L32 - Principles of Innate & Acquired Immunity Pt.1

What are the 4 Basic Functions/Principles of an Immune Response?

1. Immunological recognition → detect non-self

2. Immune effector function → contain and eliminate infection

3. Immune regulation → turn/modulate the response off

4. Immunological memory → long-term protective immunity

What is Immunological Recognition?

Detection of substances that are non-self

What is Immune Effector Function?

The mechanisms used to contain and eliminate infection.

Why is Immune Regulation important?

The immune response must be able to turn off

• Poor regulation can contribute to disease.

What is Immunological Memory?

The ability to develop long-term protective immunity, allowing a faster response after later exposure. It is the basis for vaccination

How are lymph nodes and the spleen organized for different types of immune responses?

• Lymph nodes → respond to localized infections

• Spleen → responds to systemic/blood-borne infection and acts as a filtering organ

What is the basic role of Innate Immunity?

The immediate/first-line alarm system that recognizes conserved patterns associated with pathogens or tissue damage

What does Innate Immunity recognize?

Conserved structural patterns/motifs, including PAMPs and DAMPs

What are PAMPs?

Pathogen-associated molecular patterns = conserved structures associated with pathogens

What are examples of PAMPs?

• Lipopolysaccharide (LPS) → Gram-negative bacteria

• Double-stranded RNA → viral replication

What are DAMPs?

Damage-associated molecular patterns = host-derived substances released during inflammation, necrosis, or other pathology

What is an example of a DAMP?

Extracellular ATP

What type of receptors does innate immunity use?

Genetically encoded receptors that recognize conserved patterns

Does innate immunity have immunological memory?

No

• By itself, innate immunity does not confer protective memory against a later infection

Which cells make up the adaptive immune system?

B cells and T cells

How do B cells recognize antigen?

B cells use their B-cell receptor (BCR) to interact directly with antigen

How do T cells recognize antigen?

T cells use their T-cell receptor (TCR) to recognize antigen presented in the context of MHC

What is a major professional antigen-presenting cell (APC)?

The dendritic cell

What is the basic difference between B-cell and T-cell antigen recognition?

• B cell: binds antigen directly

• T cell: recognizes peptide + MHC

What is Adaptive Immunity?

A specific immune response to an antigen that can produce protective immunity

How can adaptive immunity recognize such a huge variety of antigens?

B- and T-cell receptor diversity is generated through rearrangement of inherited gene segments

Is the specific rearranged BCR/TCR inherited from the parents?

No

• The gene segments are inherited, but their rearrangement occurs during immune-cell development

Why does the initial adaptive immune response take time to develop?

Only a small number of cells carry each receptor specificity. Once the correct cell recognizes antigen, it must proliferate to produce many copies

Why can a later adaptive immune response occur faster?

Memory B and T cells generated from previous exposure remain available for future responses

Compare Innate and Adaptive Immunity.

• Innate: conserved patterns, genetically encoded receptors, immediate, no memory

• Adaptive: highly specific antigens, rearranged receptors, slower initially, develops memory

Do innate and adaptive immunity function independently?

No

• Innate and adaptive immune cells work together

What is the lecture-summary distinction between innate and adaptive recognition?

• Innate → recognizes highly conserved structures

• Adaptive → cell development/refinement produces enormous recognition diversity

Where do all blood cells originate?

From hematopoietic stem cells in the bone marrow

What two major progenitor lines arise from hematopoietic stem cells?

1. Lymphoid progenitor

2. Myeloid progenitor

Where can immune cells migrate after development?

Into the blood, peripheral tissues, and lymphatic system

What immune cells arise from the common lymphoid progenitor?

• B cells

• T cells

• NK cells

Which common lymphoid progenitor cell belongs to innate immunity?

NK cell

Which common lymphoid progenitor cells belong to adaptive immunity?

B cells and T cells

What are the three phagocytes?

1. Macrophages

2. Dendritic cells

3. Neutrophils

What is the major function of macrophages?

Phagocytosis, activation of bactericidal mechanisms, and antigen presentation

What is the relationship between monocytes and macrophages?

• Monocyte → blood

• Macrophage → tissue

What is the major function of dendritic cells?

Antigen uptake in peripheral tissues and antigen presentation; they help activate naïve T cells

What is the major function of neutrophils?

Phagocytosis and killing of pathogens

What is the major function of eosinophils?

Killing antibody-coated parasites

What is the major function of basophils?

Promote allergic responses and augment anti-parasitic immunity

What is the major function of mast cells?

Release granules containing histamine and other active agents

What is the major function of NK cells?

Release lytic granules that kill target cells, especially virus-infected cells

What types of cells can NK cells target?

Virus-infected cells, cancer cells, and antibody-coated cells

Are NK cells part of innate or adaptive immunity?

Innate immunity, despite being lymphocytes

Do NK cells have specific rearranged antigen receptors like B and T cells?

No

Where do B cells develop/mature?

Bone marrow

B cells are primarily associated with what type of immunity?

Humoral immunity

What happens to B-cell receptors during development?

Gene segments undergo rearrangement, generating a repertoire of B cells with different BCR specificities

What does “one B cell = one type of BCR” mean?

Each individual B cell carries one receptor specificity; the diverse repertoire exists across many different B-cell clones

What three types of signals/interactions support B-cell development in bone marrow?

1. Chemokines

2. Cellular adhesion molecules (CAMs)

3. Cytokines

What is the basic role of chemokines in B-cell development?

Guide cell movement/chemotaxis through developmental locations

What is the basic role of CAMs in B-cell development?

Provide adhesion/anchoring to appropriate stromal cells

What is the basic role of cytokines in B-cell development?

Provide signals supporting development, activation, growth, and survival

What happens to an immature B cell that reacts to self?

It does not pass selection and is removed/destroyed

What happens to a B cell that passes selection in the bone marrow?

It can leave the bone marrow and travel to secondary lymphoid tissues

Where do T cells develop/mature?

Thymus

T cells are primarily associated with what type of immunity?

Cell-mediated immunity

How do T-cell progenitors reach the thymus?

They migrate there in a chemokine-dependent manner

What two major selection requirements occur during T-cell development?

Developing T cells must:

1. Be able to interact appropriately with self/MHC

2. Not react too strongly to self-antigens

What is the “Goldilocks” idea of T-cell selection?

T cells need an appropriate level of self/MHC recognition—not absent, but not excessively strong

What is the quality-control process for developing T cells called?

Positive and negative selection

What does a TCR actually recognize?

The combination of MHC + presented peptide

What does “one T cell = one type of TCR” mean?

Each T-cell clone has one receptor specificity

Why are mature T cells somewhat self-reactive?

Their function depends on being able to recognize self-MHC while avoiding excessive self-reactivity

What is the key difference between BCR and TCR after lymphocyte differentiation?

• BCR/Ig → can become secreted antibody

• TCR → always remains on the cell surface and is never secreted

Which cell secretes antibodies?

Plasma cells

What B-cell types are listed in the lecture?

1. Germinal-center B cells

2. Memory B cells

3. Plasma cells

What T-cell types are listed in the lecture?

1. Helper, cytotoxic

2. Regulatory

3. Follicular helper T cells

What are the primary lymphoid organs?

Bone marrow and thymus

What are the secondary lymphoid organs?

Lymph nodes and spleen

What is the basic function of primary lymphoid organs?

Sites where lymphocytes develop/mature and undergo selection

What is the basic function of secondary lymphoid organs?

Sites where mature immune cells can encounter antigen and become activated

Which primary lymphoid organ is associated with B-cell development?

Bone marrow

Which primary lymphoid organ is associated with T-cell development?

Thymus

Which secondary lymphoid organ is especially associated with localized immune responses?

Draining lymph nodes

Which secondary lymphoid organ is especially associated with systemic/blood-borne immune responses?

Spleen

What species-specific primary lymphoid organ exceptions are mentioned in the lecture?

• Bursa of Fabricius in birds

• Peyer’s patch in sheep

What is the basic immune-cell development pathway?

Bone marrow hematopoietic stem cell → lymphoid/myeloid progenitors → specialized immune cells

What is the basic B-cell pathway?

Bone marrow → B-cell development/receptor rearrangement + selection → secondary lymphoid organs → activation → plasma/memory cells

What is the basic T-cell pathway?

Bone marrow progenitor → thymus → TCR rearrangement + selection → secondary lymphoid organs → activation → effector T cells

What is the major relationship between Innate and Adaptive Immunity?

Innate immunity provides rapid recognition/response, while adaptive immunity provides highly specific responses and memory; the two systems work together

Innate vs. Adaptive Immunity SUMMARY

Feature	Innate Immunity	Adaptive Immunity
Main role	Immediate/first defense	Specific protective response
Recognizes	Conserved patterns	Specific antigens
Recognition examples	PAMPs + DAMPs	Specific antigen structures/peptides
Receptors	Genetically encoded	Generated through gene-segment rearrangement
Diversity	Limited	Extremely diverse
Speed	Immediately available	Takes time to develop initially
Memory	No	Yes
Main cells	Neutrophils Macrophages Dendritic cells Eosinophils Basophils Mast cells NK cells	B cells + T cells
Protective memory	No	Yes

Selected Immune Cells + Basic Functions SUMMARY

Cell	Arm	Basic Function to Know
Macrophage	Innate	Phagocytosis + bactericidal mechanisms; antigen presentation
Dendritic cell	Innate → links to adaptive	Antigen uptake + presentation; activates T cells
Neutrophil	Innate	Phagocytosis + killing of pathogens
Eosinophil	Innate	Kills antibody-coated parasites
Basophil	Innate	Allergic responses + anti-parasitic immunity
Mast cell	Innate	Releases histamine-containing granules
NK cell	Innate	Kills virus-infected/target cells
B cell	Adaptive	BCR directly recognizes antigen; humoral immunity
T cell	Adaptive	TCR recognizes peptide + MHC; cell-mediated immunity

Origin of Immune Cells SUMMARY

Starting Cell	Progenitor	Major Cells to Know
Hematopoietic stem cell	→ Lymphoid progenitor	B cells T cells NK cells
Hematopoietic stem cell	→ Myeloid progenitor	Macrophages Dendritic cells Granulocytes

B-Cell vs. T-Cell Development SUMMARY

Feature	B Cell	T Cell
Origin	Bone marrow	Bone marrow
Development/maturation	Bone marrow	Thymus
Receptor	BCR	TCR
Receptor diversity	Gene-segment rearrangement	Gene-segment rearrangement
Selection goal	Remove inappropriate/self-reactive cells	Appropriate self/MHC recognition without excessive self-reactivity
Type of immunity	Humoral	Cell-mediated
After maturation	→ Secondary lymphoid organs	→ Secondary lymphoid organs

Primary vs. Secondary Lymphoid Organs SUMMARY

	Primary Lymphoid Organs	Secondary Lymphoid Organs
Main purpose	Immune-cell development/maturation	Mature immune cells encounter antigen + become activated
Organs	Bone marrow + thymus	Lymph nodes + spleen
Bone marrow	B-cell development	—
Thymus	T-cell development	—
Lymph nodes	—	Localized immune responses
Spleen	—	Systemic/blood-borne immune responses