Immuno - basic

Question 1

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

Answer 1

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

Question 2

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

Answer 2

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

Question 3

Post-splenectomy findings

Answer 3

Howell-Jolly bodies (nuclear remnants in an RBC)

Target cellsThrombocytosis

Question 4

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

Answer 4

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)

Question 5

innate vs. adaptive immunity

Answer 5

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

adaptive - variation through VDJ recomb, based on Igs

Question 6

MHC I

Answer 6

• 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

Question 7

MHC II

Answer 7

• MHC II: HLA-DR, HLA-DP, HLA-DQ
• binds CD4
• expressed on APCs only
• loading happens in acidified endosome with invariant chain

Question 8

HLA subtypes and disease

Answer 8

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

Question 9

NK cells function, cytokines, signals for activation

Answer 9

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

Question 10

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

Give activating and inhibiting cytokines

Answer 10

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)

Question 11

Cytotoxic T cells function

Answer 11

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

Question 12

Regulatory T cells

Answer 12

Maintain specific immune tolerance by suppressing CD4/CD8 T cells

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

Question 13

Naive T-cell activation

Answer 13

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

Question 14

B-cell activation

Answer 14

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)

Question 15

Antibody structure, function, diversity (3 mechs)

Answer 15

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)

Question 16

IgG

Answer 16

fixes complement, crosses placenta

Question 17

IgA

Answer 17

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)

Question 18

IgM

Answer 18

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

Question 19

IgE

Answer 19

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

Question 20

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

Answer 20

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)

Question 21

Complement pathways

Answer 21

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

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

Question 22

Complement 3b

Answer 22

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

Question 23

Complement 3a/4a/5a

Answer 23

anaphylaxis (5a also does neut chemotaxis)

Question 24

Complement 5b-9

Answer 24

cytolysis by MAC

Question 25

Complement DAF

Answer 25

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

Question 26

Complement disorders Hereditary angioedema Severe pyogenic infections, incr. Type III hypersensitivity Incr. Neisseria bacteremia

Answer 26

C1 esterase inhibitor deficiency (results in longer C1 half life) - ACEis are contraindicated C3 deficiency C5-C9 deficiencies

Question 27

Important cytokines secreted by Macrophages

Answer 27

``` 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

Question 28

Important cytokines secreted by All T cells

Answer 28

IL-2: stimulate T cell maturation IL-3: functions like GM-CSF

Question 29

Important cytokines secreted by Th1 cells

Answer 29

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

Question 30

Important cytokines secreted by Th2 cells

Answer 30

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

Question 31

Respiratory burst, NADPH oxidase, CGD

Answer 31

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

Question 32

Interferons

Answer 32

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"

Question 33

Superantigens

Answer 33

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

Question 34

Endotoxins

Answer 34

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

Question 35

Antigenic variation

Answer 35

bacteria: Salmonella (flagella), Borrelia recurrentis (relapsing fever), N. gonorrheae (pilus) viruses: influenza, HIV, HCV parasites: trypanosomes

Question 36

Administration of preformed antibodies

Answer 36

Passive immunity Rapid onset Tetanus, Botulinum, HBV, Varicella, Robies ex: breast milk (IgA dimers), placental (IgG), antitoxin

Question 37

Exposure to foreign antigens

Answer 37

Active immunity slow onset, long-lasting protection

Question 38

Vaccine with cellular and humoral responses

Answer 38

Live, attentuated vaccine Microbe has lost pathogenicity but retains capacity for growth Life long immunity MMR, polio (sabin), intranasal flu, chicken pox, yellow fever

Question 39

Vaccine with only humoral response

Answer 39

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