CH18 - Host defenses

What is adaptive immunity?

Adaptive immunity is your body's learned defense against specific germs.

• First exposure: slow primary response

• Later exposures: fast and strong secondary response
  It has specificity (targets exact invader) and memory (remembers it for next time).

What are the two main branches of adaptive immunity?

• Humoral immunity – B cells make antibodies to fight invaders in body fluids.

• Cellular immunity – T cells attack infected or abnormal cells directly.

What makes each naïve B or T cell unique?

Each naïve B/T cell has a unique receptor created by VDJ recombination, a random DNA-cutting and splicing process during development in the bone marrow.

creates a huge variety of antigen receptors, so the immune system can recognize many different threats.

What happens when a naïve B or T cell is activated?

The cell undergoes clonal expansion, making many identical copies that have the same specific receptor to fight the detected threat.

What are memory B and T cells?

Some activated B/T cells become memory cells that stay in the body.
If the same pathogen returns, they quickly clonally expand again, making a faster and stronger secondary immune response.

Do all the daughter cells from a stimulated B/T cell have the same receptor?

Yes. All cells made from a specific B or T cell have the same receptor as the original one, created by VDJ recombination.

steps of humoral immunity

1. macrophages engulfs the pathogen

2. presents the pathogen’s antigen MHC

3. T helper activation

4. B cell activation

5. B cells turn into plasma cells and B memory cells

6. plasma cells secrete antibodies

What are antigens, epitopes, and how are they related to antibody structure?

• Antigens (immunogens): Trigger adaptive immune responses

• Epitopes: Small regions on an antigen that are recognized by antibodies or T-cell receptors

• Antibody (e.g., IgG):

  • Made of 4 chains (2 heavy, 2 light)

  • Has Y-shape

    • Variable regions bind to specific epitopes

"GAMED" – The 5 antibody types

• G – IgG, A – IgA, M – IgM, E – IgE, D – IgD

🧠 IgG – "Greatest amount"

• Mnemonic: "G = General-purpose"

• Most abundant (80%)

• Crosses placenta

• Does everything: Neutralization, opsonization, complement, etc.

🧠 IgA – "Airways and mucosa"

• Mnemonic: "A = sAliva, teArs, mucosA"

• Secretory dimer, traps pathogens in mucus

• Found in mucosal surfaces (GI, respiratory)

🧠 IgM – "Massive first responder"

• Mnemonic: "M = Mega pentamer, Main early antibody"

• Largest (pentamer), 10 binding sites

• First made in response

• Strong in agglutination and complement

🧠 IgE – "Eosinophils & allergy"

• Mnemonic: "E = Explode in allergies"

• Binds to mast cells & basophils

• Triggers allergic reactions & fights parasites

🧠 IgD – "Don't know much"

• Mnemonic: "D = Dumb mystery receptor"

• Low quantity, role unclear

• Functions mainly as B-cell receptor

neutralization

involves binding specific antibodies to antigens found on bacteria, viruses, or toxins, blocking their harmful effects and preventing infection or damage.

How do antibodies function as opsonins in the immune response?

• T – Tag the pathogen (with antibody igG)

• A – Attach via Fc receptor (phagocytic ) x Fc region of IgG of pathogens

• G – Grab and engulf (phagocytosis)

agglutination

clumping (agglutination) of pathogens

• IgM antibodies have 10 antigen-binding sites (pentamer)

• They bind to multiple bacteria simultaneously via epitopes

• This leads to clumping (agglutination) of pathogens

• Aggregates form when multiple antibodies cross-link different pathogens

What is (ADCC) and how do NK cells contribute?

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

• A – Antibodies attach to large pathogen

• D – Direct NK cell via Fc receptor binding x Fc region of pathogen

• C – Close contact between NK and target

• C – Cytotoxins released to kill the invader

Antibodies comparison

cell mediated immune response ATCTR

• A – Antigen presentation (dendritic cells capture antigen from infected cells and present to MHC I CD8 and MHC II CD4)

• T – T cell activation

  • CD8 T cells: costimulation from APCs and IL-2 from CD4

  • CD4 T cells: become activated helper T cells

• C – Clonal expansion

  • cytotoxic T cells: kill - CD8 cell mediate immune

  • helper T cells: secrete cytokines - CD4 humoral

  • memory T cells: long-term immunity - CD4 humoral

• T – Target killing

• R – Regulation & memory

dendritic cells process and present bacterial antigens to activate T cells?

“Please Let Dendrites Present My Target”

• P – Phagocytosis: Dendritic cell phagocytoses a bacterial cell into a phagosome

• L – Lysosome fusion: form phagolysosome

• D – Degradation: Antimicrobial enzymes degrade the bacterium

• P – Processing (by proteases): Proteases process antigens → select epitopes

• M – MHC II loading: Epitopes are loaded onto MHC II molecules

• T – T cell activation: Presented on the surface to CD4⁺ helper T cells, which are activated

MHC I found where

all nucleated body cells

antigen binding cleft of MHC I is formed by domain alpha 1 and alpha 2

endogenous produced proteins to CD8 T cells

cell mediated immunity

MHC II found where

found on macrophages, dendritic cells, and B cells

antigen binding cleft MHC II formed by domains alpha 1 and beta 1

Exogenous/Phagocytized antigens to CD4 T cells

humoral immunity

red bone marrow where and function

found on head of femur (thighbone), and flat bones )ilium, scapula_

production and differentiation of many blood elements (RBCs, leukocytes, platelets)

yellow bone marrow

adipose cellsi

immature T lymphocytes

produced in red bone marrow

travel to thymus for maturation

structure of thymus

• Thymus is a bi-lobed, H-shaped gland above the heart

• Surrounded by a fibrous capsule (connective tissue)

• Each lobe has lobules with:

  • Dark cortex (dense with immature T cells)

  • Light medulla (fewer, mature T cells)

• Key site for T cell maturation

• Prominent in newborns; shrinks with age (involution)

steps of thymic selection Pass, Fail, Fly"

• Pass – Positive selection: keep MHC-recognizers

• Fail – Negative selection: kill self-reactors

• Fly – Mature T cells exit thymus

• Thymic selection ensures only functional, non-self-reactive T cells mature:

✅ Step 1: Positive Selection

• Purpose: Keep T cells that can recognize self-MHC

• Kill T cells that do not bind MHC at all

• Occurs in thymic cortex

❌ Step 2: Negative Selection

• Purpose: Eliminate T cells that bind too strongly to self-antigen/MHC

• Kill T cells that could cause autoimmunity

• Occurs in thymic medulla

🩸 Step 3: Maturation/Export

• Surviving T cells become naive, mature CD4⁺ or CD8⁺ T cells

• Exit thymus to enter peripheral circulation

cytotoxic T cell function

activated by MHC I on infected body cell

release perforin and granzymes that invade infected ells => apoptosis/death

Superantigen Activation

• Superantigen bypasses normal recognition

• Bridges MHC II and TCR directly, even without antigen specificity

• Causes massive, non-specific T cell activation

  • Leads to cytokine storm and excessive inflammation

What happens during T cell-dependent activation of B cells?

• Antigen Recognition: B cell binds to specific antigen via BCR.

• Antigen Processing: B cell internalizes and presents antigen on MHC II.

• T Cell Interaction: Helper T cell recognizes the same antigen via TCR + MHC II.

• Cytokine Release: Activated T cell secretes cytokines.

• B Cell Activation: Cytokines stimulate B cell.

  • Outcome: B cell proliferates and differentiates into memory B cells and plasma cells (antibody producers).

How do T-independent antigens activate B cells?

• Antigen Structure: Repeating epitopes on T-independent antigens cross-link BCRs.

• No T Cell Help Needed: Activation occurs without T cell interaction.

• Second Signal: Often requires innate signal (e.g., TLRs binding PAMPs).

• B Cell Response: Activation leads to proliferation and differentiation into plasma cells.

• Outcome: Rapid antibody production, mainly IgM; no memory cell formation.

4 types of immunity

passive nature: acquired from antibodies pass in breast milk and placenta

passive artificial: gained from another person/animal

active natural: gained through illness and recovery

active artificial: vaccine

edward jenner

cowpoxvaccination technique to prevent smallpox

types of vaccine