VETERINARY IMMUNOLOGY 2.0

MHC 1

MHC 1

They are  found on the surface of almost all nucleated cells in the body

MHC 1

What MHC molecules present peptides from inside the cell to immune cells called cytotoxic T cells.

MHC 2

MHC that are typically found on the surface of specialized immune cells called antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells.

MHC 2

MHC class molecules present peptides from outside the cell, typically from proteins that have been ingested by the APC.

MHC 3

MHC molecules that are not directly involved in antigen presentation.

Polymorphism

This is a results in the amino acid sequences in their a1 and a2 domains.

Polymorphism

This nature of MHC ensures the immune system's ability to recognize a broad range of antigens and adapt to different pathogens, making them central to adaptive immunity.

Nonpolymorphic

This nature of MHC provide structural stability and support for antigen presentation.

Nonpolymorphic

This nature of MHC ensures that the peptide-binding groove retains its shape and integrity.

If some MHC genes are expressed in some MHC haplotypes but not in others, the effect will be to generate even more diversity than alternative combinations of alleles of a fixed genes.

Explain the relationship between MHC haplotype and disease susceptibility.

MHC 1 present antigens originate from within the body

Explain the relation of MHC I class molecules present in endogenous antigens.

Endoplasmic reticulum

Where do the binding of peptides to newly synthesized MHC happens?

CD8+ or Cytotoxic T cells

To whom do MHC 1 molecules present their antigens

CD4+ or Helper T cell

To whom do MHC 2 molecules present their antigens

MHC 2 present antigens originate from outside the body

Explain the relation of MHC II class molecules present in exogenous antigens

Dendritic cells, macrophages, and B cells

MHC class II molecules are predominantly found on the surface of what type of cells

All nucleated cells

MHC class I molecules are predominantly found on the surface of what type of cells

lysosome and endosome

What organelle do the substance ingested being perform a process of degradation

variations in the number of MHC class I genes expressed

MHC diversity is generated by

TCR-peptide-MCH complexes and the co-stimulatory receptors cluster together in the area of contact to form an immunological synapse

How the TCR recognizes ligands presented by MHC molecules on antigen-presenting cells. 

These co-receptors. CD4 is associated with helper T cells, while CD8 is associated with cytotoxic T cells

Why each TCR is also associated with either CD4 or CD8.

CD4 primarily interacts with MHC class II molecules, which present exogenous antigens.

Why each TCR is also associated with either CD4.

CD8 primarily interacts with MHC class I molecules, which present endogenous antigens from within infected or abnormal cells.

Why each TCR is also associated with either CD8.

CD4, associated with helper T cells (CD4+ T cells), primarily interacts with MHC class II molecules. CD8, associated with cytotoxic T cells (CD8+ T cells), primarily interacts with MHC class I molecules.

Compare and contrast CD4 and CD8 and describe the different roles of CD4+ and CD8+ T cells.

Processing of antigens by APCs > formation of MHC-peptide complexes > T cell recognized antigen > T cells are co-stimulated > formation of the immunological synapse

Explain the step-by-step process of how multiple signals sent by antigen-presenting cells are communicated to a T cell through an immunological synapse.

Th1 Cells (T-Helper 1 Cells)

T cells subunit that are primarily involved in cellular immune responses against intracellular pathogens, such as viruses and certain bacteria.

Th2 Cells (T-Helper 2 Cells)

T cells subunit that are key players in the immune response against extracellular parasites, such as helminths, and are involved in allergic responses.

Th17 Cells (T-Helper 17 Cells)

T cells subunit that are important in defending against extracellular bacteria and fungi.

Treg Cells (Regulatory T Cells)

T cells that are regulatory cells that help maintain immune tolerance and prevent autoimmune responses.

interleukin-2 (IL-2)

IL produced by Th1

interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13)

IL produced by Th2

 interleukin-17 (IL-17) and interleukin-22 (IL-22)

IL produced by Th17

interleukin-10 (IL-10)

IL produced by Treg cells

Alpha-beta (α/β) T cells

Most common and widely studied subset of T cells in humans and many vertebrate animals.

Their TCRs consist of α and β chains

Alpha-beta (α/β) T cells consist of

thymus, lymph nodes, and spleen

Alpha-beta (α/β) T cells are located in what organ?

γ and δ chains

Gamma-delta (γ/δ) T cells consist of

peripheral tissues such as the skin, mucosa, and gut-associated lymphoid tissue

Gamma-delta (γ/δ) T cells located in what organ

Gamma-delta (γ/δ) T cells

This subset of T cells are less prevalent in humans but are more abundant in certain non-mammalian species, including some reptiles and birds.

naïve T cells encounter antigens > activation and clonal expansion > activated T cells differentiates into memory T cells

How T cell memory develops

Classical

This pathway begins with a complement protein called C1.

Classical

Its pathway is via antigen-antibody complexes

Lectin

this pathway is via MBL-MASP complexes

Alternative

Discovered after Classical Pathway, but much older evolutionary

Alternative

This pathway utilizes a distinct C3 convertase.

C1

Classical pathway begins with

C1 > C1q> C1r> C1s > C4 and C2 > C2a and C4b > C4b2a complex > C3 convertase

Explain Classic Pathway

MBL or Ficolin > complexes with MASP-1 and MASP-2 > activation of MASP-2 > C4 and C2 > C4b2a complexes > C3 convertase

Explain Lectin pathway

C3b > cleaved to Factor B > Factor D cleave Factor B > C3bBb

Explain Alternative Pathway

C3b acts as a versatile immune sentinel by opsonizing pathogens, effectively tagging them for destruction by phagocytes.

Explain the significance of complement components, especially C3b

C5a can degranulate mast cells and stimulate platelets to release histamine and serotonin.

How does the complement system trigger inflammation?

Because some animals are genetically not normal.  Some are born homozygous and some are born heterozygous.

Why do deficiencies of some complement components result in increased susceptibility to infections?

Complement

Tightly regulated group of proteins that activated in sequence. Once activated, the system generates multiple effector molecules.

Factor P or Properdin

Enhances the activity of alternative pathway of complement system. It binds to the complex, it forms a stable C3bBbP complex with a half-life of 30 minutes.

Anaphylatoxins

Are is a small complement fragments produced during the activation of the complement system

C3a and C5a

Another name of anaphylatoxins

C3a

This anaphylotoxins acts like other antimicrobial peptides by disrupting bacterial membranes

C5a

This anaphylotoxin enhances TLR-induced production of TNF-a, IL-1b, IL-6.

M cells

They play a crucial role in transporting antigens from the gut lumen to immune cells, initiating immune responses.

Paneth cells

They produce and release antimicrobial substances, including defensins and lysozyme, to help protect the intestinal lining from bacterial invasion.

IELs (Intraepithelial Lymphocyte)

Are a specialized type of white blood cell found within the epithelial layer of mucosal tissues, such as the intestine. They contribute to immune surveillance and help maintain intestinal barrier function.

- γ/δ T cells

Are a subset of T lymphocytes that have a distinct T-cell receptor composed of gamma (γ) and delta (δ) chains. They play a role in various immune functions, particularly in mucosal immunity and early defense against pathogens.

The skin acts as a physical barrier to block pathogens from entering the body. It also contains specialized immune cells like Langerhans cells. The mammary gland provides immune protection to breast milk, offering passive immunity to newborns through antibodies and immune cells.

Explain the immune defenses of the skin and mammary gland

The intestine is considered the largest immune organ due to its extensive mucosal surfaces and the presence of numerous immune cells and tissues. It's a critical site for immune surveillance and defense because it is constantly exposed to a wide range of potentially harmful substances from the diet.

Describe why the intestine is the largest immune organ in the body

The respiratory system has mucous and cilia to trap and remove pathogens. It also contains immune cells in the respiratory epithelium. The genitourinary system includes mucus and natural flora that help prevent infections. Additionally, the bladder and urethra have urine flow, which can flush out potential pathogens.

Explain the defenses of respiratory and genitourinary system

Inductive sites

Site that are located in the body where immune responses are initiated, such as lymph nodes and Peyer's patches.

Effector sites

Sites where the immune responses are executed, like the site of infection or inflammation, where immune cells target and eliminate pathogens.

Immune exclusion

This mechanism prevents pathogens from entering tissues, often through physical barriers like tight junctions in the gut.

Immune elimination

This mechanism involves actively removing pathogens that have breached these barriers, using immune cells and molecules to clear the infection.

Oral tolerance

Is a phenomenon where the immune system learns to tolerate substances that are normally harmless when ingested, such as food proteins or commensal bacteria.

At birth, the adaptive immune system (including B and T cells) is relatively underdeveloped in newborns. Newborns rely primarily on their innate immune system, which provides immediate but nonspecific defense against pathogens Adaptive immune responses, including the production of antibodies by B cells, take time to mature, and infants have limited antibody diversity at birth

Explain the state of development of the innate and adaptive immune system at birth

Newborns receive passive immunity from their mother through the transfer of immunoglobulins (antibodies) via placenta (in humans) or colostrum (first milk). These maternal antibodies provide temporary protection. Maternal antibodies, particularly IgG, can cross the placenta in utero and protect the fetus. After birth, colostrum (rich in IgA) from the mother provides additional immune protection.

Explain how newborn mammals are temporarily protected against infection by transfer of immunoglobulins from their mother

Immunoglobulins (Ig) are transferred from the mother to the fetus via the placenta. This transfer is mainly IgG, providing protection against pathogens.  After birth, the mother continues to provide IgA through her breast milk (colostrum), which is absorbed by the neonatal intestine.

Explain how Ig is derived from the mother

Colostrum is the initial milk produced by the mother and is rich in antibodies, particularly IgA.  The neonatal intestine has specialized cells that can absorb IgA directly from colostrum, allowing the neonate to acquire passive immunity.

 

Describe the absorption of colostrum from the neonatal intestine

Colostrum

It is the initial milk produced after birth and is rich in antibodies, growth factors, and other protective molecules. It provides passive immunity and helps establish the neonate's gut microbiome.

Mature breast milk

This follows colostrum, continues to provide nutrition but has a lower antibody content. However, it still supports the infant's health and development.

IgG

Immunoglobulin in the placenta

IgA

Immunoglobulin in milk

If a mother has not been exposed to a specific pathogen, she may not have antibodies against it to pass on to her child.

Example of passive failure

Passive failure

This can occur when maternal antibodies are insufficient or their protection wanes too quickly.

Neonates often cannot be successfully vaccinated because their immune systems are not fully developed. Vaccines rely on the activation of the adaptive immune system, which is not as robust in neonates.

Explain why neonates can’t be successfully vaccinated

Leukotoxin

It is a type of bacterial toxin (cytotoxin) that targets and damages white blood cells (leukocytes), particularly neutrophils and macrophages. It impairs the host's immune response by affecting immune cell function.

Bacterin

Is a type of vaccine made from inactivated or killed bacteria. It is used to stimulate the immune system to produce an immune response against specific bacterial pathogens.

Heat Shock Proteins

These are a group of proteins produced by cells in response to various forms of stress, such as high temperature or infection. They play essential roles in cellular processes, including protein folding and cellular protection

Toxoid

It is inactivated form of a bacterial toxin (exotoxin). It is used as a component in vaccines to stimulate the immune system to produce antibodies against the toxin. Toxoids are used in vaccines to prevent diseases caused by bacterial toxins, such as tetanus and diphtheria.

Provides immediate defense against bacterial invasion. It involves physical barriers, phagocytic cells (like neutrophils and macrophages), complement proteins, and other immune components.

Explain the role of innate immunity in combating bacterial invasion.

PAMPS

What molecular pattern do innate immunity respond to

By binding to their surface, preventing them from infecting host cells or by tagging them for phagocytosis.

Explain how antibodies can neutralize and opsonize bacteria.

Because some bacteria can survive and replicate within host cells.

Describe why T-cell-mediated activation of macrophages is required to kill intracellular bacteria.

o   Formation of biofilms.

o   Antibiotic resistance.

o   Production of immune-evasion proteins.

o   Modification of surface antigens.

o   Ability to hide intracellularly.

o Expression of toxins.

List and briefly describe the multiple mechanisms by which bacteria resist immune destruction.

Type I

Is a type of hypersensitivity that is immediate

Type III

Is a type of hypersensitivity that is immune complex-mediated

Type II

Is a type of hypersensitivity that is antibody-mediated cytotoxic

Type IV

Is a type of hypersensitivity that is delayed-type

allergies

Example of Type I hypersensitivity

autoimmune hemolytic anemia

Example of Type II hypersensitivity

systemic lupus erythematosus

Example of Type III hypersensitivity

contact dermatitis

Example of Type IV hypersensitivity

Because fungi are eukaryotic organisms with complex structures, and they often invade host tissues more deeply. This is why T cells, especially CD4+ helper T cells, are required to activate phagocytic cells, like macrophages, which are essential for clearing fungal pathogens.

Explain why cell-mediated immune responses are usually required to protect against fungal infections.

They inhibit viral replication within infected cells, They activate neighboring cells, inducing an antiviral state, making it more difficult for the virus to infect nearby cells, They enhance the activity of natural killer (NK) cells, which can directly target infected cells.

Explain the antiviral mechanism of interferons