Humoral Immunity and Immunoglobulins 8/14/25

Humoral Immunity

Part of the adaptive immune system mediated by B lymphocytes that produce antibodies, contrasting with cellular immunity.

B-cell lymphocytes

Not all proliferating B-Cells become into plasma cells. Some stay Memory B-Cells through clonal selection.

Helps eliminate antigen in future

Make antibodies/immunoglobulins

Immunoglobulins

Antibodies produced by plasma cells; glycoproteins with 2 heavy (stem Fc frag) and 2 light chains (Fab arms) bound by disulfide bonds; five isotypes: IgG, IgA, IgM, IgE, IgD.

Complement System

Group of ~20 plasma proteins secreted by hepatocytes and monocytes that assist antibodies and innate defenses; activated by Classical or Alternative pathways; leads to opsonization, inflammation, and Membrane Attack Complex formation.

Antigen

Substance that is recognized by the immune system and can elicit an immune response. (bad guy)

Antigenic determinant (epitope)

Specific part of an antigen that binds to an antibody or T-cell receptor.

Plasma Cell

Differentiated B cell that secretes antibodies.

Antibody

Immunoglobulin that binds an antigen; Y-shaped; composed of Fab (antigen-binding) and Fc (constant) regions; two heavy and two light chains.

Heavy Chain

Long polypeptide chain of an antibody forming the Fc region and part of the Fab region; defines isotype class.

Light Chain

Short polypeptide chain paired with a heavy chain to form the antigen-binding site.

Fc Fragment

Constant region of the heavy chains; mediates effector functions and interacts with Fc receptors and complement.

Fab Fragment

Antigen-binding portion of an antibody consisting of one light chain and part of a heavy chain including the variable region.

GAMED (immunoglobulin classes)

Mnemonic for the five heavy-chain isotypes: Gamma (IgG), Alpha (IgA), Mu (IgM), Epsilon (IgE), Delta (IgD).

IgG

Major circulating Ig (80%); crosses placenta and protects fetus w passive immunity; activates complement cascade; opsonizes pathogens (make tasty). Secreted in milk.

IgA

Secretory antibody found in tears, saliva, gut lumen, and secretions; also in milk for neonates; secretory form with J chain and secretory component. 10-15% of Ig.

IgM

First antibody produced in a primary response; pentameric with up to five binding sites; activates complement. 5-10% of Ig.

IgE

Less than 1%. Antibody of allergy and parasite defense; binds to basophils/mast cells; mediates degranulation and hypersensitivity.

IgD

B cell surface receptor; helps recognize antigens and activates B cells to plasma cells. Less than1% Ig.

Secretory IgA

Form of IgA found in secretions with J chain and secretory component for mucosal protection.

Opsonin

Molecule (e.g., IgG) that coats a pathogen to enhance phagocytosis.

Fc Receptor

Cell-surface receptor for the Fc region of antibodies; mediates antibody-driven effector functions.

C1 (Classical Pathway Initiation)

First complex in classical complement activation (C1q, C1r, C1s) that binds IgG/IgM Fc regions.

Trimolecular complex that recognizes antibodies on antigen.

Recognition: C1q recognizes and fixes to Fc combining site on IgG (need 2) or IgM. It activates C1r from proenzyme to active molecule, which then activates C1s.

Activation: C1s cleaves C4 and C2 into C4-C2 complex (aka c3 convertase). Binding site on C4 is now able to attach to cell surface. Only substrate to C4-C2 is C3. It splits C3 into C3a and bigger C3b.

C3a leaves and acts as anaphylactoxin (C5a same). It can cause degranulation and histamine release from mast cells, smooth muscle contraction, and hydrolytic enzyme release from neuts.

C3b associates with C3 convertase to make C4-C2-C3b trimolecular complex (aka C5 convertase).

C3b generates intrinsic sites for IAP. C4-C2 attaches C3b to cell surfaces with with sites on them.

C5 gets cleaved like C3 by C5 convertase into C5a and C5b. C5b is focal point for Membrane Attack Unit (MAC).

MAC uses C5b, C6,7,8 and that attaches to target membrane and also recruits C9 to create poly C9. This opens transmembrane channel to cell interior (burrows), causing K+ to leave and water enter. Cell swells, macromolecules escape and cell is lysed.

Empty cell is phagcytosed

Genetic deficiency of MAC unit

Seen w Neisseria infections

C3 Convertase (Classical)

Enzyme complex (C4b2a) that cleaves C3 to C3a and C3b in the classical pathway.

C5 Convertase

Enzyme complex that cleaves C5 to C5a and C5b; formed after deposition of C3b.

Membrane Attack Complex (MAC)

Pore-forming complex (C5b-6-7-8-9) that lyses target cell membranes.

Anaphylatoxins

C3a and C5a; small fragments that promote inflammation and mast cell degranulation.

Immune Adherence Phenomenon

Process by which C3b-coated targets bind phagocytes to enhance phagocytosis. Occurs when opsonization facilitates the recognition and destruction of pathogens by immune cells.

Classical Pathway

Complement activation triggered by antibody-antigen complexes; sequential activation to C3 and beyond. 3 steps: Recognition, Activation, Membrane Attack

Alternative Pathway

Complement activation that can occur without antibodies, initiated by microbial surfaces.

Toll-Like Receptors (TLRs)

Innate immune receptors on macrophages/monocytes/dendritic cells recognizing microbial patterns to trigger cytokines. They are essential for initiating immune responses by detecting pathogen-associated molecular patterns (PAMPs).

Cytokines

Signaling proteins (e.g., IL-1, IL-2, IL-6, TNF) that promote inflammation and fever.

Pyrogen

Substance that causes fever; can be exogenous (toxins) or endogenous (cytokines).

Can be bacterial endotoxins, LPS, etc.

Endotoxin (LPS)

Gram-negative bacterial cell wall component that triggers fever and inflammation via LBP-CD14-TLR signaling.

Septic Shock

Severe systemic inflammatory response to infection, often with endotoxins; high mortality in ICUs.

Usually caused by gram negative (has endotoxins LPS) bacterial infections and leads to multiple organ dysfunction.

Hypothalamus

Brain region that regulates body temperature; responds to pyrogens by raising the set point via PGE2 (stimulated by IL1,2,TNF).

Fever (pyrexia)

Elevation of body temperature due to pyrogens acting on the hypothalamic thermostat.

Caused by infection, cancers (AML, ALL, lymphomas, renal cell, hepatocellular, brain tumors), autoimmune disease (lupus, RA, vasculitides), exercise, hot weather, vascular occlusions, drugs (antihistimines, antipsychotics, antidepressants, MOI, coke, PCP, LSD)

Classified local vs systemic

Fever of unknown origin

Look into respiratory, urinary, skin/soft tissue. Hypothalamus regulates temp.

Malignant hyperthemia

Autosomal dominant inherited abnormality of skeletal muscle sarcoplasmic reticulum that causes a rapid increase in intercellular calcium levels

Dendritic Cell

Professional antigen-presenting cell that initiates T-cell responses by presenting antigen via MHC.

Antigen Presenting Cell (APC)

Cells (dendritic cells, macrophages, B cells) that process and present antigens to T cells.

Macrophage

Phagocytic innate cell that processes antigen and produces cytokines to drive inflammation.

Memory B Cells

Long-lived B cells that persist after an initial antigen exposure and mount a rapid response on re-exposure.

Primary Immune Response

Initial antibody response to first exposure; lag of ~7–10 days; IgM appears first, then IgG, levels decline in same order

Secondary Immune Response

Faster, higher-magnitude antibody response upon re-exposure; predominately IgG with memory cells (some IgM).

Type I Hypersensitivity

Immediate IgE-mediated allergic reaction; mast cell degranulation; urticaria, angioedema, anaphylaxis.Involves the release of histamine, bradykinin, SRS-A, resulting in rapid allergic symptoms.

SRS-A (slow reactive substance of anaphylaxis)

A mixture of leukotrienes released by mast cells during allergic reactions, causing prolonged bronchoconstriction and inflammation.

Urticaria

Hives; pruritic, edematous wheals from localized mast cell degranulation and dermal microvascular hyperpermeability.

Angioedema

Deep tissue swelling due to mast cell degranulation in type 1 rxn; can be life-threatening with airway involvement. Egg-like swelling, rapid onset

Anaphylaxis

Systemic, rapid-onset hypersensitivity with bronchospasm and shock due to mediator release. Immediate laryngeal swelling/constriction. Asthma, hay fever, food, drugs (ex. penicillin)

Type II Hypersensitivity

Cytotoxic antibody reactions (IgG/IgM) with complement; mismatched transfusion reactions, Goodpasture syndrome, erythroblastosis fetalis.

Antibody attaches to normal tissues that absorbed antigen and complement system ensues

Type III Hypersensitivity

Immune complex-mediated; antigen-antibody complexes deposit in tissues, activate complement, recruits neuts that release lysosome enzymes causing inflammation and damage(GN, RA, SLE).

Type IV Hypersensitivity

Cell-mediated delayed hypersensitivity; Th1 cells activate macrophages; TB granulomas, contact dermatitis. Does not involve antibodies.

Classic lupus sign

butterfly rash

Antigen Presenting Cell (APC) Function

Process and present peptide antigens to T cells via MHC to activate adaptive immunity.

IgG Structure and Function

IgG has two heavy and two light chains; Fc binds complement and Fc receptors; cross placenta; opsonizes.

IgA Secretory Complex

Secretory IgA with J chain and secretory component; found in secretions and milk; protects mucosal surfaces.

IgM Structure

Pentameric IgM with up to five antigen-binding sites; first antibody in primary response; activates complement.

IgE and Allergic Mediation

IgE binds mast cells/basophils and mediates allergic responses and parasite defense.

IgD as B-Cell Receptor

IgD is expressed on naive B-cell surfaces and helps activate B cells to plasma cells.