Immuno Part 1

eesohbel's version from 2015-06-13 18:32

Lymphoid structures

Question Answer
FollicleSite of B-cell localization and proliferation - in outer cortex
1° follicle - dense and dormant
2° follicle - pale central germinal centers & active
MedullaHas cords - closely packed lymphocytes and plasma cells
Sinuses - reticular cells and macrophages
ParacortexT cells
Between follicles and medulla
Becomes greatly enlarged during an extreme cellular immune response (viral)
Not present in DiGeorge syndrome
Upper back, lateral breast drains toaxillary LN
Stomach drains toCeliac LN
Duodenum, jejunum drains toSuperior mesenteric LN
Sigmoid colon drains toColic → inferior mesenteric LN
Rectum and anal canal (above pectinate line) drain toInternal iliac LN
Anal canal (below pectinate line) drains toSuperficial inguinal LN
Testes drain toSuperficial & deep plexuses → para-aortic LN
Scrotum drains toSuperficial inguinal LN
Thigh (superficial) drains tosuperficial inguinal
Lateral side of dorsum of foot drains topopliteal
Right lymphatic ductdrains right arm, right chest, and right half of head
Thoracic ductdrains everything but the right arm, right chest, and right side of head

Spleen and Thymus

Question Answer
Macrophages found where?red pulp
T cells found where?periarterial lymphatic sheath - white pulp
B cells found where?white pulp
Macrophages remove what?encapsulated bacteria (SHiN SKiS)
How does splenic dysfunction ↑ susceptibility to encapsulated organisms?↓ IgM → ↓ complement activation → ↓ C3b opsonization → ↑ susceptibility to SHiN SKiS
What would you find postsplenectomy?Howell-Jolly bodies (nuclear remnants)
Target cells
Where do T-cells mature and differentiate?Thymus
Where do B cell mature and differentiate?Bone marrow
Embryo origination of thymusepithelium of 3rd brachial pouches
Lymphocyte originmesenchymal
Cortex of thymus containsimmature T cells
Medulla of thymus containsmature T cells
epithelial reticular cells containing Hassall's corpuscles
Positive selection occurs where?cortex
(MHC restriction)
Negative selection occurs where?Medulla
(non-reactive to self)


Question Answer
Cells of the innate immunityneutrophils, macrophages, dendritic cells, natural killer cells (lymphoid origin) and complement
Cells of the adaptive immunityT cells, B cells, and circulating antibody
MHC stands for what and is encoded by what?major histocompatibility complex
Encoded by human leukocyte antigen (HLA) genes
MHC I (made up of what, does what, and expressed where)HLA-A, HLA-B, HLA-C
Binds TCR and CD8
Expressed on all nucleated cells (not RBCs)
MHC I antigen processingAntigen is loaded in RER with mostly intracellular peptides
Mediates viral immunity
Pairs with B2-microglobulin which aids in transport to cell surface
MHC II (made up of what, does what, and expressed where?)HLA-DA, HLA-DP, HLA-DQ
Binds TCR and CD4
Expressed only on antigen-presenting cells (APCs)
MHC II antigen processingAntigen is loaded following release of invariant chain in an acidified endosome

HLA assoc'd diseases

Question Answer
A3 HLA subtype assoc with what?Hemochromatosis
B27 HLA subtype assoc with what?PAIR
Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiter's syndrome
DQ2/DQ8 HLA subtype assoc with what?Celiac disease
DR2 HLA subtype assoc with what?MS, hay fever, SLE, Goodpasture's
DR3 HLA subtype assoc with what?Diabetes mellitus type 1, Graves' disease
DR4 HLA subtype assoc with what?Rhematoid arthritis, DM type 1
DR5 HLA subtype assoc with what?Pernicious anemia → B12 def., Hashimoto's thyroiditis
NK cells do whatUse perforin and granzymes to induce apoptosis of virally infected cells and tumor cells
Kill when there is a nonspecific activation signal on target cell or an absence of class 1 MHC on target cell surface
They are the only lymphocyte member of the innate immune system
NK cells' activity is enhanced byIL-2, IL-12, IFN-B, and IFN-a

B cells and T cells

Question Answer
Major fn of B cellsMake antibody → opsonize bacteria, neutralize viruses (IgG)
Active complement (IgM, IgG)
Sensitize mast cells (IgE)
Hyperacute and humorrally mediated acute/chronic organ rejection
Type 1 hypersensitivityAllergy
Type 2 hypersensitivityCytotoxic
Type 3 hypersensitivityImmune complex
Major fn of T cellsCD4+ - help B cells make antibody and produce cytokines to activate other immune cells
CD8+ kill virus-infected cells directly
Acute/chronic cellular organ rejection
Type 4 hypersensitivityT-cells! - Delayed cell-mediated hypersensitivity
CD8+ T cell becomes what?Cytotoxic T cell
CD4+ T cell becomes what?Helper t-cell → Th1 cell and Th2 cell
Positive selectionThymic cortex
T cells expressing TCRs capable of binding surface self MHC molecules survive
Negative selectionThymic medulla
T cells expressing TCRs with high affinity for self anitgens undergo apoptosis
Antigen presenting cellsDendritic cell - only APC that can activate naive T-cell
B cell
2 signals are required for Tcell/Bcell activation and class switching
Naive T cell activation (4 steps)1. Foreign body is phagocytosed by dendritic cell
2. Foreign antigen is presented:
- on MHC II and recognized by TCR on Th (helper) cell
- on MHC I to Tc (cytotoxic) cells
3. Costimulatory signal is given by interaction of B7 and CD28
4. Th cell activates/produces cytokines
Tc cell activates and is able to recognize/kill virus-infected cells
B cell activation and class switching (4 steps)Helper T cell activation (Th cell)
2. B cell receptor-mediated endocytosis - antigen is presented on MHC II from B cell and recognized by TCR on Th cell
3. CD40 on B cell binds to CD40 ligand on Th cell
4. Th cell secretes cytokines → determines Ig class switching of B cell
- B cell activates and undergoes class switching, affinity maturation and antibody production
Th1 helper T cell secretes what and activates what?IFN-gamma and IL-2
Activates macrophages
Th2 helper T cell secretes what and activates what?IL-2,4,5,10,13
Recruits eosinophils for parasite defense and promostes IgE production by B cells
IL-10 is anti-Th1 cells
Th1/Th2 - what inhibits what?Th1 inhibits Th2 with IFN-gamma
Th2 inhibits Th1 with IL-4 and IL-10
Macrophage/lymphocyte interactionLymphs activate macs with IFN-gamma
Macs activate lymphs with IL-1 & TNF-a
Cytotoxic T cellsKill virus-infected, neoplastic, and donor graft cells by inducing apoptosis
Release cytotoxic granules containing preformed proteins
Have CD8 which binds to MHC 1 on virus-infected cells
Contents of granules of cytotoxic T cellsPerforin - helps deliver the content of granules into target cell
Granzyme - a serine protease, activates apoptosis inside target cell
Granulysin - antimicrobial, induces apoptosis
Regulatory T cells fnHelp maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions
Produce anti-inflammatory cytokines: IL-10, TGF-B
Regulatory T cells express what?CD3,4,25 (alpha chain of IL-2 receptor)

Antibody structure and function

Question Answer
Variable part of L and H chains do what?recognize antigens
Fc portion of IgM and IgG does what?fixes complement
Heavy chain does what?contributes to Fc and Fab fractions
Light chain does what?contributes only to Fab fraction
FabAntigen-Binding fragment
Determines idiotype: only 1 antigenic specificity expressed per B cell
Carboxy terminal
Complement binding at CH2 (IgG + IgM only)
Carbohydrate side chains
Determines idiotype (IgM, IgD, etc)
Antibody diversity is generated by - Random recombination of VJ (light chain) or V(D)J (heavy chain) genes
- Random combination of heavy chains with light chains
Somatic hypermutation (following antigen stimulation)
Addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase
General purpose of antibodyPromotes opsonization
Prevents bacterial adherence
Activates complement, enhancing opsonization and lysis

Immunoglobulin isotypes

Question Answer
Mature B lymphocytes express what?IgM and IgD
Isotype switching involves what?Gene rearrangement - mediated by cytokines and CD40 ligand
IgGMain antibody in 2° (delayed) response to an antigen - most abundant isotype
Fixes complement
Crosses placenta - provides passive immunity to infants
Opsonizes bacteria
Neutralizes bacterial toxins and viruses
IgAPrevents attachment of bacteria and viruses to mucous membranes
Does not fix complement
Monomer in circulation or dimer when secreted
Found in secretions (tears, saliva, mucus) and early breast milk (colostrum)
Transported by epithelial cells by transcytosis - picks up secretory component
IgMProduced in the 1° (immediate) response to an antigen
Fixes complement but does not cross the placenta
Antigen receptor on the surface of B cells
Shape of pentamer (on B cells) traps free antigens out of tissue while humoral response evolves
IgDFound on the surface of many B cells in the serum - unclear function
IgEBinds mast cells and basophils
cross-links when exposed to allergen → mediating immediate (type 1) hypersensitivity via histamine
Activates eosinophils to fight worms
Lowest concentration in serum
Thymus-independent antigensAntigens like LPS or polysaccharide capsular antigens that don't have a peptide component → stimulate release of antibodies without producing immunologic memory
Thymus-dependent antigensContain a protein component (diphtheria vaccine)
Class switching and memory occurs thanks to contact of B cells with Th cells (CD40-CD40)


Question Answer
ActivationClassic pathway - IgG or IgM mediated
Alternate pthwy - microbe surface molecules
Lectin pthwy - mannose or other sugars on microbe surface
C3b fnopsonization
C3a, C5a fnanaphylaxis
C5a fnneutrophil chemotaxis
C5b-9 fncytolysis by MAC
MAC defends what?gram-negative bacteria
OpsoninsC3b and IgG - 1°
C3b also helps clear immune complexes
InhibitorsDecay-accelerating factor
C1 esterase inhibitor
prevents complement activation on self cells (RBCs)
C1 esterase inhibitor deficiency→ hereditary angioedema
ACE inhibitors are contraindicated
C3 deficiency→ severe, recurrent pyogenic sinus and respiratory tract infections
↑ susceptibility to type III hypersensitivity reactions
C5-C9 deficiencies→ recurrent Neisseria bacteremia
DAF (GPI anchored enzyme) deficiency→ complement-mediated lysis of RBC's and paroxysmal nocturnal hemoglobinuria (PNH)


Question Answer Column 3
IL-1Fever & acute inflammation
Adhesion molecules on endothelium
Chemokine secretion → recruits leukocytes
secreted by macrophages
IL-2stimulates T cells, helper, cytotoxic, and regulatorysecreted by all T cells
IL-3stimulates bone marrow growth and differentiation
Functions like GM-CSF
secreted by all T cells
IL-4stimulates IgE production (and IgG)
Induces differentiation into Th2 cells
B-cell growth
secreted by Th2 cells
IL-5stimulates IgA production
B cell growth
eosinophils growth and differentiation
secreted by Th2 cells
IL-6Fever & acute-phase proteinsSecreted by macrophages and Th2 cells
IL-8Major chemotactic factor for neutrophils
Cleanup on aisle 8!
Secreted by macrophages
IL-12Induces differentiation of T cells into Th1 cells
Activates NK cells
Secreted by macrophages and B cells
TNF-aMediates septic shock
Activates endothelium
Leukocyte recruitment, vascular leak
secreted by macrophages
Interferon-gammaActivates macrophages and Th1 cells → ↑ MHC I and II expression in all cells
Suppresses Th2 cells
Antiviral and antitumor properties
secreted by Th1 cells
Cytokines from macrophagesIL1,6,8,12, TNF-a
Cytokines from all T cellsIL-2,3
Cytokines from Th1 cellsIFN-γ
Cytokines from Th2 cellsIL-4,5,6,10
IFN-α & βinhibit viral protein synthesis via prodction of ribonuclease
IL-10Modulates inflamatory response
Inhibits actions of activated T cells and Th1
Fn's similar to TGF-β
Th2 cells and regulatory T cells

Cell surface proteins

Question Answer
T cellsTCR
Helper T cellsCD4
CD40 ligand
Cytotoxic T cellsCD8
B cellsIg
Fc and C3b receptors (enhanced phagocytosis)
NK cellsCD16
TCRbinds antigen-MHC complex
CD3assoc w TCR for signal transduction
CD28binds B7 on APC
Igbinds antigen
CD21receptor for EBV
Fc and C3b receptorsenhanced phagocytosis
Cd16Binds Fc of IgG
CD56unique marker for NK


Question Answer
Action of superantigensStrep pyogenes & Staph aureus
cross-link the B region of the T-cell receptor to the MHC class II on APCs → can activate any T cell → massive release of cytokines
Endotoxins/LPS actionGram-negative bacteria
Bind CD14 → directly stimulating macrophages
Th cells are not involved
Antigen variation - classic bacterial examplesSalmonella - 2 flagellar variants
Borrelia - replasing fever
Neisseria gonorrhoeae - pilus protein
Antigen variation - virusinfluenza: major=shift - minor=drift
Antigen variation - classic parasite exampletrypanosomes - programmed rearrangement
When to give passive immunity after exposureTetanus toxin
Botulinum toxin
Rabies virus
Live attenuated vaccine mechanismPathogen loses pathogenicity but still grows in host
Cellular response - life-long immunity but could revert to virulent form
Live attenuated vaccine examplesMeasles
polio (sabin)
yellow fever
Inactivated (killed) vaccine mechanismPathogen is inactivated but maintains epitope structure on surface antigens
Humoral immunity - stable/safer, but requires booster shots
Inactivated (killed) vaccine examplesCholera
Hep A
Polio (salk)