Topic #3: Human Immune System

Lysosome

-enzyme made by the body (tears/sweat)

-breaks linkages in peptidoglycan

-gram - =resistant (LPS)

-gram += more susceptible

-expection = S.aureus gram + but resistant due to oatA gene

Cytokines and Chemokines

chemokines= alarm system (come here)

cytokines= recruit more attackers (induce activity state)

Host defense peptides (HDP)

-protiens made by the body to interfere with pathogens

Ex: Cathelicidian (CAmp)

Cathelicidin (Camp)

-a HDP found in lysosome of phagocytes

Antibodies (immunoglobulins) + three structures

Proteins that bind to antigens on pathogens

monomer, dimer, pentamer

Regions on the antigens and what binds to them

Fab region = binding of antibodies

Fc = binding by phagocytes

The epitode

area of binding between the antibody and antigen

Complement system

-cascade of proteins that helps (is in complement) with the immune system to kill any unnoticed pathgens

Classical pathway of the complement system

1. binding of antibody

2. c1 binding

3. C3 convertase formed + splitting to c3a and c3b

c3b=opsonization

4. C5 convertase formed + splitting to c5a and c5b

c5b= MAC formation to punch hole in membrane

Alternative pathway of the complement system

no antibody binding, forms spontaneously

-c3b and c5b form still

Factor H + bacteria

-protection of our cells

-binds to our high levels of sailic acid

-prevents the formation of c3b/c3

-c3b can't bind to this factor H + sailic acid surface

bacteria can use this by decorating themselves in sailic acid!

Megakaryocyte

-platelet factory!

-in bone marrow

Natural Killer cells (NK)

-induce apoptosis

Granulocytes

1. basophils (bad allergy) -histamines

2. eosinophiles (allergies)

3. Mast cells (tissue resident and allergies)

Neutrophils

-phagocyte, respond to imflamotory signals

-creates NETS to trap pathogens

-then can be suicidal or non-suicidal

-short lived

Monocytes

-phagocytes (can attack)

-become either:

1.macrophages

2.dentritic cells

Macrophages

-large eater (vaccuum)

-phagocyte

-tissue residents

-cytokine production + antigen presentation

Macrophages activation

1. M1: classical, ROS, pro-inflammatory (kill)

2. M2: alternative, respond + support with supressive cytokines, anti-inflammatory (chill)

Dendritic cells

-antigen presentation!

-link b/w innate and adaptive

-capture and load onto MHC 2 or MHC 1

MHC II vs. MHC I

MHC II : antigen presentation of bad guys

MHC I : surveillance, comes from "ones-self"

CD8 T cells

-Cytotoxic T cells that kill infected cells

-activated when antigens are presented (locally or migratory)

CD4 T cells

-production of cytokines when bound with antigens

-help B-cells become activated

Treg cells

Regulatory T cells that suppress immune responses

-"peacekeepers"

-prevent autoimmunity

-MHC II are presented and Tregs and binds to these safe antigens

B cells

antibody factory!

-must be activated by T cells

-become plasma cells

-switches from IgM to IgG to make antibodies

T/B cell receptors -recombination

-creation of receptors by rearrangement of segments (V,J,D) in their DNA

B-cells and somatic hypermutation

-rapid mutations in antibody genes in increase affinity for antigens, after T-cell activation

CDR loop in T-cells

-small loop regions in the T cell receptor (TCR) that directly bind the antigen to MHC complex

Memory T/B cells

-can become effector cells or memory cells (stay in lymph tissues)

Oral tolerance

The suppression of specific systemic immune responses to an antigen by the prior administration of the same antigen by the oral (enteric) route.

-in GI tract (constant sampling to T regs) -for supression

Immune privileged sites

-areas of the body that have reduced immune system activity (eyes, brain, fetus, testis)

-less MHC and more factor H

-inflammation can be a serious issue here, so must be supressed

Central tolerance (developing)

-exposure of self antigens (MHC I) to T/B cells

-if cell has high affinity=removed

-low affinity=go to the peripheral

-must eliminated self-reactive cells to protect body!

Peripheral tolerance (mature)

-mediation of T/B cells that are still binding/active after central tolerance

Treg - peripheral tolerance

-supression of self-antigen reaction

Tolerogenic Dendritic Cells - peripheral tolerance

-presentation of self-antigens to T-cells

-if it binds = must be turned off or eliminated

Lymph Node Stromal Cells - peripheral tolerance (LNSC)

-presentation of self-antigens to T-cells

-if it binds = must be turned off or eliminated

Autoimmunity

when tolerance fails!

Autoimmunity - Weakly stimulating self-antigens

-surpasses central tolerance due to weak binding, then can later become activated

Autoimmunity - Stimulating self-antigens

-surpasses tolerance and can have strong binding to T-cells and then wrong cells to be targeted

Autoimmunity - Foriegn Antigen + example

-trigger self-antigen destruction because it looks very similar to self-antigen

-molecular mimicry to attack ourselves

Ex: Rheumatic fever -proteins produced look just like heart tissue :((

Superantigens

-binding of t-cell receptor outside = very big cytokine storm trigger

-link the TCR directly to the MHC class II

-normal = 0.01% (classical) -high specificity

-superantigen = 20% (less specificity)

Examples of autoimmune diseases

-MS

-Celiac

Allergies

-when body reacts to environmental things that are harmless

-Trigger of mast cells, eosiphiles and basophiles to produce histamines and causes symptoms.