Immune System Basics

eesohbel's version from 2015-08-08 18:57

Lymphoid structures

Question Answer
FollicleWhere mature B-cell come to:
- Proliferate
- Differentiate
- Isotope switch
Where are the follicles located?Outer cortex
What are the 2 types of follicles?1° follicle - dense and dormant
2° follicle - pale central germinal centers & active
Follicles are undeveloped in what disease?Agammaglobulinemia: No B cells, No follicle!
MedullaCords: closely packed Lymphocytes and Plasma cells.
Sinuses: Macrophages
What do the medullary sinuses do?Communicate with efferent.
Contain Reticular cells and Macrophages
What are plasma cells?Mature B cell antibody factories
ParacortexT cells live here
Where is the Paracortex?Between follicles and medulla
During an extreme cellular immune response, what part of the lymph node enlarges?Paracortex. T cells proliferate during viral infection
Paracortex is underdeveloped in which disease?DiGeorge syndrome. No T cells, No paracortex
Where are Peyer's patches found?Ileum


Question Answer
Upper back drains toAxillary LN
Lateral breast drains toAxillary LN
Stomach drains toCeliac LN
Duodenum drains toSuperior mesenteric LN
Jejunum drains toSuperior mesenteric LN
Sigmoid colon drains toColic → inferior mesenteric LN
Rectum drains toPara-rectal LN
Upper Anal canal (above pectinate line) drains toInternal iliac LN
Lower Anal canal (below pectinate line) drains toSuperficial inguinal LN
Testes drain toSuperficial & deep plexuses → para-aortic LN
[Remember: testes descend] so they are internal
Scrotum drains toSuperficial inguinal LN
Thigh drains toSuperficial inguinal [Remember the thigh is superficial]
Lateral dorsum of foot drains toPopliteal
Right arm drains toRight lymphatic duct
Right head drains toRight lymphatic duct


Question Answer
Right lymphatic duct drainsRight arm
Right chest
Right half of head
Thoracic ductEverything except the Right arm, Right chest, and Right side of head
Cervical LN drainsHead and Neck
Axillary LN drainUpper back
Celiac LN drainsStomach
Upper duodenum
Superior mesenteric LN drainsDuodenum
colon to splenic flexure
Inferior Mesenteric LN drainsColon after Splenic Flexure
Upper Rectum
Internal iliac drainsLower rectum - Upper anal canal
Vagina (middle)
Para-Aortic LN drainsTestes
Ovaries and Uterus
Superficial Inguinal LN drainsThigh
Lower Anal canal
Popliteal drainsDorsolateral foot
Posterior calf

Spleen and Thymus

Question Answer
Where are Macrophages found in the spleen?Red pulp
Where are T cells found in the spleen?Periarterial lymphatic sheath (PALS) in the White pulp
Where are B cells found in the spleen?Follicles of the White pulp
Macrophages remove what?Encapsulated organisms (SHiN SKiS)
How does splenic dysfunction ↑ susceptibility to encapsulated organisms?↓ IgM → ↓ complement activation → ↓ C3b opsonization → ↑ susceptibility to SHiN SKiS
Splenic Macrophages clear out encapsulated organisms
What hematologic changes 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 thymusThird pharyngeal pouch
Lymphocyte originMesenchymal
Cortex of Thymus containsImmature T cells
Medulla of thymus containsMature T cells
Epithelial Reticular cells (fibroblasts) containing Hassall's corpuscles
Positive selection occurs where?Thymic cortex
(MHC restriction)
Negative selection occurs where?Thymic Medulla
(non-reactive to self)


Question Answer
Cells of the innate immunityNeutrophils
Dendritic cells
NK cells (lymphoid origin)
Complement mediators
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 HLA (Human Leukocyte Antigen) genes
Which HLA types encode MHC I?HLA-A, HLA-B, HLA-C
What does MHC I bind to?TCR and CD8+ on Cytotoxic T cells
Which cells express MHC I?All nucleated cells (not RBCs)
MHC I antigen processingPresents endogenously
Which HLA types encode MHC II?HLA-DR, HLA-DP, HLA-DQ
What does MHC II bind to?CD4+ on Helper T cells (Th)
Which cells express MHC II?Antigen Presenting cells (APC's) only
MHC II antigen processingPresents exogenously
What cytokines are secreted by Th1?IFN-gamma and IL-2
What cytokines are secreted by Th2?IL-4, IL-5, IL-10

HLA diseases

Question Answer
HLA A3Hemochromatosis
HLA B27PAIR: Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiter's syndrome
HLA DQ2/DQ8Celiac disease
Hay fever
HLA DR3Diabetes mellitus type 1
Graves' disease
HLA DR4Rhematoid arthritis
HLA DR5Pernicious anemia → B12 def.
Hashimoto's thyroiditis= Complement

T cells

Question Answer
What receptors are expressed on T cells?CD3
T-cell receptor
CD8+ are expressed byCytotoxic T cell
CD4+ are expressed byHelper T-cellS: Th1 cell and Th2 cell
Where do T-cells mature?Thymus (Mature from Cortex to Medulla)
Positive selectionThymic Cortex: T-cells expressing TCRs able to bind just right to self MHC molecules survive
Negative selectionThymic Medulla: T cells expressing TCRs with high affinity for self anitgens get apoptosed
What are the antigen presenting cellsDendritic cell (the only APC that can activate naive T-cell)
B cell
Which signals are required for T-cell activation?1. Antigen presented by MHC binds TCR on T cell
2. Co-stimulatory signal: B7+CD28
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+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)1. Th2 cell gets activated
2. Signal 1: Th2 TCR binds B-cell MHCII
3. Co-stimulatory signal: CD40 on B cell binds to CD40L on Th2
4. Th2 secretes cytokines → determine Ig class switching of B cell
- B cell activates and undergoes class switching, affinity maturation and antibody production
What do Th1 cells secrete and what does it activate?IFN-gamma and IL-2
Activates macrophages
What does Th2 secrete what does it activate?IL-2,4,5,10,13
Recruits Eosinophils for parasite defense
Promotes IgE production by B cells
Th1/Th2 - how do they inhibit each other?Th1 inhibits Th2 with IFN-gamma
Th2 inhibits Th1 with IL-4 and IL-10
How do Th1's and Macrophages co-stimulate?Th1 activate Macs with IFN-gamma
Macs activate Th1 with IL-1 & TNF-alpha
Cytotoxic T cellsInduce apoptosis in virus-infected, neoplastic, and donor graft cells
Release cytotoxic Granzymes and Perforins
CD8+ binds to MHC I
How do Cytotoxic T cells induce apoptosis?Perforin - helps deliver the content of granules into target cell
Granzyme - a serine protease, activates apoptosis inside target cell
Fas-R binds Fas-L ligand to activate Caspases
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 are identified byCD3, CD4, CD25 and FOXP3
What do NK cells do?Induce apoptosis of viral cells, tumor cells or an absence of MHC I
Use perforin and granzymes
[They are the only lymphocyte member of the innate immune system]
NK cells' activity is enhanced byIL-2
IFN-alpha and IFN-beta
How are Th1's inhibited?IL-4 and IL-10 (secreted by Th2)
How are Th2's inhibited?IFN-gamma (secreted by Th1)

B cells

Question Answer
What do B cells doMake 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
What surface markers are found on B cells?CD19
Where do B cells mature?In the Bone marrow
Then they live in the Lymph nodes
How are B cells activated by T-cells?Th2 activates B cell by binding to MHCII as well as CD40
How do B cells activate T-cells?Act as APC. 1. Display antigen on MHCII 2. Co-stimulatory: B7-CD28


Question Answer
Secreted by Th1 cellsIL-2, IL-3, IFN-gamma
Secreted by Th2 cellsIL-2, IL-3, IL-4, IL-5, IL-10
Secreted by MacrophagesIL-1, IL-6, IL-12, TNF-alpha
Secreted by NK cellsIFN-gamma
Secreted by all T cellsIL-2 and IL-3
Secreted by B cellsIL-12
FeverIL-1, IL-6
osteoclast activating factorIL-1
reduce effects of immune responseTGF-B and IL-10
Mediate inflammationIL-1, IL-6, TNF-alpha
Supports T-cell proliferation, differentiation and activationIL-2
Supports growth and differentiation of Bone marrow stem cellsIL-3
Growth and differentiation of B cellsIL-4 and IL-5
Growth and activation of EosinophilsIL-5
Enhances IgE and IgGIL-4 [BEG 4 it]
Class switch to IgAIL-5
Promotes B cell differentiationIL-5
Fever and aKute phase proteinsIL-6
Neutrophil chemotaxisIL-8 [Clean up on aisle 8], LTB4
Induce T cell differentiation into Th1IL-12
Induce T cell differentiation into Th2IL-4
Septic shockTNF-alpha
Activates endotheliumTNF-alpha
WBC recruitmentTNF-alpha
cachexia in malignancyTNF-alpha
Activates macrophagesIFN-gamma
Inhibits macrophagesIL-10
Inhibits production of Th1IL-10
Inhibits production of Th2IFN-gamma
Released by virus infected cellsIFN alpha and IFN-beta
Difference between C3a and C5aC5a recruits and activates neutrophils, monocytes, eosinophils and basophils C3a recruits eosinophils and basophils not neutrophils

Cell Surface Markers

Question Answer
T cellsTCR
Helper T cellsCD4
CD40 ligand
Cytotoxic T cellsCD8
B cellsIgG and IgM
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
Found on NK cells, Macrophages, Monocytes and Neutrophils
CD56unique marker for NK

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 regions
Light chain does what?contributes only to Fab only
FabAntigen-Binding fragment
Determines idiotype: only 1 antigen 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 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
What do mature B cells express?IgM and IgD
Isotype switching involves what?Gene rearrangement - mediated by cytokines and CD40 ligand
Main antibody in 2° (delayed) response to an antigenIgG
Most abundant isotypeIgG
Fixes complementIgG
Crosses placenta: provides passive immunity to infantsIgG
Opsonizes bacteriaIgG
Neutralizes bacterial toxins and virusesIgG
Prevents attachment of bacteria and viruses to mucous membranesIgA
Does not fix complementIgA
Monomer in circulation but dimer when secretedIgA
Found in secretions (tears, saliva, mucus) IgA
Found in breast milk (colostrum)IgA
Can pick up secretory component when it passes through epithelial cellsIgA
Produced in the 1° (immediate) response to an antigenIgM
[I aM infected]
Fixes complement but does not cross the placentaIgM
Antigen receptor on the surface of B cellsIgM
monomer on B cells, pentamer when secreted.IgM
Found on the surface of many B cells in the serum IgD (function is unclear)
Binds mast cells and basophils IgE
Cross-links when exposed to allergenIgE
Mediates immediate (type 1) hypersensitivity via histamineIgE
Activates eosinophils to fight wormsIgE
Lowest concentration in serumIgE
Thymus-independent antigensAntigens like LPS or polysaccharide capsular antigens that don't have a peptide component
Stimulates antibody release but no immunologic memory
Thymus-dependent antigensContain a protein component that MHC can present to T cells in thymus
Class switching and memory occurs thanks to contact of B cells with Th cells (CD40-CD40)

Complement Disorders

Question Answer
C1 esterase deficiencycauses hereditary angioedema. ACEI are contraindicated
C5aneutrophil chemotaxis
C3a, C4a, C5aanaphylaxis


Question Answer
superantigenscan activate any CD4 t cell and lead to massive release of cytokines