Lecture 4 Adaptive Immunity

2 branches in adaptive immunity

1. Humoral - B cells becoming plasma cells making antibodies

2. Cell mediated response - CD8+ T cells (killer T cells) and CD4- helper T cells (helps both branches)

Antigenicity

the ability of a substance (antigen) to be specifically recognized by the immune system, especially by antibodies or T cell receptors

Immunogenicity

the ability of a substance to provoke an immune response in the body.

• This means the molecule doesn’t just get recognized (antigenicity) — it actually activates immune cells and leads to antibody production or T cell activation.

Increasing Immunogenicity

Small molecules (Ex:drugs like penicillin) —> Lipids (Ex: (LPS) of Gram negative bacterial cell wall) —> Polysaccharides (Ex: Haemophilus influenzae capsule polysaccharides) —> Proteins (Example: hemagglutinin or neuraminidase proteins on influenza virions)

CD8+

Cytotoxic T Lymphocyte killer cells that directly kills

CD4-

Helper T Lymphocyte, promotes phagocytosis in macrophages by producing a lot of activating cytokines

Humoral Immunity

Microbes: Extracellular microbes

Responding Lymphocytes: B cells

Mechanism: B cell becomes a plasma cell that secretes antibodies

Functions: Blocks infections and eliminates extracellular microbes

Cell mediated Immunity Helper T cells

Microbes: Phagocytosed microbes that live w/in macrophages

Responding Lymphocytes: Helper T lymphocytes

Mechanism: Activated macrophage

Functions: Elimination of phagocytosed microbes

Cell mediated Immunity Killer T cells

Microbes: Intracellular cell replicating w/in infected cell

Responding Lymphocytes: cytotoxic T cells

Mechanism: Cytotoxic T cells kills infected cells

Functions: Kill infected cell and eliminate reservoirs of infections

Cells of the Adaptive Immune System

Lymphocytes (B and T), Antigen-presenting cell (dendritic, macrophages, B cells), and Effector cells (T lymphocytes and Macrphages)

Lymphocytes (B and T)

Antigen-presenting cell (dendritic, macrophages, B cells)

Effector cells (T lymphocytes and Macrphages)

Maturation and tissue differentiation of lymphocytes T cells lineage

Bone marrow cell —> T lymphocyte goes to Thymus —> move out to blood —> to the peripheral secondary lymphoid organs —> the spleen and the mucosal and cutaneous lymphoid tissue.

Maturation and tissue differentiation of lymphocytes B cells lineage

Bone marrow cell —> B lymphocyte goes to Bone marrow —> move out to blood —> to the peripheral secondary lymphoid organs —> the lymph nodes and spleen

Migration of macrophages

Fetal hematopoietic (yolk, sac, liver) stem cell (bone marrow) will produce macrophage precursors and these precursors will develop and grow into different types of residential macrophages in brain, liver, lung, or spleen

Brain macrophage

Microglial cells

Liver macrophage

Kupffer cells

Lung macrophage

Alveolar macrophage

Spleen macrophage

Sinusoidal macrophages

What triggers the Adaptive system

Capture, transport and presentation of protein antigens

Presentation of protein antigens

T cells need to get triggered to and cells do that by bringing a peicepiece of the antigen and presenting it to the T cell so the T cell can then respond

Major Histocompatibility Complexes

membrane bound protein complexes, there is MHC class 1 and MHC class 2

MHC Class I Loctaion

Found on all nucleated cells

MHC Class I what they do

Presents peptides from inside the cell intercellular (self or viral proteins) which then get recognized by CD8⁺ cytotoxic T cells

MHC Class 1 Function

lets T cells detect virus-infected or abnormal cells by antigen presentation

MHC class 2 location

Found mainly on antigen- presenting cells (APCs) such as macrophages, dendritic cells, and B cells

MHC class 2 what they do

Presents peptides from engulfed extracellular microbes which get recognized by CD4⁺ helper T cells

MHC class 2 function

helps activate immune responses against extracellular pathogens by antigen presentation

Only professional phagocytes

have MHCII (macrophages, dendritic cells, and B cells)

Epitope

the specific molecular region on an antigen that an immune cell, such as an antibody or a B or T cell, recognizes and binds to, thereby initiating an immune response

T Cell Activation: 3 signals

1. Antigen specific signals

2. Costimulatory molecule binding

3. Cytokines bind to cytokine receptors

For full activation of T cells, you need all 3 signals

CD4+ Helper T cells “Help

Both Branches of Adaptive Immunity (humoral and cell)

How does CD4+ Helper T cells help Humoral branch

Help B cells become plasma cells making antibodies

How does CD4+ Helper T cells help Cell branch

They stimulate the cytotoxic T cell killers

Subset of helper T cells that target different parts

TH1, TH2, TH17, Tfh

TH1 cells

interferon gamma stimulated and it target macrophages by intercellular pathogens

Can cause autoimmunity and chronic inflammation

TH2 Cells

Targets eosinophils by helmith (parasite) and cause allergies

Th17 cell

Targets neutrophils by extracellur bacteria and fungi, results in neutrophil recruitment and activation as well as inflammation

Tfh

Targets B cells by extracellular pathogens and results in antibody production and autoimmunity

Cytotoxic T Lymphocyte Roles in Antigen Elimination process

When a cell is infected with a virus or if it is cancerous, interferons are released
• Recruits activated T cytotoxic cells to the area
• Enhances MHC I production inside host cells
• Puts the immune system on high alert

How killer T cells actually kill:

T cytotoxic cell binds to an MHC I– antigen complex:

• Releases perforins

  -Forms pores in the target cell

• Releases granzymes

-Enter through the pore
-Break down host cell proteins
-Induce apoptosis

Antibody Structure and Isotypes

IgG, IgA, IgM, IgE

IgG

Monomer, most abundant in body, long half life

Very important b/c it crosses the placenta and gives babies immune systems

IgA

Monomer or dimer, second most abundant, the antibody that is in milk resistant to stomach acid

IgM

Monomer or pentameter, third most abundant, the first antibody you're going to see in the blood when anybody gets infected with something

IgE

Rare, fights parasites and mediates allergic reactions (e = eosinophil)

Most antigens are

T dependent, and require T helper cells to fully activate B cells

T-independent antigens

Some antigens dont need help from T cell like some polysaccharides in bacteria because they have multiple binding sites

Activated B cell (T independent)

proliferate and differentiate into plasma cells and memory cells

How antibodies eliminate invaders

Neutralization, activate complement, or Increase phagocytosis

Neutralization

Antibodies block viruses by binding to their spike proteins, which prevents the virus from attaching to and entering our cells

Primary Antigen Exposure

When your body encounters an antigen for the first time

Slower, weaker response because the immune system is “learning” the antigen

Secondary Antigen Exposure

On re-exposure to the same antigen, Memory B cells quickly recognize it and rapidly produce antibodies.

Faster, stronger, longer-lasting response (this is the basis of vaccines).

4 types of Acquisition of Humoral Immunity

1. Naturally acquired active immunity

2. Naturally acquired passive immunity

3. Artificially acquired active immunity

4. Artificially acquired passive immunity

Naturally acquired active immunity

You make your own antibodies after a natural infection.

• Example: recovering from chickenpox → long-lasting immunity.

Naturally acquired passive immunity

You receive antibodies naturally from another person.

• Example: maternal antibodies passing to baby through placenta (IgG) or breast milk (IgA).

Artificially acquired active immunity

You make your own antibodies after medical exposure to antigen.

• Example: vaccination with weakened or inactivated pathogens.

• Long-lasting immunity (with memory)

Artificially acquired passive immunity

You receive ready-made antibodies through medical treatment.

• Example: injection of antivenom or monoclonal antibodies.

• Immediate, short-term protection.

Active immunity

your body makes the antibodies → long-term (memory).

Passive immunity

you receive antibodies from outside → short-term (no memory).