Intro - Lecture 1 - 1/16/24

Immunity - state of protection against foreign pathogens or substances (Immunis → exempt)

Two types:
1. Innate is non-specific uses PAMPs to activate immune system
2. Adaptive is specific uses Antigens to activate immune system
Note:
- Timeline of initial (primary) response: Innate first, then adaptive. Innate response is 0-12 hours after
infection. Adaptive is 1 to 7 days after infection.

Category / Type of Immunity Innate Adaptive

Components Epithelial Barriers, Dendritic cells, B and T lymphocytes, Effector T

NK cells and other ILCs, Mast cells, Antibodies
Cells, Phagocytes

Specificity Non-specific (PAMPs) Specific (Antigens)

Time to Respond Quickly Slowly

Magnitude of Response (1st) Quick and semi-large Slow and Large

Secondary Response Same as Primary in size and Fast and Large

speed.
 Memory Not really ( new research→ Yes
maybe )

Self vs. non-self Yes Yes

PAMPS → Pathogen associated molecular patterns → structures that characterize a group of pathogens
that the immune system recognizes first
- Recognize them quickly via pathogen filling
- PRRs (pattern recognition receptors) in white blood cells specifically recognize these sugar residues
and other common foreign structures. More specifically, PRRs are proteins encoded in the genomic
DNA and are always expressed by many different immune cells

Crash Course Book: PPRs Vs Generation of Diversity (B cells and T cells)

This feat (potential to respond to any antigen) is accomplished by rearranging and editing the genomic DNA
that encodes the antigen receptors expressed by each B or T lymphocyte. Not unlike the error-prone DNA
replication method employed by pathogens, this system allows chance to play a role in generating a menu of
responding recognition molecules. Thus, B and T cells make surface receptors unique to each individual,
which are then not passed onto offspring. This is in direct contrast to the DNA that encodes PRRs, which are
inherited and passed on to the next generation.

Crash Course Book: Innate Immunity and Adaptive Immunity Together

Innate Immunity
● Physical + Chemical barriers + PRRs → inherited from our parents
● Pre-existing serum proteins → complement → bind common pathogens
Adaptive Immunity
● the antigen-specific receptors on T and B cells that are generated via DNA rearrangement
● evolves in real time in response to infection
Adaptive Immunity

Lymphocytes → a type of white blood cell responsible for both cellular and humoral immunity

B lymphocytes / Humoral Immunity T lymphocytes / Cell Mediated Immunity

Function: Antigen Elimination Function: Killing of infected Cells

Origin: Bone Marrow
Purpose: Combating pathogens via antibodies
produced by B cells. Antibodies can be
transferred (passive immunity)
Passive Immunity Example: Anti-Serum found in
snakes.
Origin: Thymus
Purpose: Pathogen specific T lymphocytes eradicate the
infectious agent + aid cells in work
Active Immunity: brought on by the administration of a
vaccine/infection → becomes memory → long lived.

Lymphoid organs ( → error proof checking of the immune system )

- Central: Thymus/Bone marrow → Central Tolerance
- Peripheral: Spleen/Lymphoid node →Peripheral Tolerance

Locations with Immune Privilege (immune system cannot reach)

- Eyes: Cornea (surgery is easier in most cases)
- Placenta and Fetus
- Testicles
- Hair follicles
- Central nervous system (CNS)

Study Questions
4 : Indicate to which branch(es) of the immune system the following statements apply, using H for the humoral
branch and CM for the cell-mediated branch. Some statements may apply to both branches (B).

a. Involves B cells (H)

b. Involves T cells (CM)
c. Responds to extracellular bacterial infection (B)
d. Involves secreted antibody (H)
e. Kills virus-infected self cells (CM)

13: I for innate and A for adaptive

A. Is the first to engage on initial encounter with antigen (I)

B. Is the most pathogen specific (A)
C. Employs T and B lymphocytes (A)
D. Adapts during the response (A)
E. Responds identically during a first and second exposure to the same antigen (I)
F. Responds more effectively during a subsequent exposure (A)
G. Includes a memory component (A)
H. Is the target of vaccination (A)
I. Can involve the use of PAMP receptors (I)
J. Involves antigen-specific receptors binding to pathogens (A)
K. Can be mediated by antibodies (A)

16: How are PRRs different from B- or T-cell receptors? Which is most likely to be involved in innate
immunity and which in adaptive immunity?

Innate immunity → PRRs → inherited → cannot bind to specifically distinct antigens

Adaptive immunity → B and T cell receptors → not inherited → can bind to specifically distinct antigens
Lecture 2 - 1/18/24
Recap the ‘homework’:
● Adaptive Immunity → highly specific , magnitude response is much higher than innate, second
response response is ~4x stronger (memory)
● Innate and Adaptive → have the ability to recognize self vs. non-self ( key to be part of the immune
system)
CD → cluster of differentiation → cell membrane proteins (mostly) expressed by cells of the immune
system. Note: Different types of immune cells express distinct surface markers → (CD)

Hematopoietic Stem Cells (HSCs) → Have the ability to differentiate into many types of blood cells.

● Self Renew → reproduce

● Differentiate → able to specialize
● Highly Regulated

Immune Cells are derived from HSCs (Ans to Homework Lecture 2)

Innate

Adaptive

Non-Immune

The differentiation of HSCs is tightly regulated by transcription factors (Lineage commitment) → inside
the nucleus

Note: When a stem cell divides, it first becomes an immature red blood cell, white blood cell, or
platelet-producing cell.

HSCs differentiate into two major types of progenitor cells:

1: Myeloid (innate)
Can differentiate into:
● Monocytes → macrophages (repair/remodel/destroy/present antigens {Phagocytosis } ) + dendritic
cells (ingesters of antigens + initial activation T lymph {Antigen Presentation}.)
● Granulocytes → Neutrophil → Infection
● Eosinophil → Parasites
● Basophil → Allergy
● Mast Cell → Allergy
● Megakaryocytes→ Platelets
● Red blood cells (erythrocytes)

Professional Antigen Presenting cells (APCs)

1. Internalize pathogens via phagocytosis

2. Digest into peptides → present antigens on membrane surfaces
3. Upregulate molecules for activation of T cells

Macrophages, Dendritic Cells , B Cells

2: Lymphoid (some innate + all adaptive immune cells)

Can differentiate into:

● Dendritic Cells
● B lymph
● T lymph { a subset called NKT similar to Natural Killer}
● NK cells

Activation of B,T, and NK cells

B → soluble antigen binding

T → APC presentation [ MHC2 + antigen ] → very picky!
NK → Lack of MHC/ Expressing activating Ligands → balance disturbed → Yoda type cell

Activation of CD4 + CD8 T cells

Cytotoxic Cells: CD8+ and MHC Class 1

Helper Cells : CD4+ and MHC Class 2

Easy way to remember: 8 higher priority, let that boy ride

first class. Usually those boys toxic (pride) ( MHC1)

Organs of the Immune System

Primary (Central) lymphoid organs → where they develop / immature (90%)

Secondary (Peripheral) → where the immune response is initiated

Note: May be mature in primary (10%) and be immature in secondary ( cancer )

Primary/Central Immune Organs

During embryogenesis and the fetal period, blood cell formation shifts from site to site.

Steps: Hematopoiesis begins in the yolk sack → Kidney, fetal liver → HSCs ultimately populate the bone
marrow postnatally (after birth)

B development → Bone marrow

T development → Bone marrow and Thymus

Secondary/Peripheral Immune Organs

Areas where lymphocytes:

1. encounter antigens
2. become activated
3. undergo clonal expansion
4. differentiate into effector cells

Organs include: Lymph nodes, Spleen, Mucosa (MALT), and other loosely organized areas

Connected via blood and lymphatic circulatory network (reach almost the entire body!)

All immune cells in this network are guided by adhesion molecules and small molecules, chemokines

Book Reading

1: HSCs Differentiate into Myeloid and Lymphoid blood cell lineages

- ILCs (innate lymphoid cells) have features of both innate and adaptive cells.
- As cells mature from MPP to lymphoid-primed multipotent progenitors (LMPPs) to common
lymphoid progenitors (CLPs) they progressively lose the ability to differentiate into other
leukocytes.Environmental signals upregulate transcription factors that drive the cell down one of a
number of possible developmental pathways

2: Myeloid Antigen-Presenting Cells

Myeloid progenitor give rise to three groups of phagocytic cells - monocytes, macrophages, and dendritic cells
each have professional antigen-presenting cell (pAPC)
- All cells have the capacity to present peptides from internal proteins using MHC class I molecules
- pAPCs have the ability to present peptides from external sources using MHC class II
- Remember: MHC class II (CD4) molecules can be recognized by helperT cells
- Three activities:
1. Secrete proteins to attract and activate other immune cells
2. Internalize pathogens (phagocytosis), digest into peptides, and present on cell surface
via MHC Class II
3. Upregulate costimulatory molecules required for optimal activation of helper T cells

Basically…
 ● Dendritic Cells → presenting antigen and activating naive T lymphocytes (unactivated)
● Macrophages → phagocytes and efficient at removing both pathogen and damaged host cells from
the site of infection
● Monocytes (10% white blood cell) → regulate inflammatory responses at sites of tissue damage and
infection

The Thymus is the Primary Lymphoid Organ Where T Cells Mature

T-cell development is not complete until the cells undergo selection in the thymus :
● Thymocytes (immature) → T cells
● thymocytes that bind self-MHC/peptides with intermediate affinity (5%) undergo positive selection
and mature

Book Questions

Q1: Why was Jenner’s vaccine superior to previous methods for conferring resistance to smallpox?

it carried a significantly lowered risk of serious disease. The earlier method of using material from lesions of
smallpox victims conferred immunity but at the risk of acquiring the potentially lethal disease.

Q2: Did the treatment for rabies used by Pasteur confer active or passive immunity to the rabies
virus? Is there any way to test this?

It consisted of a series of inoculations with attenuated virus. The actively immunizes the recipient who will
have anti-rabies to stop the progression of the infection.