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Flashcards in Lymphocytes Deck (59)
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1
Q

Innate immunity: mechanism

A

Germline encoded

2
Q

Innate immunity: resistance

A

Resistance persists through generations

Does not change within an organism’s lifetime

3
Q

Innate immunity: response to pathogens

A
Nonspecific 
Occurs rapidly (minutes to hours)
4
Q

Innate immunity: physical barriers

A

Epithelial tight junctions, mucus

5
Q

Innate immunity: secreted proteins

A

Lysozyme, complement, CRP, defensins

6
Q

Innate immunity: Key features in pathogen recognition

A

Toll-like receptors (TLRs): pattern recognition receptors that recognize pathogen associated molecular patterns (PAMPs)
Examples: LPS, flagellum, nucleic acids

7
Q

Adaptive immunity: components

A

TCs, BC, circulating Ab

8
Q

Adaptive immunity: Mechanism

A

Variation through V(D)J recombination during lymphocyte development

9
Q

Adaptive immunity: Resistance

A

Microbial resistance not heritable

10
Q

Adaptive immunity: response to pathogens

A

Highly specific, refined over time

Develops over long periods; memory response faster and more robust

11
Q

Adaptive immunity: Secreted protein

A

Immunoglobulins

12
Q

Adaptive immunity: Key features in pathogen recognition

A

Memory cells: activated BC and TC

Subsequent exposure to a previously encountered Ag = stronger and quicker immune response

13
Q

MHC

A

Encoded by HLA genes

Present Ag fragments to TCs and bind TCRs

14
Q

MHC I: Loci

A

HLA-A, HLA-B, HLA-C

15
Q

MHC I: Binding

A

TCR & CD8

16
Q

MHC I: Expression

A

Expressed on all nuclear end cells

Not expressed on RBCs

17
Q

MHC I: function

A

Present endogenously synthesized Ag (eg viral or cytosolic proteins) to CD8+ CTCs

18
Q

MHC I: Ag loading

A

Ag peptides loaded onto MHC I in RER after delivery via TAP (transporter associated with antigen processing)

19
Q

MHC I: associated proteins

A

Beta2 microglobulin

20
Q

MHC II: Loci

A

HLA-DP, HLA-DQ, HLA-DR

21
Q

MHC II: binding

A

TCR and CD4

22
Q

MHC II: Expression

A

Expressed on APCs

23
Q

MHC II: function

A

Present exogenously synthesized Ag (eg bacterial proteins) to CD4+ ThCs

24
Q

MHC II: Ag loading

A

Ag loaded following release of invariant chain in an acidified endosome

25
Q

MHC II: associated proteins

A

Invariant chain

26
Q

HLA subtypes & diseases: A3

A

Hemochromatosis

27
Q

HLA subtypes & diseases: B8

A

Addison disease

Myasthenia gravis

28
Q

HLA subtypes & diseases: B27

A
Psoriatic arthritis
Ankylosis get spondylitis
IBD-associated with arthritis
Reactive arthritis (formerly Reiter syndrome)
*PAIR or seronegative arthropathies*
29
Q

HLA subtypes & diseases: DQ2/DQ8

A

Celiac disease

I ate (8) too (2) much gluten at Dairy Queen

30
Q

HLA subtypes & diseases: DR2

A

Multiple sclerosis
Hay fever
SLE
Goodpasture syndrome

31
Q

HLA subtypes & diseases: DR3

A
Diabetes Mellitus type I
SLE
Graves' disease
Hashimoto thyroiditis 
Addison disease
32
Q

HLA subtypes & diseases: DR4

A

Rheumatoid Arthritis
Diabetes Mellitus type 1
Addison disease
there are 4 walls in a “rheum” (room)

33
Q

HLA subtypes & diseases: DR5

A
Pernicious anemia (vitamin B12 deficiency)
Hashimoto thyroiditis
34
Q

Natural Killer cells

A

Use perforin and granzymes to induce apoptosis of viral infected cells or tumor cells
Lymphocytic member of innate immune system
Activity enhance by IL-2, IL-12, IFN-alpha & IFN-beta
Induced to kill when expose to a nonspecific activation signal on target cell and/or to an absence of class I on MHC on target cell surface
Also kills via Ab-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound Ig, activating NK cell)

35
Q

TC functions

A

CD4+ TCs - help BCs make Ab and produce cytokines to recruit phagocytes and activate other leukocytes
CD8+ TCs - directly kill virus-infected cells
Delayed cell mediated hypersensitivity (type IV)
Acute and chronic cellular organ rejection

36
Q

BC functions

A

Recognize Ag - undergo somatic hypermutation to optimize Ag specificity
Produce Ab - differentiate into plasma cells to secrete specific immunoglobulins
Maintain immunologic memory - memory BCs persist and accelerate future response to Ag

37
Q

Positive selection of TCs

A

Thymic cortex
TCs expressing TCRs capable of binding self-MHC on cortical epithelial cells survive
BINDING TO SELF = SURVIVE

38
Q

Negative Selection of TCs

A

Thymic medulla
TCs expressing TCRs with high affinity for self-Ag undergo apoptosis
TOO HIGH OF AFFINITY FOR SELF= APOPTOSIS
Tissue restricted self Ag are expressed in thymus due to the action of autoimmune regulator (AIRE); deficiency leads to autoimmune polyendocrine syndrome-1

39
Q

Helper TCs: Th1

A

Secretes IFN-gamma
Activates MPs & CTCs
Differentiation induced by IFN-gamma and IL-12
Inhibited by IL-4 and IL-10

40
Q

Helper TCs: Th2

A

Secretes IL-4, IL-5, IL-10, IL-13
Recruits eosinophils for parasite defense and promotes IgE production by BCs
Differentiation induced by IL-4
Inhibited by IFN-gamma

41
Q

MP-lymphocytic interaction

A

MPs and other APCs release IL-12 which stimulates TCs to differentiate into Th1 cells
Th1 cells release IFN-gamma to stimulate MPs
Helper cells are CD4+, which bind to MHC II on APCs

42
Q

Cytotoxic TCs

A

Kill virus infected, neoplasticism, and donor graft cells by inducing apoptosis
Release cytotoxic granules containing preformed proteins (eg perforin, granzymes B)
CTCs have CD8 which binds MHC I on virus-infected cells

43
Q

Regulatory TCs

A

Help maintain specific immune tolerance by suppressing CD4 and CD8 TC effector functions
Identification: CD3, CD4, CD25, FOXP3
Activated regulatory TCs produced anti-inflammatory cytokines (IL-10, TGF-beta)

44
Q

Innate immunity: components

A

Neutrophils, MPs, monocytes, DCs, natural killer cells (lymphoid origin), complement

45
Q

Naive TC activation

A
  1. DC (APC) samples and processes Ag
  2. DC migrates to the draining LN
  3. TC activation (signal 1): Ag is presented on MHC II and recognized on TCR on Th (CD4+) cell. Endogenous Ag is presented on MHC I to Th (CD8+) cell
  4. Proliferation and survival (signal 2): costimulatory signal via interaction of B7 proteins (CD80/86) and CD28
  5. Th cell activates and produces cytokines. Tc cell activates and is able to recognize and kill virus infected cells
46
Q

BC activation and class switching

A
  1. Th activation as above
  2. BCR-mediated endocytosis; foreign Ag presented on MHC II and recognized by TCR on Th cell
  3. CD40 receptor on BC bind CD40 ligand (CD40L) on Th cell
  4. TH cell secretes cytokines that determine Ig class switching of BCs. BC activates and undergoes class switching, affinity maturation and Ab production
47
Q

Ab structure and function

A

Fab (containing the variable/hypervariable regions) consisting of light (L) and heavy (H) chains recognizes Ag.
Fc region of IgM and IgG fixes complement
Heavy chain contributes to Fc and Fab regions
Light chain only contributes to Fab region

48
Q

Fab region

A

Fragment, antigen binding
Determines idiotype: unique antigen-binding pocket
Only 1 antigenic specificity expressed per BC

49
Q

Fc region

A

Constant
Carboxy terminal
Complement binding
Determines isotype- IgM, IgD, etc

50
Q

Generation of Ab diversity (Ag independent)

A
  1. Random recombination of VJ (L) and VDJ (H) genes
  2. random addition of nucleotides by terminal deoxynucleotidyl transferase (TdT)
  3. Random combination of heavy and light chains
51
Q

Generation of Ab diversity (Ag dependent)

A
  1. Somatic hypermutation and affinity maturation (variable regions)
  2. Isotype switching (constant region)
52
Q

Immunoglobulin isotypes

A

All isotypes can exist as monomers
Mature, naive BCs prior to activation express IgM and IgD on their surfaces. They may differentiate in germinal centers of LNs by isotype switching (gene rearrangement; mediated by cytokines and CD40L) into plasma cells that secrete IgA, IgE, or IgG

53
Q

IgG

A

Main Ab in second (delayed) response to Ag
Most abundant isotype in serum
Fixes complement, crosses placenta (provides infant with passive immunity), opsonizes bacteria, neutralizes bacterial toxins and viruses

54
Q

IgA

A

Prevents attachment of bacteria and viruses to mucous membranes; does not fix complement
Monomer (in circulation) or dimer (with J chain) when secreted)
Crosses epithelial cells by transcytosis
Produced in the GI tract (eg Peyer patches) and protects against gut infections (eg Giardiasis)
Most produce Ab overall, but lowest serum concentrations
Released into secretions (tears, saliva, mucus) and breast milk.
Picks up secretory component from epithelial cells, which protects the Fc portion from luminal proteases

55
Q

IgM

A

Produce in the primary (immediate) response to Ag.
Fixes complement but does not cross the placenta
Ag receptor on the surface of BCs
Monomer on the BC, pentamer with J chain when secreted (enables bid gin to Ag while humoral response evolves)

56
Q

IgD

A

Unclear function

Found on surface of many BCs and in serum

57
Q

IgE

A

Binds mast cells and basophils
Cross-links when exposed to allergen, mediating immediate (type 1) hypersensitivity through release of inflammatory mediators such as histamine
Mediates immunity to worms by activating eosinophils. Lowest concentration in serum

58
Q

Ag type & memory: thymus-independent antigens

A

Ag lacking peptide component (eg LPS from gram - bacteria)
Cannot be represented by MHC to TCs
Weakly immunogenic
Vaccines often require boosters and adjuvants (eg pneumococcal polysaccharide vaccine)

59
Q

Ag type & memory: thymus-dependent Ag

A

Ag containing a protein component (eg diptheria vaccine)

Class switching and immunologic memory occur as a result of direct contact of BCs with Th cells (CD40-CD40L interaction)