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Flashcards in Section 1 Deck (52):
1

DiGeorge syndrome lymphatic abnormality

Underdeveloped paracortex

2

Lymph drainage (top to bottom)

Cervical
Hilar
Mediastinal
Axillary
Celiac
Superior mesenteric
Inferior mesenteric
Internal iliac
Para-aortic
Superficial inguinal
Popliteal

**Right lymphatic duct drains right body above diaphragm
**Thoracic duct drains everything else into junction of left subclavian and internal jugular veins

3

Spleen organization

White pulp inside rings of red pulp with "barrel hoop" BM

White pulp: contains T cells in periarteriolar lymphatic sheath + B cells in follicles

Marginal zone is between red and white, contains APCs and specialized B cells

Macrophages found nearby remove encapsulated bacteria and IgM --> complement activation --> opsonization of it and killing of encaps bacteria

Vasculature and RBCs in red pulp

4

Examples of PAMPs

Pattern-associated molecular patterns recognized by PRRs (eg Toll-like receptors):

ex: LPS (G- bacteria), flagellin (bacteria), ssRNA (viruses)

5

MHC I vs MHC II

MHC I encoded by HLA-A, B, C genes

Binds TCR and CD8 receptor - presents endogenous antigens (intracellular material) to CD8+ cytotoxic T cells (delivered to MHCI in RER by TAP)

MHC II encoded by HLA-Ds, presents exogenous antigen to CD4+ cells

6

HLA A3 mutation

Hemochromatosis

7

HLA B27 mutation

PAIR:

Psoriatic arthritis
Ankylosing spondylitis
arthritis of IBD
Reactive arthritis/Reiter syndrom

8

HLA DQ2/DQ8 mutation

Celiac

9

HLA DR2

MS, hay fever, SLE, Goodpasture

10

HLA DR3

T1 DM, SLE, Graves, Hashimoto thyroiditis

11

HLA DR4

RA, T1DM

12

HLA DR5

Pernicious anemia, Hashimoto thyroiditis

13

Three ways to induce NK cells to kill

1. Exposure to nonspecific activation signal on target cell

2. Lack of MHCI on target cell surface

3. CD16 binds Fc region of antibody-antigen complex, activating NK cell

14

Treg surface receptors

CD3, CD4, CD25, FOXP3

Make anti-inflamm cytokines (eg IL-10)

15

Th1 (helper T) - activated by ___, activates ____, inhibited by

- activated by IFN-gamma and IL-12

- activates macrophages and CD8 cells by secreting IFN-gamma

- inhibited by IL-4 and 10 (from Th2)

16

Th2 (helper T) - activated by ___, activates ___, inhibited by ___

- activated by IL-4
- secretes IL-4,5,10,13 to recruit eos and promote IgE production to fight parasites

- inhibited by IFN-gamma (from Th1)

17

T and B cell activation steps

APC (dendritic cell) samples and processes antigen --> lymph node --> presents antigen via MHC to activate T cell via TCR and costim (B7 on dendritic cell binds CD28 on T cell) --> T cell activated

Activated Th finds B cell that has picked up the antigen and binds/activates it; costim = CD40 rec (on B cell) and CD40L (on Th) --> turns B on --> class switching, affinity maturation, Ig production

18

Lymph node organization

Follicle - B cell (primary = dormant; 2ary = active, pale centers)

Medulla - cords (lymphs and plasma cells) and sinuses (retics and macrophages)

Paracortex (T cells, expands during CMI, contains HEV)

19

IgM

Produced in primary (immediate) response to antigen

Doesn't cross placenta!

Switches isotype in lymph nodes via gene rearrangement --> IgA, IgE, IgG

20

IgG

Secondary (delayed) response to antigen

Crosses the placenta --> passive immunity

Fixes complement --> opsonization, neutralizes bacterial toxins and viruses

21

Thymus-dependent vs -independent antigens

Dependent: antigen contains protein component so can be processed and presented to B cells by Th1 --> memory B cells

Independent: antigens lack peptide component (eg LPS) so can't be presented by MHC to T cells --> weakly or nonimmunogenic

22

Acute phase reactants are made in the ___ and induced by ___

Liver, IL-6

23

Acute-phase reactants

CRP (opsonin)
Ferritin (sequesters iron)
Fibrinogen (coag, endoth repair)
Hepcidin (prevents release of iron bound by Ferritin)
Serum amyloid A

Decreased with inflamm:
Albumin (saves AAs for increased reactants)
Transferrin (less of it --> sequestration of iron)

24

Complement pathways

Classic - IgG/M complexes (G- opsonization; starts with C1)
Lectin - mannose and lectin on bacterial surfaces (pathway starts with C1-like complex and C4 --> C3 convertase)
Alternative respond to microbial surfaces (pathway starts with C3)

All end in C3 --> C3b --> C4b2b3b (C5 convertase) which turns C5 into C5b, at which point C6-9 enter and form the membrane attack complex (MAC)

25

Inhibitors of complement on self cells

Delay-accelerating factor (DAF, aka CD55)

C1 esterase inhibitor

26

C1 esterase inhibitor deficiency

Can't inhibit complement, Get Hereditary angioedema

ACEi contraindicated

27

C3 deficiency

Increases risk of infection and susceptibility to type 3 hypersensitivity

28

C5-C9 deficiency

Increased susc to recurrent Neisseria bacteremia

29

Cytokines (ILs)

Hot T-bone stEAK

IL-1: fever, secreted by macrophages (OC activating, acute inflamm, activates endothelium to express adhesion mcs + induce chemokines to recruit WBCs)

IL-2: stimulate T cells (secreted by T cells)

IL-3: stimulate bone marrow (secreted by T cells)

IL-4: stimulate IgE production (induces differentiation of T cells to Th2, secreted by Th2 cells, enhances class switching to IgE)

IL-5: stimulate IgA production +growth of eos, promotes differentiation of B cells, secreted by Th2 cells

IL-6: produce aKute-phase proteins and causes fever, secreted by macrophages

IL-8: Chemotactic factor for neutrophils, secreted by macrophages

IL-10: attenuates immune response, secreted by Th2 (decreased expression of MHC II and Th1 cytokines, inhibits APCs)

IL-12: released by macrophages -> T cells differentiate into Th1 and NK cells activated

TNF-alpha: activates endothelium --> septic shock

IFN-gamma: Th1 cells secrete it to activate macrophages and more NK cells (Th1)

30

Chronic granulomatous disease (CGD)

Defective enzymes (especially NADPH oxidase) make phagocytic cells unable to generate ROS, which would activate the phagocytic cells --> kill bug

Rely on bug to make ROS, so increased susc to bugs that neutralize their ROS (catalase positive bugs)

31

B7 surface protein

on APCs with MHCII, serves as co-stim second signal by binding to CD28 on T cells and thus activating them

32

CD40L

surface protein on Helper T cells (CD4+) that serves as co-stim second signal, activating B cells and macrophages

33

CD21

EBV receptor on B cells

34

CD 19, 20, 21

surface proteins on B cells

35

CD14

macrophage surface protein - directly stimulated by endotoxins/LPS (G-) --> phagocytosis of bug

aka TLR4

36

CD16

NK cell surface protein - binds Fc of IgG

37

CD56

unique marker for NK cells (surface protein)

38

CD34

hematopoeitic stem cell surface protein

39

Examples of live attenuated vaccine

MMR, Polio (Sabin), Varicella, Flu (intranasal), Yellow fever

40

Examples of inactivated or killed vaccine

Rabies, Influenza (IM), Polio (Salk), Hep A

41

Type I hypersensitivity

Antigen binds preformed (fast) IgE, which is cross-linked and bound to pre-sensitized mast cells and basophils

Binding --> release of vasoactive amines (eg histamine)

42

Type II hypersensitivity

IgM, IgG bind antigen that's fixed to cell and target that cell for destruction by complement, opsonization/phag, or antibody-mediated cell dysfxn

Test with Coombs (direct - Ig on RBCs, or indirect - serum Ig that can adhere to RBCs)

43

Type III hypersensitivity

Ag-Ig complexes form, bind complement, and attrack PMNs, which release lysosomal enzymes

Serum sickness - complexes deposited in membranes, fix complement there and --> tissue damage within 5-10 days of exposure, fever, urticaria, arthralgia etc

Arthus rxn = serum sickness but in skin (antigen = intradermal)

44

Type IV hypersensitivity

Delayed, T cell mediated

T cells find antigen and release cytokines --> activate macrophages (no Ig involved)

45

Hypersensitivity disorders

Type I - rhinitis, hay fever, eczema, anaphylaxis (eg bee sting)

Type II - AIHA, bullous pemphigoid, Goodpasture, Graves, Guillain-Barre, MG, pemphigus vulgaris, pernicious anemia, RF

Type III - Arthus, Serum sickness, SLE, PSGN

Type IV - Contact dermatitis, GVHD, MS, PPD

46

Aldesleukin

Recombinant IL2 used to treat RCCA and metastatic melanoma

47

Filgrastim and Sargramostim ("-stim")

Recombinant G(M)-CSF used for bone marrow recovery

48

IFN-alpha

Chronic hepatitis, Kaposi sarcoma, malignant melanoma

49

IFN-beta

MS

50

IFN-gamma (treats what?)

CGD

51

Recombinant cytokines used to treat thrombocytopenia

Romiplostim, eltrombopag, Oprelvekin (IL-11)

52

CD28

costim receptor on T cells, binds to B7 on APC