Basic principles

Question 1

Lymph node

Answer 1

Follicle: (cortex) B cell localization and proliferation

• 1’ follicle: dense and dormant
• 2’ follicle: pale central germinal centers and active

Paracortex: T cells, between cortex and medulla. High endothelial venules via which B and T cells enter from blood.

• In an extreme cellular response, paracortex becomes greatly enlarged
• Underdeveloped in DiGeroge, as no thymus so no T cells

Medulla: inner most, consists of medullary cords (densely packed lymphocytes, and plasma cells) and medullary sinuses.
-Medullary sinuses communicate with efferent lymphatics and contain reticular cells and MP

Question 2

Sinusoid of spleen

Answer 2

Long, vascular channels in red pulp with fenestrated “barrel loop” basement membrane, macrophages found nearby

PALS: T cells found in periarterial lymphatics sheath of the white pulp (surrounding central ateriole)

vs. B cells found in the follicles within the white pulp
vs. APC in the marginal zone

Splenic dysfunction: low IgM, low complement, low C3b opsonization.

Postsplenectomy:

• Howell Jolly bodies (nuclear remnants)
• Target cells
• Thrombocytosis

Question 3

Thymus

Answer 3

T cell differentiation, encapsulated
From epithelium of 3rd branchial pouches

Lymphocytes of mesenchymal origin

Cortex is dense with immature T cells
Medulla is male with MATURE T cells and epithelial reticular cells containing Hassall’s corpuscle.

Positive selection occurs in the cortex and negative selection occurs in the medulla.

Question 4

HLA

Answer 4

MHC1 : HLA A, B, C, antigen loaded in RER, binds to beta microglobulin

MHC2: HLA DR, DP, DQ, antigen loaded following release of invariant chain in an acidified endosome

Question 5

NK cells

Answer 5

Perforin and granzyme to induce apoptosis of virally infected cells and tumor cells

Activated by IL2, 12, IFN b, IFNa

CD56 specific

Question 6

T cell differentiation

Answer 6

Positive selection in thymic cortex CD4/8+ and TCR
Negative selection in thymic medulla

Then goes to LN to

• CD8 gets activated
• CD4 gets differentiated into
  1) TH1 with IL12 stimulation
  2) TH2 with IL4 stimulation

Question 7

T and B cell activation

Answer 7

APC: dendritic, MP, and B cells

Dendritic cells = the only APC that can activate naive T cells.

Question 8

Naive T cell activation

Answer 8

Presented by DC, presented on MHC II or I
Costimulation B7 (from DC) and CD28 (from T cell)

Activated TH goes to meet B cells
CD40 L on TH cells bind to CD40 on B cells
T cells secrete cytokines to induce proper class switching.

Question 9

Th cells

Answer 9

Th1: secretes IFN gamma, activates MP, inhibited IL4 (from TH2) and IL10 (antiinflam also from TH2).

Th2: secretes IL4,5,10,13, recruits eosinophils for parasite defense and promotes IgE production by B cells, inhibited IFNgamma (from Th1)

MP-lymphocyte intearction: activated lymphocyte release IFN gamma and macrophage release IL 1 and TNFa to stimulate each other

Question 10

T reg

Answer 10

Help maintain tolerance by suppressing CD4 and 8 effector functions.

Express CD3, 4, 25 (alpha chain of IL2 receptor)

Activated T reg produce IL 10 and TGFbeta

Question 11

Antigen type

Answer 11

Thymus independent antigen: no peptide so no memory

Thymus dependent antigen: yes peptide so yes memory

Question 12

Complements

Answer 12

Activation

1) classic: by IgG and IgM
2) alternative: spontaneous and microbacterial surface
3) lectin pathyway: mannose or other sugars on the microbacterial surface

Function:
C3b: opsonization (b binds bateria)
C3a, C5a: anaphylaxis
C5a: neutrophil chemotaxis
C5b-9: cytolysis by MAC

Opsonins:
C3b and IgG two 1’ opsonins in bacterial defense;
C3b also helps clear immune complex

Inhibitors:
DAF and C1 esterase inhibitor help prevent complement activation on RBCs

Question 13

Anergy

Answer 13

Self reactive T cells become nonreactive without costimulation.

B cells also become anergic, but tolerance is LESS complete than T cells

Question 14

Effect of bacterial toxin

Answer 14

Superantigens: bind to beta region of TCR to MHC II on APC, thus activating any T cell, leading to massive cytokine storm

Endotoxin/lipopolysaccharide: directly stimulates MP by binding to endotoxin receptor CD14; TH cells are NOT involved.

Question 15

Antigen variation

Answer 15

Bacteria: salmonella (two flagellar variants), Borrelia (relapsing fever), N gonorrhea (pillus protein)

Virus: influenza (major shift, minor drift)

Parasite: trypanosomes (programmed rearrangement)