immunity non specific to acquired

immunity

body’s ability to resist or eliminate potentially harmful foreign materials or abnormal cells

Immune System

defend against pathogens

removes worn out cells

identifies and destroys abnormal/mutant cells

innate imune system (non-specific)

works immediately

targets a wide variety of pathogens

first line of defense (rapid but limited)

external barriers

• skin

• mucous membrane

internal defense

• phagocytes

• antimicrobial cells

first line defenses (barriers)

surface barriers and mucosa

• linings, coating coverings

mechanical barriers (physical obstruction)

chemical defenses

• acidic secretions → mucosa (skin, oral, stomach, pH 3-5)

• lysozyme in saliva → destroys bacteria

mucus

• traps pathogen in respiratory and digestive pathogens

inflammation (innate response)

non-specific response to invasion

isolate, destroy, inactive invaders

remove debris

prepare for healing

inflammation response

macrophage ingest and release cytokines to attract other WBC

• increasing capillary permeability

blood vessels constrict and then dilate blood vessel → increases blood flow

migration of neutrophils via positive chemotaxis → engulf bacteria and destroy w/ enzymes → forms pus

• adhere to vessel wall

inflammation + swelling → redness, heat, pain

fibrin formation walls of infected area

phagocyte mobilization

leukocytosis → increase of neutrophils from bone marrow

• margination = inflamed areas sprout CAM’s (cell adhesion molecules) providing footholds for neutrophils cling to damaged areas

• diapedesis = neutrophils squeeze through capillary walls

• chemotaxis = neutrophils follow chemical gradient to the site of the injury

tissue repair

cell division replaces damaged cells

nonregenerative tissue (nerve/muscle) → scar tissue

medications

• salicylates (aspirin): decrease histamine + fever

• glucocorticoids: suppress inflammatory response

interferons

cytokines that interfere w/ viral replication

triggers virus-blocking enzymes

slow cell division

warn neigh boring cells

alpha interons

from infected leukocytes

beta interferons

from fibroblasts

gamma interferons

from T and NK cells → activate macrophages

NK (natural killer cells)

destroy virus-infected and cancer cells

lyse target cell membrane

Complement System

plasma proteins made by liver

~20-30 proteins

circulate inactive

non-specific but can assist adaptive immunity

forms MAC (membrane attack complex)

• destroy foreign pathogens in the body

• amplifies inflammation

• punch holes in pathogens (by lysis) → cell death

Opsonization: C3b tags pathogen

Inflammation: C3a, C5a

Cell Lysis: MAC C3b5B6789

Fever

caused by pyrogen

increase temperature → increase in metabolic reactions

• kills bacteria

limits bacterial growth

liver isolates iron/zinc (needed for bacteria)

Dendritic Cells

link between innate and adaptive immunity

pick up antigen markers

process and present antigens

activate T and B cells

Adaptive Immunity (specific)

target specific antigens

has memory

stronger and faster upon re-exposure

B cells

• antibodies → humoral immunity

T cells

• cell-mediated immunity

Memory Cells = long-term immunity, remembers the pathogen/antigen

Effector Cells = actively fight infection

• cytotoxic T cells

• plasma B cells

Humoral Immunity (B-cell)

B-cell

• develop in bone marrow

• produce antibodies

  • IgM = first response

  • IgG = stronger, secondary response

• circulates in lymph nodes, spleen and lymphoid nodules

antigen binds to BCR (b-cell receptor)

Clonal expansion

• b cell differentiates and proliferates

• produces memory and effector cells

Cell-mediated Immunity (T-cell)

T cells

• develop in the thymus

• migrate to lymph nodes and lymph tissues

Helper T cells (CD4 = MHC I) → coordinate immune response

• present to B cells and cytotoxic T cells

Cytotoxic T cells (CD8 = MHC II) → kill infected cells

• release toxins

Regulatory/Suppressor T cells → dampening immune response when its no longer needed

• down regulate effector T cells

antigen

foreign substances that trigger immune response

“non self” = not you

“self cell” = you

complete antigen = immunogenicity + reactivity

• stimulates proliferation of lymphocyte + antibodies

Hapten = small molecules → reactions (allergies) when attached

antigen presentation

done by: dendritic and macrophages

• swallow pathogens and display it onto tis cells surface

• travel to lymph nodes and present to T cells

MHC (major histocompatibility complex) class molecules

Class I: on all nucleated cells

• present to CD8 cells

• recognized by Cytotoxic T cells

Class II: on APC’s → dendritic, macrophage, B cells

• present to CD4 cells

• recognized by Helper T cells

antibodies

2 heavy chains + 2 light → monomer

variable regions = antigen binding sites

constant regions = determines function/class

IgA

dimer = 4 antigen binding sites

rare = limited amounts in plasma

found in secretions of the body

• prevents attachment of pathogens to epithelial surface

IgE

monomer

big

secreted by plasma cells

histamine release → inflammation

allergies

IgD

monomer

always attached to B-cell surface

• used for B cell activation for clonal selection

IgG

monomer

most abundant + GOAT → most effective

main antibody for primary and secondary immune system

infection

IgM

pentamer = 10 antigen binding sites

• powerful agglutination

first to show up → binds + hold

• done by plasma cells

shown if it is a recent infection

Macrophage

phagocytosis of microbes

process antigen into peptides → bind to MHC molecules

prsented on cell surface to lymphocytes

secrete interleukins → stimulates cell proliferation

Helper T cells

assist B cells

enhance immune systemx

Clonal Selection

antigen activates lymphocyte

cells proliferate

• become effector and memory cell

Immunological Memory

ability to reognize and quickly respond to previously encountered antigens

lead to faster, stronger and more effective responses to re-exposure

First Exposure

first exposure to antigen

some lymphocyte (w/ antigen specific receptors) recognize the antigen

Lymphocyte

• get activated

• proliferate (clonal expansion)

• differentiate into:

  • short-lived effector cell → eliminate antigen

  • long-lived memory cell → remain in resting state

Phase

• lag (3-6) days → proliferation and differentiation of plasma cells

• stationary phase

• declining phase

Antibodies

• IgM appears first

• B cells switch to IgG producing cells

• antigen specificity remains the same

Secondary Resopnse

faster, longer and more effective

memory cells are prsent

rapid differentiation into:

• effector and new memory cells

shorter lag phase

Antibody production

• IgM → smaller amounts, shorter duration

• IgG → produced sooner, in larger quantities

• IgA and IgE may appear

• higher antibody titer in the blood

Immune Tolerance

prevents immune system from attacking self-antigens

mechanisms

1. Clonal deetion → apoptosis of self-reactive cells

2. clonal anergy → single signal turns off lymphocyte

3. receptor activity → B cells change receptors

4. Antigen sequestration → self antigens hidden

5. immune privilege → protected tissues

Immune Survelliance

tumors

• benign = localized, non-invasive

• malignant = invasive, cancerous, metastasize

Immune defense against cancer

• NK cells = first line

• Cytotoxic T cells = target virus induced cancers

• macrophages = remove debris

• interferons assist

Immune Disorders

multiple sclerosis

myasthenua gravis

graves’ disease

SLE (lupus)

rheumatoid arthritis

glomerulononephritis

Immune Deficiency

weak or insufficient immune response

autoimmune disease

loss of tolerance → attack cell

Type I Hypersenstivity

IgE recognizes soluble antigen and binds to Mast cell

• histamine release which causes allergy symptoms

antibody-mediated

Type II hypersensitivity

IgG and IgM targets cellular antigens

• causes cellular destruction → cytotoxicity

antibody-mediated

Type III hypersensitivity

immune (antigen-antibody) complexes deposit in tissue

activates complement cascade → MAC and neutrophil degranulation

• destroys the tissue around them

causes inflammation and tissue damage

Type IV hypersensitivity

regulated T-cell

known as delayed hypersensitivity

• T cells attack

• causes a strong reaction → allergy, rash or major reaction

cell-mediated

immediate response

within seconds

IgE mediated

histamine release

subacute resposnse

within 1-3 hours

cytotoxic

immune complexda

delayed response

within 1-3 days

T cell-mediated

cytokine driven → inflammation