Ch. 14 Immunology

Front 1

What is innate immunity?

Back 1

-Nonspecific, present regardless of antigen exposure
-Intensity of response doesn't increase with repeat exposure
-1st part: factors that prevent microbes from entering (intact epithelium, cilia in resp., alveolar macrophages)
-2nd part: factors that destroy/limit growth of pathogens (NK cells, phagocytes, complement, interferon, iron sequestering proteins, fever, inflammation)

(Basically all immunity that doesn't involve the actions of B or T cells after antigen exposure)

Front 2

What is adaptive/acquired immunity?

Back 2

-Response of B or T cells after antigen exposure
-Characterized by memory (results in faster, stronger, more efficient response)

Front 3

Effector cells in innate immunity (6)

Back 3

Neutrophils
Basophils
Eosinophils
Macrophages
Mast cells
NK cells

(NOT B or T lymphocytes)

Front 4

Effector cells in adaptive/acquired immunity

Back 4

B cells
Plasma cells
Helper T cells (CD4)
Cytotoxic T cells (CD8)

Front 5

Which chemical mediators are part of innate immunity? Which are acquired immunity?

Complement?
Cytokines?
Interferons?
Lysosomal enzymes?
Acute phase proteins?
Antibodies?

Back 5

Complement - Innate (though can be activated by antibody/antigen complexes)
Cytokines - Acquired
Interferons - Innate
Lysosomal enzymes - Innate
Acute phase proteins - Innate
Antibodies - Acquired

Front 6

Cell mediated vs. humoral immunity

What does each defend against?

Back 6

Cell mediated:
1) Viruses, fungi, mycobacteria
2) Tumors
3) Hypersensitivity
4) Causes graft rejection

Humoral:
1) Bacteria (some viruses and toxins can be neutralized by antibodies)

Front 7

Cell mediated vs. humoral immunity

Which elements are innate? Which are acquired?

Back 7

Innate:
-Cell mediated: macrophages, NK cells
-Humoral: Complement, lysozyme

Acquired:
-Cell mediated: CD4 helper T cells, CD8 cytotoxic T cells
-Humoral: Antibodies

Front 8

Antibodies can independently neutralize some viruses/toxins but require the help of ________ or _______ to kill bacteria.

Back 8

complement (antibody-antigen complex bind C1)

or

phagocytes (IgG is ligand for Fc receptor)

Front 9

T lymphocytes have T-cell receptors (TCRs) that interact with _____ on other cells.

Back 9

major histocompatibility complex (MHC)

Front 10

MHC class I vs. class II

Which is found on all cells?
Which presents exogenous non-self peptides (obtained cia phagocytosis/endocytosis)?
Which presents non-self peptides that have been processed intracellularly (i.e. viral infection)?
Which marks the cell for destruction when presenting non self peptides?

Back 10

Which is found on all cells? Class I
Which presents exogenous non-self peptides? Class II
Which presents non-self peptides that have been processed intracellularly? Class I
Which marks the cell for destruction when presenting non self peptides? Class I

Front 11

Which cells present MHC class II?

Back 11

Antigen presenting cells

(dendritic cells, macrophages, memory B cells)

Front 12

When MHC class II presents non-self peptides, it leads to activation of a ________ cell with the TCR appropriate for that peptide.

Back 12

CD4+ Helper T cell

(leads to release of cytokines-->macrophage activation & proliferation of appropriate plasma cells)

Front 13

How do antibodies eliminate extracellular pathogens? Intracellular?

Back 13

Extracellular: bind and opsonize (IgG) so phagocytic cells phagocytose it and present on MHC II to perpetuate humoral response; IgG/M can activate complement to lyse, neutralize or opsonize

Intracellar: IgG binds antigens on infected cells so cells with Fc receptor (phagocytes, NK cells) destroy them

Front 14

Which Ig is found as a dimer in secretions and a monomer in blood?

Back 14

IgA

Front 15

Which Ig is bound on the surface Fc receptors of tissue mast cells and blood basophils?

Back 15

IgE

Front 16

Which Ig mediates type 1 hypersensitivity?

Back 16

IgE (allergic rxns)

Front 17

correr

Back 17

to run, to race, to flow

courrir

Front 18

Which Ig is the ligand for Fc receptors on NK cells or phagocytes?

Back 18

IgG

Front 19

Which Ig is most abundant in primary immune response? Secondary?

Back 19

Primary=IgM
Secondary=IgG

Front 20

Which Ig can activate the classical complement pathway?

Back 20

IgG and IgM

Front 21

In the T-cell independent response, which antibodies can be made?

Back 21

Only IgM

(memory B cells require a helper T cell for isotype switching and a secondary immune response to occur)

Front 22

How are there more unique Ig molecules than there are unique Ig genes?

Back 22

Gene rearrangement

-The light chains (gamma and kappa) can be mixed and matched with heavy chains (1 for each isotype)
-V, D, J segments can be rearranged in variable region

Front 23

Which complement components cause cell lysis?

Back 23

C5b-C9 (form membrane attack complex)

Front 24

Which complement components cause degranulation of mast cells and basophils?

Back 24

C3a, C4a, C5a (anaphlylatoxins)

Front 25

Which complement components cause opsonization of particulate antigens?

Back 25

C3b, C4b (opsonins)

Front 26

Which complement components cause chemotaxis of leukocytes (mainly PMNs)?

Back 26

C5a, C3a, C5b67 (chemotactic factors)

Front 27

Which complement components are involved in viral neutralization?

Back 27

C3b, C5b-C9

Front 28

Which complement components allow for solubilization and clearance of immune complexes?

Back 28

C3b

Front 29

How are each the 3 pathways of complement activated?

Back 29

Classical: C1q binds antigen antibody complex (IgG/M) on pathogen surface

Mannose-binding lectin: acute phase protein (mannose binding lectin) binds mannose residues on pathogen leading formation of C3 convertase and follows classical pathway from there

Alternative pathway: C3 is activate spontaneously by hydrolysis (usually by molecules with repeating chemical structures on pathogen surface; polysaccharides, lipopolysacchrides, teichoic acid) then follow classical pathway

Front 30

Which complement pathways require acquired immunity elements? Which don't?

Back 30

Classical needs antibodies to start

MBL and alternative pathway don't (innate immunity)

Front 31

C1 esterase inhibitor deficiency

Back 31

Overproduction in anaphlotoxins (C3a, C4a, C5a)

Leads to recurrent episodes of angioedema (degranulation of mast cells/ basophils)

AD inheritance (hereditary angioneurotic edema)

Front 32

C3 deficiency

Back 32

Reduced C3b predisposes to recurrent pyogenic infections

Front 33

C5-C8 deficiency (or mannose binding lectin deficiency)

Back 33

Greatly increase risk of Neisseria infections (C5b-C9 forms MAC which can kill most unencapsulated gram - organisms)

Front 34

Decay accelerating factor deficiency

Back 34

Paroxysmal nocturnal hemoglobinuria

Decay accelerating factor (on all human cells) destabilizes C3 and C5 convertase so can't make MAC on human cells

Front 35

Potent antigen presenting cell that forms extensive web in tissues for trapping and phagocytosing antigen

Back 35

Dendritic cell (Langerhans cell in epidermis)

Front 36

Which cells use oxygen dependent and indepent mechanisms to generate antimicrobial substances?

Back 36

Neutrophils and macrophages

Front 37

Found in blood and migrates into tissues to defend against parasites

Back 37

Eosinophils

Front 38

Effector mechanism of eosinophils

Back 38

Exocytosis of granules containing extremely basic proteins (fight parasites)

Front 39

What releases histamine and other vasoactive amines upon crosslinging of surface bound IgE by allergen?

Back 39

Basophils (blood) and mast cells (tissues)

Front 40

What cells do NK cells lyse?

Back 40

Virally infected (antibody dependent) & tumor cells with decreased levels of MHC class I

Front 41

Large, granular lymphocytes with no markers in common with B or T cells, not MHC restricted

Back 41

NK cells

Front 42

CD20+ lymphocyte with membrane bound Ig

Back 42

B cell

Front 43

B cells can endocytose and present antigen on _____ , thus functioning as antigen presenting cells in the activation of T helper cells

Back 43

MHC II

Front 44

Can free penicillin cause anaphylaxis?

Back 44

No, can only bind one arm of an antibody. When bound to a carrier protein (i.e. amoxicillin) it can crosslink IgE and cause anaphylaxis

Front 45

What type of hypersensitivity is anaphylaxis?

Back 45

Type 1

Front 46

Can anaphylaxis occur on the 1st exposure to an antigen?

Back 46

No, produce IgE after a few days which bind to the Fc receptors on mast cells (sensitization). 2nd exposure cross-links the IgE bound mast cells and causes degranulation.

Front 47

What is the treatment for anaphylaxis?

Back 47

Epinephrine
-beta2 bronchodialates (leukotrienes bronchoconstricted)
-alpha1 prevents vascular leakage and increases BP

Diphenhydramine: H1 receptor antagonist (histamine usually causes vascular permeability and smooth muscle contraction)

Methylprednisolone:
-Works synergistically with epi
-Inhibits phospholipas A2 so less arachidonic acid to make prostaglandins and leukotrienes

Front 48

Why are 2nd gen H1 receptor antagonists (fexofenadine/Allegra, loratadine/Claratin) better than 1st gen (diphenhydramine)?

Back 48

2nd gen doesn't cross BBB so less drowsiness

Front 49

Cromolyn sodium

Back 49

Prophylactic inhibitor of mast cell degranulation; stabilizer (asthma/allergic rhinitis)

(can't treat once degranulation has occured)

Front 50

Anti-inflammatory
Block production of cytokines
Treat allergic asthma

Back 50

Corticosteroids

Front 51

Omalizumab

Back 51

Monoclonal anti-IgE antibody (prevent IgE binding to receptors by binding receptor)
Treat severe asthma uncontrolled with corticosteroids

Front 52

Zileuton

Back 52

5-lipoxygenase inhibitor (prevent leukotriene synthesis so no bronchoconstriction in asthma)

Front 53

Zafirlukast, montelukast

Back 53

Cysteinyl leukotriene receptor antagonists (less leukotriene effects=bronchodilation=asthma treatment)

Front 54

Histamine and leukotrienes play a major role in __________ which involves bronchospasm, urticaria, hypotension, and GI problems

Back 54

Anaphylactic shock

Front 55

Pt. develops high indirect bilirubin, high reticulocytes, and + direct Coomb's test after taking antibiotic

What is this and what type of hypersensitivity?

Back 55

Drug induced warm autoimmune hemolytic anemia (AIHA)

Type II; antibiotic on RBC is bound as an antigen by IgG (extravascular hemolysis)

Front 56

What type of hypersensitivity reaction is serum sickness?

Back 56

Type III

Front 57

What is a type III hypersensitivity reaction? Does it require sensitization?

Back 57

Antibody-antigen (immune) complexes deposit in tissues. Eventually causes the activation of complement.

Don't need sensitization if exogenous antigen is given in large excess at 1st exposure.

Front 58

What is the pathogenesis of serum sickness?

Back 58

2 days to 2 weeks after patient exposed to foreign serum, IgG is produced in high enough amounts to make enough immune complexes (usually w/Fc regions of foreign antibodies as antigens) that can't be cleared fast enough and start depositing in tissues. Symptoms will subside once phagocytes clear antigen.

Front 59

What are signs/symptoms of serum sickness?

Back 59

1) Urticaria, tight throat, and facial swelling (anaphylatoxins from activated complement cause release of leukotrienes and histamine from mast cells)
2) Proteinuria, hematuria (immune complex deposition in renal glomeruli (like post strep glomerular nephritis))
3) Joint pain (immune complex deposition in synovial tissue)

Symptoms present about 2 days to 2 weeks after serum given (need time to make IgG)

Front 60

Does serum sickness increase or decrease serum complement levels?

Back 60

Decrease, use it up

Front 61

Administration of non-human antibodies can lead to _________, but making the Fc region nonantigenic can avoid this.

Back 61

serum sickness

(chimeric antibody=Fab nonhuman, Fc human)

Front 62

2 types of contact dermatitis

Back 62

Allergic type (contact with irritant one has been immunologically sensitized to like poison ivy; rxn can be more severe with each subsequent exposure)

Irritant type (repetitive irritation like washing)

Front 63

Which type hypersensitivity?

IgE mediated immediate hypersensitivity

Back 63

Type I

Front 64

Which type hypersensitivity?

Mast cell degranulation induced by allergen cross-linked IgE

Back 64

Type I

Front 65

Which type hypersensitivity?

Anaphylaxis, allergic rhinitis, bronchial asthma

Back 65

Type I

Front 66

Which type hypersensitivity?

Atopic dermatitis

Back 66

Type I

Front 67

Which type hypersensitivity?

Antibody mediated cytotoxic hypersensitivity

Back 67

Type II

Front 68

Which type hypersensitivity?

Antibodies directed against cell bound antigens induce destruction of cells or tissues

Back 68

Type II

Front 69

Which type hypersensitivity?

Transfusion reactions, hemolytic disease of the newborn, autoimmune hemolytic anemia

Back 69

Type II

Front 70

Which type hypersensitivity?

Immune complex mediated hypersensitivity

Back 70

Type III

Front 71

Which type hypersensitivity?

Antibodies directed against soluable serum antigen form immune complexes that deposit in tissues. Damage is complement mediated (lysis and neutrophil attraction)

Back 71

Type III

Front 72

Which type hypersensitivity?

Post strep glomerulonephritis, serum sickness

Back 72

Type III

Front 73

Which type hypersensitivity?

Systemic lupus erythematosus, rheumatoid arthritis, hypersensitivity pneumonitis

Back 73

Type III

Also post strep glomerulonephritis, serum sickness

Front 74

Which type hypersensitivity?

Cell-mediated delayed hypersensitivity

Back 74

Type IV

Front 75

Which type hypersensitivity?

Antigen specific helper T cells activate tissue macrophages and stimulate local inflammation over 12-72 hrs

Back 75

Type IV

Front 76

Which type hypersensitivity?

Contact dermatitis, tuberculin-type/granulomatous hypersensitivity, acute graft rejection

Back 76

Type IV

Front 77

Which type hypersensitivity?

Decreased complement in serum

Back 77

Type III

Front 78

Which type hypersensitivity?

+ direct and indirect Coombs test

Back 78

Type II

Front 79

What is the principle mediator (cell or Ig) of each type of hypersensitivity?

Back 79

I: IgE
II: IgG or IgM
III: IgG
IV: Helper T cell 1

Front 80

SCID involves what cell types?

Back 80

T cells (absent)
B cells (low normal to absent)
NK cells (normal to low)

Front 81

What types of pathogens are infants w/SKID more susceptible to?

Back 81

Opportunistic infection with intracellular organisms

(No cell mediated immunity b/c no T cells. Humoral is compromised too but babies have mom's IgG (transplacental) and IgA (breast milk). After about ~6mo old, have problems with humoral too.)

Front 82

How do you treat SCID?

Back 82

Bone marrow transplant (or else fatal)

Front 83

Baby with multiple infections (esp. intracellular), weight loss

Normal numbers of CD20+ cells, absence of CD3+ cells, unresponsive to B & T cell mitogen (pokeweed)

Back 83

SCID

T cells (absent)
B cells (low normal to absent)
NK cells (normal to low)

Front 84

Mutations in gamma subunit of IL-2 receptor is found in the most common type of SCID (X-linked). How does this mutation cause disease?

Back 84

This subunit is important in the functioning of many IL receptors responsible for development/proliferation of B and T cells

Front 85

Primary immunodeficiency in child with normal cell mediated immunity but absent plasma immunoglobulins

Back 85

Bruton's agammaglobulinemia

Front 86

Bruton's agammaglobulinemia is a defect in _____.

Back 86

B cells (and thus immunoglobulin)

Front 87

Which common immunodeficiency is associated with anaphylactic transfusion reactions?

Back 87

IgA deficiency (most common immunodeficiency)

(Defect in heavy chain isotype switching. Develop IgE against IgA.)

Front 88

Child with frequent infections with staph and other catalase + organisms. Normal WBC count and serum antibodies in high-normal range

Back 88

Chronic granulomatous disease

Front 89

What is deficient in chronic granulomatous disease?

Back 89

Mutation in gene for NADPH oxidase (catalyzes production of superoxide which is used to make hydrogen peroxide by SOD)

Front 90

What are 2 mechanisms a phagocyte can use to kill phagocytosed bacteria?

Back 90

1) Respiratory burst (NADPH oxidase catalyzes produciton of superoxide. SOD converts that to H2O2)
2) Myeloperoxidase converts H2O2 to hypoclorite (HOCl-)

(Can also kill with lysozyme and cytotoxic peptides without using O2)

Front 91

What's in a granuloma and why are they formed?

Back 91

Collection of epitheliod cells (modified macrophages) and giant cells (fusion of may macrophages) surrounded by a firbous capsule

Wall off an intracellular pathogen that is resistant to elimination (but can be sterile)

Front 92

Patients with chronic granulomatous disease are most susceptible to which organisms?

Back 92

Staph aureus, Serratiea, Burkholderia cepacia, Asperfillus, and Candida

(can kill catalase - strep by stealing H2O2 made by strep and converting it to hypochlorite with myeloperoxidase)

Front 93

Neutrophils and macrophages fail to reduce nitroblue tetrazolium

Back 93

Chronic granulomatous disease (no oxidative respiratory burst)

Front 94

Autosomal recessive disorder in which lysosomes of neutrophils are incapable of fusing with phagosomes. Normal nitroblue tetrazolium.

Back 94

Chediak-Higashi

Unlike CGD, susceptible to staph AND strep (catalase -) and has functional NADPH oxidase

Front 95

Facial abnormalities, cleft palate, micrognathia, hypocalcemia, lymphopenia, boot shaped heart, absent thymic shadow

Back 95

DiGeorge

Front 96

Which pouches are not properly formed in DiGeorge syndrome?

Back 96

Third pouch:
-Thyroid
-Inferior 2 parathyroid glands

Fourth pouch:
-Superior 2 parathyroid glands

Front 97

What is the inheritance of DiGeorge syndrome? What is mutated?

Back 97

AD

microdeletions on Q arm of chr22

Front 98

Classic manifestations of DiGeorge syndrome?

Back 98

Congenital heart abnormalities (i.e. truncus arteriosus or tetralogy of Fallot)
Abnormal facial features
Thymic aplasia
Cleft palate
Hypocalcemia (hypoparathyroidism)
22q deletion

(CATCH-22)

Front 99

How are T cells selected in the thymus?

Back 99

Positive and negative selection ensures mature T cells will be MHC restricted and self-tolerant respectively.

(T cells that bind MHC don't undergo apoptosis (+). T cells that bind self peptide in association with MHC undergo apoptosis (-))

Front 100

Which is affected in DiGerorge syndrome: humoral or cell-mediated immunity?

Back 100

Initially cell mediated b/c no thymus to mature T cells.

Eventually humoral (need heper T cells and their cytokines for B cell proliferation and differentiation. Lose humoral at ~6mo old as maternal antibodies drop off.

Front 101

Brutton's agammaglobulinemia (X-linked hypogammaglobulinemia)

What type of immune deficiency?
Immune defect?
Susceptibility?

Back 101

B-cell deficiency

Few to no B cells (only Ig is IgG found at very low levels)

Recurrent pyogenic infections after 6mo old

Front 102

IgA deficiency

What type of immune deficiency?
Immune defect?
Susceptibility?

Back 102

B cell

B cell fails to produce IgA

Recurrent sinus, respiratory, and GI infections (IgA is found in secretions)

*Anaphylactic transfusion rxns

Front 103

X-linked hyper-IgM syndrome

Immune defect?
Susceptibility?

Back 103

No B0 cell class switching from IgM to other isotypes due to defect in CD40 ligand or other problem in interaction between B0 cell and helper T cell

Pyogenic infections; poor response to immunization

Front 104

Common variable immunodeficiency

What type of immune deficiency?
Immune defect?
Susceptibility?

Back 104

B cell

Late onset (25-30yo) agammaglobulinemia that has acquired and inherited characteristics; commonly follows viral infection

Pyogenic infections, increased risk of various autoimmune dz. and lymphoma

Front 105

DiGeorge syndrome

What type of immune deficiency?
Immune defect?
Susceptibility?

Back 105

T cell

T cell deficit due to thymic dysplasia

Opportunistic viral and fungal (need cell mediated immunity)

Front 106

Chronic mucocutaneous candidiasis

What type of immune deficiency?
Immune defect?
Susceptibility?

Back 106

T cell

T cell dysfunction specific to Candida albicans

Front 107

Chronic granulomatous disease

What type of immune deficiency?
Immune defect?
Susceptibility?

Back 107

Phagocyte deficiency

Phagocytes lack NADPH oxidase so can't produce H2O2 to kill bacteria with catalase

Catalase + bacteria, certain fungi; widespread granuloma formation

Front 108

Chediak-Higashi syndrome

What type of immune deficiency?
Immune defect?
Susceptibility?

Back 108

Phagocyte deficiency

Lysosomes can't fuse with phagosomes

Staph and strep (catalase - susceptible unlike CGD)

Front 109

Leukocyte adhesion deficiency

Immune defect?
Susceptibility and other features?

Back 109

Defective neutrophil integrin (LFA-1 mediated adhesion) so defective migration

Severe pyogenic infections; delayed umbilical cord separation

Front 110

What is used to screen for HIV? What test is confirmatory?

Back 110

Screen: ELISA

Confirm: Western blot (pt.'s antibodies react with HIV proteins in acrylamide gel)

Front 111

What drug classes are used in highly active antiretroviral therapy (HAART)?

Back 111

Nucleoside analog reverse transcriptase inhibitors:
reverse transcriptase puts them into DNA strand where they block further extension (Zidovudine (AZT), lamivudine, etc.)

Nonnucleoside analogs (reverse transcriptase inhibitors):
delavirdine, nevirapine, etc.

Protease inhibitors:
bind and inhibit protease (all end in -navir)

Front 112

Missing doses of HAART therapy can rapidly lead to resistance because __________ is extraordinarily error-prone.

Back 112

HIV reverse transcriptase

(can result in mutation that leads to drug resistance if virus can replicate while sporadically using HAART)

Front 113

What type of virus is HIV?
What cell types does it infect?

Back 113

Encapsulated retrovirus

Infects CD4+ T cells (and macrophages, dendritic cells, and microglial cells that express appropriate coreceptor for gp120 and gp41 on viral envelope)

Front 114

Once macrophages or dendritic cells are infected with HIV, they express DC-SIGN which allows them to bind and directly infect _____.

Back 114

T cells

Front 115

What are 3 major mechanisms of CD4+ T cell depletion in HIV infection?

Back 115

1) Viral replication in T cell --> host cell lyses and release virions
2) Expression of HIV peptides on infected cells --> cytotoxic T cells recognize and kill
3) Activation of uninfected CD4+ T cells --> activation induced apoptosis

Front 116

When is an HIV+ pt. considered to have AIDS?

Back 116

T cells <200/microL

or

presents with one of the AIDS defining opportunistic infections/malignancies

Front 117

HIV with gp120 an gp41 infects T cells that express ____ and either CXCR4 or CCR5. It can also infect phagocytic cells.

Back 117

CD4+

Front 118

What is the most common significant opportunistic infection in HIV patients? How does it present?

Back 118

Pneumocystis jiroveci

Pneumonia with diffuse symmetric intersititial infiltate (usually in pts. with T cell < 200/microL)

Front 119

What should an HIV patient be on as prophylaxis for PCP?

Back 119

Trimethoprimsulfamethoxazole (can treat it too)

Front 120

Anti transplant rejection drug that inhibits calcineurin (prevents transcription of important cytokines like IL-2)

Back 120

Cyclosporine

(can cause nephrotoxicity and HT)

Front 121

Hyperacute rejection

Back 121

Preformed anti-ABO antibodies occlude vessels of graft w/in minutes of transplant (organ turns white during surgery)

Front 122

Acute rejection

Back 122

T cell mediated destruction of graft parenchyma usually due to human leukocyte antigen (HLA) mismatches.

Occurs w/in days-weeks. Can be treated with immunosuppressive drugs

Front 123

Chronic rejection

Back 123

Graft vascular damage seen months to years after transplantation

(could be caused by antibodies or immunosuppresive drug adverse effects, like OKT3)

Front 124

What are anthithymocyte globulin and OKT3 used for?

Back 124

Immunosuppression (prevent graft rejection)

Both antibodies against lymphocytes

(AGT is heterologous antibody against T cells)

(OKT3, aka muromonab, is antibody against CD3. Inhibits T cell recognition of alloantigen and reduces T cell counts)

Front 125

In graft vs. host disease, donor _____ attack immunocompromised host.

Back 125

T cells

Front 126

In graft vs. host disease, which tissues are most affected?

Back 126

Skin and GI

(2 major sites of pathogen entry so have cells with high MHC expression density)