The document summarizes key differences between innate and adaptive immunity. The innate immune system is non-specific, has limited diversity, lacks memory, and utilizes anatomical and chemical barriers, complement proteins, phagocytes, and natural killer cells. The adaptive immune system is specific, has high diversity, possesses memory, and relies on lymphocytes and antibodies. The document also provides an overview of hematopoiesis and the development of various immune cells from stem cell progenitors.

3. Characteristics Innate Adaptive
Specificity Non-specific Specific
Diversity Limited High
Memory No Yes
Self-reactivity No No
Anatomical and
chemical Barriers
Skin, mucosa,
chemicals, pH, temp
Lymph nodes,
spleen, MALT
Blood proteins Complement Antibodies
Cells Phagocytes Lymphocytes
(not NK)

10. IL-7
Thymocyte
NK Cell
T Helper
B Lymphocyte
T CytotoxicT Progenitor
Lymphoid
Stem cell
B Progenitor
Bone
Marrow
Plasma Cell
Myeloid
Stem Cell
Erythroid progenitor
Megakaryocyte
IL-3
Thymus
Basophil
EosinophilIL-5
Granulocyte/
Monocyte
progenitor
Neutrophil
Dendrite cell
Erythrocyte
Macrophage
Monocyte
Mast Cell
Platelets
IL-11

11. B Cell
Antibody
Receptor
B-cell signal transduction
complex is:
• Ig-α
• Ig-β
• CD19
• CD21
And gene
rearrangement

12. T Cell
Antibody
Receptor
1. It can only bind small peptides
2. Peptides need to be processed
3. They need to be presented by MHC
T-cell signal transduction complex is a:
Multichain structure (CD3)
When it activates: Cellular
proliferation and cytokine
production.

13. Property B cell Ag Receptor T cell Ag Receptor
Molecules/cell 100,000 100,000
Idiotypes
(specificity for
antigen)
1 1
Isotypes 2 (IgM and IgD) 1 (α/β)
Secreted Yes No
Binding sites 2 1
Mobility Flexible (hinge) Rigid
Signal transduction Ig-α, Ig-β, CD19,
CD21
CD3

14. Allelic Exclusion.
We have 4 chances for a B-cell
We have 2 chances for a T-cell
When we have a successful
recombination, the rest of the alleles
shut off so that we have just ONE
specificity.
TDT is an enzyme that randomly
inserts bases after gene
rearrangement at the junctions DJ
(heavy chain) or VJ (light chain). It’s
also a marker for ALL

15. V-D-J μ α2εγ2α1γ1γ3δ γ4
Constant Domain Addition
The first heavy chain transcribed is IgM, then IgD through alternative splicing. It’s their first choice.
After the B-cell comes in contact with antigen can access the other constant regions.
Class switching happens inside the Germinal Centers of the lymph node, depending on the IL
Syndrome Inheritance Defect Signs
Omenn
Syndrome
AR Missense mutation
in rag genes
Absence of B cells
and decreased T
cells
SCID AR Nonsense mutation
in rag genes
Absence of B and T
cells

16. Ig heavy chain
rearrangement
Rag expression
Tdt
MCH II
CD19, 20, 21, 40
Bone Marrow Spleen/Periphery
Ig LIGHT chain
rearrangement
Cytoplasmic μ
Completes
maturation until
contact with antigen IgG+, IgA+ or
IgE+
This is where
clonal deletion
happens

17. Precursor
Make sure that T-
cell can bind MHC
Make sure that T-
cell can bind MHC
MHC I
MHC II

19. Germinal Center: Humoral
immunity, class
switching, somatic
hypermutation
Constantly recirculates.
They come every day.

20. B-cell
T-cell
Activated B and T cells
Constantly recirculates.
They come every week.

21. Haptens and
Drug Allergies:
• Streptomycin
• Aspirin
• Sulfa drugs
• Succinyl choline
• Some opiates
• Penicillin

22. Chemo-attractive
Molecule
Origin Function
Chemokines (IL-8) Macrophages Recruit white cells to an
area of inflammation
Complement split
product C5a
Endotelial damage -->
Activation of Hageman factor
(CID cause)--> Plasmin
activation
Leukotriene B4 Made by white cells via
break down of arachidonic
acid and phospholipids
Formyl methionyl
peptides
Bacteria-made proteins with
formyl methionyl peptides.

23. 2. Neutrophils, 1st ones
to arrive (peak 6 hrs)
They die and make pus Monocytes, macrophages and
eosinophils follow. They arrive 5-6
hours later in response to neurophil-
released mediators
1. Tissue damage and
introduction of bacteria,
I-CAM and CD18 helps
cells to bind to the site
3. Macrophages become
activated by and phagocyte
bacteria, releases cytokines.
IL-1, IL-6, IL-8
4. IL-8 adds cell adhesion
markers on the vascular
endothelium, pus formation
C5a
5. C5a activates and recruit
cells from the endothelium
C5a
C3a
6. Mast cells adhere to proteins
and act as anaphylotoxin. Releases
histamine, PG and leukotrienes
LKT-4
7. Leukotriene B4 is activated
and recruits more cells

24. Rolling
Activation
Adhesion
Leukocyte Adhesion
Deficiency (LAD)
Autosomal Recessive
ABSENCE OF CD18
Mutations in cell adhesion markers
required for the adhesion/arrest
stage.
• Leukocytosis
• No pus/abscess formation
• Chronic recurrent infections
• Omphalitis (and delayed
separation of umbilical cord)P-selectin (Weibel-Palade bodies)
E selectin (induced by TNF and IL-1)
Sialyl Lewis X
Mediated by IL-1 and TNF
of postcapillary
venules

25. Macrophage Fc Receptor
(CD16) IgG Immunoglobulin
C3bC3b receptor
Bacterial Organism
Opsonization

27. 1
23
4
5
6
1. Viral pathogen enters the cell
2. Gets converted into protein
3. Proteasome cleaves it onto
small molecules
4. Molecules approach the
Endoplasmic reticulum
5. They go through the TAP to
enter the ER
6. Molecules get loaded onto
MHC I
7. Exit to the Golgi apparatus
8. Exit the cell membrane through
exocytosis and expressed.
7
8
Endogenous pathway of
Antigen Presentation

28. 1
2
3
4
5
6
1. Antigen enters the cell
2. Macrophage swallows it
3. Macrophage cleaves it onto
small molecules
4. MHC II approaches with an
invariant chain
5. MHC II goes through the Golgi
6. MHC vesicle and peptide vesicle
fuses to create the
phagolysosome, invariant chain
gets degraded.
7. Exit the cell membrane through
exocytosis and expressed.7
Exogenous pathway of
Antigen Presentation

29. MCH Class I MCH Class II
Names HLA- A, B, C HLA- DP, DQ, DR
Tissue
distribution
All nucleated cells Macrophages,
monocytes, dendritic
cells
Recognized by CD8 CD4
Peptides bound Endogenous Exogenous
Function Elimination of
abnormal hosts cells
Presentation of foreign
antigens
Invariant chain No Yes
β2 Microglobulin Yes No
Specifics Proteasome Phagolysosome

30. 1. TCR flanked by signaling molecule
CD3 binds to MHC II as well as CD4 to
present antigen
2. CD28 – B7 costimulatory molecule
3. Cell adhesion marker IgCAM (CD2)
and LFA-3 keeps the cells together so
the cytokines can interchange
4. Proinflammatory cytokine exchange.
Specially IL-1 (activates T-cell)
5. T-cell starts to upregulate its IL-2
receptor and secrete IL-2
6. Gives the macrophage IFN-y to
activate it. (Important for
granulomas)
7. B7 will bind to CTLA-4 to turn off the
T-cell response.
T-helper cell
CD4
TCR
MHC II
Macrophage
CD3
CD28
B7
CTLA-4
1
2
Integrin
LFA-3
CD2
IL-1
IL-6
TNF-a
IL-12
IL-2 receptor
TLR
IFN-y
3
4
5
6
7

31. 1. Superantigen binds outside the
antigen-binding cleft
2. They activate any clones of T cells
expressing a particular variable B
sequence.
3. Polyclonal activation of T-cells,
resulting in over production of IFN-y
4. This will activate macrophages,
resulting in over expression of IL-1,
IL-6 and TNF-a.
5. Excess of cytokines induce system
toxicity.
T-helper cell
CD4
TCR
MHC II
Macrophage
CD3
1
2
IL-1
IL-6
TNF-a
IL-12
IFN-y
3
4
Super-
antigen
Known superantigens
• Staphylococcal enterotoxins
• Toxic-shock syndrome toxin (TSST-1)
• Streptococcal pyrogenic exotoxins

32. Present in outer membrane of ALL Gram -

33. Type of regulation
of CTLA-4
Drug Name Clinical Use
Agonists Abatacept Rheumatoid Arthritis
Belatacept Renal transplants
Antagonists Ipilimumab Melanoma
Monoclonal Antibody Clinical Use
Abciximab Anti-platelet – Antagonist of Iib/IIIa receptors
Infliximab Rheumatoid Arthritis and Chron disease, binds TNF
Trastuzumab Breast cancer – antagonist to ERB-B2
Dacliximab Kidney transplants – Blocks IL-2 receptors
Muromonab Kidney transplants – Blocks CD3
Palivizumab Respiratory Syncytial virus – Blocks fusion protein
Rituximab Non-Hodgkin Lymphoma – Binds to CD20 (B-cells)

34. 1. B-cell presents antigen through its
receptor and then internalizes it.
2. B-cell then presents it to MHC II
3. CD28 – B7 costimulatory molecule,
step needed for activation
4. CD40 and CD40L need to interact for
class switching and memory response
5. T-cell gives cytokines to B-cell
6. LFA and CD2 keep the cells together.
T-helper cell
CD4
TCR
MHC II
B-cell
CD3
1
2
CD40
CD40L
IL-4
IL-5
IL-6
IL-13
TGFb
B-cell Receptor
Cytokines
4
5
6
Integrin
LFA-3
CD2
CD28
B7
3
Another way to activate B-cells is to bind
antigen by surface IgM or IgD, which
sends a signal and becomes a plasma cell
secreting IgM or IgD.

35. Extracellular
Bacterial and Fungal infections
IL-23, IL-6, TGF-b
Parasitic infections
IL-4
Intracellular infections
IL-12
TH1 TH2 TH17
TH0
IFN-y, IL-2 IL-4, IL-5, IL-10 IL-17, IL-22
Part of the humoral response.
• IL-4 promotes class switching to IgG, IgE
• IL-5 promotes class switching to IgA
• IL-4 and IL-10 will switch off any TH-1 cells
• IL-5 activates and matures eosinophils
• IL-2 required for CD8 to become cytotoxic.
• IFN-y shuts off any TH-2 cells
• IL- 2 promotes class switching to IgG
• IFN-y promotes formation of granulomas
(epitheloid histiocytes)
• IL-17 activates tissues to secrete
cytokines to recruit neutrophils.
• IL-17 and IL-22 make epithelial
cells secrete anti-microbials
T-helper Subsets

36. CASPASES
activation for
APOPTOSIS
3rd pathway: CD8+ T-cell dumps
granzymes which activates
caspases

38. • It can bind 2 per IgM = Valence
10, has the highest avidity.
• Traps free antigen and helps to
remove it
• Activates complement along with
IgG
• FIRST ANTIBODY is always IgM
Is a classic.
IgM Pentamer

39. Recruitment of Inflammatory
Cells and Anaphylotoxins
C3a
C4a
C5a
Killing of Pathogens
Membrane attack complex –
Puts holes in the membrane to
allow for lysis.
Opsonization of Pathogens
Clearance of Immune
complexes
1 32
C3b
C3b

41. Type of Immunity Acquired Through Examples
Natural
Active means Recovery from infection
Passive means Placental IgG transport, colostrum
Artificial
Active means
• Hepatitis B component vaccine
• Diphtheria, tetanus, pertussis toxoid vaccine
• Haemophilus capsular vaccine
• Polio live or inactivated
• Measles, mumps, rubella attenuated vaccine
• Varicella attenuated vaccine
Passive means
• Horse antivenin against black widow spider bite or
snake bite
• Horse antitoxin against botulism, diphtheria
• Pooled human immune globulin versus Hep A and B,
measles, rabies, varicella zoster or tetanus
• “Humanized” monoclonal antibodies versus RSV

42. Virus Vaccine Vaccine Type
Rotavirus RV Live
Polio
IPV Killed (Salk)
OPV Live (Sabin)
Influenza
IIV Inactivated (killed)
LAIV Live
Varicella zoster VAR Live
Hepatitis A HepA Inactivated (killed)
Human Papilloma HPV Component
Hepatitis B HepB Component
Measles
MMR LiveMumps
Rubella
Yellow Fever Live
Adenovirus Live (Not attenuated)
Small Pox Live
Always
Rabies
Influenza
Polio
A Hepatitis
(Killed Vaccines)

43. Defects of Phagocytic Cells (Immunodeficiencies)
Disease Molecular Defects Symptoms
Chronic granulomatous disease Deficiency of NADPH oxidase,
failure to generate Oxygen radicals.
X-linked
Infections with catalase + bacteria and
fungi
Leukocyte-adhesion deficiency Absence of CD18 (helps cells to
bind to the vascular epithelium to
act on site of infection)
Recurrent infections, failure to form pus,
omphalitis, gum infections
Chediak-Higashi syndrome Granule structural defect, absent
NK. Microtubule defect, can’t move
things around the cell.
Recurrent infections with pyogenic
infections, neutropenia, giant granules in
leukocytes, partial albinism
G6PD Deficiency Deficiency of essential enzyme in
hexose monophosphate shunt
Same as CGD with associated anemia
Myeloperoxidase (MPO)
deficiency
Granule enzyme deficiency, unable
to generate hypochlorite
Mild or none
Hyperimmunoglobulin E
Syndrome (Job Syndrome)
TH1 cells can’t make IFN-y, PMNs
don’t respond to stimuli
Coarse facies, cold abscess, retained
primary teeth, elevated IgE, eczema,
increased TH2
Familial Mediterranean Fever Dysfunction of Neutrophils
(Autosomal Recessive)
Fever and acute serosal inflammation. High
SAA attacks with deposits of AA amyloid.

45. Humoral Immunodeficiency syndromes
Condition B-cell
count
IgG IgA IgM IgE Specifics
CD40 Ligand deficiency
(Hyper IgM) X-linked
Normal No class switching for this patients,
pyogenic, mucosal infections.
Common variable hypo-γ
immunodeficiency
Normal Onset on late teens. Overtime
increases autoimmune dx and
lymphoma
Transient hypo-γ-
gobulinemia of infancy
Normal Delayed onset of IgG synthesis,
resolves by 16-30 months
Job Syndrome (Hyper-
IgE)
Normal Normal Normal Normal
Selective IgA deficiency
(most common)
Normal Normal Normal Respiratory, autoimmune (Lupus)
and gastrointestinal, increased
atopy, celiac dx
Bruton X-linked
agammaglobulinemia
Bruton’s Tyrosine kinase deficiency
(needed for B cell maturation)
Immunoglobulin decrease causes bacterial, enterovirus and Giardia infections

46. Deficiencies of Complement
Classical pathway C3b deficiency (no
opsonization)
Increase in immune complex
diseases, infections with
pyogenic bacteria
Both pathways Membrane Attack Complex
deficiency (c5-c9)
Increased Neisseria
infections
C3 Recurrent bacterial
infections, immune complex
disease
Deficiency in
regulatory proteins
C1-INH (Hereditary
angioedema)
Compliment chain can’t
stop, severe inflammation.
Edema at skin and mucosal
surfaces (periorbital)

47. Selective T-Cell deficiencies
More susceptible to viral infections
Disease Defect Clinical Manifestations
DiGeorge syndrome Failure of formation of 3rd and
4th pharyngeal pouches,
thymic aplasia
Microdeletion of 22q11
Facial abnormalities (fish lip),
hypoparathyroidism, cardiac
malformations, T-cell
deficiency, only IgM is made.
MHC Class I deficiency Failure of TAP1 molecules to
transport peptides to ER
CD8 T-cells deficiency,
recurrent viral infections,
recessively inherited.
MHC Class II deficiency (Bare
Lymphocyte Syndrome)
No MHC II expression, defects
in transcription factors
CD4 T-cell deficiency, no DHT
response, no class switching,
no graft VS host disease.
Pyogenic, opportunistic
infections (clinically as SCID)

48. Combined B-T cell deficiencies
Disease Defect Clinical Manifestations
Wiskott-Aldrich
Syndrome (Partial)
Defect in cytoskeletal WAS
glycoprotein (actin cytoskeleton
rearrangement) X-linked
Triad. Immunodeficiency,
thrombocytopenia
(microthrombocytes) and
eczema. Decreased IgM and CMI.
IgA and IgE may be elevated.
Ataxia telangiectasia
(Partial)
Defect in ATM kinase involved in
detection of DNA damage
Ataxia, telangiectasias (broken
blood vessels), deficiency of IgA,
IgE, also T-cell deficiency.
SCID (Total) 1. X-linked.- Defect in common
γ of IL-2 receptor
2. Adenosine deaminase
deficiency (boy in bubble)
3. Rag1, Rag2 gene nonsense
mutations
1. Recurrent
viral/bacterial/fungi
infections of many types,
opportunistic infections, cells
unresponsive.
2. Plus neurologic deficiency
3. Total absence of B, T cells

49. Hypersensitivity
Type Immune
mechanism
Mechanism of Tissue
Injury
Diseases
Type I -
Immediate
IgE Mast cells and their
mediators
Allergic Rhinitis, Systemic anaphylaxis, food allergies, wheal &
flare (allergy test) and Asthma (eosinophils).
Type II –
Antibody
Mediated
IgM, IgG
antibodies
against cell or
tissue antigens.
Igs activate complement
and recruit PMNs to a
non-existent
inflammatory site, bind
directly to cell/tissue
Goodpasture (type IV collagen in basement membrane of kidney
and lungs) Acute rheumatic fever (ab cross-reaction) Autoimmune
hemolytic anemia (RBC membrane proteins), transfusion reaction,
thrombocytopenic purpura (platelet membrane proteins), Graves
disease (ab stimulation of TSH), Myasthenia Gravis (ab inhibits Ach)
Type III –
Immune
complex-
mediated
Immune
complexes of
circulating
Antigens and
IgM or IgG
Same as II, except for
the circulating immune
complexes.
Systemic Lupus Erythematosus (dsDNA), Post-streptococcal
Glomerulonephritis (glomerular basement membrane lumpy-
bumpy), Serum Sickness, Arthus Reaction (injected protein),
Polyarteritis Nodosa (Hep B virus antigen)
Type IV –
Delayed
type
Mediated by
TH1 CD4 cells
Macrophage activation
(granuloma formation)
cytokine mediated
inflammation
PPD test, Multiple sclerosis (myelin basic protein), contact
dermatitis (nickel, poison ivy, NO IgE), Hashimoto Thyroiditis,
Rheumatoid Arthritis, Type I Diabetes, Guillain-Barré sx (Peripheral
nerve myelin or gangliosides), Celiac disease (CD4 -gliadin, CD8-
HLA), Chron disease, Sjögren Syndrome

50. 1. First exposure to
allergen
TH2
2. TH2 release of IL-4
and IL-13 to stimulate
B cell and produce IgE
3. IgE attaches to Fc receptor
on a mast cell which can remain
for months or years
4. Second exposure is received by
mast cell receptors and
degranulation of histamine
happens.
Primary Mediators
1. Histamine
2. Heparin
3. Eosinophil chemotactic factor A
Secondary Mediators
1. Prostaglandin D2, E2, F2a
2. Leukotriene C4, D4, E4
3. Leukotriene B4

51. Autograft – From one part of the person to themselves. Will not be
rejected, NO immuno-supressive drugs. (Burns grafts, Bypass
surgery)
Isograft – Between Identical twins, there’s little rejection
Allogeneic graft – Most common type, in between persons of the
same species.
Xenogeneic graft – In between different species (Heart valve
replacement)

52. Universal donor
Universal recipient

53. + / +
- / -
CD4 T Helper cells
T cells
Other cells