Human Immune System OAT

Immune system

The immune system is the body’s defense system

Pathogens

Harmful microorganisms that cause disease

Leukocytes

White blood cells

Lymphocytes

White blood cells that originate from bone marrow, primarily found in lymphatic organs

• T cells

• B cells

• Natural Killer Cells

Where do T cells mature

The thymus

Where do B cells mature

Bone marrow

What is the Innate Immune System

• First line of defense, generates a nonspecific (generalized) immune response

External Immunity: Innate immune system

• Examples

• External immunity: Physical/physiological barriers that prevent pathogen entry

  • Includes skin, hair, cilia, mucous membranes, chemical secretions, and symbiotic bacteria

Internal Immunity: Innate immune system

• Internal immunity: Internal defenses activated by the innate immune system to neutralize pathogens that have entered

  • Composed of the inflammatory response, complement proteins, and phagocytic and natural killer cells

Inflammatory Response: Innate immune system

• What triggers it

• main activations

• Mast Cells

• Swelling

• Loss of function

• increased heat

• pain

Mast Cells in immune response

Leukocytes responsible for the first part of the inflammatory response

• Known as the rally signal

• Sit in the tissue in preparation for injury

• In the presence of injury, mast cells release histamine, which dilates blood vessels and increases their permeability, allowing immune cells to enter the tissue

• Mast cells also release heparin, an anticoagulant that prevents blood clotting

All steps of inflammatory response

• What do they do

• Pnemonic

• Swelling: Permeable capillaries result in fluids leaking into tissues

• Loss of function: Body part with inflammation becomes less usable

• Increased heat: Increased blood flow increases cutaneous temperature

• Pain: Throbbing pain caused by swelling, which puts continuous pressure on nerve endings

• Redness: Increased blood flow causes redness of skin

SLIPR

Diapedesis

• Definition

• What is directed by

• The process by which cells move from capillaries to the tissues in order to fight pathogens

• Directed by chemokine signaling

Diapedesis Steps

Tissue injury

• Damaged cells release cytokines (inflation) and histamine (increases permeability)

Cytokines trigger inflammation

• Blood vessels dilate, increasing blood flow, and become more permeable

Endothelial cells express adhesion molecules

• White blood cells stick to vessel walls

Chemokines (in charge of chemotaxis) form a gradient

• White blood cells follow the chemical trail toward the site of injury (chemotaxis)

Diapedesis occurs

• White blood cells squeeze through vessel walls into the interstitial space

At the injury site, inflammation continues to amplify cytokine and chemokine release, attracting more immune cells until the threat or damage is cleared

Chemotaxis

organisms direct their movement toward or away from specific chemicals in their environment

Granulocytes

• Cells in the innate immune system with specific granules in their cytoplasm

  • Include neutrophils, eosinophils, basophils, and mast cells

everything minus Monocytes and Lymphocytes

Abundance of Leukocytes + mneomonic

Neutrophils

Leukocytes

Monocytes and macrophates

Eosinophils

Basophils

Neva Let Monkeys Eat Bananas

Neutrophils

Neutrophils: Innate immunity phagocytes

• Most common leukocyte found in the blood, accounting for over half of all leukocytes

• One of the first cells recruited to a site of inflammation

Lymphocytes

• Three subsections

• What is their mechanism of attack

B cells, T-cells, and NK cells (natural killer)

• B and T cells are part of adaptive immunity and must be activated. They are the most common type of leukocyte found in lymph

• NK cells are part of innate immunity, attacking virally infected and cancerous cells

• NK cells lyse target cells using perforin (create holes) and granzymes (stimulate apoptosis)

Monocytes and Macrophages

Phagocytes in innate immunity

Monocytes: Immature form found in the blood vessels

Macrophages: Mature form following diapedesis with secondary ability to act as antigen-presenting cells, activating adaptive immunity

Eosinophils

Eosinophils: Innate immune cells with granules that can be released to kill pathogens (particularly parasites)

Basophils

Contain granules with histamine (dilates vessels) and heparin (anticoagulant)

• Least numerous leukocyte

• Very similar to mast cells, except basophils circulate as mature cells while mast cells circulate as immature cells

Dendritic Cells

• Innate immune cells that scan tissues using pinocytosis (cell “drinking” of fluids and solutes) and phagocytosis (cell “eating” of solid particles)

• Antigen-presenting cells that migrate to the lymph nodes to activate adaptive immunity

Antigen presenting immune Cells

• Macrophages and dendritic cells use toll-like receptors (TLRs) to recognize conserved parts of the microbes

• Binding to these receptors triggers phagocytosis and activates the innate immune system

• Specifically, they make sure to bind to conserved parts of microbes (parts that microbes must have to survive)

Interferons

Secreted by virally or bacterially infected cells, binding to non-infected cells to prepare them for attack

RED FLAG, WE NEED TO DEFEND, INTERFERE PLEASE

Platelets

• Platelets: Anucleate cell fragments that are involved in blood clotting and in activating the innate immune system

• Help regulate macrophages and dendritic cells

Complement System

• Complement system: ~30 proteins that aid immune cells in fighting pathogens

• Proteins turn each other on through the activation of a complement cascade, which produces a large effect

• Upon recognizing a pathogen, a chain reaction of protease activity is triggered for the proteins to activate each other

Complement Protein Actions

• Complement protein actions:

• Tag antigens for phagocytosis in a process called opsonization

• Increase histamine release and inflammatory response via mast cells

• Membrane attack complex (MAC) pokes holes in and lyses pathogens

Adaptive Immune system

• Adaptive immunity is a specific immune response

  • Specific antigens are targeted

Antigen:

• Antigen: An immunogenic foreign molecule that is the target of the immune response

Epitope

• Epitope: A portion of the antigen that is recognized by the immune cells

MHC Molecules

• Major histocompatibility complex (MHC): Molecules that allow the immune system to recognize foreign cells and antigens

  • Located on immune cells

  • Once recognized, the immune system destroys the foreign or infected cell

  • MHC can be divided into MHC class I and MHC class II

MHC Class 1

• Major histocompatibility complex (MHC) class I: Surface molecule on all nucleated cells that present intracellular antigens

• Each genetically different individual will have a unique MHC I molecule

• The immune system can utilize this inherent uniqueness to distinguish between self and non-self cells

MHC Class 2

• Major histocompatibility complex (MHC) class II: Surface molecule on antigen-presenting cells (dendritic cells, macrophages) that present extracellular antigens

Organ Transplants and difficulties with MHC1

• Individuals receiving transplants where MHC I molecules do not match may lead to failure or rejection

• Immunosuppressants are given to transplant patients to try to prevent this

• Autoimmune diseases occur when the immune system attacks self MHC I

• Identical twins have identical MHC molecules, allowing these individuals to transplant to each other without the need for immunosuppressants

  • The donated organ cells will not be marked as foreign and attacked

b Cells

• Control antibody-mediated immunity (humoral immunity)

  • Manage the production and release of antibodies

• Can also act as antigen-presenting cells

• B cell receptors (BCRs): Located on B cells, binding to antigen epitopes either free floating or on the surface of pathogens

• Each B cell has a unique BCR

Clonal Selection + Clonal expansion

• Types of B cells

Clonal Selection Model: Describes the development of one type of BCR for every B cell

Clonal expansion: B cells divide into either plasma cells or memory B cells

• Plasma cells: Produce and secrete antibodies

• Memory B cells: Can be activated later in case of another attack

Memory B Cells

• Survive for long periods and lie dormant until reactivated by the same antigen that triggered the original clonal expansion

• The key to vaccinations

  • Vaccines stimulate the production of memory B cells, which can later be reactivated

• Massive antibody production

Antibodies (immunoglobins)

• What are they like structurally

• Where do they go around

• What do they consist of and what is that bonded by

• what is the recognizing region.

• Antibodies (immunoglobulins): Structurally identical to BCRs but freely circulate in the blood and lymph

• Can tag antigens for phagocytosis, neutralize antigens by coating them, or activate the complement system

• Antibodies contain light chains and heavy chains that are linked together by disulfide bonds

• The variable region recognizes different antigens while the constant region is the same for antibodies within the same class

5 main antibody classes

● IgM

● IgA

● IgE

● IgD

● IgG

lgM Antibodies

The largest antibody, present in a pentameric form

• The first antibody to be produced

• Activates the complement system

LgA Antibodies

Present in a dimeric form

• Most abundant in bodily secretions

• Newborns receive passive immunity through breast milk containing IgA

lgE Antibodies

Monomers present on basophils and mast cells as antigen receptors

• Triggers histamine release and an allergic reaction when bound to an allergen

• Think “Ig-sneEze”

lgD Antibodies

Monomer with very little information known (produced in small amounts)

Dih is mysterious

IgG antibodies:

Monomer that is the most abundant antibody in circulation

• The only antibody to cross the placenta, providing a fetus with passive immunity

• Aids the complement system in causing opsonization (marking for death) by tagging antigens for phagocytosis

• Helps IgM acivate the complement systemt

T Cells

T cells: Control cell-mediated immunity

• Directly act on cells rather than releasing antibodies

• T cell receptors (TCRs): Unique (similar to BCRs), binding to only one type of antigen per T cell

• T cells also undergo clonal selection just like B cells

How are T-Cells Activated

• T cells must bind to antigens on antigen-presenting cells (APCs) to be activated

• This can occur via MHC I or MHC II

T-Cells with MHC 1

• MHC I presentation: T cells differentiate into cytotoxic T cells (CD8+)

  • Directly kill infected cells through perforin (pokes holes) and granzymes (cause apoptosis)

  • These are different than NKCs because they are more specific and require antigen presentation

T-Cells with MHC II

• MHC II presentation: T cells differentiate into T helper cells (CD4+)

• Release interleukins to boost both innate and adaptive immunity

• Interleukins help attract innate immune cells and increase proliferation of other T and B cells

Passive Immunity

The immunity one organism gains from receiving antibodies from another organism that already has immunity

• Ex: A fetus gain immunity via IgG crossing the placenta

• Ex: Newborns gain immunity via IgA in breast milk

• The fetus and newborn in these examples are referred to as immuno-naive, as they do not yet have their own active immunity

Immunonaive

immuno-naive: An organism without their own active immunity

Active Immunity

• Active immunity: The immunity one gains from being infected once already by a pathogen

• Vaccination: Introduces antigens or inactivated pathogens to stimulate active immunity

  • Referred to as artificial immunity

  • Induces the formation of memory B and T cells

Interleukins

Attract innate immune cells and increase proliferation of other T and B cells

• Occurs when T cells differentiate into T helper cells (cd4+)

Bacterial Diseases

• Pnemounic

Tuberculosis

Gonorrhea

Leprosy

Syphilis

E. coli

Streptococcus, Bacillus, Staphylococcus, Mycoplasma, Spirochete infections

Tony Go Long, Said Eli

Viral Diseases

• Pneuomonic

Influenza

Hepatitis

Herpes

Chicken pox

Human papillomavirus (HPV)

Human immunodeficiency virus (HIV)

Measles

Polio

Icy Hens Hatch Chickens Having Huge Messy Pox

Genetic Diseases

Down syndrome

Cystic fibrosis

Huntington’s disease

Sickle cell

Tay-Sachs

“Down Cyclops!”, Hercules Said Tiredly

Parasitic Diseases

Malaria

Tapeworms

Fungal Diseases

Yeast infections

Athlete’s foot

Fungal and Parasitic Diseases Mneominic

● Please Make Time For Your Aunt

● Parasitic

● Malaria

● Tapeworm

● Fungal

● Yeast infections

● Athletes foot

Humoral Immunity

the aspect of adaptive immunity mediated by antibodies produced by B cells

Cell Mediated Immunity

In the adaptive immune response, T cells are responsible for cell-mediated immunity. Unlike B cells, which release antibodies to attack pathogens (humoral response), T cells directly kill pathogens themselves (cell-mediated response).

Pallor

Abnormal Paleness of the Skin

What are fevers controlled by?

NOT A LOCAL RESPONSE

It is controlled by the brain, and is used to kill temperature sensitive pathogens or to slow down their growth.

Toll Like Receptors

• What uses them

• What do they trigger

(tlr)

Macrophages and dendritic cells

• They are used to trigger phagocytosis and activates immune response.

• They recognize the conserved parts of microbes

MAC (membrane attack complex)

Part of the complement system with innate immunity

• Allows salts and fluids to enter a pathogen membrane causing to to swell and lyse.

What cells have MHC1 complexes

EVERY NUCLEATE CELL

• so no erythrocyte or platelets

What are immunoglobins

Antibodies

Immunogens

antigens

Relationship of BCR’s and Antibodies

THEY ARE THE SAME,

• save for the fact that BCR’s are attatched to B cells while antibodies are free floating.

TCR’s

• How many antigens can they bind do

• Can they clone

• Can they recognize free floating antigens?

What cells would cause adaptive immunity to cease to exist?

Helper T cells

Adaptive immunity has two divisions:

• Antibody-mediated immunity (aka humoral immunity) involves B cells that produce antibodies.

  • B cells encounter and process antigens. Helper T cells (CD4+) subsequently activate B cells by recognizing the antigen-MHC II and releasing interleukins, prompting B cell division into plasma cells.

• Cell-mediated immunity relies on cytotoxic T cells (CD8+) to directly attack and eliminate infected or abnormal cells.

  • Helper T cells recognize antigen-MHC I on antigen-presenting cells and release cytokines, which activate and help proliferate cytotoxic T cells for targeted cell killing.

Helper T cells play critical roles in activating both of these pathways. Without helper T cells, antibody-mediated and cell-mediated immunity would cease to exist.