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Flashcards in Immuno - basic Deck (39):
1

Lymph node structureWhere are...B-cells?T-cells?Lymphos/plasma cells?Macs/retics?

fxn: nonspecific filtration by macs, lympho storage

follicle - B-cells! primary (outer) = dense/dormant. secondary (inner) = germinal centers, active

medulla - medullary cords (lymphos + plasma cells), sinuses (reticular cells, macs)

paracortex - houses T cells, T/B cells enter from blood, site of engorgement during immune response

2

Spleen sinusoidsWhere are...T cells?B cells?APCs?

Red pulp = mechanical filtration of RBCs by fenestrated BM and macs, led to trabeculae

White pulp =
- periarteriolar lymphatic sheath (PALS): T cells
- follicles: B cells

Marginal zone = APCs capture blood-borne antigens for recognition by lymphocytes

3

Post-splenectomy findings

Howell-Jolly bodies (nuclear remnants in an RBC)
Target cellsThrombocytosis

4

Thymus structure
Where are...
immature T cells?
mature T cells?
Where do positive and negative selection occur?

T-cell differentiation and maturation
derived from Third pharyngeal pouch

Cortex = immature T cells (site of positive selection: only T cells expressing TCRs that bind self-MHC survive)
Medulla = pale, mature T cells (site of negative selection: T cells with TCRs for high-affinity self-antigen binding are apoptosed)

5

innate vs. adaptive immunity

innate - secreted proteins: lysozyme/complement/CRP, TLRs recognize PAMPs (LPS, flagellin, ssRNA)

adaptive - variation through VDJ recomb, based on Igs

6

MHC I

- MHC I: HLA-A, HLA-B, HLA-C, all nucleated cells

- present viral/cytosolic proteins to CD8 cells

- loading happens in RER- assoc with B-microglobulin

7

MHC II

- MHC II: HLA-DR, HLA-DP, HLA-DQ

- binds CD4
- expressed on APCs only

- loading happens in acidified endosome with invariant chain

8

HLA subtypes and disease

A3 - hemochromatosis
B27 - PAIR: psoriatic arthritis, ank spondy, IBS, reactive arthritis
DQ2/DQ8 - celiac disease
DR2 - multiple sclerosis, hay fever, SLE, Goodpasture
DR3 - DM Type I, SLE, Graves, Hashimoto
DR4 - DM Type I, Rheum (4 walls in a room)
DR5 - pernicious anemia

9

NK cells function, cytokines, signals for activation

Apoptosis induction (using perforin and granzymes)

Enhanced by IL-2, IL-12, IFN-a, IFN-B

2 signals: non-specific activation signal, absence of class I MHC

10

Helper T cells (CD4+)Th1 (phagocytosis/cell-mediated) vs. Th2 (antibody response)

Give activating and inhibiting cytokines

Th1 = secretes IFN-y, macs/cytotoxic T, activated by IFN-y and IL-12 (from macs), inhibited by IL-4/10 (from Th2)

Th2 = secretes IL-4/5/10/13, activate B cells and recruit eosinophils, activated by IL-4, inhibited by IFN-y (from Th1)

11

Cytotoxic T cells function

Release cytotoxic granules containing preformed proteins (perforin, granzyme) to induce apoptosis

12

Regulatory T cells

Maintain specific immune tolerance by suppressing CD4/CD8 T cells

Look for: CD3/4/25, FoxP3Produce IL-10, TGF-B

13

Naive T-cell activation

1. DC samples/processes antigen
2. DC migrates to draining lymph node
3. MHC II/I presents foreign antigen to CD4/8
4. Costimulatory signal is given by interaction of B7 and CD28 (if no second signal, then anergy)
5. Th cell activates and produces cytokines. Tc cell activates and destroys

14

B-cell activation

1. Th cell activation
2. B-cell receptor mediated endocytosis, foreign antigen is presented to helper T
3. CD40 receptor on B cell binds CD40L on helper T cell
4. Helper T secretes cytokines to stimulate Ig class switching of B cell (IL-4, IL-5)

15

Antibody structure, function, diversity (3 mechs)

Light and heavy chains (light = Fab only, heavy = both),

Fc binds complement (one arm, Constant, Carboxy terminal, Complement, Carbo side chains)
Fab binds antigen (two arms)

Diversity: VJ/VDJ recomb, somatic hypermutation, terminal deoxynucleotidyl transferase (DNA nuc addition)

16

IgG

fixes complement, crosses placenta

17

IgA

prevents microbe attachment to mucous membranes, does not fix complement, produced in GI tract to protect against GI infxns, released in secretions as a dimer (notably breast milk)

18

IgM

immediate response to antigen, serves as antigen receptor to B cells, pentamer form allows avid binding to antigen

19

IgE

binds mast cells/basophils, cross-links when exposed to allergen, mediates Type I hypersensi rxn, mediates worm resistance through Eos

20

Acute phase reactants (produce in liver in response to inflammation, induced by IL-6)

Upregulated: CRP (fixes complement), ferritin (sequesters iron), fibrinogen (coagulation factor, correlates with ESR), hepcidin (prevents release of iron bound to ferritin, leads to AOCD)

Downregulated: albumin (reduction conserves amino acids for acute phase proteins), transferrin (sequester iron)

21

Complement pathways

Classic - IgG, IgM mediated (GM makes classic cars), C1

Alternative - microbe surface molecules, C3Lectin - mannose or other sugars on microbe surface, C1-like complex

22

Complement 3b

opsonization, C3b binds bacteria (also helps clear immune complexes)

23

Complement 3a/4a/5a

anaphylaxis (5a also does neut chemotaxis)

24

Complement 5b-9

cytolysis by MAC

25

Complement DAF

Inhibitors: DAF = CD55, combines with C1 esterase inhibitor to help prevent complement activation on self cells

26

Complement disorders

Hereditary angioedema

Severe pyogenic infections, incr. Type III hypersensitivity

Incr. Neisseria bacteremia

C1 esterase inhibitor deficiency (results in longer C1 half life) - ACEis are contraindicated

C3 deficiency

C5-C9 deficiencies

27

Important cytokines secreted by Macrophages

Hot T-Bone stEAK:
1 = fever
2 = stimulate T cells
3 = bone marrow (GM-CSF analog)
4= IgE
5= IgA
6= aKute phase reactants

IL-8: chemotaxis for neutrophils
IL-12: differentiation of T cells into Th1 cells, NK activator
TNF-a: septic shock, WBC recruitment, vascular leak

28

Important cytokines secreted by All T cells

IL-2: stimulate T cell maturation

IL-3: functions like GM-CSF

29

Important cytokines secreted by Th1 cells

IFN-y: stimulates macs to kill pathogens (also activates NK cells to kill virus-infected cells)

30

Important cytokines secreted by Th2 cells

IL-10: modulates inflammatory response, decreases cytokines, inhibits macs/DCs (works in concert with TGF-b)

31

Respiratory burst, NADPH oxidase, CGD

Activation of neutrophil NADPH oxidase, leads to rapid release of ROS/hypochlorite to kill microbes

In CGD, phagocytes don't make their own peroxide (due to lack of NADPH oxidase) so they use microbial peroxide. However, microbes with their own catalase (which breaks down peroxide) survive! Watch for S. aureus and Aspergillus

32

Interferons

Glycoproteins synthesized by virus-infected cells that act locally on non-infected cells to ramp up viral defenses (selectively degrade viral nucleic acid/protein)

Essentially results in apoptosis

"Interfere with viruses"

33

Superantigens

cross-link beta-region of T-cell receptor to the MHC class II on APCs

- T cells (IL-2) and macrophages (IL-1 and TNF-a) lead to massive cytokine release

34

Endotoxins

Endotoxin: direct stimulation of macrophages by binding to endotoxin receptor TLR4/CD14

35

Antigenic variation

bacteria: Salmonella (flagella), Borrelia recurrentis (relapsing fever), N. gonorrheae (pilus)

viruses: influenza, HIV, HCV

parasites: trypanosomes

36

Administration of preformed antibodies

Passive immunity

Rapid onset

Tetanus, Botulinum, HBV, Varicella, Robies

ex: breast milk (IgA dimers), placental (IgG), antitoxin

37

Exposure to foreign antigens

Active immunity

slow onset, long-lasting protection

38

Vaccine with cellular and humoral responses

Live, attentuated vaccine

Microbe has lost pathogenicity but retains capacity for growth

Life long immunity

MMR, polio (sabin), intranasal flu, chicken pox, yellow fever

39

Vaccine with only humoral response

Inactivated/Killed vaccine

Epitope structure is maintained on surface antigens

Weaker immune response, ***booster shots required***

RIP Always: Rabies, Influenza (shot), Polio (Salk), hep A