overview on immunology and introduction to innate immunity

Overview on Immunology and Introduction to Innate

Immunity

Over view What are the main types of

white blood cells? Name the two main types of

immunity? What are the main distinctions

between these two categories? What cells are involved in which

aspects of the immune system?

Lymphocytes Many types; important

in both humoral and cell-mediated immunity

B-cells produce antibodies (APC cell)

T- cells Cytotoxic T cells Helper T cells

Memory cells

Lymphocytes Natural Killer cells

Large granular lymphocytes (not B or T)

Kills tumor cells Kills cells infected with certain

viruses (intracellular pathogens)

Monocytes/Macrophage Phagocytosis and killing

of microorganisms Activation of T cells and

initiation of immune response

Monocyte is a young macrophage in blood

There are tissue-specific macrophages

APC cells

Dendritic Cells Phagocytosis and killing

of microorganisms Function as antigen

presenting cells (APC) In the blood and tissues

– mature and migrate to the lymph nodes

Neutrophil Granulocyte

Cytoplasmic granules Polymorphonuclear Phagocytosis Short life span (hours) Very important at “clearing” bacterial

infections Innate Immunity

Eosinophils Kills Ab-coated parasites

through degranulation Involved in allergic

inflammation A granulocyte Double Lobed nucleus Orange granules contain

toxic compounds

Basophils Might be “blood Mast

cells’ A cell-killing cells

Blue granules contain toxic and inflammatory compounds

Important in allergic reactions

Antigen-presenting cells (APC) Highly specialized Process antigen and display

peptide fragments on cell surface Involved in T-cell activation Macrophages, dendritic cells and

B-cells

Over view What are the main types of white

blood cells? Name the two main types of

immunity? What are the main distinctions

between these two categories? What cells are involved in which

aspects of the immune system?

Immune system divisions Innate immunity

First line of defense Adaptive (acquired) immunity

Takes time to develop Humoral immunity

(antibody–mediated specific immunity)

Cell-mediated immunity (The aspect of the adaptive immune response where antigen-specific T cell have a main role)

Active immunity

Passive or maternal immunity

Injection of Immunoglobulin

Absorption of maternal antibodies

Innate vs. adaptive immunity

Innate immunity First line of defense (present in all individuals at all

times) Immediate (0 – 4 hours) Non-specific Does not generate lasting protective immunity

Adaptive immune response (late: > 96 hours) Is initiated if innate immune response is not adequate (>

4 days) Antigen-specific immunity Generates lasting protective immunity (e.g. Antibodies,

memory T-cells)

Over view What are the main types of white

blood cells? Name the two main types of

immunity? What are the main distinctions

between these two categories? What white blood cells are

involved in which aspects of the immune system?

Immune system cells Innate immunity

Granulocytes (i.e. neutrophils)

Macrophages Dendritic cells Natural killer (NK)

cells

Adaptive immunity Lymphocyte

B cells T cells

Cytotoxic T cells (CTLs) Helper T cells (Th)

Memory cells

Innate immune system The first line of defense:

Penetration of the epithelial surface of the body by microorganism (e.g. bacteria)

Engulfment of microorganism by macrophages, neutrophils, and dendritic cells

Release of cytokines and chemokines Inflammation

(Immunology animation: Janeway) http://www.blink.biz/immunoanimations/#

Killing by granulocytes Macrophages and neutrophils recognize pathogen by

means of cell-surface receptors Example: mannose receptor, CD14 receptor, scavenger

receptors, glucan receptor etc. Binding of MØ/neutrophils with pathogen leads to

phagocytosis Bound pathogen is surrounded by phagocyte membrane Internalized (phagosome) Killing of pathogen (Phagolysosome*)

Oxidative burst (synthesis of hydrogen peroxide (H2O2)or free oxygen radicals)

Acidification Antimicrobial peptides (e.g. defensins)

* Phagolysosome = lysosome +phagosome

Phagocytosis

The macrophage expresses receptors for

many bacterial constituents

Mannose

receptor

LPS receptor (CD14)

Scavenger

receptor

Bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of

inflammation

Lipid mediators

Cytokines

Lysosome

Phagolysosome

Phagosome

Macrophages engulf and digest bacteria to

which they bind

Phagocytosis (Immunology animation: Janeway)

http://www.blink.biz/immunoanimations/#

Immune response (IV) 9.1 - Phagocytosis

Humoral immune response Cell-surface

immunoglobulin receptors (BCR) detect extracellular pathogens

Once activated, secrete immunoglobulins as soluble antibodies

Antibodies Variable region (2 identical

antigen-binding sites) Constant region (determines

how antibody disposes of the pathogen once it is bound)

Fc region

V region; At binding

Cell killing – NK cells NK cells do not require

prior immunization or activation

They attach to ‘target’ cells (ADCC)

Cytotoxic granules are released onto surface of cell

Effector proteins penetrate cell membrane and induce programmed cell death

Inflammation

Cytokines

Chemokines

FluidsProteins

Bacteria trigger

macrophages to

release cytokines

and chemokines

Vasodilation and increased vascular premeability cause redness, heat, and

swelling

Inflammatory cells migrate into tissue,

releasing inflammatory

mediators that cause pain

Cytokines Low molecular weight, soluble proteins that are

produced in response to an antigen and function as chemical messengers for regulating the innate and adaptive immune system

Innate immune system Macrophages and Dendritic cells

Tumor necrosis factor-alpha (TNF-) Interleukin-1 (IL-1) Interleukin-12 (IL-12)

Adaptive immune system T-lymphocytes

Interleukin-2 (IL-2) Interleukin-4 (IL-4)