGE

A

Type III Hypersensitivity

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72
Q

Steps for Type III Hypersensitivity

A
  1. Antibody combines with excess soluble antigen, forming large quantities of Ab/Ag complexes
  2. Circulating immune complexes become lodged in the basement membrane of epithelia in sites such as kidneys, lungs, joints, skin
  3. Fragments of complement cause release of histamine and other mediator substances
  4. Neutrophils migrate to the site of immune complex deposition and release enzymes that cause severe damage in the tissues and organs involved
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73
Q

Which type of reaction involves serum sickness and an Arthus reaction?

A

Type III

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74
Q

What is serum sickness?

  • Acute is due to?
  • Chronic due to ?
A
  • Acute form classically due to non-human protein antigen (diphtheria antitoxin)
  • Chronic form usually due to self-antigens (i.e. lupus)
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75
Q

What is a Arthus reaction?

A

Arthus reaction: local reaction

  • Experimentally seen in rabbits injected with horse serum
  • Rare local effect of vaccination
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76
Q

What type of test to you perform to help identify the disease process by the pattern of antibody deposition?

What is the process?

A

Immunofluorescence
- An anti-Ig antibody tagged with fluorescent dye is added to a sample. It binds to any antibodies present in the tissues being tested

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77
Q

What type of reaction has smooth, linear immunofluorescence?

A

Type II

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78
Q

What type of reaction has grainy, granular immunofluorescence?

A

Type III

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79
Q

Which type?

- In the heart, post-streptococcal cross-reactive antibodies DIRECTLY act on the myocardium

A

Type II

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80
Q

Which type?

- In the KIDNEY, post-streptococcal cross-reactive antibodies are forming immune complexes that deposit in the glomeruli

A

Type III

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81
Q

What occurs in Type IV?

A

T-cells turn!

•CD4+ response

  • Cytokine release
  • Inflammation

•CD8+ response
- Cytotoxic against Ag on surface of a target cell

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82
Q

Which disease do you REALLY REALLY need to associate with Type IV?

A

Type I diabetes mellitus

T cells destroy the insulin producing cells in pancreas

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83
Q

What is one hallmark of Type IV reactions?

A

Granuloma

- Presence of blobs in histo= giant cells with rim of nuclei around the periphery

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84
Q

Type IV:

What is caused by a variety of agents that are capable of inducing a PERSISTENT T cell-MEDIATED IMMUNE RESPONSE?

A

Immune granuloma

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85
Q

Type IV:
Rheumatoid Arthritis

  • Specificity of Pathogenic T cells:
  • Principle Mechanism of Tissue Injury:
  • Clinicopathologic Manifestations:
A

• Specificity of Pathogenic T cells:

  • Collagen?
  • Citrullinated self proteins?

• Principle Mechanism of Tissue Injury:
- Inflammation mediated by TH17 (and TH1?) cytokines; role of antibodies and immune complexes?

• Clinicopathologic Manifestations:
- Chronic arthritis with inflammation, destruction of articular cartilage

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86
Q

Type IV:
Multiple Sclerosis

  • Specificity of Pathogenic T cells:
  • Principle Mechanism of Tissue Injury:
  • Clinicopathologic Manifestations:
A

• Specificity of Pathogenic T cells:
- Protein antigen in myelin (e.g., myelin basic protein)

• Principle Mechanism of Tissue Injury:
- Inflammation mediated by TH1 and TH17 cytokines, myelin destruction by activated macrophages

• Clinicopathologic Manifestations:
- Demyelination in CNS with perivascular inflammation; paralysis

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87
Q

Type IV:
Type I diabetes mellitus

  • Specificity of Pathogenic T cells:
  • Principle Mechanism of Tissue Injury:
  • Clinicopathologic Manifestations:
A

• Specificity of Pathogenic T cells:
- Antigens of pancreatic islet B cells (insulin, glutamic acid decarboxylase, others)

• Principle Mechanism of Tissue Injury:
- T cell-mediated inflammation, destruction of islet cells by CTLs

• Clinicopathologic Manifestations:
- Insulitis (chronic inflammation in islets), destruction of B cells; diabetes

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88
Q

Type IV:
Inflammatory bowel disease

  • Specificity of Pathogenic T cells:
  • Principle Mechanism of Tissue Injury:
  • Clinicopathologic Manifestations:
A

• Specificity of Pathogenic T cells:
- Enteric bacteria; self antigens?

• Principle Mechanism of Tissue Injury:
- Inflammation mediated by TH1 and Th17 cytokines

• Clinicopathologic Manifestations:
- Chronic intestinal inflammation, obstruction

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89
Q

Type IV:
Psoriasis

  • Specificity of Pathogenic T cells:
  • Principle Mechanism of Tissue Injury:
  • Clinicopathologic Manifestations:
A

• Specificity of Pathogenic T cells:
- Unknown

• Principle Mechanism of Tissue Injury:
- Inflammation mediated mainly by TH17 cytokines

• Clinicopathologic Manifestations:
- Destructive plaques in the skin

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90
Q

Type IV:
Contact sensitivity

  • Specificity of Pathogenic T cells:
  • Principle Mechanism of Tissue Injury:
  • Clinicopathologic Manifestations:
A

• Specificity of Pathogenic T cells:
- Various environmental chemicals (e.g., urushiol from poison ivy or poison oak)

• Principle Mechanism of Tissue Injury:
- Inflammation mediated by TH1 (and TH17?) cytokines

• Clinicopathologic Manifestations:
- Epithelial necrosis, dermal inflammation, causing skin rash and blisters

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91
Q

What kind of reaction is the Mantoux test?

A

Delayed Type IV hypersensitivity

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92
Q

Tolerate self-antigens

A

Immunologic tolerance

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93
Q

Learned prior to release from generative lymphoid organs

A

Central tolerance

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94
Q

Ongoing regulation in peripheral tissues

A

Peripheral tolerance

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95
Q

Central Tolerance:

- What happens in the thymus?

A
  • Production of T-cell receptors that cross-react with self-antigens are detected
  • APOPTOSIS
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96
Q

Central Tolerance:

- What happens in the bone marrow?

A
  • B lymphocytes may recognize self antigens
  • RECEPTOR EDITING
  • (or APOPTOSIS)
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97
Q

What happens in Peripheral tolerance?

A
  • Anergy

- Suppression by Treg cells

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98
Q

Anergy:
What are the inhibitory receptors on T lymphocytes that help T cells down regulate when self antigens are present? (tumors and viruses use this to evade immune destruction)

A
  • CTLA

- PD-1

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99
Q

What can we do for tumor immunotherapy?

A

Block PD-1 or CTLA-4 signaling
- By blocking this interaction with antibodies directed against PD-1 and CTLA, we can intensify the immune response against cancer cells

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100
Q

Most common Treg cells are?

A
  • Induced by TGF-B
  • Positive for CD4
  • Express CD25 and FOXP3
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101
Q

What do FOXP3 Treg cells do?

A

Tell pregnant mom not to attack the baby’s antigens that are from the dad

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102
Q

What are the 4 mechanisms of peripheral self-tolerance?

A
  • Normal response
  • T cell anergy
  • T cell suppression
  • T cell deletion
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103
Q

Murphy’s law:

- A mutation in the AIRE gene can lead to ?

A
  • Polyendocrine disorders due to autoimmunity
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104
Q

Murphy’s law:

- A autoimmune disease called IPEX can cause ?

A
  • Systemic disease in humans
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105
Q

3 requisite factors for defining pathologic autoimmunity

A
  1. An immune reaction is directed against a self-antigen
  2. The immune reaction is primarily responsible for a pathologic condition
  3. There is no other pathophysiology responsible
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106
Q

Genetic and environmental contribution to autoimmune disease?

A

• Genetic
- Susceptibility genes

• Environmental
- Infection
- Damaged tissues
~ Epitope spreading

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107
Q
  • Typically hereditary inflammatory conditions of the joints, particularly the spine
  • Inflammation leads to degeneration and then fusion of the vertebrae
A

Ankylosing Spondylitis

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108
Q

Ankylosing Spondylitis is strongly associated with Class ?

A

Class I HLA allele B27 *

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109
Q

Crohn Disease
- Polymorphisms in the ? gene render Paneth cells in intestinal epithelium ineffective at microbial killing

  • Defective killing and clearance allows accumulation of bacteria and an exaggerated immune response
A

NOD-2 (non-HLA)

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110
Q

NOD gene encodes ?

A

NOD-like receptor

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111
Q

What disease is associated with epitope spreading?

A

Oral Lichen Planus

112
Q

What occurs in Oral Lichen Planus?

A
  • Initial T cell response leads to keratotic lesions in oral and conjunctival mucosa
  • Basement membrane disruption exposes antigenic proteins
  • A secondary B cell response occurs
113
Q

Which autoimmune diseases are associated with anti-nuclear antibody (ANA)?

A

• Systemic Lupus Erythematosus

  • Discoid Lupus
  • Drug-induced Lupus
  • Sjogren syndrome
  • Systemic sclerosis
114
Q

What is ANA?

A
  • A sensitive test for multiple autoimmune diseases

- Its presence can prompt more specific testing to confirm the particular diagnosis

115
Q

What are the specific tests for Lupus?

A
  • Anti DS DNA

- Anti Smith

116
Q

What are the specific tests for Sjogren syndrome?

A
  • Anti Ro/SS-A

- Anti La/SS-B

117
Q

What are the specific tests for Systemic Sclerosis?

A
  • Anti DNA topoisomerase (Sci-70)
118
Q

What kind of ANA staining pattern is anti-DNA?

A

Homogenous

119
Q

What kind of ANA staining pattern is anti-Sm, anti-Ro and La, and anti-Scl-70?

120
Q

What are the 4 ANA staining patterns?

A
  • Homogenous
  • Speckled
  • Nucleolar
  • Centromere
121
Q

Autoimmune disease associated with “vast array” of autoantibodies

A

Systemic Lupus Erthematosus

122
Q

What are the genetic and environmental influences that degrade self-tolerance in SLE?

A
  • Genetic: family patterns, HLA-DQ
  • Female bias: X chromosome
  • UV light
123
Q

What immune mechanisms are involved with SLE?

A
  • B cells and CD4+ T cells

- Immune complex formation

124
Q

Types of rashes in SLE

A
  • Malar rash (butterfly)

- Discoid (scarring anywhere on face or scalp)

125
Q

When do we suspect Lupus?

A

(Tendency toward younger females)

  • Hemolytic anemia = 100%
  • Arthritis
  • Skin rashes
  • Fever
  • Fatigue
  • Edema

You also can see hair loss, muscle aches, fingers and toes turn white, blue or red with exposure to cold or stress (Raynaud phenomenum), chest pain, swollen lymph nodes

126
Q

Need 4 or more of these criteria to be SLE

A
  1. Malar rash
  2. Discoid rash
  3. Photosensitivity
  4. Oral ulcers
  5. Arthritis
  6. Serositis (inflammation of organs)
  7. Renal disorder
  8. Neurologic disorder
  9. Hematologic disorder
  10. Immunologic disorders
  11. Antinuclear antibody
127
Q

What is the first and last category for Lupus Nephritis

A
  • Minimal mesangial (I) = first

- Advanced sclerosis Lupus nephritis (VI) = last

128
Q

What is the most common pattern of Lupus nephritis?

A

Diffuse Lupus Nephritis (IV)

129
Q

Diffuse Lupus Nephritis (class IV)

  • Patients are ?
  • Glomeruli show?
  • Granular pattern of ?
A

• Symptomatic
- Proteinuria, hematuria

• Glomeruli show increased cellularity

  • Proliferation of endothelial, mesangial, and epithelial cells
  • EM shows immune deposits in the subendothelium
  • Granular pattern of IgG antibody- containing complexes
  • Immune complex-mediated disease (type III)
130
Q

Skin changes in SLE

A
  • Basal layer degeneration of the skin (vacuolated spaces between degenerating cells)
  • Positive immunofluorescence
131
Q

Cardiovascular complications of SLE

A

• Libman-Sacks endocarditis

  • “Verrucous” (warty) valve deposits
  • comprised of fibrin
  • NOT infective
  • Can embolize (rare)

• Coronary Artery Disease
- contribution from anti-phospholipid antibody syndrome?

132
Q

A neutrophil or macrophage that ingests the nucleus of a damaged cell

  • Not used for diagnosis but can be seen in blood or body fluids
133
Q

Big signs of SLE (vs Discoid)

A
  • Malar rash **
  • Discoid rash
  • Renal disease **
  • Heart disease **
  • Hematologic disorders **
  • Positive ANA
  • Positive DS DNA **
  • Positive immunofluorescence
134
Q

Big signs of Discoid Lupus Erythematosis

A
  • Discoid rash
  • Positive ANA
  • Positive Immunofluorescence
135
Q

Discoid Lupus
• What physical abnormalities?
• Test results?
• How can it progress?

A

• Usually just face and scalp are affected

  • Positive ANA
  • Negative Anti-DS DNA

• Progression is possible

  • Disseminated skin lesions
  • Systemic organ involvement (late occurence, 5-10% of patients)
136
Q

Big signs of Drug-induced Lupus

A
  • Arthralgias (joint aches), fever
  • Positive ANA
  • Discoid rash
  • Hematologic disease
  • Positive immunofluorescence
137
Q

Big Signs of SLE (vs Drug Lupus)

A
  • Etiology unknown **
  • Arthralgias (joint aches), fever
  • Positive ANA
  • Discoid rash
  • Renal and CNS disease **
  • Hematologic disease
  • Positive DS DNA **
  • Positive Immunofluorescence
138
Q

Drug- Induced Lupus:
• What meds involved with the medication-induced breakdown of self-tolerance

  • Arthralgia, fever –>
  • Positive for ?
  • Resolves with?

• HLA high-risk linkages: ?
- Meds associated with HLA

A

• Meds:

  • Procainamide
  • Hydralazine
  • Arthralgia, fever –> Positive ANA
  • Anti-Histone Ab *****
  • Resolves with drug discontinuation
  • HLA high-risk linkages
  • Hydralazine confers high risk for DIL in people with the HLA- DR4 allele **
  • Procainamid confers risk for DIL in people with the HLA-DR6 allele **
139
Q
  • Autoimmune disease resulting in destruction of lacrimal and salivary gland tissue
  • Pathogenesis includes B and T cell mediated inflammatory reaction to target tissues with inflammatory damage followed by fibrotic destruction
A

Sjogren syndrome

140
Q

Signs of Sjogren Syndrome

A
  • Dry eye and dry mouth
  • Root caries on teeth
  • Smooth tongue (papillary atrophy) with superimposed candida yeast infection
141
Q

Sjogren:

  • Clinical presentation
  • Diagnosis
  • Complications
A

• Clinical:

  • Dry, irritated eyes
  • Dry mouth (xerostomia), difficulty swallowing

• Diagnosis

  • Anti-Ro/SS-A and Anti-La/SS-B
  • Biopsy of lip to look for inflammation of minor salivary gland tissue **

• Complications

  • Extraglandular disease: PULMONARY FIBROSIS
  • Lymphoid proliferation becoming clonal: LYMPHOMA
142
Q

Disease with fibrosis throughout the body

A

Systemic Sclerosis (scleroderma)

143
Q

Systemic Sclerosis:
• what areas of the body have fibrosis?
• Can occur in a limited form?
• Can be part of what syndrome?

A

• Fibrosis in body

  • SKIN
  • GI tract
  • Kidneys
  • Heart
  • Lungs

• Limited form

  • Skin
  • Late visceral involvement

• CREST syndrome

144
Q

What does the histo for systemic sclerosis show?

A

Dense collagenous deposition consistent with subcutaneous fibrosis

145
Q

What can Systemic Sclerosis progress to?

A
  • Raynaud phenomenum
  • Cold, ischemic fingers can become necrotic
  • Can have ischemic resorption
146
Q

What additional manifestations are there for Systemic Sclerosis?

A

• GI tract

  • GI reflux
  • Esophageal ulceration

• Renal Vascular Disease
- May be associated with life-threatening renal crisis

• Pulmonary

  • Pulmonary hypertension
  • Pulmonary fibrosis
147
Q

ANA fluorescence pattern for systemic sclerosis

A

Speckled

- Anti Scl-70 (anti DNA topoisomerase)

148
Q

ANA fluorescence pattern for CREST syndrome

A

Centromere

- Anticentromere antibody

149
Q
  • A unique form of limited sclerosis

- Better prognosis than diffuse sclerosis

A

CREST syndrome

150
Q

What does CREST stand for?

A

Symptoms:

  • Calcinosis - calcium deposits in the skin
  • Raynaud’s phenomenon - spasm of blood vessels in response to cold or stress
  • Esophageal dysfunction - acid reflux and decrease in motility of esophagus
  • Sclerodactyly- thickening and tightening of the skin on the fingers and hands
  • Telangiectasias - dilation of capillaries causing red marks on surface of skin
151
Q

Mixed Connective Tissue Disease includes a mix of which diseases?

A
  • SLE
  • Systemic Sclerosis
  • Polymyositis
152
Q

Mixed Connective Disease has a high titer for?

A

Anti-ribonucleoprotein (RNP)

153
Q

Common presenting feature of Mixed Connective Disease?

A

Raynaud Phenomenon

154
Q

IgG4-related disease ties together which diseases?

A
  • Autoimmune pancreatitis
  • Riedel thyroiditis
  • Mikulicz’s syndrome (attacking salivary gland)
  • Idiopathic retroperitoneal fibrosis
  • Inflammatory pseudotumors
  • Inflammatory aortitis
155
Q

What is the uniting pathophysiology of IgG4-related diseases?

A
  • IgG4-producing PLASMA CELLS, T lymphocytes, FIBROSIS

- Eventual fibrotic scarring and irreversible damage to involved areas

156
Q

Big difference between direct and indirect pathway for allorecognition?

A
  • Direct = Donor antigen-presenting cell in the graft

- Indirect = Recipient’s antigen-presenting cell

157
Q

B-cell mediated rejection

A
  • Hyperacute rejection
  • Acute antibody-mediated rejection
  • Chronic antibody-mediated rejection
158
Q

Hyperacute Rejection:

  • Occurs within ?
  • Mediated by ?
  • Marked inflammation followed by ?
A
  • Minutes to hours
  • Pre-formed antibodies ABO!
  • Thrombotic microvasculopathy
159
Q

Histo for acute-antibody mediated rejection

A

Inflammation with complement C4d breakdown product

160
Q

Histo for chronic antibody-mediated rejection

A

Fibrosis with primary effect on vessels

161
Q

Acute cellular rejection (T cell-mediated)

- Occurs within?

A

Within days, months, years of transplant

162
Q

Treatment:

  • Important immunosuppressive?
  • T lymphocyte-mediated cellular rejection Treatment?
  • Antibody-mediated (humoral) rejection Treatment?
A

• Corticosteroids

• T lymphocyte-mediated cellular rejection
- Treatment = Tacrolimus

• Antibody-mediated (humoral) rejection

  • Immune globulin
  • Rituximab (anti CD20 recombinant antibody)
163
Q 
What happens when we use transplant treatment? 
• Pro: 
• Con:
- Types of infection?
- Types of tumors?
A

• Pro: yay no more rejection

• Con: issues having to do with immunosuppression 
- Infection:
~ VIRAL: POLYOMAVIRUS, Cytomegalovirus 
~ Fungal 
~ Bacterial
  • Tumors:
    ~ Viral-induced tumors: Lymphomas, Kaposi sarcoma
    ~ Squamous carcinomas
164
Q

Steps to Hematopoietic stem cell transplant

A
  • Therapy for hematologic malignancies and other conditions
  • Ablative chemotherapy and radiation destroys recipient bone marrow
  • Stem cell transplant is administered
165
Q

What is super important about hematopoietic stem cell transplant?

A

You get a brand new immune system!!

166
Q

Graft versus Host Disease:

  • ? mediated
  • What organs and symptoms involved
A

• T lymphocyte-mediated

• Skin 
- rash --> desquamation 
• Liver 
- Jaundice --> cholestasis 
• Intestines 
- Bloody diarrhea --> strictures
167
Q

Primary (genetic):

Disorders of leukocyte function

A
  • Chediak Higashi

- Chronic granulomatous disease

168
Q

Primary (genetic):

Disorders of complement function

A
  • Membrane attack complex deficiency

- Hereditary angioedema

169
Q

Primary (genetic):

Disorders of lymphocyte maturation

A
  • Severe combined immunodeficiency syndrome
  • X-linked agammaglobulinemia
  • DiGeorge syndrome
170
Q

Primary (genetic):

Disorders of lymphocyte function

A
  • Hyper IgM syndrome
  • Common variable immunodeficiency
  • Isolated IgA deficiency
  • X-linked immunoproliferative disorders
171
Q

Primary (genetic):

Immunodeficiencies associated with systemic disease

A
  • Wiskott Aldrich syndrome

- Ataxia-Telangiectasia

172
Q

Secondary (acquired) immunodeficiency syndromes

A
  • Immunosuppression

- Acquired Immunodeficiency syndrome (AIDS)

173
Q

B cell deficiencies:

Histopathology and lab abnormalities

A
  • Often absent or reduced follicles and germinal centers in lymphoid organs
  • Reduced serum Ig levels
174
Q

B cell deficiencies:

Common infectious consequences

A

Pyogenic bacterial infections, enteric bacterial and viral infections

175
Q

T cell deficiencies:

Histopathology and lab abnormalities

A
  • May be reduced T cell zones in lymphoid organs
  • Reduced DTH reactions to common antigens
  • Defective T cell proliferative responses to mitogens in vitro
176
Q

T cell deficiencies:

Common infectious consequences

A
  • Viral and other intracellular microbial infections (e.g., Pneumocystis jiroveci, other fungi, nontuberculous mycobacteria)
  • Some cancers (e.g., EBV-associated lymphomas, skin cancers)
177
Q

Innate immune deficiencies:

Histopathology and lab abnormalities

A
  • Variable, depending on which component of innate immunity is defective
178
Q

Innate immune deficiencies:

Common infectious consequences

A

Variable; pyogenic bacterial and viral infections

179
Q

Chediak Higashi Syndrome:

  • Autosomal ? disorder
  • Failure of ? fusion
  • Increased ?
  • Fatal without ?
  • You can observe the failure of fusion on a ?
A
  • Autosomal recessive
  • phagolysosomal
  • Increased bacterial infections
  • stem cell transplant
  • Peripheral smear
180
Q

Chediak Higashi:

  • Defect in ?
A

Defects in melanocytes lead to albinism or grey hair streaks in these patients

181
Q

Chediak Higashi:

Histo

A

GIANT granules

182
Q
  • Group of genetic disorders
  • Common mechanism is failure of superoxide production within phagocytes
  • Accumulation of macrophages “walls off” infection
A

Chronic granulomatous disease

183
Q

Membrane Attack Complex Deficiency:

  • Terminal components ?
  • Without the final MAC, the lysis of the ?
  • ? infections are common
A
  • C5, 6, 7, 8, 9 (any can be affected)
  • microbial membrane can’t occur
  • Neisseria infections are common
    ~ Which can produce Meningitis
184
Q

Hereditary Angioedema

  • Autosomal ?
  • Deficiency of ?
A
  • Autosomal dominant

- Deficiency of C1 inhibitor

185
Q

Symptoms of Hereditary Angioedema

A
  • Head - headache, dizziness, voice alterations, possible visual alterations and signs of paralysis
  • Throat - Swelling of the airway, laryngeal edema beginning with difficulty swallowing, change in voice pitch, hoarseness, difficulty breathing and in extreme cases asphyxiation
  • Intestinal Region - Vomiting, abdominal pain, diarrhea, cramping and discomfort
  • Bladder - Burning sensation when urinating, bladder and lumbar region pain, symptoms similar to urinary tract infection
  • Genitals - swelling of the scrotum and vulva
  • Cutaneous edema - Sensation of tightness, pressure and swelling
  • Extremities (Arms and Legs) - Swelling, decrease in normal mobility and difficulty walking
186
Q

Many forms of this deficiency, common theme is deficiency in BOTH B cell and T cell lineages due to defect in T cell function

187
Q 
SCID:
• X-linked 
- Gender?
- Mutations in ?
- ? reduced in number 
- ? present but unable to make Ab without T cell help 
• Autosomal recessive:
- ? deficiency (most common)
- Accumulation of ?
~ Block ? formation 
~ Some ? influence, but again, lack of helper T cells also suppresses humoral immune function
A

• X-linked

  • Males
  • Mutations in IL receptors
  • T cell reduced
  • B cells present
• Autosomal recessive 
- Adenosine deaminase deficiency 
- Accumulation of toxic purine metabolites 
~ Blocks T lymphocyte formation 
~ Some B cell influence
188
Q

Treatment for SCID

A
  • Stem cell transplantation

- Gene therapy

189
Q

Primary deficiency of T lymphocytes due to failure (partial or total) of pharyngeal pouches 3 and 4

A

DiGeorge syndrome

190
Q

Organ systems involved with DiGeorge?

A
  • Thymus
  • Parathyroids
  • Heart, great vessels
191
Q

DiGeorge Syndrome:

- May be inherited in a ?

A

• Sporadic or familial pattern

- Many cases are 22q11 deletions **

192
Q

DiGeorge Clinical Manifestations

A
  • Facial and palatal abnormalities (small chin, cleft lip..)
  • Cardiac abnormalities
  • Tetany
  • Immune deficiency
  • T cell deficiency
  • Humoral deficiency, if T cell function is poor enough (A form of SCID)
193
Q

• Defect in Bruton tyrosine kinase (BTK) gene on the X chromosome
- inability of pre-B cells to mature

• Risk for infection increases after maternal antibodies wane, may even present in late childhood

A

X-linked Agammaglobulinemia

194
Q

Presentation of agammaglobulinemia

A

• Encapsulated bacteria

  • Streptococcus pneumonias
  • Haemophilus influenzae type B
  • Streptococcus pyogenes
  • Pseudomonas aeruginosa
  • Staphlococcus aureus

• Viruses

• Protozoa
- Giardia lamblia (get diarrhea)

195
Q

Hyper- IgM syndrome

- ? infections predominate due to lack of opsonizing antibodies

A

Encapsulated bacterial infections

196
Q

Hyper-IgM Syndrome:
• ? mutations
- Interfere with T cells helping B cells to class switch

  • Increased ? levels, but lower levels of other classes
  • Treatment?
A
  • CD40/CD40L mutations
  • Increased IgM
  • Treat with IVIg
  • Stem cell transplantation
197
Q
  • Multiple disorders resulting in hypogammaglobulinemia
  • Most common significant primary immunodeficiency
  • Encapsulated bacterial infections like X-linked agammaglobulinemia
  • Disease of EXCLUSION
  • Later presentation
A

Common Variable Immunodeficiency (CVID)

198
Q

CVID clinical manifestations

A

• Recurrent sinus and pulmonary infections
- Pyogenic bacteria

• Granulomas

• Chronic diarrhea
- Giardia lamblia

• Autoimmune disease

  • Anemia
  • Thrombocytopenia
199
Q 
IgA deficiency (isolated) 
•  Can occur in both ? forms

• Loss of IgA means less defense against inhaled and ingested pathogens. What kind of infections?
- Anaphylactic reaction against ?

A
  • Both familial and acquired forms
  • Infections:
  • Sinus and respiratory infections
  • Urinary bladder infections
  • GI infections
  • Autoimmune disease and allergies
  • Anaphylactic reaction against red cell transfusion
200
Q

Possible first indication of IgA deficiency?

What can prevent reactions?

A
  • Transfusion-related anaphylaxis

- Red cell washing

201
Q

Triad of Wiskott Aldrich syndrome

A
  1. Thrombocytopenia
  2. Eczema
  3. Recurrent infections (T cell loss; Hypogammaglobilinemia)
202
Q

What is the gene mutation fro Wiskott Aldrich?

Treatment?

A
  • WASP gene

- Stem cell transplant

203
Q

Neurodegenerative disease and vascular malformation?

A

Ataxia Telangiectasia

204
Q

Ataxia Telangiectasia
• Immune deficiency of ?
- Kinds of consequences?

• Autosomal ?
- ? gene mutation

A

• IgA and IgG

  • Respiratory infections
  • Autoimmune disease
  • Cancer

• Autosomal recessive
- ATM gene mutation: defective DNA repair

(also have sterility and radiosensitivity)

205
Q

AIDs is the MANIFESTATION of what occurs when the ? affects the body to a degree where immune dysfunction results in
1.
2.
3.

A
  • HIV
    1. Opportunistic infections
    2. Secondary neoplasms
    3. Neurologic manifestations
206
Q

Where is AIDS coming from?

A

Retrovirus

207
Q

How does HIV spread?

A
  • Sex without a condom
  • Passed from mother to baby
  • Sharing injecting equipment (parenteral)
  • Contaminated blood transfusions and organ transplants (parenteral)
208
Q

Who is at risk of HIV?

A
  • Homosexual/bisexual men
  • IV drug abusers
  • Hemophiliacs
  • Other recipients of blood/blood components
  • Heterosexual contacts of the above groups
  • Newborns in areas with high female prevalence
209
Q

Synergistic effect of HIV and non-HIV STD’s: ?

A
  • Inflammation

- Ulceration

210
Q

How does the HIV virus go into bloodstream?

A

Breaching the mucosal barrier (whether anal or vaginal) introduces virus into bloodstream or infects mucosal dendritic cells

211
Q

How does mother to child HIV occur?

A
  • In utero through placental –> fetal transfer of virus
  • During delivery with contact of secretions in the birth canal
  • After birth with ingestion of breast milk
212
Q

Risk of seroconversion (contacting a disease from a patient) after needlestick accident for HIV? For Hep C/B?

A
  • HIV : 0.3%

- Hep B: 30%

213
Q

What family does HIV come from?

A

Lentivirus family

214
Q 
HIV-1 
•  Capsid proteins?
• Glycoproteins?
• Viral enzymes?
•  HIV-1 RNA genome?
A

• Capsid proteins

  • p24
  • We can test for p24 antigen

• Glycoproteins
- gp120 and gp41
- Important for attachment
~ Good drug/vaccine targets!

• Viral enzymes

  • Protease
  • Reverse transcriptase
  • Integrase

• HIV-1 RNA genome
- gag, pol, env retroviral genes

215
Q

HIV-1: Regions to know!! (shared by all retroviruses)

A
  • LTR: initiates transcription, binds transcription factors
  • gag: Encodes for the PROTEINS INSIDE the virus
  • env: Encodes for the SURFACE GLYCOPROTEINS
  • pol: Encodes the VIRAL ENZYMES
216
Q

3 big parts to the life cycle of HIV

A
  1. Virus entry
  2. Virus Replication
  3. Virus release
217
Q

HIV virus entry steps

A
  1. HIV uses a CD4** molecule for a receptor. Coreceptors may include chemokine receptors (CCR5, CXCR4)
  2. gp120 binding to CD4 allows secondary binding to the co-receptor
  3. After this binding occurs, gp41 can now use the fusion peptide to drill into the host target cell membrane, inserting the viral genome
218
Q

HIV virus replication steps

A
  1. Reverse transcriptase synthesizes proviral DS DNA from the original RNA genome
  2. Integrase inserts the proviral DNA sequence into the host genome
  3. Host cell activation occurs, triggering LTR to initiate transcription of HIV viral RNA
  4. Antigenic stimulation causes release of NF-kB
    - What its supposed to do: Upregulate the T cell response
    - What it actually does: Initiates viral transcription through the LTR
219
Q

HIV virus release step

A
  • The viral replication in the cell is responsible for host cell death (DIRECT CYTOPATHIC EFFECT)
220
Q

An inflammasome-mediated programmed death pathway responsible for cell death in non-replicating viral infection

A

Pyroptosis

221
Q

HIV tropism allows infection of non-T cells (3)?

A

• Macrophages:
- Reservoir of HIV in certain tissues, resistant to cytopathic effects

• Dendritic cells:

  • In mucosa, used for transport to lymph nodes
  • In lymph nodes, additional reservoirs for HIV

• Microglia

  • Infection by monocytes to microglial cells in the brain allows HIV access to the CNS
  • Neuronal damage from viral product
222
Q

B lymphocytes in HIV
• Proliferative response
- Possibly due to ?

  • May become ? - LYMPHOMA
  • Non specific ?
  • Impaired humoral immunity
  • Reduced ?
  • Reduction in ?
A
  • Secondary infection (EBV)
  • Clonal
  • Nonspecific hypergammaglobulinemia

• Impaired humoral immunity

  • Reduced isotype switching
  • Reduction in antibody production
223
Q

Pathogenesis of HIV steps

A
  1. Infection of mucosal tissues
    - Mucosal injury increases rate of viral entry
  2. Death of mucosal memory CD4+ T cells
    - Dendritic cells transport virus to CD4 cells in the lymph nodes
  3. Infection established in lymphoid tissues, e.g., lymph node
    - Viral replication occurs in the lymph node
  4. Spread of infection throughout the body = Viremia (2-3 weeks) (viral load)
  5. Immune response: partial control of viral replication (3-7 weeks) (seroconversion)
  6. Clinical latency: Establishment of chronic infection; virus concentrated in lymphoid tissues; low-level virus production (can be years)
  7. Increased viral replication
  8. AIDs: Destruction of lymphoid tissues: depletion of CD4+ T cells
224
Q

What is the first, second, and third detectable substance for testing HIV positive?

A
  • First= Viral RNA: Nucleic Acid Test (NAT)
  • Second= Protein antigen p24
  • Third = antibody to HIV
225
Q

What is the window period for NAT?

A

7-14 day window period from exposure to positive results

226
Q

Symptoms of Acute Retroviral Syndrome

A
  • Fever, sore throat, muscle aches

- Self-limited

227
Q
  • end of initial viremic spike

- may predict CD4 cell loss

A

Viral set point

228
Q
  • Period of “silent massacre” of CD4 cells

- May last years without symptoms

A

Clinical latency

229
Q

How do you know to diagnose AIDs?

A

Declining CD4+ counts and/or the onset of opportunistic infection or neoplasms usher in the diagnosis of AIDs

230
Q

AIDs case definition

A
  • HIV-related encephalopathy
  • Cytomegalovirus Retinitis (with loss of vision)
  • Pneumocystis Jiroveci Pneumonia
  • Chronic intestinal cryptosporidiosis
  • Invasive cervical cancer
231
Q

What does it mean if you see CNS toxoplasmosis?

232
Q
  • opportunistic fungal infection
  • AIDs-defining illness
  • Can be diffuse or focal or anything radiographically
A

Pneumocystis Jiroveci (carinii)

233
Q

Diarrhea in AIDs patients

A
  • Protozoa
  • Bacteria
  • Mycobacteria
  • Viral
  • Fungi
234
Q

What kind of tumor is Kaposi sarcoma?

A

Vascular tumor

235
Q

What 3 things are associated with the development of a Kaposi sarcoma?

A
  • Human herpesvirus 8 (KS herpesvirus)
  • Primary effusion lymphoma
  • Castleman’s disease
236
Q
  • HIV allows opportunistic viral infection, including ? reactivation
  • HIV decreases cellular immunity, which usually checks ?
A
  • Epstein Barr Virus (EBV)

- B-cell proliferation

237
Q

B cell lymphomas with translocations

A
  • Burkitt lymphoma (MYC)

- Large B cell lymphoma (BCL6)

238
Q

Virus-associated B cell lymphomas

A
  • EBV+ large cell lymphoma
  • KSHV+ primary effusion lymphoma
  • EBV+ Hodgkin lymphoma
239
Q

What virus is associated with cervical cancer?

240
Q
  • Protein synthesis and secretion is tightly maintained
  • In cases of mutations or incorrect processing in certain diseases, MISFOLDING occurs, yielding an insoluble beta-pleated sheet
  • If it isn’t broken down, it can accumulate
A

Amyloidosis

241
Q

If amyloid is localized what is causing it?

A
  • Local disease

- Tumor

242
Q

If amyloid is systemic what is causing it?

A
  • Primary (plasma cell disorder) or secondary (inflammatory)
243
Q

Amyloid
What protein involves:
- Native folded protein
- Monomers assemble to form B-sheet structure

244
Q

Amyloid
What protein involves:
- Acquired mutations
- Immunoglobin LIGHT chains

A

AL protein

245
Q

Amyloid
What protein involves:
- Chronic inflammation
- SAA protein

A

AA protein (AMYLOID ASSOCIATED)

246
Q

Amyloid
What protein involves:
- Mutation
- Mutant transthyretin

A

ATTR Protein

247
Q

Amyloid:

Which proteins are associated with production of abnormal amounts of protein

A
  • AL protein

- AA protein

248
Q

Which proteins are associated with production of normal amounts of mutant protein (e.g., transthyretin)

A

ATTR protein

249
Q

3 categories of Amyloidosis

A
  • Systemic (generalized) Amyloidosis
  • Hereditary Amyloidosis
  • Localized Amyloidosis
250
Q

Types of systemic amyloidosis

A

• Immunocyte dycrasias with amyloidosis (primary amyloidosis)

  • Associated disease: MULTIPLE MYELOMA AND OTHER MONOCLONAL PLASMA CELL PROLIFERATIONS
  • Fibril protein: AL

• Reactive systemic amyloidosis (secondary amyloidosis)

  • Associated disease: CHRONIC INFLAMMATORY CONDITIONS
  • Fibril protein: AA

• Hemodialysis-associated amyloidosis

  • Associated disease: CHRONIC RENAL FAILURE
  • Protein: AB2m
251
Q

Types of Hereditary Amyloidosis

A

• Familial Mediterranean fever
- Fibril Protein: AA

• Familial amyloidotic neuropathies (several types)
- Protein: ATTR

• Systemic senile amyloidosis
- Protein: ATTR

252
Q

Types of Localized Amyloidosis

A

• Senile cerebral

  • Associated disease: Alzheimer disease
  • Fibril protein: AB

• Endocrine
- Associated disease: TYPE 2 DISEASE

• Medullary carcinoma of thyroid
- Protein: A Cal

• Islets of Langerhans
- Protein: AIAPP

• Isolated atrial amyloidosis
- Protein: AANF

253
Q

How else can you diagnose systemic amyloidosis?

A

In an abdominal fat pad biopsy

254
Q

If amyloid occurs in the kidney, the disruption of the glomeruli may result in ? –> ?

A

• Result in proteinuria –> edema

255
Q

If amyloid occurs in the heart, the disruption of the myocardium may result in ?

A

Dysrhythmias

256
Q
  • When you see the “bubble gum” pink deposits in histo, you can demonstrate the presence of amyloid with the ?
  • This will show “apple green” birefringence in the presence of amyloid when examined under ?
A
  • Congo red stain

- polarized light

257
Q

Recognize aspects on microbes that are essential for them to survive and are thus very conserved

A

Pattern Recognition Receptors

258
Q

Protection from infectious pathogens

259
Q

Big points about PRRs

  • Toll like =
  • NOD-like =
  • C-type lectin =
  • RIG-like =
A
  • TLR = activate NFkB –> proinflammatory
  • NOD-like = Inflammasome, gout, atherosclerosis, IL-1, caspase-1
  • C-type lectin = fungal glycan
  • RIG-like = intracellular nucleic acids (i.e. viral RNA)
260
Q

Disease associated with PTPN22 (non-HLA)?

A

Rheumatoid Arthritis

261
Q

Immune response against one self-antigen causes tissue damage and the release of other antigens which then in turn activate more lymphocytes by these newly encountered epitopes

A

Epitope spreading

262
Q

Renal allograft rejection pattern: Hyperacute

A
  • kidney becomes cyanotic, mottled, and flaccid, and can excrete a few drops of bloody urine
  • Ig and complement are deposited in the vessel wall causing endothelial injury and fibrin-platelet thrombi
  • Neutrophils accumulate in arterioles, glomeruli, and peritubular capillaries
  • Glomeruli undergo thrombotic occlusion of capillaries and there is fibrinoid necrosis in arterial walls
  • Kidney cortex undergoes outright necrosis (infarction) and have to be removed
263
Q

Renal allograft rejection pattern: Acute

A

• T cell mediated

  • Tubulointerstitial pattern - extensive interstitial inflammation with infiltration of tubules = vasculitis
  • Vascular pattern - inflammation of vessels = endotheliitis

• Antibody mediated
- damage to glomeruli and small blood vessels

264
Q

Renal allograft rejection pattern: Chronic

A
  • Progressive renal failure with a rise in serum creatinine over a period of 4 to 6 months
  • Vascular changes
  • thickening with inflammation
  • glomerulopathy
  • peritubular capillaritis
  • Intersticial fibrosis and tubular atrophy
  • Intersticial mononuclear cell infiltrates (NK cells and plasma cells)
265
Q

Acquired deficiency of complement regulatory factors

A

Paroxysmal nocturnal hemoglobinuria

266
Q
  • Disease caused by mutations in the FAS gene?
  • Characterized by an inability to eliminate Epstein-Barr virus eventually leading to fulminant infectious mononucleosis and the development of B tumors
  • Usually due to mutation in gene encoding adaptor molecule SLAM-associated protein (SAP). Unable to form germinal centers or produce high affinity antibodies
A

X-linked lymphoproliferative syndrome

267
Q

If HIV diagnosis is made early ?

A

•Highly active anti-retroviral therapy
(HAART) initiated

•CD4 counts monitored and
treatment adjusted appropriately

•Disease may progress despite
therapy, but typically is well
controlled

•Prophylactic treatment against
infections utilized

268
Q

Manifestation of AIDs

A

•Opportunistic infection

  • Pneumocystis pneumonia
  • Tuberculosis
  • Toxoplasma
  • Candida mucositis
  • Cryptosporidium diarrhea

•Neoplasia

  • Kaposi sarcoma
  • Lymphoma
269
Q

Most common fungal infection in patients with AIDs, and infection of the oral cavity, vagina, and esophagus are its most common clinical manifestations

A

Candidiasis

270
Q

AIDs

  • May cause disseminated disease but usually affects the eyes and GI tract
  • Occurs almost exclusively in patients with CD4+ T cell counts less than 50 per microliter
A

Cytomegalovirus

271
Q

Causes persistent diarrhea in AIDs

A

Cryptosporidium

272
Q

AIDs

  • occur at an increased rate
  • With new therapy the incidence has fallen
  • Unchecked proliferation of B cells infected with oncogenic herpesviruses in the setting of profound T cell depletion
  • Germinal center B-cell hyperplasia in the setting of early HIV infection
273
Q
  • Self-limited meningoencephalitis occurring at the time of seroconversion
  • Aseptic meningitis
  • Vascuolar myelopathy
  • Peripheral neuropathies
  • Most common: progressive encephalopathy called HIV-associated neurocognitive disorder
A

CNS Disease

274
Q

Renal Amyloidosis Symptoms

A
  • Gives rise to proteinuria that could become nephrotic syndrome
  • Could ultimately get renal failure and uremia
275
Q

Cardiac Amyloidosis Symtoms

A
  • Congestive Heart Failure which could be fatal if leads to arrhythmias and conduction disturbances
276
Q

GI Amyloidosis Symptoms

A
  • Could be asymptomatic
  • Tongue: enlargement so can’t speak or swallow
  • Stomach and intestine: malabsorption, diarrhea, and digestion disturbance
277
Q

Vascular Amyloidosis Symptoms

A
  • Vascular fragility that can lead to bleeding

MOD Exam 2 (6 decks)

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