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Immunology Flashcards

1
Q

Lymph node

A

A secondary lymphoid organ that has many afferents (to the lymph node) and 1 or more efferents (away from lymph node).

Encapsulated, with trabecular.

Functions are nonspecific filtration by macrophages, storage of B and T cells, and immune response activation

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2
Q

Lymph node follicle

A

Site of B cell localization and proliferation

Located in outer cortex of lymph node

Primary follicles are dense and dormant

Secondary follicles have pale central germinal center and are active

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3
Q

Medulla

A

Consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses

Medullary sinuses communicate with efferent lymphatics and contain reticular cells and macrophages

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4
Q

Paracortex

A

House T cells

Region of cortex between follicles and medulla

Contains high endothelial venues through which T cells and B cells enter from the blood

Not well developed in patients w/ DiGeroge syndrome

Paracortex enlarges in an extreme cellular immune response such as response to viral infection

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5
Q

Lymph drainage

A

Cervical: head and neck

Hilar: lungs

Mediastinal: esophagus and trachea

Axillary: upper limb, breast, skin above umbilicus

Celiac: liver, stomach, spleen, pancreas, upper duodenum

Superior mesenteric: lower duodenum, jejunum, ileum, colon to splenic flexure

Inferior mesenteric: colon from splenic flexure to upper rectum

Internal iliac: lower rectum to upper anal canal, bladder, vagina, prostate

Para-aortic: uterus, ovaries, testes, kidneys

Superficial inguinal: lower anal canal, skin below umbilicus

Popliteal: foot, calf

Right lymphatic duct: drains right side of body above diaphragm

Thoracic duct: drains everything else into junction of left subclavian and internal jugular veins

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6
Q

Sinusoids of spleen

A

Long, vascular channels in red pulp with fenestrated “barrel hoop” basement membrane where macrophages are found nearby

T cells are found in periarterial lymphatic sheet within white pulp

B cells are found in follicles within the white pulp

The marginal zone (in between white and red pulp), contains APCs and specialized B cells and is where APCs present blood-borne antigens

Macrophages in spleen remove encapsulated bacteria (SHiNE SKiS)

Splenic dysfunction leads to decreased opsonization and increased susceptibility to encapsulated organisms

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7
Q

Thymus

A

Site of T-cell differentiation and maturation (B cell mature in bone marrow)

From epithelium of 3rd pharynges pouches

Cortex is dens with immature T cells, medulla is pale with mature T cells

Hassall corpuscles contain epithelial reticular cells, which help T cells mature by exposing them with wide variety of self genome that they express

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8
Q

Innate immunity

A

Neutrophils, macrophages, dendritic cells, NK cells, complements

Resistance persists through generations and does not change within an organism’s lifetime

Nonspecific response to antigens

Occurs rapidly (minutes to hours)

Physical barrier include epithelial junctions and mucus

Secret lysozymes, complements, CRPs, and defensins

TLR: pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMP) such as LPS, flagellin, ssRNA (viruses)

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9
Q

Adaptive immunity

A

T cells, B cells, antibodies

Variation through VDJ recombination during lymphocyte development and microbial resistance not heritable

Highly specific to specific antigens

Develops over long periods of time, but memory response is much faster

Secrete immunoglobulins

Memory cells: activated B and T cells, subsequent exposure to a previously encountered antigen leads to stronger and quicker immune response

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10
Q

MHC I

A

Coded by HLA genes

HLAA, B, C

Binds to TCR and CD8

Expressed on all nucleated cells. Not expressed on RBCs

Present endogenously synthesized antigens (e.g. viral) to CD+ cytotoxic T cells

Antigen peptides loaded onto MHCI in RER after delivery via TAP transporter w/ help of Beta2 microglobulin

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11
Q

MHC II

A

Coded by HLA genes

HLADR, DP, DQ

Binds to TCR and CD4

Expressed only in APCs

Present exogenously synthesized proteins (e.g. bacterial, viral capsid) to T-helper cells

Antigen loaded following release of invariant chain in an acidified endosome

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12
Q

Natural killer cells

A

Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells

Only lymphocyte member of innate immune system

Activity enhanced by IL2, IL12, IFNalpha, and IFNbeta

Induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface

Also kills via antibody dependent cell-mediated cytotoxicity (CD16 binds to Fc region of bound Ig activating the NK cell)

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13
Q

B cell functions

A

Recognize antigen: undergoes somatic hypermutation to optimize antigen specificity

Produce antibody: differentiate into plasma cells to secrete specific immunoglobulin

Maintain immunologic memory: memory B cells persist and accelerate future response to antigen

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14
Q

T cell functions

A

CD4+ T cells help B cells make antibody and produce cytokines to activate other cells of immune system

CD8+ T cells kill virus-infected cells directly

Delayed cell-mediated hypersensitivity (type 4)

Acute and chronic organ rejection

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15
Q

T cell differentiation

A

Bone marrow: T cell precursors synthesized

Thymus cortex: positive selection

Thymus medulla: negative selection

Lymph node: Tc cells and Th cells are distributed

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16
Q

Positive selection

A

Thymic cortex

T cells expressing TCRs capable of binding self MHC molecules survive

Apoptosis in T cells unable to recognize

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17
Q

Negative selection

A

Thymic medullar

T cells expressing TCRs with high affinity for self-antigens undergoes apoptosis

Remaining cells survive

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18
Q

Naive T cell activation

A
  1. Foreign body is phagocytksed by dendritic cell
  2. Foreign antigen is presented on MHCII and recognized by TCR on Th cell. Antigen presented on MHCI to Tc cells
  3. Costimulatory signal is then given by interaction of B7 (from dendritic cell) and CD28 (T cells) after MHC/TCR binding
  4. Th cell activates and produce cytokines
  5. Tc cells activates and is able to recognize and kill virus infected cells
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19
Q

B cell activation and class switching

A
  1. Th cell activation
  2. B cell receptor-mediated endocytosis, foreign antigen is presented on MHCII and recognized by TCR on Th cell
  3. Costimulatory signal is given by CD40 ligand (Th cell) interaction w/ CD40 of B cell after MHC/TCR binding
  4. Th cell secrets cytokines that determines Ig class switching of B cell.
  5. B cell activates and undergoes class switching, affinity maturation, and antibody production
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20
Q

Th1 cells

A

Secrete IFNgamma

Activates macrophages and Tc cells

Inhibited by IL4 (secreted from Th2 cells) and IL10 (secreted from Tregs)

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21
Q

Th2 cells

A

Secrete IL4, IL5, IL6

Recruits eosinophils for parasite defense

Promotes IgE production by B cells

Inhibited by IFNgamma (secreted by Th1)

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22
Q

Macrophage-lymphocyte interaction

A

Macrophages release IL12, which stimulates T cells to differentiate into Th1 cells

Th1 cells release IFNgamma to stimulate macrophages

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23
Q

Tc cells

A

Kill virus infected, neoplastic, and donor graft cells by inducing apoptosis

Release cytotoxic granules containing perforin (helps to deliver the content of granules into target cells) and granzyme (serene protease, activates apoptosis inside target cell), andgranulysin (antimicrobial, induce apoptosis)

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24
Q

Regulatory T cells (special Th2 cells)

A

Help maintain specific immune tolerance by suppressing CD4 and CD8 T cell effector functions

Identified by expression of surface markers CD3, CD4, CD25, and transcription factor FOXP3

Activated Treg cells produce anti-inflammatory cytokines and TGFbeta

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25
Q

Antibody structure and function

A

Variable region of L and H chains recognize antigens

Fc region of IgM and IgG fixes complements

Heavy chain contributes to Fc and Fab fractions

Light chain contributes to only Fab fraction

Fab: antigen binding fragment, determines idiotype or the unique antigen binding pocket (only 1 antigenic specificity expressed per B cell)

Fc: Constant, Carboxyl terminal, Complement binding, Carbonhydrate side chains
Determines isotype (IgM, IgG, etc)

Antibody diversity is determined by:
Random “recombination” of VJD/VD genes
Random combination of heavy chains w/ light chains
Somatic hypermutation (following antigen stimulation)
Addition of nucleotides to DNA during recombination

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26
Q

IgG

A

Main antibody in 2ndary (delayed) response to antigen.

Most abundant isotope in serum

Fixes complements, cross placenta, opsonizes bacteria, neutralizes bacteria toxins and viruses (prevent entry)

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27
Q

IgA

A

Prevents attachment of bacteria and viruses to mucus membranes

Does not fix complements

Monomoer (in circulation) or dimer (when secreted)

Crosses epithelial cells by transcytosis

Most produced antibody overall, but majority released into secretions (tears, saliva, mucus)

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28
Q

IgM

A

Produced in the primary response to antigen (immediate)

Fixes complements but does not cross the placenta

Antigen receptor on the surface of B cells

Monomers on B cell or pentamers when secreted

Pentamer allows it to efficiently trap free antigens out of tissue while humoral response evolves

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29
Q

IgD

A

Unclear function

Found on surface of many B cells and in serum

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30
Q

IgE

A

Binds mast cells and basophils

Cross-linked when exposed to allergen, mediating immediate (type 1) hypersensitivity through release of inflammatory mediates such as histamine

Mediates immunity to worms by activating eosinophils

Lowest concentration in serum

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31
Q

Thymus independent antigens

A

Antigen lacking a peptide component (LPS), cannot be presented by MHC to T cells

Weakly or nonimmunogenic: vaccines from these often require boosters or conjugation w/ peptides

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32
Q

Thymus dependent antigens

A

Antigens containing a peptide component

Class switching and immunological memory occur as a result of direct contact of B cells w/ Th cells

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33
Q

Acute phase reactants

A

Factors released in response to inflammation, produced by liver and induced by IL1, IL6, TNFalpha, and IFNgamma

Serum amyloid A: prolonged elevation and lead to amyloidosis

CRP: opsonin, fixes complements and facilities phagocytosis

Ferritin: binds and sequesters iron to inhibit microbial iron scavenging

Fibrinogen: coagulation factor, promotes endothelial repair

Hepcidin: prevents release of iron bound by ferritin (anemia of chronic disease)

Albumin (decreased): reduction conserves amino acid for positive reactants

Transferrin (decreased): internalized by macrophages to sequester iron

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34
Q

Complement functions

A

System of interacting plasma proteins that play a role in innate immunity and inflammation

Membrane attack complex (MAC) defense against gram-negative bacteria

C3b: opsonization, clear immune complexes
C3a, C4a, C4a: anaphylaxis
C5b-9: cytolysis activated w/ MAC

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35
Q

Complement activation

A

Classic pathway: antigen-antibody complex –> C1 –> C3 convertase –> C5 convertase –> MAC –> lysis

Alternative pathway: microbe surface molecule–> C3 –> C3b –> C3 convertase –> C5 convertase –> MAC –> lysis

Lectin pathway: mannose or other microbial sugar –> C1-like complex –> C3 convertase –> C5 convertase –> MAC –> lysis

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36
Q

Complement inhibition

A

Decay-accelerating factor (DAF/CD55), C1 esterase inhibitor

Prevent complement activation on self cells (RBCs)

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37
Q

C1 esterase inhibitor deficiency

A

Hereditary angioedema (inflammation 2ndary to lack of inhibition of complements)

ACE inhibitors are contraindicated

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38
Q

C3 deficiency

A

Increase risk of severe, recurrent pyogenic sinus and respiratory tract infections

Increased susceptibility to typeIII hypersensitivity

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39
Q

C5-C9 deficiency

A

Increase susceptibility to recurrent Neisseria bacterimia

40
Q

DAF deficiency

A

Complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria

41
Q

IL1

A

Secreted by macrophages

Endogenous pyrogen, causes fever and acute inflammation

Induces chemokine secretion to recruit leukocytes

42
Q

IL2

A

Secreted by all T cells

Stimulate growth of ALL T cells

43
Q

IL3

A

Secreted by all T cells

Suppor the growth and differentiation of bone marrow stem cells into lymphoid and myeloid progenitors

44
Q

IL4

A

Secreted from Th2 cells

Induce differentiation into Th2 cells

Promote growth of B cells

Enhances class switching to IgE and IgG

45
Q

IL5

A

Secreted by Th2 cells

Promote differentiation of B cells

Enhances class switching to IgA

Stimulate growths and differentiation of eosinophils

46
Q

IL6

A

Secreted by macrophages

Causes fever and stimulate production of acute phase proteins

47
Q

IL8

A

Secreted by macrophages

Major chemotactic factor for neutrophils, neutrophils are recruited to clear infections

48
Q

IL12

A

Secreted by macrophages

Induce differentiation of T cells into Th1 cells

Activates NK cells

49
Q

TNFalpha

A

Secreted by macrophages

Mediates septic shock

Activates endothelium causing leukocyte recruitment and vascular leak

50
Q

IFNgamma

A

Secreted by Th1 cells

Has antiviral and antitumor properties

Activates NK cells to kill virus-infected cells

Increases MHC expression and antigen presentation in all cells

51
Q

IFNalpha and IFNbeta

A

Part of innate host defense against both RNA and DNA viruses

Glycoproteins synthesized by viral-infected cells that act locally on uninfected cells, “priming” them for viral defense

Viral dsRNA in primed cells activates:
RNAase: degradation of viral/host mRNA
Protein kinase: inhibition of viral/host protein synthesis

Essentially results in apoptosis of infected cell and thereby interrupting w/ viral amplification

52
Q

Anergy

A

Self-reactive T cells become nonreactive without costimulatory molecule

53
Q

Passive immunity

A

Receiving preformed antibodies

Rapid onset

Short life span of antibodies

IgA in breast milk, maternal IgG crossing placenta, humanized monoclonal antibodies injected

54
Q

Active immunity

A

Exposure to foreign antigen

Slow onset

Long lasting protection (memory)

Natural infection, vaccination

55
Q

Hypersensitivity type 1

A

Anaphylactic and atopic

Free antigen cross-links IgE on presensitized mast cells and basophils, triggering immediate release of vasoactive amines (histamine) that act at post capillary venules.

Reaction develops rapidly after antigen exposure because of preformed antibody

Test: skin tests for specific IgE

Disorders: anaphylaxis (bee sting, food allergies), hives, eczema, hay fever

ACID:
Anaphylactic and atopic (type 1)
Cytotoxic (type 2)
Immune complex (type 3)
Delayed cell mediated (type 4)
56
Q

Hypersensitivity type 2

A

IgM, IgG bind to fixed antigen on “enemy” cell, leading to cellular destruction

3 mechanisms:
Opsonization leading to phagocytosis or complement activation
Complement mediated lysis
Antibody dependent cell-mediated cytotoxicity, usually due to NK cells or macrophages

Tests:
Direct Coombs: detects antibodies on RBCs (use antihuman antibodies)
Indirect Coombs: detects antigens that can lead to antibody binding on RBCs(use anti RBC antigen antibodies followed by antihuman antibodies)

Disorders: autoimmune hemolytic anemia, pernicious anemia, ITP, bullous pemphigoid, rheumatic fever

57
Q

Hypersensitivity type 3

A

Antigen-antibody (IgG) complexes activate complements, which attracts neutrophils, neutrophils release lysosomal enzymes

Test: immunoflurorescent staining

Disorders: SLE, Serum sickness, arthus reaction, post-strep glomeruloneprhitis

58
Q

Hypersensitivity type 4

A

Sensitized T lymphocytes encounter antigen and then release lymphokines, which lead to macrophage activation

NO antibodies involved

Test: patch test, PPD

Disorders: multiple sclerosis, Guillian-Barre syndrome, graft vs host disease, contact dermatitis

59
Q

Blood transfusion reactions

A

Allergic reaction: type I against plasma proteins, urticaria, fever, treat w/ antihistamines

Anaphylactic reaction: severe allergic reaction, dyspnea, respiratory arrest, shock

Febrile nonhemolytic transfusion reaction: type 2, host antibodies against donor HLA antigens and leukocytes, fever, headaches, flushing

Acute hemolytic transfusion reaction: type 2, intravascular hemolysis or extravascular hemolysis (against foreign antigen on donor RBCs), fever, hemoglobinemia, jaundice

60
Q

X-linked agammaglobulinemia

A

B cell disorder (Bruton), X linked recessive

Defect in BTK, no B cell maturation

Recurrent bacterial and enteroviral infections

Normal B cell count, decreased Ig of all classes

61
Q

Selective IgA deficiency

A

B cell disorder

Most common primary immunodeficiency

Majority asymptomatic, can have airway and GI infections and anaphylaxis to IgA containing products

Low IgA w normal IgG and IgM

62
Q

Common variable immunodeficiency

A

B cell disorder

Defect in B cell differentiation

Increase risk of autoimmune disorders, bronchiectasis, lymphoma

Decreased plasma cells and decreased immunoglobulins (all)

63
Q

Thymic aplasia (Digeorge)

A

T cell disorder

22q11 deletion, failure to develop thymus

Recurrent viral/fungal infections

Decreased T cells, absent thymic shadow on CXR

64
Q

IL12 receptor deficiency

A

T cell disorder

Decreased Th1 response

Disseminated myobacterial and fungal infections

Decreased IFNgamma

65
Q

Autosomal dominant IgE syndrome

A

T cell disorder

Deficiency of Th17, impaired recruitment of neutrophils

Coarse facies, abscesses, eczema

Increased IgE, decreased IFNgamma

66
Q

Chronic mucocutaneous candidasis

A

T cell disorder

T cell dysfunction

Noninvasive Candida infection of skin and mucus membranes

Absent T-cell proliferation in response to Candida

67
Q

Severe combined immunodeficiency (SCID)

A

Both B and T

Adenosoine deaminase deficiency (decreased lymphocyte proliferation due to lack of DNA synthesis)

Failure to thrive, chronic diarrhea, recurrent infections

Decreased lymphocyte count

Treatment: bone marrow transplant

68
Q

Ataxia-telangiectasia

A

Both B and T

Lack of double strand repair leading to cell cycle arrest

Cerebellar defect, spider angiomas, IgA deficiency

Increased AFP, decreased Ig

69
Q

Hyper IgM

A

Both B and T

CD40 ligand defect –> class switching defect

Severe pyogenic infections, opportunistic infecdtions

Increased IgM, close to zero for other Ig

70
Q

Wiskott-Aldrich syndrome

A

Both B and T

WAS gene mutation, T cells unable to reorganize actin cytoskeleton

Thrombocytopenia purpura, Eczema, Recurrent infections

Decreased IgG, IgM, increased IgE, IgA

71
Q

Leukocyte adhesion deficiency

A

Defect in integrin on phagocyte, impaired migration and chemostasis

Recurrent bacterial skin and mucosal infection, impaired wound healing, delayed separation of umbilical cord

Increased neutrophils but absent at infection site

72
Q

Chediak-Higashi syndrome

A

Defect in lysosomal trafficking regulator, microtubule dysfunction in phagosome-lysosome fusion

Recurrent infections, progressive neurodegeneration

Giant granules in neutrophils and platelets

73
Q

Chronic granulomatous disease

A

Defect of NADPH oxidase, decreased reactive oxygen species available for respiratory burst in neutrophils

Susceptibility to catalase positive organisms

Abnormal dihydrorhodamine (can be normally oxidized and produce fluorescence if tagged) test

74
Q

Hyperacute transplant rejection

A

Within minutes

Type 2 reaction due to pre-existing antibodies to donor antigen

Widespread thrombosis of graft vessels, graft must be removed

75
Q

Acute transplant rejection

A

Weeks to months

Cellular: Tc activated against donor MHCs (seen as foreign)
Humoral: type 2, but antibodies develop later

Vasculitis of graft vessels, prevent/reverse w/ immunosuppressants

76
Q

Chronic transplant rejection

A

Months to years

Recipient T cells perceive donor MHC as recipient MHC but react against donor antigens presented. Both cellular and humoral

Irreversible damage such as atherosclerosis and vanishing bile ducts

77
Q

Graft vs host disease

A

Grated immunocompetent T cells proliferate in the immunocompromised host and reject host cells w/ “foreign” proteins –> severe organ dysfunctions

Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly

Usually in bone marrow and liver transplants

Potentially beneficial in bone marrow transplant for leukemia (graft vs tumor effect)

78
Q

Cyclosporine

A

Calcineurin inhibitor: binds T cell activation by preventing IL2 transcription

Used for transplant rejection prophylaxis and RA

Nephrotoxicity, hypertension, hyperlipidemia, hyperglycemia, gingival hyperplasia

79
Q

Tacrolimus

A

Calcineurin inhibitor: blocks T cell activation by preventing IL 2 transcription

Used for transplant rejection prophylaxis

Nephrotoxicity, increased risk of diabetes and neurotoxicity

80
Q

Sirolimus

A

mTOR inhibitor: blocks T cell activation and B cell differentiation by preventing IL2 signal transduction

Kidney transplant rejection prophylaxis

Causes anemia, leukopenia, thrombocytopenia, NOT nephrotoxic

81
Q

Basiliximab

A

Monocolonal antibody blocking IL2 receptor

Kidney transplant rejection prophylaxis

Edema, hypertension

82
Q

Azathioprine

A

Inhibits lymphocyte proliferation by blocking nucleotide synthesis (blocking 6-MP)

Transplant rejection prophylaxis, RA, Crohns, glomerulonephritis

Anemia, leukopenia, thrombocytopenia

83
Q

Glucocorticoids

A

Inhibit NFkB, suppresses both B and T cell function by decreased transcription of cytokines

Transplant rejection prophylaxis, autoimmune disorders

Hyperglycemia, osteoporosis, central obesity, muscle breakdown, iatrogenic Cushing syndrome

84
Q

Epoetin alfa

A

Erythropoietin

Used to treat anemias especially in renal failure

85
Q

Filgrastim/Sargramostim

A

Granulocyte/macrophage colony stimulating factor

Recovery of bone marrow

86
Q

Oprelvekin

A

Thrombopoietin

Used to treat thrombocytopenia

87
Q

Alemtuzumab

A

Target CD52 to treat CLL

88
Q

Bevacizumab

A

Target VEGF to treat colorectal and renal cell cancer

89
Q

Cetuximab

A

Target EGFR to treat colorectal, head and neck cancer

90
Q

Rituximab

A

Target CD20 to treat B cell non-Hodgkin lymphoma, RA, ITP

91
Q

Trastuzumab

A

Target HER2 to treat breast cancer

92
Q

Infliximab

A

Target TNFalpha to treat IBD, RA, and psoriasis

93
Q

Natalizumab

A

Target alpha4 integrin to treat multiple sclerosis and Crohns, can cause PML in MS patients w/ JC virus

94
Q

Abciximab

A

Target glycoprotein IIb/IIIa as anti platelet agent to prevent ischemic complications

95
Q

Palivizumab

A

Target RSV F protein as prophylaxis for high risk infants

96
Q

Denosumab

A

Target RANKLigand (control bone remodeling) for osteoporosis by inhibiting osteoclast maturation

97
Q

Omalizumab

A

Target IgE for allergic asthma

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