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Pathophysiology > eRobbins Ch 4 - Diseases of the Immune System > Flashcards

eRobbins Ch 4 - Diseases of the Immune System Flashcards

1
Q

Innate Immunity

A

Natural/Native immunity

Mediated by cells/proteins that are always present & poised to fight

Immediate

Epithelial barriers (mucosa, skin, respiratory tract, GI tract)
Phagocytes (Neutrophils & Macrophages)
NK Cells
Compliment Cascade -> INFLAMMATION

Cytokine: IL 12, IFN-gamma, IL-23, TNF-alpha & IL-1

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2
Q

Adaptive Immuntiy

A

Acquired/Specific Immunity
Specialized APC

Humoral & Cell Mediated Immunity

B Lymphocytes = antibodies
T Lymphocytes = Helper or attack cells

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3
Q

Humoral Immunity

A

Antibodies bind to microbes & tag them for removal

Antibodies = Soluble proteins produced by B Lymphocytes/B Cells

Antibodies attack EXTRACELLULAR microbes in the blood (attach to outside of free floating microbes/peptides)

Effector cell = plasma cells that secrete antibodies

BACTERIAL

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4
Q

Cell-Mediated Immunity

A

Medicated by T Cells/Lymphocytes

Designed to phagocytose infected cells = VIRUSES

Cytotoxic T Lymphocytes (CTL) = Directly kill infected cells

Helper T Cells = activate phagocytes (to phagocytose microbes & then kill) via cytokines

Effector Cell = CTL mostly, but also Helper T Cells

Naive T cells are activated by antigen & co-stimulators to proliferate & differentiate

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5
Q

T Lymphocytes

A

Thymus derived

1) Memory Cells
2) Effector Cells = CD8 & CD4

CTL (CD8 + MHC I) = that kill

Helper T cells (CD4 + MHC II) = secrete cytokines that increase B cell response/antibody production & phagocytosis

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6
Q

MHC

A

presents peptide fragment to CD4/CD8 for recognition

to mature T Cell

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7
Q

MHC Restriction

A

a T cell will recognize a peptide antigen only when it is bound to a host body’s own MHC molecule

won’t recognize an MHC peptide complex that’s not the own bodies

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8
Q

T Cell Receptor (TCR)

A

heterodimer with a disulfide linked alpha & beta chain
(analogous to BCR’s Ig alpha & beta)

5 invariant polypeptide chains (3 CD3 proteins & 2 other chain - weird greek letter) = signal transduction

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9
Q

B Cell Receptor (BCR)

A

Membrane IgM or IgD & associated signal proteins Ig alpha & beta

CD21 = CR2 receptor for complement protein that promotes B Cell activation & attached to BCR
(CR2 = Type 2 Complement Receptor)

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10
Q

CD4+

“Helper” T Cells

A

Secrete cytokines that:

1) Increase B cell response/antibody production
2) Recruit macrophages for phagocytosis

Release IFN-gamma, IL-2, IL-4, IL-5

IL-2

HIV = no CD4

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11
Q

CD8+

“Cytotoxic T Lymphocytes (CTL)

A

CTL (CD8 + MHC I) = that kill

Kill cells that express foreign antigen IN THEIR CYTOPLASM

Secrete Cytokines that directly kill

VIRAL

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12
Q

Natural Killer (NK) Cells

A

Innate Immune System lymphocyte

Not variable, very general

Inhibitory or Activating:
- Inhibitory = recognized self MHC class I & tells to not attack
-default is to stay inhibitory; but then
become activated
- Activating = recognizes expressed/up-regulated on stressed/infected/DNA damaged cells -> then cells are eliminated)

Kills by tagging & then gets opsonized/phagocytosed

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13
Q

CD28

A

Cluster of Differentiation 28

Co-stimulator protein on TCR complex

Stimulatory signals required for T cell activation and survival

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14
Q

MHC

A

MHC for humans = HLA (Human Leukocyte Antigen) Complex

Chromosome 6 & HIGHLY polymorphic

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15
Q

MHC Class I

A

CD8+ Cytotoxic T Lymphocytes

HLA-A, HLA-B, HLA-C

Structure:
1 alpha chain with 3 domains
1 Beta microglobulin

Peptide in cleft is from proteins synthesized int he cytoplasm

VIRAL

longer peptide because open ends?

Binds peptides that are 8-10 AA in length

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16
Q

MHC Class II

A

CD4+ “Helper T Cell”

HLA-D
Structure: Heterodimer
1 Alpha Chain with 2 alpha domains
1 Beta Chain with 2 beta domains

Binds peptides that are 15-24 AA in length

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17
Q

B Lymphocytes

A

Memory Cells

Effector Cells = produce Antibodies

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18
Q

Dendritic Cells

A

Major APC

Interdigitating DC - lots of MHC I & costimulatory molecules to capture & present to T CELLS

Langerhans cells = Under epthelia

Follicular DC (FDC)= located in germinal centers of lymph FOLLUCLES

  • bear receptors for Fc tails of IgG & complement proteins that work to trpap antigens bound to antibodies/complement (antigen filter)
  • Then present to B CELLS
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19
Q

APC

A

Captures microbial antigens & displays them on membrane to lymphocytes

Dendritic Cells
Macrophages
B Cells -> Helper T Cells

Protein antigens are proteolytically digested & then displayed on MHC clefts

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20
Q

IgM

A

membrane bound Ig/Antibody expressed on cell’s surface

Forms the B Cell Receptor (BCR)

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21
Q

IgA

A

Secreted in mucosal tissues

Neutralizes microbes in the lumen of mucosal tissues (respirator & GI tracts)

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22
Q

IgE

A

Surface of mast cells & Eosinophils

Coats helminthic parasites & kills them

TH2 cells

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23
Q

IgD

A

expressed on the surface of B Cells

NOT secreted

24
Q

Primary/Generative Lymphoid Organ

A

Bone Marrow & Thymus

25
Q

Secondary/Peripheral Lymphoid Organ

A

adaptive immune response develops & lymphocytes mature/specialize

26
Q

IFN-gamma

A

ACTIVATES macrophages

Released by activated macrophages & DC, endothelial cells, lymphocytes & mast cells

secreted by NK cells

early innate immune response

activates macrophages, stimulates B cell antibody production, activates complement & coats microbes for phagocytosis

27
Q

IL-2

A

Activates T Cells & tells to proliferate & differentiate

Regulate lymphocyte response & effector functions in ADAPTIVE immunity
Proliferation & Differentiation of lymphocytes

growth factor that acts on CD4+ & stimulates proliferation

28
Q

Helper T cell Cubsets

A

TH1

  • Recognize antigens of microbes ingested by phagocytes & activates phagocytes to kill microbes
  • produce IFN-gamma (activates macrophages, stimulates B cell antibody production, activates complement & coats microbes for phagocytosis)

TH2

  • Activate Eosinophils
  • Think allergies & asthma
  • Produces IL-4 (stimulates B cell differentiation into IgE secreting plasma cells)
  • Produces IL-5 (activates eosinophils)
  • Produces IL-13 (activates mucosal epithelial cells to secrete mucus & expel microbes)

TH17

  • Enhance leukocyte recruitment & stimulate inflammation
  • Produces IL-17 (recruits neutrophils & promotes inflammation)
29
Q

IL 12

A

early innate immune response

Released by activated macrophages & DC, endothelial cells, lymphocytes & mast cells

30
Q

IL-23

A

early innate immune response

Released by activated macrophages & DC, endothelial cells, lymphocytes & mast cells

31
Q

TNF-alpha

A

chemoattractant
early innate immune response

Released by activated macrophages & DC, endothelial cells, lymphocytes & mast cells

32
Q

IL-1

A

chemoattractant
early innate immune response

Released by activated macrophages & DC, endothelial cells, lymphocytes & mast cells

33
Q

IL-4

A

Regulate lymphocyte response & effector functions in ADAPTIVE immunity
Proliferation & Differentiation of lymphocytes

stimulates B cell differentiation into IgE secreting plasma cells

34
Q

IL-5

A

activates eosinophils

35
Q

Colony Stimulating Factor

A

stimulates hematopoiesis

Increase output of Leukocytes from bone marrow

36
Q

CD40 & CD40Ligand

A

Co-stimulatory protein on APC ( B Cells & Macrophages)

CD40 & CD40 Ligand bind & activate APC

37
Q

IL-13

A

Activates mucosal epithelial cells to secrete mucus & expel microbes

38
Q

IL-17

A

recruits neutrophils & promotes inflammation

released by TH17

39
Q

Affinity maturation

A

process of Helper T cells that stimulate the production of antibodies with higher antigen affinity

refinement of antibody production

40
Q

IL-22

A

a

41
Q

TGF - Beta

A

a

42
Q

IL-23

A

a

43
Q

IL-6

A

a

GO BACK THROUGH ALL CYTOKINES*

44
Q

IgG

A

Antibodies coat/opsonize microbes & target them for phagocytosis by Neutrophils & macrophages

Express Fc tails

Activates Complement system by Classical Pathway

Stimulates by IFN-gamma & TH! cells

Actively transported across placenta to create passive immuntiy

45
Q

Immediate (Type I) Hypersensitivity

A

Hallmark - Production of IgE antibodies

vascular permeability & smooth muscle contraction

Disorders:
Allergy, asthma, allergic rhinitis, conjunctivitis Hives/uticaria, Anaphylaxis, atopy

Mechanism: 
Activation of T2 helper cell & antibody class switching -> IgE

MEDIATORS OF TYPE I RESPONSE

  • CD4+ T helper cell subtype: “Th2 cell”
  • IL-4 promote switching of B cells from IgM to IgE production and further Th2 development
  • IL-5 induce expansion and activation of eosinophils
  • IL-13 promote switching of B cells from IgM to IgE production and stimulate mucus secretion by epithelial cells

3 groups of mediators released:

Immediate: vasoactive amines released from mast cells

1) Vasoactive Amines released/degranulate (histamine, proteases, ECF/NCF) (EARLY)
2) Membrane Phospholipids/lipid mediators (AA pathway = Prostaglandins & Leukotrienes)

Late Phase: cytokines/inflammatory response

3) Cytokine secretion
- > immediate release from mast cells & later recruits inflammatory cells (LATE) - TNF; amplifying TH2 response

Symptoms:
vascular dilation, edema, smooth muscle contraction, mucus production, inflammation

EOSINOPHILS - late phase
*Eosinophil chemotactic factor (ECF) produced by mast cells recruit eosinophils to tissue site.
*IL-5 produced by Th2 cells promote growth and activation of eosinophils.
*Secrete major basic protein and eosinophil
cationic protein toxic to epithelial cells
*Produce leukotriene C4 and platelet
activating factor (PAF) that directly activate
mast cells

46
Q

Antibody-mediated (Type II) Hypersensitivity

A

IgG & IgM production

*Specific antibody binding to cell surface antigen results in injury to cell via variety of potential mechanisms

Disorders:
Autoimmune, hemolytic anemia (Fetal Rh attack), Good pasture syndrome (Table 4-3)

Mechanism:
1) Opsonization/phagocytosis (Fetal Rh factor); Antibodies IgG & IgM bind to antigen on cell surface (either intrinsic (auto antigen) or exogenous (foreign) [e.g. drug] that attaches to cell surface) =>

2) Complement & Fc receptor mediated inflammation (Good pasture - Kidney & lung functions)
degranulation of mast cells => recruitment of leukocytes

3) Antibodies bind to ACh receptor & stimulate/block signaling
(block = Myasthenia Gravis; stimulate = Graves disease/hyperthyroidism)

Symptoms:
variety - see Table 4-3
Phagocytosis & lysis of cells, inflammation, functional derangements without cell/tissue injury

47
Q

Immune complex-mediated (Type III) Hypersensitivity

A
  • Soluble antigen & free floating complex, activates complement & inflammatory cascade

Disorders:

  • Vasculitis, lupus, glomerulonephritis, serum sickness, Arthus reaction
  • Lots of “-itis”es

Mechanism:

  • Antibody binds to circulating antigens to form immune complex
  • Immune complexes deposit in preferred tissue sites and elicit inflammatory response:
    - Blood vessel wall (vasculitis)
    - Glomeruli (glomerulonephritis)
    - Joints (arthritis)
  • Immune complex activates complement to recruit neutrophils; mechanism of injury similar regardless of tissue site
  • Large IC (Immuno Complex) - rapidly cleared because so big/obstructive
  • Small - poorly cleared, circulate, & deposit in tissues (filters); deposit inflammatory mediators -> causing inflammation

Symptoms:
Abnormal & location specific Inflammation
Inflammation, necrotizing vasculitis/fibrinoid necrosis

48
Q

Cell Mediated (Type IV) Hypersensitivity

A

T Cells gone awry

Disorders: Contact dermatitis/poison ivy, MS, DM1, TB

Mechanism:
- CD4+ T cells react to foreign or self-antigens, release cytokines and differentiate into:
-Th1 cells (IFN-γ TNF-α); macrophage activation
-Th17 cells (IL-17, IL-22): neutrophils activation
- CD4+ T cells recruit CD8+ T cells [cytotoxic T
lymphocytes (CTL)]

2 Types:

1) DTH = CD4 mediated
S/s: Contact dermatitis

2) Cellular cytotoxicity = CD8 mediated
S/s: CD8+ attacking own cells (MS = myelin sheath, DM1 = Islet cells )

  • Type I diabetes mellitis: T cells react with antigens of pancreatic islet β cells (insulitis)
  • Multiple sclerosis: T cells react with antigens in CNS myelin (perivascular inflammation in white matter and demyelination)
  • Rheumatoid arthritis: T cells react with antigens in joint synovium (chronic arthritis)
  • Contact sensitivity: T cells react with antigens of poison ivy and poison oak (dermatitis with blisters)

Symptoms: perivascular cellular infiltrates, edema, granuloma formation & cell distruction

49
Q

Sjogren Syndrome

A

destroy the exocrine glands, specifically the salivary and lacrimal glands

xerostomia (dry mouth) 
keratoconjunctivitis sicca (dry eyes)

Primary Sjögren’s = occurs by itself
Secondary Sjögren’s = another connective tissue disease is present (RA & SLE)

50
Q

Mikulicz Syndrome

A

Benign enlargement of the parotid and/or lacrimal glands

Sometimes, but not always, associated with Sjögren’s syndrome

51
Q

Scleroderma/Systemic Sclerosis

A

Characterized by thickening of the skin caused by accumulation of collagen, and by injuries to the smallest arteries

Limited cutaneous scleroderma = skin on the face, hands and feet

Diffuse cutaneous scleroderma = covers more of the skin, and is at risk of progressing to the visceral organs, including the kidneys, heart, lungs and gastrointestinal tract

CREST syndrome
C = Calcinosis
R = Raynaud's phenomenon
E = Esophageal dysfuction
S = Sclerodactyl (skin thickening)
T = Telangiectasias (dialated capillaries on face, hands, mucous membranes)
52
Q

Amyloidosis

A

amyloidosis is a non-specific term that refers to a number of different diseases

Amyloids are proteins whose secondary structure changes, causing the proteins to fold in a characteristic form, the beta-pleated sheet

Normally soluble proteins=> amyloids, they become insoluble and deposit in organs or tissues, disrupting normal function

Congo Red => Apple green under polarized microscope

Systemic = more than one organ system
Localized = 1 organ system/tissue type
Primary = disordered immune cell function
Secondary/Reactive = complication of some other chronic inflammatory/tissue-destroying disease
53
Q

Systemic Lupus Erythematosus (SLE)

A

Immune system attacks healthy tissues
Remissions

Characteristic rash - thought to be from wolf bite

Systemic = Type II & III Hypersensitivity
Discoid = skin lesions
Drug-induced = chronic use of certain drugs
Neonatal = infant from mother with SLE
54
Q

Polymyositis/Dermatomyositis

A

Polymyositis = Inflammation of many muscles

Dermatomyositis = Inflammation of muscles & skin

follows after pregnancy

Side effect of Statins

55
Q

Fc Receptor

A

Protein that binds to antibodies and is attached to infected cells or invading pathogens

Stimulates phagocytic or cytotoxic cells to destroy microbes

On:
B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils and mast cells

Pathophysiology (15 decks)

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