Immunology 1: Block 2 Flashcards

1
Q

List the characteristics of the innate and adaptive immune response.

A

Innate:

  • discriminate self from non-self
  • responds to broad groups of foreign agents
  • present at birth
  • rapid réponse (minutes)
  • no memory

Adaptive:

  • can discriminate self from non-self
  • exquisite specificity
  • slow response (days)
  • memory/anamnestic response
  • improved by vaccination
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2
Q

List the components of innate and adaptive immune response systems

A

Innate:

  • Physical and chemical defenses of the body
  • Leukocytes; phagocytes, granulocytes, natural killer cells, antigen-presnting cells
  • Soluble factors; cytokines, acute phase proteins
  • Normal flora microorganisms

Adaptive:

  • Leukocytes; B & T lymphocytes
  • Antibodies/immunoglobulins
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3
Q

Best control for intracellular pathogens such as viruses, intracellular bacteria and intracellular protozoans:

A
  • Interferon
  • Natural Killer Cells, stimulated by cytokines secreted by TH1 cells
  • Macrophages activated by cytokines secreted by TH1 cells
  • Tc Cells, stimulated by cytokines secreted by TH1 cells
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4
Q

Best control for extracellular bacteria:

A
  • Neutrophils
  • Antibody
  • Complement
  • CRP: Antibody, compliment and CRP are OPSONINS that coat bacteria, making the bacteria easier to recognize and phagocytose by neutrophils, monocytes, and macrophages.
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5
Q

Best control for worms:

A
  • IgE, secreted by B lymphocytes in response to cytokines secreted by TH2 cells.
  • Eosinophils, activated by cytokines secreted by TH2 cells.
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6
Q

Best control for fungi:

A
  • Neutrophils
  • Macrophages activated by cytokines secreted by TH1 cells.
  • TH17 cells
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7
Q

Define leukocytosis and possible etiologies.

A

Increase in the absolute number of WBCs. Indicates infection, inflammatory disease, leukemia or tissue trauma. >10,000 WBC/uL

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8
Q

Define lymphocytosis and possible etiologies.

A

increase in WBCs is chiefly due to lymphocytes. Indication of an acute viral infection or certain chronic infections, i.e. tuberculosis.

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9
Q

Define neutrophilia and possible etiologies.

A

A leukocytosis in which the increased in WBC is chiefly neutrophils. Usually indicates acute bacterial infection.
-May be due to increased bands/stands (immature neutrophils); this is called a LEFT shift.

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10
Q

Define eosinophilia and possible etiologies.

A

Leukocytosis in which the increased in WBCs is chiefly in eosinophils. Usually indicates worm infection or an allergy.

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11
Q

Define leukopenia and possible etiologies.

A

A decrease in the number of circulating WBCs. Indicates bone marrow failure due to certain infections, radiation exposure, or chemotherapeutic drug use. <4,000 WBC/uL

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12
Q

Understand normal WBC count and differential values.

A
Total WBC: 5,000-10,000 WBC/uL
Neutrophils: 40-60%
Lymphocytes: 20-40%
Monocytes: 2-8%
Eosinophils: 1-4%
Basophils: 0.5-1%
Bands/Stabs: 0-3%
Normal Platelet Count: 150,000-400,000/uL
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13
Q

Immune system cell linages, which cells fall under which lineage

A

Myeloid:

  • Erythrocytes - RBCs
  • Megakaryocytes - platelets and inflammation
  • Myeloid leukocytes
  • -Polymorphonuclear granulocytes - neutrophils, basophils, eosinophils
  • -Mononuclear phagocytes - macrophages, monocytes

Lymphoid:

  • B cells
  • T cells, TH/TC
  • Natural Killer cells
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14
Q

Name the various recombinant cytokines and their clinical uses.

A

Erythropoietin; Epoetin, EPO. Used for anemia.
Granulocyte colony stimulating factor (G-CSF): Filgrastim. Recovery of bone marrow (PMNs)
Granulocyte-monocyte colony-stiumlating factor (GM-CSF): Sargramoostim. Recovery of bone marrow (PMNs, monocytes, macrophages).
Interleukin-11: Oprelvekin, Thrombocytopenia
Thrombopoietin: TPO, Thrombocytopenia

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15
Q

Cells of the Lymphoid lineage, their common CD markers, major cell function.

A

B lymphocytes: CD19, CD20, CD21, CD40. Antibody secretion - humoral immunity.
All T Lymphocytes: CD3
-Helper T cells: CD3, CD4, CD28, CD40L. Cytokine secretion.
-Cytotoxic T cells: CD3, CD8. Killing of infected or neoplastic cells, rejection of grafts.
Natural Killer cells: CD16 (FcyR), CD56(NCAM). Killing of infected or neoplastic cells.

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16
Q

Mononuclear phagocytes; characteristics, phagocytosis process

A
  • 10-18 um diameter
  • includes circulating monocytes and fixed macrophages
  • long lived cells the function in phagocytosis and antigen presentation
  • Phagocytosis
  • -extension of pseudopodia
  • -formation of phagosome
  • -formation of phagolysosome
  • -respiratory burst: release of oxygen radicals, NO and hydrogen peroxide
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17
Q

Neutrophils; characteristics, function

A
  • primary fx is phagocytosis of extracellular bacteria
  • secondary fx is to promote inflammation
  • multi-lobed nucleus and purple-staining granules
  • -primary granules contain acid hydrolases, lysozyme, myeloperoxidase, and defensins
  • -secondary granules contain lysozyme and lactoferrin
  • live 2-3 days in circulation

*Green snot secondary to heme in neutrophils

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18
Q

Eosinophils; characteristics, function

A
  • Possess low affinity Fc receptors for IgE
  • fight parasitic (worm) infections
  • important in allergic responses (immediate hypersensitivity)
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19
Q

Basophils (and mast cells); characteristics, function

A
  • Least prevalent of leukocytes
  • Possess high affinity Fc receptors for IgE
  • Release the chemical mediators of immediate hypersensitivity (allergy) - histamine
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20
Q

Dendritic cells; characteristics, function

A
  • found under epithelia and in most organs
  • most efficient antigen-presenting cells (APCs)
  • Antigen presentation
  • -antigen taken up by pinocytosis
  • -antigens are digested and paired with major histocompatablity proteins (MHC)
  • -antigen/MHC complex is transported to outer surface where presented to T-cells
  • –Class I: present antigen to CD8+ TC cells
  • –Class II: present antigen to CD4+ TH cells
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21
Q

Megakaryocyte; characteristics, function

A
  • large lobulated nucleus, found in bone marrow

- give rise to platelets (2,000-5,000 platelets per cell)

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22
Q

Platelets/thrombocytes

A
  • anucleated

- normal lab value 150,000-400,000/uL of blood

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23
Q

Which are primary and which are secondary lymphoid organs?

A

Primary:

  • Thymus
  • Bone marrow

Secondary:

  • Tonsil
  • Lymph node
  • Spleen
  • Peyer’s patch in small intestine
  • Mucosa-associated lymphoid tissue (MALT)
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24
Q

What takes place in BONE MARROW, important characteristics, other info.

A
  • Site of B-cell differentiation and maturation, site where B-cells begin expressing surface immunoglobin.
  • Major site of hematopoiesis
  • Hematopoietic stem cells express CD34 and stem cell antigen-1 (Sca-1)
  • Stem cell differentiation is stimulated by colony-stimulating factor and interleukins produced by stromal cells and macrophages in the marrow.
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25
Q

What takes place in the TYHMUS, important characteristics, other info.

A
  • Site of T-cell differentiation, where T-cells begin expressing TCR
  • Developed from third pharyngeal (branchial) pouch
  • Cortex and Medulla
  • -Cortex is dense with immature T-cells
  • -Medulla contains mature T-cells and Hassall’s corpuscles
  • -Between cortex and medulla self-reactive T-cells are eliminated, this helps prevent autoimmune-diseases.
  • Chromosome 22q11.2 deletion are born with little or no thymus - suffer from DiGeorge syndrome. Patients are highly susceptible to viral infections due to few/no functional T-cells.
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26
Q

What takes place in the LYMPH NODES, important characteristics, other info.

A

-Function to survey lymph by macrophages, storage and activation of B and T cells, Antibody production.

Cortex (B cell area)

  • Primary follicles in the codex contain naive B cells
  • Secondary follicles contain germinal centers composed of B cells undergoing mitosis in response to antigen stimulation

Paracortex (T cell area)

  • Houses T cells, between cortex and medulla
  • Lymphocytes can enter node via high-endothelial venues (HEV)
  • Enlargers during extreme cellular immune responses.
  • Poorly developed in DiGeorge syndrome.

Medulla

  • cords contain closely packed lymphocytes and plasma cells
  • sinuses contain macrophages
  • sinuses communicate with efferent lymphatics
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27
Q

What takes place in the SPLEEN, important characteristics, other info.

A
  • responds to blood-borne antigens
  • antibodies are synthesized and released into circulation here
  • Asplenic persons are highly susceptible to infection by bacteria

White Pulp:

  • -T-cells arranged in periarteriolar lymphoid sheath (PALS) around central arteriole
  • -B cell rich follicles occupy space between the PALS and marginal sinus
  • -Specialized macrophages and additional B cells comprise the marginal zone at the outer boundary of the white pulp

Red Pulp:

  • Sinusoids comprising long, vascular channels with fenestrated barrel hood basement membrane
  • Splenic cords that contain plasma cells, resident macrophages, erythrocytes, platelets, granulocytes and lymphocytes
  • main function is HEMOCATHERESIS, distraction of aged platelets and erythrocytes.
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28
Q

List the stimuli the induce inflammation:

A
Infections
Injury
Allergies
Neoplasms
Necrosis
Bone fractures
Cuts
Burns
Ischemic events
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29
Q

List the local and systemic signs of inflammation:

A

PRISH

  • Pain - dolor
  • Redness - rubor
  • Immobility/loss of function (function laesa)
  • Swelling (tumor)
  • Heat (calor)
30
Q

Describe the pathogen-assoicated molecular patterns (PAMPs) expressed by microbes, and the pattern recognition receptors (PRRs) that phagocytes use to recognize them.

A
  • Bacteria and other types of microbes express pathogen-assoicated molecular patterns (PAMPs) that can be recognized by pattern recognition receptors (PRRs) on leukocytes.
  • Recognition of PAMPs enhances phagocytosis and signals the phagocyte to up-regulate adhesion molecule expression and cytokine production.

Other important PRRs:

  • -Toll-like receptors (TLRs) - recognize bacterial cell membrane and cell wall components like flagellin and nucleic acids.
  • -NOD-like receptors (NLRs) - located in leukocyte cytosol, recognize structural components (peptidogylcan) and toxins produced by intracellular bacteria.
  • -Scavenger receptors - recognize anionic polymers and acetylated low-density lipoproteins expressed by certain pathogens and dying (effete) RBCs.
  • -The phagocyte receptor for manna binding lectin (MBL) - serum protein that binds to mannose residues on bacteria and certain viruses.
31
Q

Describe the biological significance of the interaction between TLR4/CD14 and LPS.

A
  • When a complex comprising TLR-4 and CD14 on the phagocyte bind to endotoxin/lipoplysaccharide/LPS in Gram-negative bacteria membrane, the phagocyte is induced to produce IL-1 and tumor necrosis factor alpha (TNFa).
  • TNFa is the major cytokine responsible for septic shock.
  • IL-1 and TNFa production also increase adhesion molecule expression on leukocytes and vascular endothelium to aid extravasation, and stimulate the release of acute phase protein from the liver.
32
Q

Describe the respiratory burst and NO production by phagocytes:

A
  • Important products of respiratory burst:
  • -Hydrogen peroxide & Superoxide anion, production of both is catalyzed by phagocyte NADPH oxidase.
  • -Hyperchlorate, catalyzed by myeloperoxidase (PMNs) .
  • -Also produces Nitric Oxide (NO) by inducible nitric oxide synthase.
  • Important host-protective enzymes
  • -Superoxide dismutase
  • -Catalase
  • -Gluthione
33
Q

List the pro-inflammatory cytokines and describe their functions:

A

-IL-1, TNFa, IL-8

34
Q

List the major acute phase proteins and describe their functions:

A

Complement:

  • -causes bacterial cell lysis
  • -opsonizes bacteria for phagocytosis
  • -chemotactic for neutrophils
  • -induces mast cell degranulation

CRP:

  • -binds phosphcholine residue on strep. pneumonia and other microbes
  • -opsonizes bacteria for phagocytosis
  • -induces the CLASSICAL complement pathway
  • -clinically useful as general marker for inflammation and infection

Serum amyloid A:

  • -involved in tissue repair
  • -remodels extracellular matrix
  • -prevents oxidative tissue damage by neutrophils
  • -inhibits platelet activation
35
Q

Describe the steps involved in extravasation, including the roles of IL-1, TNFa, and the chemokine IL-8.

A
  • Rolling: E or P-selectin adhesion molecules on vasculature or stroma and Sialyl Lewis X carbohydrate on leukocytes.
  • Tight Binding: ICAM-1 on vasculature or stroma and LFA-1 (integrin) on leukocyte.
  • Diapedesis: Platelet/endothelial cell adhesion molecule 1 (PECAM-1) on vasculature or stroma and PECAM-1 on leukocyte.
  • Migration/Chemotaxis: Bacterial products - e.g. f-Met-Leu-Phe and Host products - C5a, IL-8, LTB4, kallikrein on vasculature and stroma. Receptors for those products on leukocytes.
36
Q

List the biological functions of complements, including the specific functions of the compliment split products C3b, C4b, C3a, C4a, C5a.

A

C3b>C4b: opsonization, recognized by comp lent receptors CR1, CR2, CR3 and CR4 on macrophages.

C5a»C3a>C4a: Anaphylatoxins, inactivated by carboxypeptidase N. Cause degranulation of mast cells, basophils and eosinophils.

C5a: activator and chemotaxins for all myeloid cells, induces PMN degranulation, induces IL-1 and IL-6 production in monocytes. Most potent anaphylatoxin.

C3a: Chemotactic for eosinophls.

C5b6789n: Membrane attack complex (MAC). Causes lysis of gram-negative, but no gram-positive bacteria.

37
Q

Describe how the classical, alternative, and lectin complement pathways are activated.

A

Classic Pathway:
-induced by CRP, IgG, or IgM bound to the surface of a cell target

Alternative Pathway:
-induced when C3b binds to endotoxin/LPS on gram-negative bacteria or zymosan on yeast.

Lectin Pathway:
-induced by mannose residues on bacteria and other microbes

All pathways lead to the formation of the membrane attack complex (MAC) that can directly lyse gram-negative bacteria.

38
Q

Describe the structure and function of the membrane-attack complex.

A

-All pathways lead to the formation of the membrane attack complex (MAC) or C5b6789n, that can directly lyse gram-negative bacteria.

39
Q

Describe the roles of C1INH and DAF in the regulation of complement activity.

A
  • C1 esterase inhibitor (C1INH) disrupts the C1qur complex, the MASP complex and C3bBb.
  • C1INH deficiency leads to hereditary angioedema
40
Q

Describe the basic structure of the antibody molecule, and the functions of the Fab and Fc fragments.

A

Fab fragment:

  • Antigen binding fragment
  • Determines idiotype:
  • -unique antigen binding pocket; only 1 antigenic specificity expressed per B-cell.

Fc (fragment-carboxyl termini): bottom portion

  • Constant
  • Complement binding at CH2 (IgG and IgM only)
  • Carbohydrate side chains
  • Determines isotype (IgM, IgD, etc.)
41
Q

List the antibody classes (isotypes) and subclasses found in humans. Describe the structural features and functions unique to each antibody class.

A

-

42
Q

Define isotype, idiotype, and allotype.

A
  • Structural differene in antibodies that distinguish one class from another are called ISOTYPIC differences.
  • Within a class or subclass of antibody, the constant region may display minor allelic polymorphisms between individuals of the same species (one to a few amino acids). These are called ALLOTYPIC differences.
  • The hypervariable regions of an antibody comprise its IDIOTOPE. These differences occur between all antibodies specific for dissimilar antigens.
43
Q

List the five sources of antibody diversity.

A

-

44
Q

Describe the roles of the VDJ recombinase, RAG-1, RAG-2, terminal deoxyribonucleotidyl transferase, and AID enzymes in expression of antibody genes.

A

-

45
Q

Describe the roles of the CD40-CD40L interaction and Th-derived cytokines in class-switching.

A

-

46
Q

Explain how an agglutination reaction is performed and interpreted.

A
  • Occurs when particulate antigens are cross-linked by antibodies, resulting in clumping of the particles.
  • The particles must have two or more epitopes (antigenic determinate) that can act as antibody binding sides before the cross-linking will occur.
  • Antibody must have a valence of at least 2
47
Q

Explain how human ABO and Rh (D) blood typing is performed and interpreted.

A
  • If RBCs are agglutinated by anti-A their blood type is TYPE A.
  • If agglutinates with anti-Rh, then Rh positive.
  • If agglutinates with anti-A and anti-B, type is AB.
  • If no agglutination then Type O.
48
Q

Explain the difference between the direct and indirect Coombs (antiglobin) test.

A

Direct Coombs test

  • detects human antibodies already bound to the surface of erythrocytes, platelets, or other cells
  • -often used to test the RBCs of newborn suspected of having hemolytic disease of the newborn (erythroblastosis fettles) for the presence of maternal IgG antibodies bound to the Rh antigen.

Indirect Coombs test

  • detects circulating IgG antibodies that are specific for surface antigens on RBCs, platelets, or other cells.
  • -often used to detect anti-Rh IgG antibodies in the circulation of Rh- women who have given birth to Rh+ children.
49
Q

Explain the heterophile antibody test for infectious mononucleosis.

A
  • Infection by Epstein-Barr virus induces the formation of heterophile antibodies early after the onset of symptoms of infectious mononucleosis.
  • These antibodies can agglutinate the RBCs of certain animal species such as horse.
50
Q

Explain how in-gel precipitation reactions (Ouchterlong, RID, immunoelectrophoresis) are performed and interpreted.

A

-

51
Q

Explain how the solid-phase immunoassays (EIA, ELISA, RIA) are performed and interpreted.

A

-

52
Q

Explain how a western blot is performed and interpreted.

A

-

53
Q

Explain how fluorescently tagged antibodies can be used to detect antigens in tissues (by immunoflourescence) or to separate cell populations on the basis of their surface markers (by fluorescence-activated cell sorting).

A

-

54
Q

Describe the screening and confirmatory tests used to determine HIV infection status.

A

-

55
Q

Determine the titer of an antiserum.

A

-

56
Q

Understand IgG, characteristics, life span, etc.

A
  • 4 subclasses; IgG1-4
  • Longest half-life @ 23 days, major type in serum @70-80%
  • Complement activation
  • Opsonization
  • Participates in antibody-dependent cell-mediated cytoxicity (ADCC) in conjunction with CD16-bearing NK cells.
  • Toxin and virus neutralization
  • Agglutination of antigens due to valence of 2 and flexibility in hinge region
  • ONLY class that cross the PLACENTA
  • -provides newborns passive protection, fully maternal in-utero
  • -accounts for 100% @ birth but fully replaced by infants own IgG by 5-6 months, production begins at 3 months gestation.
  • Major type synthesized during the secondary (anamnestic) immune response
57
Q

Understand IgM, characteristics, life span, etc.

A
  • First class of antibody made in response to ALL antigens, major class of the primary immune response.
  • made of five IgG-like molecules linked by the J-chain
  • comprises 10% of serum immunoglobin pool
  • COMPLEMENT activation
  • agglutinator of antigens due to valence of 10
  • Only class produced by the fetus
  • -look for this in fetal serum to determine if infection was in-untero or during birth
  • includes natural isohemagglutinins, which are natural IgM antibodies against erythrocyte ABO antigens.
58
Q

Understand IgA, characteristics, life span, etc.

A
  • Two subclasses, IgA1 & IgA2
  • IgA2 most important, exists in seromucous secretions as dimeric secretory IgA (alga).
  • Has two monomers held together by J-chain, provides valence of 4
  • contains secretory component (SC) produced by epithelial cells that protect the alga molecule from proteases made by microbes and digestive enzymes in the human host.
  • slgA protects MAT from microbial invasion and certain toxins
  • Serum IgA 3.5mg/mL, no known biological function
59
Q

Understand IgE, characteristics, life span, etc.

A
  • Similar structure to IgG but less hinge flexibility, hence poor agglutinator
  • Trace levels in serum
  • becomes bound to surface of cells with FCER; basophils, mast cells, and eosinophils
  • cross-linking of IgE by worm antigens or allergens causes degranulation.
  • originally evolved to combat helminthic infection
  • associated with immediate hypersensitivity diseases such as hay fever and asthma
60
Q

Understand IgD, characteristics, life span, etc.

A
  • similar structure to IgG.
  • found with IgM on surface of mature but naive B lymphocytes
  • after stimulation the B cell differentiates into a plasma cell that secretes large amounts of IgM but low amounts of IgD which quickly degrades.
61
Q

Describe the structure and function of the HLA Class 1 and 2 molecules:

A

Class 1:

  • present antigen to CD8+ TC cells
  • found on all nucleated cells
  • expression enhanced by interferons alpha and beta.

Class 2:

  • present antigen to CD4+ TH cells
  • expressed only on professional antigen-presenting cells such as dendritic cells, macrophages and B lymphocytes
  • expression can be induced on other cell types by interferon-gamma (IFNy).
62
Q

Diagram the gene loci encoding the HLA and describe the inheritance pattern of the HLA.

A
  • Class 2 has 3 loci and at each loci there are separate genes encoding the Alpha and Beta polypeptides.
  • Ordered DP/DQ/DR
  • Class 1 has 3 loci, ordered B/C/A.
  • A set of Class 1 and 2 genes on the chromosome are referred to as a haplotype. These are inherited en bloc (as a unit) and are co-dominately expressed; a child will share 50% of HLA molecules with each parent. There is a 25% change that a child will be a perfect HLA match to one of their siblings.
63
Q

Describe endogenous and exogenous processing and presentation to Tc and TH cells, respectively.

A
  • endogenous uses Class 1 HLA molecules to CD8 bearing Tc cells.
  • -viral antigens are processed by proteasomes into peptide fragments which are transported to the ER by TAP (transporter of antigenic peptide) molecules.
  • -inside the ER the peptides are bound to the groove of the Class 1 molecule and then moved to the host cell surface for presentation to Tc cells with TCRs specific for the viral peptide.
  • Class 2 HLA molecules present exogenous antigens to CD4-bearing TH cells.
  • -bacteria are endocytosed and degraded while at the same time Class 2 molecules are being made with an invariant chain (which holds the binding site open). When the phagocytosed vessel binds with the Class 2 molecules the peptides are attached to the Class 2 molecule and this migrades to the surface of the host cell for presentation to TH cells.
64
Q

Describe the structure and function of the TCR:

A
  • T cell receptor for antigen (TCR)
  • associated with the TCR is CD3, this is the portion that transmits the signal to the T cell when the TCR binds it’s specific antigen.
  • 95% ab heterodimer, 5% gamma/delta.
  • T cells do not class-switch and do not undergo affinity maturation.
  • T cells with the ab TCR can only respond to protein antigens
  • T cells with the gamma/delta TCR are found at mucosal epithelial sites such as skin, gut and lung. They respond to phospholipid or glycolipid antigens.
65
Q

Compare TCR gene expression with immunoglobulin gene expression.

A

-

66
Q

Describe the “two signal” theory of how T-cells are activated. Include the roles of TRC, CD3, CD28, and CD40L molecules.

A

T Cells:

  • Signal 1 comes from the TCR and the peptide/MCH complex on the APC. CD4 or CD* act as co-receptor molecules.
  • Signal 2 comes by multiple co-stimulatory interactions between cell surface molecules on the T cell and the APC.
  • Relationships: T Cell/APC/Comments
  • -CD28/B7/induces secretion of IL-2 and expression of the IL-2 receptor; required for T cell activation and proliferation
  • -CD40L/CD40/enhances CD28-B7 interaction; causes class switching in B cells
  • -CTLA-4/B7/inactivates the T cell, leading to a waining of the the immune system.

B Lymphocytes:

  • Signal 1: surface immunoglobulin binds to antigen
  • Signal 2: B cell interacts with TC cells by virtue of the cell surface interactions above and cytokine stimulation.
67
Q

List the imunosupressive therapies that target IL-2 synthesis and expression.

A
  • Many immunosupprressive therapies aimed at preventing graft-host rejection target IL-2 activation and receptor expresion because these molecules are central to T cell activation and proliferation.
  • Cyclosporine, Tacrolimus (FK506), and Sirolimus (rapamycin)
68
Q

List the CD4+ T cell subsets. List the signature cytokines produced by each subset and describe the functions of these cytokines.

A
  • TH1 cells promote cell-mediated immunity
  • -Interferon gamma (INFy)
  • –activates macrophages, enhances ability of respiratory burst
  • –activates NK cells
  • -enhances MHC (HLA) expression on cells
  • –prevents maturation of TH2 subset
  • -IL-2, activates and causes proliferation of all T cell subsets
  • TH2 cells promote humoral immunity against worms and cause allergies by secreting
  • -IL-4 and IL-13, they induce class switching to IgE and IgG4, IL-4 also prevents maturation of TH1 subset
  • -IL-5, activates eosinophils
  • TH17 enhance immunity against certain extracellular bacteria and fungi. Implicated in human autoimmune inflammatory conditions (RH, MS, IBS)
  • -IL-17 promotes neutrophil migration and differentiation, also IL-1, IL-6 and TNFa synthesis
  • -IL-22, induces cells in skin and digestive system to synthesize defensins
  • Treg suppress differentiation of all others by:
  • -IL-10, suppressive for TH cells and macrophages
  • -transforming growth factor B (TGFB), inhibits T cell and macrophage function which promotes fibroblast growth and wound healing
69
Q

Describe the mechanisms by which Tc cells kill virus-infected and neoplastic host cells.

A
  • production of perforin and granzymes that induce capase-mediated apoptosis of targets
  • production of granulysin, which kills intracellular bacteria that infect macrophages and dendritic cells
  • expression of the membrane protein Fas ligand (FasL) that binds to a “death receptor” called Fas (CD59) on the infected cell. Engagement of Fas activates camases and induces apoptosis
  • cells that have undergone apoptosis are rapidly phagocytksed
  • production of IFNy which activates macrophages to destroy the phagocytksed microbes
70
Q

Describe the “three signal” theory of how Tc cells are activated.

A

Signal 1:
-recognition of foreign peptide on infected cell via interaction of TCR/CD8 with viral peptide/Class 1 MHC

Signal 2:
-co-stimulatory molecule interactions; e.g. CD-28/B7 and CD40/CD40L

Signal 3:
-Cytokines (IL-2, IL-12, INFa, INFB) supplied by TH1 cells, dendritic cells and infected cells.

71
Q

Describe the way in which superantigens stimulate T cells. List some common superantigens processed by Staph. aureus and Staph. pyogenes. Describe the outcome of TNFa over-production.

A
  • microbial toxins that stimulate as high as 20% of T cells.
  • Do not need to be processed by an APC in order to stimulate T cells.
  • Simultaneously stimulate the Beta chain on either TH or TC cells and the Class 2 MHC molecules on antigen presenting cells. Leads to killing of APCs that are attached to Tc cells, or cause unregulated release of cytokines by TH cells and APCs.
  • Caused by:
  • -enterotoxins produced by Staph. aureus
  • -Staphylcoccal toxic shock syndrome toxin-1 (TSST-1)
  • -pyrogenic exotoxins of streptococci, especially streptococci progenies
  • -exotoxins produced by mycoplasmas