Lecture 21: Adaptive Immunity (Specific)

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Adaptive Immunity

• defenses that target a specific pathogen

  • occurs when innate immunity “fails”

• functions:

  • ability to distinguish self from non-self

  • specifically react to each antigen

  • have heterogeneity (different B and T cells) that can respond to every antigen

  • have memory

Primary Response

first time the immune system combats a particular foreign substance & often involves a lag or latent period of 4-7 days

Secondary Response

later interactions with the same foreign substance & much faster and more effective due to “memory” from initial exposure

Humoral Immunity

• immune action taken within extracellular fluids

  • B cells targeting free-floating antigens

• involves the action of antibodies (immunoglobulin) combating antigens (foreign)

• antibodies are secreted into body’s fluids, like blood and lymphatic fluid (humors)

• fights invaders and threats outside cells

  • ex. extracellular bacteria, toxins, and viruses before entering the host

B cells

lymphocytes that are created and mature in red bone marrow

primary involvement in adaptive humoral immunity

• recognize free-floating antigens and make antibodies

• once mature, they reside in the blood and lymphoid organs

Cellular Immunity (Cell-Mediated)

• immune action taken within the host cell

  • involves T lymphocytes

• best for fighting viral-infected cells and intracellular bacteria

• attacks antigens that have already entered the cells

  • ex. viruses (require host) and intracellular bacteria

T lymphocytes

• recognize antigenic peptides presented on MHC molecules

• mature in the thymus and reside in blood and lymphoid organs

• have T cell receptors (TCRs)

• primary involvement in adaptive cell-mediated immunity

T Cell Receptors

on the surface of T cells that make contact with antigens presented by MHC molecules

Clonal Deletion

removes potentially harmful self-reactive B cells

Thymic Selection

eliminates immature and self-reactive T cells

Cytokines

• chemical messengers produced in response to a stimulus

  • ex: ILs, chemokines, IFNs, TNF-a, and hematopoietic cytokines

• overproduction may lead to a cytokine storm

Interleukins (ILs)

type of cytokine: communicate between leukocyte

Chemokines

type of cytokine: induces migration (chemotaxis) of leukocytes

Interferons (IFNs)

interferes with viral infections of host cells

Tumor Necrosis Factor Alpha (TNF-a)

involved in inflammation and autoimmune diseases (direct toxic effect on tumor cells)

Hematopoietic Cytokines

control stem cells that develop into red and white blood cells

Cytokine Storm

“out of control” release of cytokines

could result in several conditions and diseases, like pneumonia, pulmonary edema, multiorgan dysfunction, acute respiratory distress syndrome, and COVID-19 fatalities

Antigen

• substances that cause the production of antibodies

  • typically components of invading microbes of foreign substances

    • ex: virulence factors → capsules, cell walls, flagella, fimbriae, toxins, viral capsids, and viral spike proteins

  • could also include nonmicrobial agents, like egg whites, pollen, etc

• antibodies interact with specific regions (epitopes or antigenic determinants) on the antigen

  • depends on size, shape, and chemical structure of the binding site on the antibody molecule

Haptens

molecules too small to be antigenic and require attachment to carrier molecules to provoke an immune response (ex. pencillin)

Immunoglobulins

• also known as antibodies

• soluble compact globular proteins that recognize and bind to specific antigens

• made up of four protein chains that form a Y: two identical light chains and two identical heavy chains joined by disulfide links

Valence

the number of antigen-binding sites on an antibody

Variable (V) Region

make up the ends of the antibody arms which bind to epitopes

the AA sequence differs from B cell to B cell

Constant (C) Region

the stem and lower parts of the arms, which is identical for a particular Ig class

Fragment crystallizable (Fc) Region

stem of an antibody that can bind to certain immune cells, like complement

IgG

• structure: monomer

• makes up most of total serum antibody

• location: blood, lymph, intestine

• long-lived

• function: enhances phagocytosis (opsonization), protect fetus (transplacental), neutralizes toxins, and triggers complement system

IgM

• structure: pentamer

• location: blood, lymph, B cell surface

• function: helps with agglutination of antigens AND are the first antibodies produced when infection occurs

IgA

• structure: dimer

• location: secretions, blood, lymph

• function: localized protection on mucosal surfaces by preventing attachment

IgD

• structure: monomer

• location: B cell surface, blood, lymph

• function: presence on B cells and functions in initiation of immune response (antigen-binding)

IgE

• structure: monomer with longer tail

• location: bound to mast and basophils, blood

• function: allergic response AND possible lysis of parasitic worms

Clonal Selection

B cell is activated when B-cell receptor (BCR) binds to its antigen

Clonal Expansion and Differentiation

the activated B cells proliferates and differentiates into plasmocytes (plasma cells) that secrete antibody and memory B cells

T-dependent antigens

requires a T-helper cell (T_H) and must have both B and T_H to recognize the antigen, which helps prevent unintentional autoimmune response

Activation of B cells against T-dependent antigens

• BCR binds to antigen

• B cell internalizes and processes the antigen

• antigen is displayed on MHC class II on B cell surface

• attracts T_H to contact the antigen and releases cytokines to activate B cells

• B cells → proliferate and differentiate → antibody-producing plasmocytes and memory cells

T-independent antigens

do not need the T_H assistance and do not require the internalization for B cell activation

provokes a weaker immune response, producing IgM, and no memory is made

Activation of B cells against T-independent antigens

the repeating subunits of polysaccharides from bacterial capsules or LPS help bind to multiple B cell receptors

Antigen-Antibody complex

• when antibodies bind to antigens

• strength of bond is affinity

• protects the host by tagging foreign molecules or cells for destructions

Agglutination

• IgM is more effective due to valence (pentamer)

• antibodies cause antigens to clump together to be more easily ingestible

Opsonization

• coating of antigens with antibodies or complement proteins

• enhances ingestion by phagocytic cells

Neutralization

• blocking attachment to host cells

• surrounding the pathogenic components of microbe = reduce pathogenicity, toxicity

Activation of Complement System

inflammation → coating of microbe with protein → complex attachment to microbe → lyses and attracts phagocytes and complement

Antibody-Dependent Cell-Mediated Cytotoxicity

• belongs to the adaptive immunity while leveraging innate immune cells

• triggered by antibodies from B cells interacting with antigens on target cell

• the effector cells: natural killer cells, macrophages, and eosinophils

• contributes to the extracellular killing immune response against various pathogens, including protozoa and helminths

  • they are too large to be phagocytized, so they are coated with antibodies

  • the effector cells attach the Fc regions of the antibodies and lyse the target with secreted chemicals

Natural Killer (NK) cells

• granular leukocytes that destroy body cells that lack or have reduced MHC class I expression

  • like viral-infected cells, tumor cells, and large, extracellular parasites

• belong to innate immune response; not immunologically specific because it is not stimulated by an antigen

• release cytotoxic granules containing perforin and granzymes that induce apoptosis in the target cells

Helper T cells

• release cytokines to activate other immune cells (gets help)

• CD4+ → MHC class II

Cytotoxic T cells

• kill virus-infected cells, cancer cells, and transplanted cells directly

• CD8+ → MHC class I

Macrophages and Dendritic Cells

• present antigens to T cells and get activated by cytokines

• dendritic: main APCs that induce immune response by T cells

• macrophages: ingestion of antigenic material and enhanced by cytokines produced by helper T cells

Clusters of Differentiation

help classify the different T cells by their surface glycoproteins

CD4+

• binds to MHC class II

• helper T cells: secrete cytokine that help activate B cells

• regulatory T cells: subset of CD4+ cells that carry an additional CD25 molecule to help suppress T cells against self

  • protect intestinal bacteria needed for digestion and protect fetus

CD8+

• binds to MHC class I

• cytotoxic T cells: kill host cells infected with virus and intracellular bacteria AND tumor cells and non-self cells of transplanted tissue

Antigen-Presenting Cells (APCs)

must display antigen on their surface in association with MHC class protein

Major Histocompatibility complex (MHC)

• encode molecules on the cell surface

• two types: class I and class II

Class I MHC

• found on the membrane of nucleated cells

• identifies a cell as “self”

• present peptide antigens to CD8+ cytotoxic T cells

Class II MHC

• found on the surface of APCs

• present peptide antigens to CD4+ helper T cells

Dendritic Cells (DCs)

• type of APCs

• engulf and degrade microbes and display them to T cells

• found in the skin, genital tract, lymph nodes, spleen, thymus, and blood

Macrophages

• type of APCs

• activated by cytokines or ingestion of antigenic material

• migrate to the lymph tissue, presenting antigen to T cells

Activation of CD4+ T Helper Cells

1. an APC encounters and ingests microorganism; then, displays short peptide and MHC class II on surface

2. TCR on CD4+ T Helper cell binds to MHC-antigen complex; then, T helper secretes cytokines

   1. activated CD4+ T helper cells differentiation into various subsets and memory T helper cells

3. Cytokines cause T_H to contribute to T helper cell activation and other immune cells

Activation of a Naive T_C Cell

• TCR on naive T_C cell must bind to an antigenic peptide presented by a class I MHC on an APC

• once activated, T_C undergoes clonal expansion and differentiation into cytotoxic T lymphocytes (CTLs), all specific to the same antigen

  • also memory cytotoxic T cells

• effector CTL attack infected target cells displaying same antigen with perforin (pore forming) and granzymes (proteases), causing apoptosis

Apoptosis

• programmed cell death

• prevents the spread of infectious intracellular pathogen into other cells

• cell cuts their genome into fragments, causing the membrane to bulge outward via blebbing

Primary Response

immune response on first exposure to an antigen; slower response

Secondary (Memory or Anamnestic) Response

occurs after initial exposure to an antigen; rapid differentiation into antibody-production plasmocytes; more rapid, lasts many days, greater in magnitude; memory cells produced in response and are activated here

Class switching

where the initial IgM (primary) response shifts to IgG, IgE, and IgA (secondary), occurs

Antibody Titer

the relative amount of antibody in the serum which reflects the intensity of the humoral immune response

Naturally Acquired Active Immunity

when own body produces its own immune response because of infection

Naturally Acquired Passive Immunity

when antibodies are passed down through placenta from mother or via colostrum

Artificially Acquired Active Immunity

injection that afflicts an infection to produce an immune resposne

Artificially Acquired Passive Immunity

injection of antibodies from serum